Endoscopic submucosal dissection: the first reported experience from a New Zealand centre
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Cancers of the gastrointestinal tract (GIT) account for 26% of cancers diagnosed and 35% of all cancer related deaths worldwide.[[1]] Both internationally and within New Zealand, oesophageal, gastric and colon cancer incidence are increasing.[[2–5]] Strategies such as screening programmes have been introduced to aid in detection, with resultant earlier stage diagnosis of cancer.[[6–9]]
Curative endoscopic therapy is possible for such cancers or precancerous lesions if they are detected at an early stage when the depth of neoplastic invasion is small and therefore the risk of lymph node metastasis is low.[[10]] Attempts at endoscopic treatment of such lesions have been largely performed in the western world and in New Zealand using endoscopic mucosal resection (EMR). This technique was first described in 1955 in rigid sigmoidoscopy[[11]] and later adapted for flexible colonoscopy in 1973.[[12]] This procedure involves injection of a fluid cushion into the submucosal space to separate the lesion from the underlying muscular layer, with final resection using a metal snare. EMR of larger lesions (≥15mm) may require removal in fragmented pieces (“piecemeal”), which limits histological assessment, tumour staging, subsequent stratification of therapeutic approach and potential cure.[[13]] This method also results in a significantly increased risk of recurrence.[[14,15]] Inability to determine adequacy of resection according to oncologic standards (en-bloc and R0) may lead to organ resection surgery which may not have been necessary.
To overcome these issues, endoscopic submucosal dissection (ESD) was pioneered in 1998 in Japan initially to treat early gastric cancer.[[16]] This has now expanded to include the entire GIT and is considered the standard of care for neoplastic lesions in Japan and Korea, as well as being included in Western society guidelines as the gold-standard treatment for superficial lesions.[[17,18]] When the criteria for anatomopathological curability are met, ESD has the same treatment efficacy as surgical resection.[[19–23]]
The essence of the technique is similar to EMR. However, the methodology of cutting the lesion differs. ESD generally employs a small (1.5–2mm) electrocautery metal needle to precisely cut freehand the lesion away from the muscular layer in one section (en-bloc). ESD thus allows higher en-bloc and curative resection compared with EMR in the oesophagus, stomach and colon.[[15,24–27]] In addition to patient acceptability with organ preservation, decreased length of hospital stay (11 vs 2 days; p<0.0001) and lower morbidity (28% vs 14%; p=0.06), there is a significant lower cost (€8960 vs €1770; p<0.0001) when compared to surgery.[[21,28,29]] It has comparable costs with EMR for large lesions in the colorectum, with additional benefit of reduction of burden of follow-up endoscopy.[[30,31]]These benefits come at the expense of significantly increased procedural time and an increased complication rate, including bleeding and perforation (OR 2.20 and OR 4.09), compared to EMR.[[15,32,33]] Therefore, particularly in the colorectum, case selection is paramount.[[34]]
Traditionally the majority of ESD literature emanates from Asia, with series and outcomes from high volume centres and experienced practitioners, which may not reflect local experience. However, more recently large publications from Western centres have shown comparable results, particularly in the upper GIT.[[35–40]] Whilst ESD has been performed in New Zealand by a select few practitioners over the years, no data have been published on cases and outcomes, and Australasian data in general are similarly scarce.[[41,42]]
Prior to this study, ESD had been performed infrequently at Waitemāta District Health Board (WDHB). This hospital services a population of nearly 630,000 people. To further develop this service, Dr Schauer was awarded a scholarship from the Japanese Society of Gastroenterology for a Fellowship programme at NTT Hospital in Tokyo, Japan. This hospital is one of the highest-volume ESD centres in the world, performing over 900 resections per year, including duodenal and oropharyngeal cases.[[43]] This fellowship involved systematic teaching on lesion detection and staging with image-enhanced endoscopy to ensure correct indications for ESD, tutoring of resection principles, animal model workshops, case observation and finally supervised procedures with patients.[[44]]
We present the first report of patient demographics, outcomes and complications of ESD from a single tertiary centre in New Zealand.
Methods
Following specific advice and systematic suggestion for building and maintaining a high-quality service,[[45–47]] we began to prospectively collect key performance indicators for all patients undergoing ESD between January 2020 and July 2021. Regular review of lesion selection and ESD practice was undertaken by recorded video assessment with Dr Yohei Minato from NTT Hospital, with subsequent feedback and discussion.
Patient selection
The indication in each patient was according to consensus Japanese guidelines.[[48–50]] All patients with lesions possibly amenable for ESD were discussed in a multidisciplinary meeting (MDM). Referrals were gained from gastroenterology, upper gastrointestinal and colorectal surgery. In addition, cases were referred from Whangārei Hospital via the MDM.
Lesions were accepted for ESD for either primary curative, diagnostic and/or curative intent, or less common staging (assumption of deep malignant invasion but unclear as to extent with other modalities). All procedures were performed at North Shore Hospital by three senior endoscopists, who had also attended international hands on ESD courses. All patients gave informed consent prior to their procedures.
Procedure and pathological review
Procedures were completed under either local sedation with fentanyl or midazolam, anaesthetist-assisted propofol or general anaesthesia. Submucosal injectate was either gelofusion with methylene blue or Orise gel (Boston Scientific). Knives used were either dual-knife J or IT-knife (Olympus). In all cases, we used a high frequency electrosurgical unit (Erbe Elektromedizin, Tübingen, Germany).
Submucosal fibrosis is known to increase the rate of perforation and effect the success rate of en-bloc resection. This was assessed and recorded based on the findings identified at the time of ESD and classified F0 (no fibrosis), F1 (mild fibrosis) and F2 (severe fibrosis).[[51,52]] Traction was not used in any cases.
All pathological specimens were pinned flat to cork to assist histological assessment and fixed in 10% formalin, with review performed by GIT pathologists including assessment for clearance of both vertical and lateral margins.
Endoscopic outcomes
“En-bloc resection” was defined as removal of a lesion in one piece. A successful histological resection (R0) was one where the lesion was removed with clear vertical and lateral margins. “R1” was defined as a lesion with a positive margin. “Curative resection” was defined as tumour-free vertical or lateral margins in a resected lesion and absence of vascular or lymphatic involvement. It was also defined by invasion <1,000μm, <500μm and <200μm from the muscularis mucosa in colorectal, gastric and oesophageal lesions respectively (ie, meeting the criteria for indication of treatment).[[17]] Significant bleeding was pre-determined to be defined as that requiring blood transfusion and repeat endoscopy after the ESD procedure. “Deep injury” was defined as visible damage to the muscularis propria layer without perforation. Perforation was defined as complete muscular defect requiring closure, categorised as either immediate or delayed (occurring after the conclusion of the procedure). All patients were followed up to assess the site and check for recurrence.
Results
Between January 2020 and July 2021, 29 ESD procedures were performed in 27 patients (Table 1). The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median and mean lesion diameter resected was 30mm (interquartile range (IQR) 20–58mm) and 42mm (SD 28mm) respectively. The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180), giving an average dissection speed of 0.08cm[[2]]/minute.
In total, 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one, an 82-year-old lady with a 15mm, poorly differentiated gastric cancer, which was invading 450μm into the submucosa. The patient opted against operative management offered and will undergo surveillance.
Muscular defects (deep injury) without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. In one patient with an 80mm rectal lesion, perforation was identified at time of endoscopy and treated, but subsequently required readmission on day five post procedure, with fever and a retroperitoneal collection seen on imaging that resolved after five days of intravenous antibiotics (this is the single case of severe adverse event within 30 days). There were no cases of immediate or delayed bleeding or death.
Gastric ESD was most commonly performed, including two synchronous lesions. Five lesions were located in the antrum, three in the cardia, three in the corpus, three on the incisura and one in the pyloric channel. One perforation in a patient was closed at the time of procedure without complication. Two of the cases located in the cardia were felt to be highly suspicious for deep submucosal invasive cancer (SMIC), but the MDM agreed a diagnostic ESD was required to confirm or refute the suspected diagnosis, given the possibility of extensive surgery required. Similarly, a 55mm lesion within Barrett’s oesophagus was suspicious for deep SMIC, but the patient and treating team requested diagnostic ESD. Deep SMIC was demonstrated in these Three cases. Seven (70%) of the colorectal cases were performed in the rectum. The other three cases were located in the transverse, descending and sigmoid colon. Two rectal lesions were performed for previous failed EMR including adenocarcinoma arising with a traditional serrated adenoma with significant (F2) fibrosis. The third case with severe fibrosis was a polyp growing over a previous haemorrhoidal banding scar.
In the eight cases with R1 resection (28%), four gastric lesions had deep SMIC and proceeded to gastrectomy. An oesophageal lesion with deep SMIC and positive vertical margin proceeded to Ivor-Lewis oesophagogastrectomy, and another oesophageal lesion with a positive lateral margin was site checked without recurrence. One rectal lesion with a positive lateral margin was site checked without recurrence, and a descending colon lesion with a positive lateral margin was site checked with regrowth of HGD requiring further endoscopic treatment.
Table 1: Patient demographics, lesion characteristics and results. View Table 1.
Discussion
In this first New Zealand prospective report of ESD, we demonstrate clinical success, efficacy and safety of this procedure.
En-bloc and R0 resection rates of 86% and 72% are slightly better than a similar Australian centre’s series (80% and 60% respectively)[[41]] and are in keeping with larger Western series at 77–92% and 73–100% respectively.[[46,53–56]] Our overall R0 resection rate is reduced by three diagnostic cases where the vertical margins were positive in lesions which pre-procedure were highly suspicious of deep SMIC.
There were no cases of delayed bleeding, perforation or death, which we attribute to fastidious post-ESD resection bed review, including cautious inspection of possible muscular injury and subsequent clip placement. This likely contributed to an over-estimation of deep injury (34%). Patients are currently admitted post-ESD for observation on a case-by-case basis, depending on lesion location, size, difficulty, age, co-morbidity, geographical residence (ie, travelling from rural area) and sedation type. There is suggestion that perhaps more cases could be done as day-stay procedures,[[57,58]] which may make ESD even more cost-effective. Six of our cases were discharged same day, and with no cases of delayed complication, more patients may be able to be considered for this in the future.
We have placed great emphasis on case and lesion evaluation, decision-making with regard to proper indication and thorough discussion of each patient as a group and at the MDM. Although some centres avoid biopsy of lesions prior to consideration of endoscopic resection for fear of causing scarring and fibrosis, we have generally encouraged this to assist in our decision-making. This is in conjunction with fastidious mucosal inspection protocols, magnified endoscopic vascular and structural pattern analysis and chromoscopy to most exactly determine predicted final pathology. This is reflected in our 93% pre-endoscopic prediction accuracy, and high curative resection rate. We believe this time taken on lesion assessment and risk stratification is important to avoid possible over or undertreatment, and provide the safest, most resourceful outcome tailored to pathology.[[13]] Although it is not an internationally benchmarked indicator, we feel review of our final histological outcomes confirms an overall appropriate lesion selection.
The additional time required for ESD is often discussed and debated in the literature as a drawback, with a number of techniques and devices utilised to improve dissection speed. An overall speed of dissection benchmark of 0.15cm[[2]]/min is suggested.[[46]] Although this was obtained in the colorectum (0.16cm[[2]]/min), likely owing to the larger size of rectal cases and stable endoscopic access, we were slower in stomach and oesophagus (0.08cm[[2]]/min). Although we have initially emphasised safety, efficiency of the procedure is vital, in particular in the upper GIT tract when cases are performed with local sedation only and procedural time is limited by patient tolerance. Ongoing video review of cases with experts to improve technique will further improve efficacy and efficiency.
ESD is the standard of care and a well-established procedure in Asia, but it has been slower to penetrate Western countries. This delay in uptake has been widely criticised, discussed and debated and is likely multifactorial.[[45–47,59]]It is postulated to be due to its high technical proficiency requirement, the time commitment for both learning and doing procedures and steep learning curve, a lack of mentors, interdisciplinary conflicts, concern regarding complications and a lack of support from institutions and interfacing departments.[[47]] There is a comparatively low frequency of early gastric cancers compared to Eastern populations, which limits skill acquisition and training opportunities.[[47]] Finally, its uptake has been further limited by the absence of appropriate reimbursement systems in countries such as USA where this is an important factor.[[28]] However, demand for this procedure in New Zealand is likely to grow as rates of GIT tumours increase. Oesphageal cancer is increasing in incidence. In New Zealand in 1950, the age standardised registration rate was 2.2/100,000 with 46 cases diagnosed, which increased to 4.3/100,000 with 364 cases diagnosed by 2000.[[3]] In addition, over 400 new cancers of gastric cancer are diagnosed each year.[[4]] Both have documented significant ethnic inequality, with Māori having both an increased incidence and mortality.[[60–62]] These rates are expected to rise with increased immigration from Asian countries where rates are over five-times higher.[[2,63]] Finally, colorectal cancer (CRC) is both the second most common cancer diagnosed and cause of cancer death in New Zealand, as absolute rates continue to rise in the face of an ageing and increasing population.[[5,64]] Improved access to endoscopic evaluation, earlier detection of lesions through the National Bowel Cancer Screening Programme and increased awareness of detection of early cancer are likely to further drive ESD volume and growth. Such volume is key to ongoing improvement of outcome measures and rates of complications.[[65]] Current short-term projections for our service demonstrate referral growth and capacity to complete at least 3–4 cases per month.
Finally, critical in success of this programme is ongoing support from surgical, gastroenterology, pathology, oncology and anaesthetic colleagues. We have fostered an understanding and supportive environment, where patients are able to be presented with a full picture of pros, cons, risks and alternatives for potential options for management of their lesion. Additional assistance is needed from hospital management teams to accommodate these procedures while competing with other interventional third-space procedures, such as peroral endoscopic myotomy (POEM), endoscopic diverticulotomy, submucosal tunnelling endoscopic resection (STER) and full thickness resection (FTR). An important area of improvement to target must include formalising inter-district-health-board referral pathways, such that patients may have equal access to this procedure, and be seen and treated in a timely manner, irrespective of their geographical location. We hope publication of this work will help to inform clinicians that this procedure is available and accessible. Furthermore, ongoing data collection and audit with respect to ethnicity and inequality must be paramount. It is known that Māori present with more advanced disease, which may explain why none were treated in this series. However, there is a demonstrably higher overall mortality irrespective of stage, with access to specialised cancer services postulated to be contributory, and we must review our service with this in mind.[[66,67]]
Strengths of this paper include reflection of a real-world experience of cases with varying location, difficulty, fibrosis and size. This series also included a 10cm gastric antral lesion (Figure 1) that was completely resected, en-bloc and R0. Prospective sequential patient data collection and complete data and follow-up limit bias. Study outcomes include all defined quality indicators for ESD.
Limitations of note include lack of collection and reporting of all cases referred for ESD. Many patients, in particular proximal laterally spreading colonic lesions were deferred for piecemeal EMR with its current superior speed, safety and efficacy.[[34]] Not all lesions were followed to final treatment outcome and histological review, some of which may have been inaccurately assessed and perhaps were better suited for ESD removal. In spite of the favourable ESD outcomes achieved in this study, some lesions may have been adequately treated with EMR techniques based on the retrospective assessment of the final ESD histology. A full financial assessment was not performed and is beyond the scope of this paper, but should be considered in future studies to assess cost effectiveness compared to possible surgery, but also EMR. Lastly, at the time of publication, patients have not been followed for the requisite years to assess for potential long-term recurrence rates, and both cancer-specific and all-cause mortality.
In conclusion, this initial prospective ESD data demonstrates clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Figure 1: Endoscopic submucosal dissection (ESD) of gastric lesion.
Summary
Abstract
Aim
Endoscopic submucosal dissection (ESD) is internationally accepted as a minimally invasive procedure to treat early gastrointestinal cancers endoscopically. Uptake of this procedure in the West is limited. No published data are available in New Zealand. We aimed to evaluate outcomes of this procedure at North Shore Hospital, Auckland.
Method
Following an overseas fellowship training period, we prospectively collected clinical outcomes, complications and defined quality indicators for patients undergoing ESD referred following a multidisciplinary meeting.
Results
Between January 2020 until July 2021, 29 ESD procedures were performed in 27 patients, including 14 gastric, five oesophageal and 10 colorectal cases. The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median lesion size resected was 30mm (interquartile range (IQR) 20–58mm). The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180). 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one. Muscular defects without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. There were no cases of delayed bleeding, perforation or mortality.
Conclusion
These data demonstrate clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Author Information
Acknowledgements
Correspondence
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Competing Interests
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Endoscopic submucosal dissection: the first reported experience from a New Zealand centre
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Cancers of the gastrointestinal tract (GIT) account for 26% of cancers diagnosed and 35% of all cancer related deaths worldwide.[[1]] Both internationally and within New Zealand, oesophageal, gastric and colon cancer incidence are increasing.[[2–5]] Strategies such as screening programmes have been introduced to aid in detection, with resultant earlier stage diagnosis of cancer.[[6–9]]
Curative endoscopic therapy is possible for such cancers or precancerous lesions if they are detected at an early stage when the depth of neoplastic invasion is small and therefore the risk of lymph node metastasis is low.[[10]] Attempts at endoscopic treatment of such lesions have been largely performed in the western world and in New Zealand using endoscopic mucosal resection (EMR). This technique was first described in 1955 in rigid sigmoidoscopy[[11]] and later adapted for flexible colonoscopy in 1973.[[12]] This procedure involves injection of a fluid cushion into the submucosal space to separate the lesion from the underlying muscular layer, with final resection using a metal snare. EMR of larger lesions (≥15mm) may require removal in fragmented pieces (“piecemeal”), which limits histological assessment, tumour staging, subsequent stratification of therapeutic approach and potential cure.[[13]] This method also results in a significantly increased risk of recurrence.[[14,15]] Inability to determine adequacy of resection according to oncologic standards (en-bloc and R0) may lead to organ resection surgery which may not have been necessary.
To overcome these issues, endoscopic submucosal dissection (ESD) was pioneered in 1998 in Japan initially to treat early gastric cancer.[[16]] This has now expanded to include the entire GIT and is considered the standard of care for neoplastic lesions in Japan and Korea, as well as being included in Western society guidelines as the gold-standard treatment for superficial lesions.[[17,18]] When the criteria for anatomopathological curability are met, ESD has the same treatment efficacy as surgical resection.[[19–23]]
The essence of the technique is similar to EMR. However, the methodology of cutting the lesion differs. ESD generally employs a small (1.5–2mm) electrocautery metal needle to precisely cut freehand the lesion away from the muscular layer in one section (en-bloc). ESD thus allows higher en-bloc and curative resection compared with EMR in the oesophagus, stomach and colon.[[15,24–27]] In addition to patient acceptability with organ preservation, decreased length of hospital stay (11 vs 2 days; p<0.0001) and lower morbidity (28% vs 14%; p=0.06), there is a significant lower cost (€8960 vs €1770; p<0.0001) when compared to surgery.[[21,28,29]] It has comparable costs with EMR for large lesions in the colorectum, with additional benefit of reduction of burden of follow-up endoscopy.[[30,31]]These benefits come at the expense of significantly increased procedural time and an increased complication rate, including bleeding and perforation (OR 2.20 and OR 4.09), compared to EMR.[[15,32,33]] Therefore, particularly in the colorectum, case selection is paramount.[[34]]
Traditionally the majority of ESD literature emanates from Asia, with series and outcomes from high volume centres and experienced practitioners, which may not reflect local experience. However, more recently large publications from Western centres have shown comparable results, particularly in the upper GIT.[[35–40]] Whilst ESD has been performed in New Zealand by a select few practitioners over the years, no data have been published on cases and outcomes, and Australasian data in general are similarly scarce.[[41,42]]
Prior to this study, ESD had been performed infrequently at Waitemāta District Health Board (WDHB). This hospital services a population of nearly 630,000 people. To further develop this service, Dr Schauer was awarded a scholarship from the Japanese Society of Gastroenterology for a Fellowship programme at NTT Hospital in Tokyo, Japan. This hospital is one of the highest-volume ESD centres in the world, performing over 900 resections per year, including duodenal and oropharyngeal cases.[[43]] This fellowship involved systematic teaching on lesion detection and staging with image-enhanced endoscopy to ensure correct indications for ESD, tutoring of resection principles, animal model workshops, case observation and finally supervised procedures with patients.[[44]]
We present the first report of patient demographics, outcomes and complications of ESD from a single tertiary centre in New Zealand.
Methods
Following specific advice and systematic suggestion for building and maintaining a high-quality service,[[45–47]] we began to prospectively collect key performance indicators for all patients undergoing ESD between January 2020 and July 2021. Regular review of lesion selection and ESD practice was undertaken by recorded video assessment with Dr Yohei Minato from NTT Hospital, with subsequent feedback and discussion.
Patient selection
The indication in each patient was according to consensus Japanese guidelines.[[48–50]] All patients with lesions possibly amenable for ESD were discussed in a multidisciplinary meeting (MDM). Referrals were gained from gastroenterology, upper gastrointestinal and colorectal surgery. In addition, cases were referred from Whangārei Hospital via the MDM.
Lesions were accepted for ESD for either primary curative, diagnostic and/or curative intent, or less common staging (assumption of deep malignant invasion but unclear as to extent with other modalities). All procedures were performed at North Shore Hospital by three senior endoscopists, who had also attended international hands on ESD courses. All patients gave informed consent prior to their procedures.
Procedure and pathological review
Procedures were completed under either local sedation with fentanyl or midazolam, anaesthetist-assisted propofol or general anaesthesia. Submucosal injectate was either gelofusion with methylene blue or Orise gel (Boston Scientific). Knives used were either dual-knife J or IT-knife (Olympus). In all cases, we used a high frequency electrosurgical unit (Erbe Elektromedizin, Tübingen, Germany).
Submucosal fibrosis is known to increase the rate of perforation and effect the success rate of en-bloc resection. This was assessed and recorded based on the findings identified at the time of ESD and classified F0 (no fibrosis), F1 (mild fibrosis) and F2 (severe fibrosis).[[51,52]] Traction was not used in any cases.
All pathological specimens were pinned flat to cork to assist histological assessment and fixed in 10% formalin, with review performed by GIT pathologists including assessment for clearance of both vertical and lateral margins.
Endoscopic outcomes
“En-bloc resection” was defined as removal of a lesion in one piece. A successful histological resection (R0) was one where the lesion was removed with clear vertical and lateral margins. “R1” was defined as a lesion with a positive margin. “Curative resection” was defined as tumour-free vertical or lateral margins in a resected lesion and absence of vascular or lymphatic involvement. It was also defined by invasion <1,000μm, <500μm and <200μm from the muscularis mucosa in colorectal, gastric and oesophageal lesions respectively (ie, meeting the criteria for indication of treatment).[[17]] Significant bleeding was pre-determined to be defined as that requiring blood transfusion and repeat endoscopy after the ESD procedure. “Deep injury” was defined as visible damage to the muscularis propria layer without perforation. Perforation was defined as complete muscular defect requiring closure, categorised as either immediate or delayed (occurring after the conclusion of the procedure). All patients were followed up to assess the site and check for recurrence.
Results
Between January 2020 and July 2021, 29 ESD procedures were performed in 27 patients (Table 1). The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median and mean lesion diameter resected was 30mm (interquartile range (IQR) 20–58mm) and 42mm (SD 28mm) respectively. The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180), giving an average dissection speed of 0.08cm[[2]]/minute.
In total, 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one, an 82-year-old lady with a 15mm, poorly differentiated gastric cancer, which was invading 450μm into the submucosa. The patient opted against operative management offered and will undergo surveillance.
Muscular defects (deep injury) without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. In one patient with an 80mm rectal lesion, perforation was identified at time of endoscopy and treated, but subsequently required readmission on day five post procedure, with fever and a retroperitoneal collection seen on imaging that resolved after five days of intravenous antibiotics (this is the single case of severe adverse event within 30 days). There were no cases of immediate or delayed bleeding or death.
Gastric ESD was most commonly performed, including two synchronous lesions. Five lesions were located in the antrum, three in the cardia, three in the corpus, three on the incisura and one in the pyloric channel. One perforation in a patient was closed at the time of procedure without complication. Two of the cases located in the cardia were felt to be highly suspicious for deep submucosal invasive cancer (SMIC), but the MDM agreed a diagnostic ESD was required to confirm or refute the suspected diagnosis, given the possibility of extensive surgery required. Similarly, a 55mm lesion within Barrett’s oesophagus was suspicious for deep SMIC, but the patient and treating team requested diagnostic ESD. Deep SMIC was demonstrated in these Three cases. Seven (70%) of the colorectal cases were performed in the rectum. The other three cases were located in the transverse, descending and sigmoid colon. Two rectal lesions were performed for previous failed EMR including adenocarcinoma arising with a traditional serrated adenoma with significant (F2) fibrosis. The third case with severe fibrosis was a polyp growing over a previous haemorrhoidal banding scar.
In the eight cases with R1 resection (28%), four gastric lesions had deep SMIC and proceeded to gastrectomy. An oesophageal lesion with deep SMIC and positive vertical margin proceeded to Ivor-Lewis oesophagogastrectomy, and another oesophageal lesion with a positive lateral margin was site checked without recurrence. One rectal lesion with a positive lateral margin was site checked without recurrence, and a descending colon lesion with a positive lateral margin was site checked with regrowth of HGD requiring further endoscopic treatment.
Table 1: Patient demographics, lesion characteristics and results. View Table 1.
Discussion
In this first New Zealand prospective report of ESD, we demonstrate clinical success, efficacy and safety of this procedure.
En-bloc and R0 resection rates of 86% and 72% are slightly better than a similar Australian centre’s series (80% and 60% respectively)[[41]] and are in keeping with larger Western series at 77–92% and 73–100% respectively.[[46,53–56]] Our overall R0 resection rate is reduced by three diagnostic cases where the vertical margins were positive in lesions which pre-procedure were highly suspicious of deep SMIC.
There were no cases of delayed bleeding, perforation or death, which we attribute to fastidious post-ESD resection bed review, including cautious inspection of possible muscular injury and subsequent clip placement. This likely contributed to an over-estimation of deep injury (34%). Patients are currently admitted post-ESD for observation on a case-by-case basis, depending on lesion location, size, difficulty, age, co-morbidity, geographical residence (ie, travelling from rural area) and sedation type. There is suggestion that perhaps more cases could be done as day-stay procedures,[[57,58]] which may make ESD even more cost-effective. Six of our cases were discharged same day, and with no cases of delayed complication, more patients may be able to be considered for this in the future.
We have placed great emphasis on case and lesion evaluation, decision-making with regard to proper indication and thorough discussion of each patient as a group and at the MDM. Although some centres avoid biopsy of lesions prior to consideration of endoscopic resection for fear of causing scarring and fibrosis, we have generally encouraged this to assist in our decision-making. This is in conjunction with fastidious mucosal inspection protocols, magnified endoscopic vascular and structural pattern analysis and chromoscopy to most exactly determine predicted final pathology. This is reflected in our 93% pre-endoscopic prediction accuracy, and high curative resection rate. We believe this time taken on lesion assessment and risk stratification is important to avoid possible over or undertreatment, and provide the safest, most resourceful outcome tailored to pathology.[[13]] Although it is not an internationally benchmarked indicator, we feel review of our final histological outcomes confirms an overall appropriate lesion selection.
The additional time required for ESD is often discussed and debated in the literature as a drawback, with a number of techniques and devices utilised to improve dissection speed. An overall speed of dissection benchmark of 0.15cm[[2]]/min is suggested.[[46]] Although this was obtained in the colorectum (0.16cm[[2]]/min), likely owing to the larger size of rectal cases and stable endoscopic access, we were slower in stomach and oesophagus (0.08cm[[2]]/min). Although we have initially emphasised safety, efficiency of the procedure is vital, in particular in the upper GIT tract when cases are performed with local sedation only and procedural time is limited by patient tolerance. Ongoing video review of cases with experts to improve technique will further improve efficacy and efficiency.
ESD is the standard of care and a well-established procedure in Asia, but it has been slower to penetrate Western countries. This delay in uptake has been widely criticised, discussed and debated and is likely multifactorial.[[45–47,59]]It is postulated to be due to its high technical proficiency requirement, the time commitment for both learning and doing procedures and steep learning curve, a lack of mentors, interdisciplinary conflicts, concern regarding complications and a lack of support from institutions and interfacing departments.[[47]] There is a comparatively low frequency of early gastric cancers compared to Eastern populations, which limits skill acquisition and training opportunities.[[47]] Finally, its uptake has been further limited by the absence of appropriate reimbursement systems in countries such as USA where this is an important factor.[[28]] However, demand for this procedure in New Zealand is likely to grow as rates of GIT tumours increase. Oesphageal cancer is increasing in incidence. In New Zealand in 1950, the age standardised registration rate was 2.2/100,000 with 46 cases diagnosed, which increased to 4.3/100,000 with 364 cases diagnosed by 2000.[[3]] In addition, over 400 new cancers of gastric cancer are diagnosed each year.[[4]] Both have documented significant ethnic inequality, with Māori having both an increased incidence and mortality.[[60–62]] These rates are expected to rise with increased immigration from Asian countries where rates are over five-times higher.[[2,63]] Finally, colorectal cancer (CRC) is both the second most common cancer diagnosed and cause of cancer death in New Zealand, as absolute rates continue to rise in the face of an ageing and increasing population.[[5,64]] Improved access to endoscopic evaluation, earlier detection of lesions through the National Bowel Cancer Screening Programme and increased awareness of detection of early cancer are likely to further drive ESD volume and growth. Such volume is key to ongoing improvement of outcome measures and rates of complications.[[65]] Current short-term projections for our service demonstrate referral growth and capacity to complete at least 3–4 cases per month.
Finally, critical in success of this programme is ongoing support from surgical, gastroenterology, pathology, oncology and anaesthetic colleagues. We have fostered an understanding and supportive environment, where patients are able to be presented with a full picture of pros, cons, risks and alternatives for potential options for management of their lesion. Additional assistance is needed from hospital management teams to accommodate these procedures while competing with other interventional third-space procedures, such as peroral endoscopic myotomy (POEM), endoscopic diverticulotomy, submucosal tunnelling endoscopic resection (STER) and full thickness resection (FTR). An important area of improvement to target must include formalising inter-district-health-board referral pathways, such that patients may have equal access to this procedure, and be seen and treated in a timely manner, irrespective of their geographical location. We hope publication of this work will help to inform clinicians that this procedure is available and accessible. Furthermore, ongoing data collection and audit with respect to ethnicity and inequality must be paramount. It is known that Māori present with more advanced disease, which may explain why none were treated in this series. However, there is a demonstrably higher overall mortality irrespective of stage, with access to specialised cancer services postulated to be contributory, and we must review our service with this in mind.[[66,67]]
Strengths of this paper include reflection of a real-world experience of cases with varying location, difficulty, fibrosis and size. This series also included a 10cm gastric antral lesion (Figure 1) that was completely resected, en-bloc and R0. Prospective sequential patient data collection and complete data and follow-up limit bias. Study outcomes include all defined quality indicators for ESD.
Limitations of note include lack of collection and reporting of all cases referred for ESD. Many patients, in particular proximal laterally spreading colonic lesions were deferred for piecemeal EMR with its current superior speed, safety and efficacy.[[34]] Not all lesions were followed to final treatment outcome and histological review, some of which may have been inaccurately assessed and perhaps were better suited for ESD removal. In spite of the favourable ESD outcomes achieved in this study, some lesions may have been adequately treated with EMR techniques based on the retrospective assessment of the final ESD histology. A full financial assessment was not performed and is beyond the scope of this paper, but should be considered in future studies to assess cost effectiveness compared to possible surgery, but also EMR. Lastly, at the time of publication, patients have not been followed for the requisite years to assess for potential long-term recurrence rates, and both cancer-specific and all-cause mortality.
In conclusion, this initial prospective ESD data demonstrates clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Figure 1: Endoscopic submucosal dissection (ESD) of gastric lesion.
Summary
Abstract
Aim
Endoscopic submucosal dissection (ESD) is internationally accepted as a minimally invasive procedure to treat early gastrointestinal cancers endoscopically. Uptake of this procedure in the West is limited. No published data are available in New Zealand. We aimed to evaluate outcomes of this procedure at North Shore Hospital, Auckland.
Method
Following an overseas fellowship training period, we prospectively collected clinical outcomes, complications and defined quality indicators for patients undergoing ESD referred following a multidisciplinary meeting.
Results
Between January 2020 until July 2021, 29 ESD procedures were performed in 27 patients, including 14 gastric, five oesophageal and 10 colorectal cases. The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median lesion size resected was 30mm (interquartile range (IQR) 20–58mm). The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180). 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one. Muscular defects without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. There were no cases of delayed bleeding, perforation or mortality.
Conclusion
These data demonstrate clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
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Endoscopic submucosal dissection: the first reported experience from a New Zealand centre
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Cancers of the gastrointestinal tract (GIT) account for 26% of cancers diagnosed and 35% of all cancer related deaths worldwide.[[1]] Both internationally and within New Zealand, oesophageal, gastric and colon cancer incidence are increasing.[[2–5]] Strategies such as screening programmes have been introduced to aid in detection, with resultant earlier stage diagnosis of cancer.[[6–9]]
Curative endoscopic therapy is possible for such cancers or precancerous lesions if they are detected at an early stage when the depth of neoplastic invasion is small and therefore the risk of lymph node metastasis is low.[[10]] Attempts at endoscopic treatment of such lesions have been largely performed in the western world and in New Zealand using endoscopic mucosal resection (EMR). This technique was first described in 1955 in rigid sigmoidoscopy[[11]] and later adapted for flexible colonoscopy in 1973.[[12]] This procedure involves injection of a fluid cushion into the submucosal space to separate the lesion from the underlying muscular layer, with final resection using a metal snare. EMR of larger lesions (≥15mm) may require removal in fragmented pieces (“piecemeal”), which limits histological assessment, tumour staging, subsequent stratification of therapeutic approach and potential cure.[[13]] This method also results in a significantly increased risk of recurrence.[[14,15]] Inability to determine adequacy of resection according to oncologic standards (en-bloc and R0) may lead to organ resection surgery which may not have been necessary.
To overcome these issues, endoscopic submucosal dissection (ESD) was pioneered in 1998 in Japan initially to treat early gastric cancer.[[16]] This has now expanded to include the entire GIT and is considered the standard of care for neoplastic lesions in Japan and Korea, as well as being included in Western society guidelines as the gold-standard treatment for superficial lesions.[[17,18]] When the criteria for anatomopathological curability are met, ESD has the same treatment efficacy as surgical resection.[[19–23]]
The essence of the technique is similar to EMR. However, the methodology of cutting the lesion differs. ESD generally employs a small (1.5–2mm) electrocautery metal needle to precisely cut freehand the lesion away from the muscular layer in one section (en-bloc). ESD thus allows higher en-bloc and curative resection compared with EMR in the oesophagus, stomach and colon.[[15,24–27]] In addition to patient acceptability with organ preservation, decreased length of hospital stay (11 vs 2 days; p<0.0001) and lower morbidity (28% vs 14%; p=0.06), there is a significant lower cost (€8960 vs €1770; p<0.0001) when compared to surgery.[[21,28,29]] It has comparable costs with EMR for large lesions in the colorectum, with additional benefit of reduction of burden of follow-up endoscopy.[[30,31]]These benefits come at the expense of significantly increased procedural time and an increased complication rate, including bleeding and perforation (OR 2.20 and OR 4.09), compared to EMR.[[15,32,33]] Therefore, particularly in the colorectum, case selection is paramount.[[34]]
Traditionally the majority of ESD literature emanates from Asia, with series and outcomes from high volume centres and experienced practitioners, which may not reflect local experience. However, more recently large publications from Western centres have shown comparable results, particularly in the upper GIT.[[35–40]] Whilst ESD has been performed in New Zealand by a select few practitioners over the years, no data have been published on cases and outcomes, and Australasian data in general are similarly scarce.[[41,42]]
Prior to this study, ESD had been performed infrequently at Waitemāta District Health Board (WDHB). This hospital services a population of nearly 630,000 people. To further develop this service, Dr Schauer was awarded a scholarship from the Japanese Society of Gastroenterology for a Fellowship programme at NTT Hospital in Tokyo, Japan. This hospital is one of the highest-volume ESD centres in the world, performing over 900 resections per year, including duodenal and oropharyngeal cases.[[43]] This fellowship involved systematic teaching on lesion detection and staging with image-enhanced endoscopy to ensure correct indications for ESD, tutoring of resection principles, animal model workshops, case observation and finally supervised procedures with patients.[[44]]
We present the first report of patient demographics, outcomes and complications of ESD from a single tertiary centre in New Zealand.
Methods
Following specific advice and systematic suggestion for building and maintaining a high-quality service,[[45–47]] we began to prospectively collect key performance indicators for all patients undergoing ESD between January 2020 and July 2021. Regular review of lesion selection and ESD practice was undertaken by recorded video assessment with Dr Yohei Minato from NTT Hospital, with subsequent feedback and discussion.
Patient selection
The indication in each patient was according to consensus Japanese guidelines.[[48–50]] All patients with lesions possibly amenable for ESD were discussed in a multidisciplinary meeting (MDM). Referrals were gained from gastroenterology, upper gastrointestinal and colorectal surgery. In addition, cases were referred from Whangārei Hospital via the MDM.
Lesions were accepted for ESD for either primary curative, diagnostic and/or curative intent, or less common staging (assumption of deep malignant invasion but unclear as to extent with other modalities). All procedures were performed at North Shore Hospital by three senior endoscopists, who had also attended international hands on ESD courses. All patients gave informed consent prior to their procedures.
Procedure and pathological review
Procedures were completed under either local sedation with fentanyl or midazolam, anaesthetist-assisted propofol or general anaesthesia. Submucosal injectate was either gelofusion with methylene blue or Orise gel (Boston Scientific). Knives used were either dual-knife J or IT-knife (Olympus). In all cases, we used a high frequency electrosurgical unit (Erbe Elektromedizin, Tübingen, Germany).
Submucosal fibrosis is known to increase the rate of perforation and effect the success rate of en-bloc resection. This was assessed and recorded based on the findings identified at the time of ESD and classified F0 (no fibrosis), F1 (mild fibrosis) and F2 (severe fibrosis).[[51,52]] Traction was not used in any cases.
All pathological specimens were pinned flat to cork to assist histological assessment and fixed in 10% formalin, with review performed by GIT pathologists including assessment for clearance of both vertical and lateral margins.
Endoscopic outcomes
“En-bloc resection” was defined as removal of a lesion in one piece. A successful histological resection (R0) was one where the lesion was removed with clear vertical and lateral margins. “R1” was defined as a lesion with a positive margin. “Curative resection” was defined as tumour-free vertical or lateral margins in a resected lesion and absence of vascular or lymphatic involvement. It was also defined by invasion <1,000μm, <500μm and <200μm from the muscularis mucosa in colorectal, gastric and oesophageal lesions respectively (ie, meeting the criteria for indication of treatment).[[17]] Significant bleeding was pre-determined to be defined as that requiring blood transfusion and repeat endoscopy after the ESD procedure. “Deep injury” was defined as visible damage to the muscularis propria layer without perforation. Perforation was defined as complete muscular defect requiring closure, categorised as either immediate or delayed (occurring after the conclusion of the procedure). All patients were followed up to assess the site and check for recurrence.
Results
Between January 2020 and July 2021, 29 ESD procedures were performed in 27 patients (Table 1). The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median and mean lesion diameter resected was 30mm (interquartile range (IQR) 20–58mm) and 42mm (SD 28mm) respectively. The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180), giving an average dissection speed of 0.08cm[[2]]/minute.
In total, 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one, an 82-year-old lady with a 15mm, poorly differentiated gastric cancer, which was invading 450μm into the submucosa. The patient opted against operative management offered and will undergo surveillance.
Muscular defects (deep injury) without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. In one patient with an 80mm rectal lesion, perforation was identified at time of endoscopy and treated, but subsequently required readmission on day five post procedure, with fever and a retroperitoneal collection seen on imaging that resolved after five days of intravenous antibiotics (this is the single case of severe adverse event within 30 days). There were no cases of immediate or delayed bleeding or death.
Gastric ESD was most commonly performed, including two synchronous lesions. Five lesions were located in the antrum, three in the cardia, three in the corpus, three on the incisura and one in the pyloric channel. One perforation in a patient was closed at the time of procedure without complication. Two of the cases located in the cardia were felt to be highly suspicious for deep submucosal invasive cancer (SMIC), but the MDM agreed a diagnostic ESD was required to confirm or refute the suspected diagnosis, given the possibility of extensive surgery required. Similarly, a 55mm lesion within Barrett’s oesophagus was suspicious for deep SMIC, but the patient and treating team requested diagnostic ESD. Deep SMIC was demonstrated in these Three cases. Seven (70%) of the colorectal cases were performed in the rectum. The other three cases were located in the transverse, descending and sigmoid colon. Two rectal lesions were performed for previous failed EMR including adenocarcinoma arising with a traditional serrated adenoma with significant (F2) fibrosis. The third case with severe fibrosis was a polyp growing over a previous haemorrhoidal banding scar.
In the eight cases with R1 resection (28%), four gastric lesions had deep SMIC and proceeded to gastrectomy. An oesophageal lesion with deep SMIC and positive vertical margin proceeded to Ivor-Lewis oesophagogastrectomy, and another oesophageal lesion with a positive lateral margin was site checked without recurrence. One rectal lesion with a positive lateral margin was site checked without recurrence, and a descending colon lesion with a positive lateral margin was site checked with regrowth of HGD requiring further endoscopic treatment.
Table 1: Patient demographics, lesion characteristics and results. View Table 1.
Discussion
In this first New Zealand prospective report of ESD, we demonstrate clinical success, efficacy and safety of this procedure.
En-bloc and R0 resection rates of 86% and 72% are slightly better than a similar Australian centre’s series (80% and 60% respectively)[[41]] and are in keeping with larger Western series at 77–92% and 73–100% respectively.[[46,53–56]] Our overall R0 resection rate is reduced by three diagnostic cases where the vertical margins were positive in lesions which pre-procedure were highly suspicious of deep SMIC.
There were no cases of delayed bleeding, perforation or death, which we attribute to fastidious post-ESD resection bed review, including cautious inspection of possible muscular injury and subsequent clip placement. This likely contributed to an over-estimation of deep injury (34%). Patients are currently admitted post-ESD for observation on a case-by-case basis, depending on lesion location, size, difficulty, age, co-morbidity, geographical residence (ie, travelling from rural area) and sedation type. There is suggestion that perhaps more cases could be done as day-stay procedures,[[57,58]] which may make ESD even more cost-effective. Six of our cases were discharged same day, and with no cases of delayed complication, more patients may be able to be considered for this in the future.
We have placed great emphasis on case and lesion evaluation, decision-making with regard to proper indication and thorough discussion of each patient as a group and at the MDM. Although some centres avoid biopsy of lesions prior to consideration of endoscopic resection for fear of causing scarring and fibrosis, we have generally encouraged this to assist in our decision-making. This is in conjunction with fastidious mucosal inspection protocols, magnified endoscopic vascular and structural pattern analysis and chromoscopy to most exactly determine predicted final pathology. This is reflected in our 93% pre-endoscopic prediction accuracy, and high curative resection rate. We believe this time taken on lesion assessment and risk stratification is important to avoid possible over or undertreatment, and provide the safest, most resourceful outcome tailored to pathology.[[13]] Although it is not an internationally benchmarked indicator, we feel review of our final histological outcomes confirms an overall appropriate lesion selection.
The additional time required for ESD is often discussed and debated in the literature as a drawback, with a number of techniques and devices utilised to improve dissection speed. An overall speed of dissection benchmark of 0.15cm[[2]]/min is suggested.[[46]] Although this was obtained in the colorectum (0.16cm[[2]]/min), likely owing to the larger size of rectal cases and stable endoscopic access, we were slower in stomach and oesophagus (0.08cm[[2]]/min). Although we have initially emphasised safety, efficiency of the procedure is vital, in particular in the upper GIT tract when cases are performed with local sedation only and procedural time is limited by patient tolerance. Ongoing video review of cases with experts to improve technique will further improve efficacy and efficiency.
ESD is the standard of care and a well-established procedure in Asia, but it has been slower to penetrate Western countries. This delay in uptake has been widely criticised, discussed and debated and is likely multifactorial.[[45–47,59]]It is postulated to be due to its high technical proficiency requirement, the time commitment for both learning and doing procedures and steep learning curve, a lack of mentors, interdisciplinary conflicts, concern regarding complications and a lack of support from institutions and interfacing departments.[[47]] There is a comparatively low frequency of early gastric cancers compared to Eastern populations, which limits skill acquisition and training opportunities.[[47]] Finally, its uptake has been further limited by the absence of appropriate reimbursement systems in countries such as USA where this is an important factor.[[28]] However, demand for this procedure in New Zealand is likely to grow as rates of GIT tumours increase. Oesphageal cancer is increasing in incidence. In New Zealand in 1950, the age standardised registration rate was 2.2/100,000 with 46 cases diagnosed, which increased to 4.3/100,000 with 364 cases diagnosed by 2000.[[3]] In addition, over 400 new cancers of gastric cancer are diagnosed each year.[[4]] Both have documented significant ethnic inequality, with Māori having both an increased incidence and mortality.[[60–62]] These rates are expected to rise with increased immigration from Asian countries where rates are over five-times higher.[[2,63]] Finally, colorectal cancer (CRC) is both the second most common cancer diagnosed and cause of cancer death in New Zealand, as absolute rates continue to rise in the face of an ageing and increasing population.[[5,64]] Improved access to endoscopic evaluation, earlier detection of lesions through the National Bowel Cancer Screening Programme and increased awareness of detection of early cancer are likely to further drive ESD volume and growth. Such volume is key to ongoing improvement of outcome measures and rates of complications.[[65]] Current short-term projections for our service demonstrate referral growth and capacity to complete at least 3–4 cases per month.
Finally, critical in success of this programme is ongoing support from surgical, gastroenterology, pathology, oncology and anaesthetic colleagues. We have fostered an understanding and supportive environment, where patients are able to be presented with a full picture of pros, cons, risks and alternatives for potential options for management of their lesion. Additional assistance is needed from hospital management teams to accommodate these procedures while competing with other interventional third-space procedures, such as peroral endoscopic myotomy (POEM), endoscopic diverticulotomy, submucosal tunnelling endoscopic resection (STER) and full thickness resection (FTR). An important area of improvement to target must include formalising inter-district-health-board referral pathways, such that patients may have equal access to this procedure, and be seen and treated in a timely manner, irrespective of their geographical location. We hope publication of this work will help to inform clinicians that this procedure is available and accessible. Furthermore, ongoing data collection and audit with respect to ethnicity and inequality must be paramount. It is known that Māori present with more advanced disease, which may explain why none were treated in this series. However, there is a demonstrably higher overall mortality irrespective of stage, with access to specialised cancer services postulated to be contributory, and we must review our service with this in mind.[[66,67]]
Strengths of this paper include reflection of a real-world experience of cases with varying location, difficulty, fibrosis and size. This series also included a 10cm gastric antral lesion (Figure 1) that was completely resected, en-bloc and R0. Prospective sequential patient data collection and complete data and follow-up limit bias. Study outcomes include all defined quality indicators for ESD.
Limitations of note include lack of collection and reporting of all cases referred for ESD. Many patients, in particular proximal laterally spreading colonic lesions were deferred for piecemeal EMR with its current superior speed, safety and efficacy.[[34]] Not all lesions were followed to final treatment outcome and histological review, some of which may have been inaccurately assessed and perhaps were better suited for ESD removal. In spite of the favourable ESD outcomes achieved in this study, some lesions may have been adequately treated with EMR techniques based on the retrospective assessment of the final ESD histology. A full financial assessment was not performed and is beyond the scope of this paper, but should be considered in future studies to assess cost effectiveness compared to possible surgery, but also EMR. Lastly, at the time of publication, patients have not been followed for the requisite years to assess for potential long-term recurrence rates, and both cancer-specific and all-cause mortality.
In conclusion, this initial prospective ESD data demonstrates clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Figure 1: Endoscopic submucosal dissection (ESD) of gastric lesion.
Summary
Abstract
Aim
Endoscopic submucosal dissection (ESD) is internationally accepted as a minimally invasive procedure to treat early gastrointestinal cancers endoscopically. Uptake of this procedure in the West is limited. No published data are available in New Zealand. We aimed to evaluate outcomes of this procedure at North Shore Hospital, Auckland.
Method
Following an overseas fellowship training period, we prospectively collected clinical outcomes, complications and defined quality indicators for patients undergoing ESD referred following a multidisciplinary meeting.
Results
Between January 2020 until July 2021, 29 ESD procedures were performed in 27 patients, including 14 gastric, five oesophageal and 10 colorectal cases. The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median lesion size resected was 30mm (interquartile range (IQR) 20–58mm). The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180). 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one. Muscular defects without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. There were no cases of delayed bleeding, perforation or mortality.
Conclusion
These data demonstrate clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
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Contact diana@nzma.org.nz
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Endoscopic submucosal dissection: the first reported experience from a New Zealand centre
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Cancers of the gastrointestinal tract (GIT) account for 26% of cancers diagnosed and 35% of all cancer related deaths worldwide.[[1]] Both internationally and within New Zealand, oesophageal, gastric and colon cancer incidence are increasing.[[2–5]] Strategies such as screening programmes have been introduced to aid in detection, with resultant earlier stage diagnosis of cancer.[[6–9]]
Curative endoscopic therapy is possible for such cancers or precancerous lesions if they are detected at an early stage when the depth of neoplastic invasion is small and therefore the risk of lymph node metastasis is low.[[10]] Attempts at endoscopic treatment of such lesions have been largely performed in the western world and in New Zealand using endoscopic mucosal resection (EMR). This technique was first described in 1955 in rigid sigmoidoscopy[[11]] and later adapted for flexible colonoscopy in 1973.[[12]] This procedure involves injection of a fluid cushion into the submucosal space to separate the lesion from the underlying muscular layer, with final resection using a metal snare. EMR of larger lesions (≥15mm) may require removal in fragmented pieces (“piecemeal”), which limits histological assessment, tumour staging, subsequent stratification of therapeutic approach and potential cure.[[13]] This method also results in a significantly increased risk of recurrence.[[14,15]] Inability to determine adequacy of resection according to oncologic standards (en-bloc and R0) may lead to organ resection surgery which may not have been necessary.
To overcome these issues, endoscopic submucosal dissection (ESD) was pioneered in 1998 in Japan initially to treat early gastric cancer.[[16]] This has now expanded to include the entire GIT and is considered the standard of care for neoplastic lesions in Japan and Korea, as well as being included in Western society guidelines as the gold-standard treatment for superficial lesions.[[17,18]] When the criteria for anatomopathological curability are met, ESD has the same treatment efficacy as surgical resection.[[19–23]]
The essence of the technique is similar to EMR. However, the methodology of cutting the lesion differs. ESD generally employs a small (1.5–2mm) electrocautery metal needle to precisely cut freehand the lesion away from the muscular layer in one section (en-bloc). ESD thus allows higher en-bloc and curative resection compared with EMR in the oesophagus, stomach and colon.[[15,24–27]] In addition to patient acceptability with organ preservation, decreased length of hospital stay (11 vs 2 days; p<0.0001) and lower morbidity (28% vs 14%; p=0.06), there is a significant lower cost (€8960 vs €1770; p<0.0001) when compared to surgery.[[21,28,29]] It has comparable costs with EMR for large lesions in the colorectum, with additional benefit of reduction of burden of follow-up endoscopy.[[30,31]]These benefits come at the expense of significantly increased procedural time and an increased complication rate, including bleeding and perforation (OR 2.20 and OR 4.09), compared to EMR.[[15,32,33]] Therefore, particularly in the colorectum, case selection is paramount.[[34]]
Traditionally the majority of ESD literature emanates from Asia, with series and outcomes from high volume centres and experienced practitioners, which may not reflect local experience. However, more recently large publications from Western centres have shown comparable results, particularly in the upper GIT.[[35–40]] Whilst ESD has been performed in New Zealand by a select few practitioners over the years, no data have been published on cases and outcomes, and Australasian data in general are similarly scarce.[[41,42]]
Prior to this study, ESD had been performed infrequently at Waitemāta District Health Board (WDHB). This hospital services a population of nearly 630,000 people. To further develop this service, Dr Schauer was awarded a scholarship from the Japanese Society of Gastroenterology for a Fellowship programme at NTT Hospital in Tokyo, Japan. This hospital is one of the highest-volume ESD centres in the world, performing over 900 resections per year, including duodenal and oropharyngeal cases.[[43]] This fellowship involved systematic teaching on lesion detection and staging with image-enhanced endoscopy to ensure correct indications for ESD, tutoring of resection principles, animal model workshops, case observation and finally supervised procedures with patients.[[44]]
We present the first report of patient demographics, outcomes and complications of ESD from a single tertiary centre in New Zealand.
Methods
Following specific advice and systematic suggestion for building and maintaining a high-quality service,[[45–47]] we began to prospectively collect key performance indicators for all patients undergoing ESD between January 2020 and July 2021. Regular review of lesion selection and ESD practice was undertaken by recorded video assessment with Dr Yohei Minato from NTT Hospital, with subsequent feedback and discussion.
Patient selection
The indication in each patient was according to consensus Japanese guidelines.[[48–50]] All patients with lesions possibly amenable for ESD were discussed in a multidisciplinary meeting (MDM). Referrals were gained from gastroenterology, upper gastrointestinal and colorectal surgery. In addition, cases were referred from Whangārei Hospital via the MDM.
Lesions were accepted for ESD for either primary curative, diagnostic and/or curative intent, or less common staging (assumption of deep malignant invasion but unclear as to extent with other modalities). All procedures were performed at North Shore Hospital by three senior endoscopists, who had also attended international hands on ESD courses. All patients gave informed consent prior to their procedures.
Procedure and pathological review
Procedures were completed under either local sedation with fentanyl or midazolam, anaesthetist-assisted propofol or general anaesthesia. Submucosal injectate was either gelofusion with methylene blue or Orise gel (Boston Scientific). Knives used were either dual-knife J or IT-knife (Olympus). In all cases, we used a high frequency electrosurgical unit (Erbe Elektromedizin, Tübingen, Germany).
Submucosal fibrosis is known to increase the rate of perforation and effect the success rate of en-bloc resection. This was assessed and recorded based on the findings identified at the time of ESD and classified F0 (no fibrosis), F1 (mild fibrosis) and F2 (severe fibrosis).[[51,52]] Traction was not used in any cases.
All pathological specimens were pinned flat to cork to assist histological assessment and fixed in 10% formalin, with review performed by GIT pathologists including assessment for clearance of both vertical and lateral margins.
Endoscopic outcomes
“En-bloc resection” was defined as removal of a lesion in one piece. A successful histological resection (R0) was one where the lesion was removed with clear vertical and lateral margins. “R1” was defined as a lesion with a positive margin. “Curative resection” was defined as tumour-free vertical or lateral margins in a resected lesion and absence of vascular or lymphatic involvement. It was also defined by invasion <1,000μm, <500μm and <200μm from the muscularis mucosa in colorectal, gastric and oesophageal lesions respectively (ie, meeting the criteria for indication of treatment).[[17]] Significant bleeding was pre-determined to be defined as that requiring blood transfusion and repeat endoscopy after the ESD procedure. “Deep injury” was defined as visible damage to the muscularis propria layer without perforation. Perforation was defined as complete muscular defect requiring closure, categorised as either immediate or delayed (occurring after the conclusion of the procedure). All patients were followed up to assess the site and check for recurrence.
Results
Between January 2020 and July 2021, 29 ESD procedures were performed in 27 patients (Table 1). The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median and mean lesion diameter resected was 30mm (interquartile range (IQR) 20–58mm) and 42mm (SD 28mm) respectively. The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180), giving an average dissection speed of 0.08cm[[2]]/minute.
In total, 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one, an 82-year-old lady with a 15mm, poorly differentiated gastric cancer, which was invading 450μm into the submucosa. The patient opted against operative management offered and will undergo surveillance.
Muscular defects (deep injury) without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. In one patient with an 80mm rectal lesion, perforation was identified at time of endoscopy and treated, but subsequently required readmission on day five post procedure, with fever and a retroperitoneal collection seen on imaging that resolved after five days of intravenous antibiotics (this is the single case of severe adverse event within 30 days). There were no cases of immediate or delayed bleeding or death.
Gastric ESD was most commonly performed, including two synchronous lesions. Five lesions were located in the antrum, three in the cardia, three in the corpus, three on the incisura and one in the pyloric channel. One perforation in a patient was closed at the time of procedure without complication. Two of the cases located in the cardia were felt to be highly suspicious for deep submucosal invasive cancer (SMIC), but the MDM agreed a diagnostic ESD was required to confirm or refute the suspected diagnosis, given the possibility of extensive surgery required. Similarly, a 55mm lesion within Barrett’s oesophagus was suspicious for deep SMIC, but the patient and treating team requested diagnostic ESD. Deep SMIC was demonstrated in these Three cases. Seven (70%) of the colorectal cases were performed in the rectum. The other three cases were located in the transverse, descending and sigmoid colon. Two rectal lesions were performed for previous failed EMR including adenocarcinoma arising with a traditional serrated adenoma with significant (F2) fibrosis. The third case with severe fibrosis was a polyp growing over a previous haemorrhoidal banding scar.
In the eight cases with R1 resection (28%), four gastric lesions had deep SMIC and proceeded to gastrectomy. An oesophageal lesion with deep SMIC and positive vertical margin proceeded to Ivor-Lewis oesophagogastrectomy, and another oesophageal lesion with a positive lateral margin was site checked without recurrence. One rectal lesion with a positive lateral margin was site checked without recurrence, and a descending colon lesion with a positive lateral margin was site checked with regrowth of HGD requiring further endoscopic treatment.
Table 1: Patient demographics, lesion characteristics and results. View Table 1.
Discussion
In this first New Zealand prospective report of ESD, we demonstrate clinical success, efficacy and safety of this procedure.
En-bloc and R0 resection rates of 86% and 72% are slightly better than a similar Australian centre’s series (80% and 60% respectively)[[41]] and are in keeping with larger Western series at 77–92% and 73–100% respectively.[[46,53–56]] Our overall R0 resection rate is reduced by three diagnostic cases where the vertical margins were positive in lesions which pre-procedure were highly suspicious of deep SMIC.
There were no cases of delayed bleeding, perforation or death, which we attribute to fastidious post-ESD resection bed review, including cautious inspection of possible muscular injury and subsequent clip placement. This likely contributed to an over-estimation of deep injury (34%). Patients are currently admitted post-ESD for observation on a case-by-case basis, depending on lesion location, size, difficulty, age, co-morbidity, geographical residence (ie, travelling from rural area) and sedation type. There is suggestion that perhaps more cases could be done as day-stay procedures,[[57,58]] which may make ESD even more cost-effective. Six of our cases were discharged same day, and with no cases of delayed complication, more patients may be able to be considered for this in the future.
We have placed great emphasis on case and lesion evaluation, decision-making with regard to proper indication and thorough discussion of each patient as a group and at the MDM. Although some centres avoid biopsy of lesions prior to consideration of endoscopic resection for fear of causing scarring and fibrosis, we have generally encouraged this to assist in our decision-making. This is in conjunction with fastidious mucosal inspection protocols, magnified endoscopic vascular and structural pattern analysis and chromoscopy to most exactly determine predicted final pathology. This is reflected in our 93% pre-endoscopic prediction accuracy, and high curative resection rate. We believe this time taken on lesion assessment and risk stratification is important to avoid possible over or undertreatment, and provide the safest, most resourceful outcome tailored to pathology.[[13]] Although it is not an internationally benchmarked indicator, we feel review of our final histological outcomes confirms an overall appropriate lesion selection.
The additional time required for ESD is often discussed and debated in the literature as a drawback, with a number of techniques and devices utilised to improve dissection speed. An overall speed of dissection benchmark of 0.15cm[[2]]/min is suggested.[[46]] Although this was obtained in the colorectum (0.16cm[[2]]/min), likely owing to the larger size of rectal cases and stable endoscopic access, we were slower in stomach and oesophagus (0.08cm[[2]]/min). Although we have initially emphasised safety, efficiency of the procedure is vital, in particular in the upper GIT tract when cases are performed with local sedation only and procedural time is limited by patient tolerance. Ongoing video review of cases with experts to improve technique will further improve efficacy and efficiency.
ESD is the standard of care and a well-established procedure in Asia, but it has been slower to penetrate Western countries. This delay in uptake has been widely criticised, discussed and debated and is likely multifactorial.[[45–47,59]]It is postulated to be due to its high technical proficiency requirement, the time commitment for both learning and doing procedures and steep learning curve, a lack of mentors, interdisciplinary conflicts, concern regarding complications and a lack of support from institutions and interfacing departments.[[47]] There is a comparatively low frequency of early gastric cancers compared to Eastern populations, which limits skill acquisition and training opportunities.[[47]] Finally, its uptake has been further limited by the absence of appropriate reimbursement systems in countries such as USA where this is an important factor.[[28]] However, demand for this procedure in New Zealand is likely to grow as rates of GIT tumours increase. Oesphageal cancer is increasing in incidence. In New Zealand in 1950, the age standardised registration rate was 2.2/100,000 with 46 cases diagnosed, which increased to 4.3/100,000 with 364 cases diagnosed by 2000.[[3]] In addition, over 400 new cancers of gastric cancer are diagnosed each year.[[4]] Both have documented significant ethnic inequality, with Māori having both an increased incidence and mortality.[[60–62]] These rates are expected to rise with increased immigration from Asian countries where rates are over five-times higher.[[2,63]] Finally, colorectal cancer (CRC) is both the second most common cancer diagnosed and cause of cancer death in New Zealand, as absolute rates continue to rise in the face of an ageing and increasing population.[[5,64]] Improved access to endoscopic evaluation, earlier detection of lesions through the National Bowel Cancer Screening Programme and increased awareness of detection of early cancer are likely to further drive ESD volume and growth. Such volume is key to ongoing improvement of outcome measures and rates of complications.[[65]] Current short-term projections for our service demonstrate referral growth and capacity to complete at least 3–4 cases per month.
Finally, critical in success of this programme is ongoing support from surgical, gastroenterology, pathology, oncology and anaesthetic colleagues. We have fostered an understanding and supportive environment, where patients are able to be presented with a full picture of pros, cons, risks and alternatives for potential options for management of their lesion. Additional assistance is needed from hospital management teams to accommodate these procedures while competing with other interventional third-space procedures, such as peroral endoscopic myotomy (POEM), endoscopic diverticulotomy, submucosal tunnelling endoscopic resection (STER) and full thickness resection (FTR). An important area of improvement to target must include formalising inter-district-health-board referral pathways, such that patients may have equal access to this procedure, and be seen and treated in a timely manner, irrespective of their geographical location. We hope publication of this work will help to inform clinicians that this procedure is available and accessible. Furthermore, ongoing data collection and audit with respect to ethnicity and inequality must be paramount. It is known that Māori present with more advanced disease, which may explain why none were treated in this series. However, there is a demonstrably higher overall mortality irrespective of stage, with access to specialised cancer services postulated to be contributory, and we must review our service with this in mind.[[66,67]]
Strengths of this paper include reflection of a real-world experience of cases with varying location, difficulty, fibrosis and size. This series also included a 10cm gastric antral lesion (Figure 1) that was completely resected, en-bloc and R0. Prospective sequential patient data collection and complete data and follow-up limit bias. Study outcomes include all defined quality indicators for ESD.
Limitations of note include lack of collection and reporting of all cases referred for ESD. Many patients, in particular proximal laterally spreading colonic lesions were deferred for piecemeal EMR with its current superior speed, safety and efficacy.[[34]] Not all lesions were followed to final treatment outcome and histological review, some of which may have been inaccurately assessed and perhaps were better suited for ESD removal. In spite of the favourable ESD outcomes achieved in this study, some lesions may have been adequately treated with EMR techniques based on the retrospective assessment of the final ESD histology. A full financial assessment was not performed and is beyond the scope of this paper, but should be considered in future studies to assess cost effectiveness compared to possible surgery, but also EMR. Lastly, at the time of publication, patients have not been followed for the requisite years to assess for potential long-term recurrence rates, and both cancer-specific and all-cause mortality.
In conclusion, this initial prospective ESD data demonstrates clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Figure 1: Endoscopic submucosal dissection (ESD) of gastric lesion.
Summary
Abstract
Aim
Endoscopic submucosal dissection (ESD) is internationally accepted as a minimally invasive procedure to treat early gastrointestinal cancers endoscopically. Uptake of this procedure in the West is limited. No published data are available in New Zealand. We aimed to evaluate outcomes of this procedure at North Shore Hospital, Auckland.
Method
Following an overseas fellowship training period, we prospectively collected clinical outcomes, complications and defined quality indicators for patients undergoing ESD referred following a multidisciplinary meeting.
Results
Between January 2020 until July 2021, 29 ESD procedures were performed in 27 patients, including 14 gastric, five oesophageal and 10 colorectal cases. The mean age was 72 (standard deviation (SD) 10.6). The majority of cases (62%) were done under general anaesthesia. The median lesion size resected was 30mm (interquartile range (IQR) 20–58mm). The pre-endoscopic diagnosis was accurate as confirmed on final histology in 93% of cases. Thirty-four percent of lesions were T1 adenocarcinoma and completely resected. The median total duration of the procedure was 90 minutes (IQR 55–180). 86% of lesions were resected en-bloc. R0 resection was achieved in 72% of cases. All cases with R0 resection were curative except one. Muscular defects without perforation were seen and clipped at the time of endoscopy in 34% of cases. Two perforations were identified and sealed at the time of endoscopy. There were no cases of delayed bleeding, perforation or mortality.
Conclusion
These data demonstrate clinical success, efficacy and safety of ESD at our centre. A larger study, comparison with other centres and longer clinical follow-up is required to confirm findings and further improve outcomes.
Author Information
Acknowledgements
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Competing Interests
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Endoscopic submucosal dissection: the first reported experience from a New Zealand centre
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