Society: SSAT

LIVE STREAM SESSION

Background
Sentinel node navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy to tailor the extent of lymphadenectomy in patients with high-risk T1 esophageal adenocarcinoma (EAC). This is the first study to investigate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS.

Methods
In this prospective, multicenter pilot study, 10 patients underwent SNNS in two tertiary hospitals after radical endoscopic resection of a high-risk T1 EAC (i.e. deep submucosal invasion ≥500μm, poor differentiation, and/or lymphovascular invasion) without the clinical presence of lymph node or distant metastases (i.e. cN0M0). A hybrid tracer of technetium-99m nanocolloid and indocyanine green (^99mTc-ICG-nanocolloid) was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During thoracoscopy and laparoscopy, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection and subsequently resected (Figure 1). Endpoints were surgical morbidity, incidence of gastroesophageal functional disorders, rate of detectable SNs, and number of resected (tumor-positive) SNs per patient.

Results
Localization and dissection of SNs was feasible in all patients (10 male, median age 69), with a median of 3 SNs (range 1-7) on preoperative imaging and a median of 3 SNs (range 1-6) during surgery. The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs could not be identified due to a lack of ICG fluorescence. In four patients (40%), additional peritumoral SNs were resected after fluorescence-based detection. These SNs were not detected on preoperative imaging or intraoperatively with the laparoscopic gammaprobe as a result of the high background radioactivity of the injection site. Total procedure time was median 125 minutes (range 46-213), and patients were hospitalized for a median of 2 days (range 1-3). One patient (10%) experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional disorders. In two patients (20%), a metastasis was found in one of the resected SNs. Both patients are undergoing strict endoscopic and radiologic follow-up, which was determined in a multidisciplinary meeting based on patient’s older age (n=1) and patient's choice in combination with micrometastasis (n=1).

Conclusion
SNNS with ^99mTc-ICG-nanocolloid appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC who underwent a prior radical endoscopic resection. The exact position of this new strategy in the treatment algorithm for high-risk T1 esophageal cancer needs to be studied in future research with long-term follow-up.

<b>Figure 1. Identification of sentinel node located at the </b><b>aortopulmonary window.</b><br /> A) Lymphoscintigraphy 2 hours after endoscopic injection of the hybrid tracer showed the injection site and an intrathoracic sentinel node. B) This was combined with a SPECT/CT to detect the sentinel node location. C) The laparoscopic gammaprobe confirmed high radioactivity uptake during the thoracic phase of surgery, D) after which the sentinel node could be identified. E) The sentinel was also clearly visualized as indocyanine green positive when the camera view was switched to near-infrared. F) Subsequently, laparoscopic resection of the sentinel node was performed under near-infrared vision.

Figure 1. Identification of sentinel node located at the aortopulmonary window.
A) Lymphoscintigraphy 2 hours after endoscopic injection of the hybrid tracer showed the injection site and an intrathoracic sentinel node. B) This was combined with a SPECT/CT to detect the sentinel node location. C) The laparoscopic gammaprobe confirmed high radioactivity uptake during the thoracic phase of surgery, D) after which the sentinel node could be identified. E) The sentinel was also clearly visualized as indocyanine green positive when the camera view was switched to near-infrared. F) Subsequently, laparoscopic resection of the sentinel node was performed under near-infrared vision.

Background. A wrong diagnosis of nature is common in pancreatic cystic neoplasms (PCNs). The aim of the current study is to reappraise the diagnostic errors for presumed PCNs undergoing surgery.
Methods. All pancreatic resections performed for presumed PCNs at the Verona Pancreas Institute between 2011 and 2020 were analyzed. “Misdiagnosis” was defined as the discrepancy between preoperative diagnosis of nature and final pathology. “Mismatch” was defined as the discrepancy between the preoperative suspect of malignancy (or its absence) and final pathology. Features considered suggestive for malignancy at preoperative work-up and at final pathology are described in Figure 1. Diagnostic errors considered “clinically relevant” implied a potential over- or under-treatment for the patient.
Results. A total of 601 patients were included. Endoscopic Ultrasound (EUS) was performed in 301 (50%) patients. Overall misdiagnosis and mismatch were 19% and 34%, respectively, with no significant benefit for those patients who underwent EUS. The highest rate of misdiagnosis was reached for cystic neuroendocrine tumors (61%) and the lowest for solid pseudopapillary tumors (6%). Several diagnostic errors had clinical relevance, including 7 (13%) presumed serous cystic neoplasms eventually found to be other malignant entities, 50 (24%) intraductal papillary mucinous neoplasms (IPMN) with high-risk stigmata (HRS) revealed to be non-malignant, and 38 (33%) IPMN without HRS revealed to be malignant at final pathology. A preoperative presumption of malignant mucinous cystic neoplasm was correct in only 20 (16%) patients (Table 1).
Conclusions. Despite not always clinically relevant, diagnostic errors are still common among resected PCNs when applying International Guidelines. New diagnostic tools beyond EUS are needed to refine diagnosis of those lesions at higher risk for unnecessary surgery or accidentally observed nevertheless being malignant.

<b><i>Figure 1. Features of malignancy at preoperative work-up and at final pathology.</i></b><br /> <i>HRS, High Risk Stigmata; IAP, International Association of Pancreatology; IPMN, Intraductal Papillary Mucinous Neoplasms; MCN, Mucinous Cystic Neoplasms; MPD, Main Pancreatic Duct; NET, Neuroendocrine Tumor; PDAC, Pancreatic Ductal Adenocarcinoma; SCN, Serous Cystic Neoplasms; SPT, Solid Pseudopapillary Tumor. </i>

Figure 1. Features of malignancy at preoperative work-up and at final pathology.
HRS, High Risk Stigmata; IAP, International Association of Pancreatology; IPMN, Intraductal Papillary Mucinous Neoplasms; MCN, Mucinous Cystic Neoplasms; MPD, Main Pancreatic Duct; NET, Neuroendocrine Tumor; PDAC, Pancreatic Ductal Adenocarcinoma; SCN, Serous Cystic Neoplasms; SPT, Solid Pseudopapillary Tumor.

<b><i>Table 1. Correct diagnosis and misdiagnosis rate between preoperative diagnosis and final pathology.</i></b><br /> <i>HRS, High Risk Stigmata; IPMN, Intraductal Papillary Mucinous Neoplasms; MCN, Mucinous Cystic Neoplasms; NET, Neuroendocrine Tumor; PDAC, Pancreatic Ductal Adenocarcinoma; SCN, Serous Cystic Neoplasms; SPT, Solid Pseudopapillary Tumor. Correct diagnoses are showed inside black-contoured squares. Clinically relevant errors are showed inside grey squares. </i>

Table 1. Correct diagnosis and misdiagnosis rate between preoperative diagnosis and final pathology.
HRS, High Risk Stigmata; IPMN, Intraductal Papillary Mucinous Neoplasms; MCN, Mucinous Cystic Neoplasms; NET, Neuroendocrine Tumor; PDAC, Pancreatic Ductal Adenocarcinoma; SCN, Serous Cystic Neoplasms; SPT, Solid Pseudopapillary Tumor. Correct diagnoses are showed inside black-contoured squares. Clinically relevant errors are showed inside grey squares.

Introduction: Mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, to date, studies have excluded patients with proctitis, anal canal involvement, vaginal involvement, and an ileal pouch in situ. We sought to assess the safety and efficacy of a direct injection of MSCs for the treatment of perianal, rectovaginal, and peripouch Crohn’s fistula(s).

Methods: Three phase IB/IIA randomized control trials of perianal (n=23), rectovaginal (n=19) and peripouch (n=22) Crohn’s related fistulas were conducted to determine safety and efficacy of MSCs for refractory phenotypes of perianal Crohn’s disease. Crohn’s patients with perianal, rectovaginal, and peripouch Crohn’s fistulizing disease were offered enrollment into a clinical trial. A total of 75 million MSCs were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million MSCs was administered at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events were collected at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes were assessed at the same time points.

Results: A total of 64 patients were enrolled and treated; 49 were treatment and 15 were control. There were no adverse or serious adverse events reported related to investigational product. At twelve months, overall combined clinical and radiographic healing was achieved in 70% of perianal, 37.5% of rectovaginal, and 46.2% of ileal pouch fistulas, respectfully. In the control cohorts, 12 month healing was 0%, 0%, and 0% in the three clincial trials respectively. The perianal Crohn’s disease activity index and VanAssche score all significantly decreased in treatment patients at six and twelve months, but not in the control groups.

Conclusion: Allogeneic bone marrow derived MSCs offer a safe and effective alternative treatment approach for severe phenotypes of perianal fistulizing Crohn’s disease.

Justin Ream

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