Natural Orifice Translumenal Endoscopic Surgery in Humans: A Review

Natural orifice translumenal endoscopic surgery (NOTES) had its origins in numerous small animal studies primarily examining safety and feasibility. In human trials, safety and feasibility remain at the forefront; however, additional logistic, practical, and regulatory requirements must be addressed. The purpose of this paper is to evaluate and summarize published studies to date of NOTES in humans. The literature review was performed using PUBMED and MEDLINE databases. Articles published in human populations between 2007 and 2011 were evaluated. A review of this time period resulted in 48 studies describing procedures in 916 patients. Transcolonic and transvesicular procedures were excluded. The most common procedure was cholecystectomy (682, 75%). The most common approach was transvaginal (721, 79%). 424 procedures (46%) were pure NOTES and 491 (54%) were hybrid NOTES cases. 127 (14%) were performed in the United States of America and 789 (86%) were performed internationally. Since 2007, there has been major development in NOTES in human populations. A preponderance of published NOTES procedures were performed internationally. With further development, NOTES may make less invasive surgery available to a larger human population

Abstract

BackgroundThe current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) -2-cm.MethodsPatients who underwent curative resection for -2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM.ResultsA total of 392 -2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P-=-.026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P-=-.019). Patients with tumors measuring 1.5-2-cm had a two-fold increase in the incidence of LNM vs patients with tumors <1.5-cm (17.9% vs 8.7%, odds ratio, 2.59; P-=-.022), as well as a higher risk of advanced tumor grade and higher Ki-67 levels (both P-<-.01). After curative resection, a total of 14 (8.0%) patients with a tumor of 1.5-2-cm and 10 (4.5%) patients with tumor <1.5-cm developed tumor recurrence.ConclusionSurgical resection with lymphadenectomy should be considered for patients with NF-pNETs -1.5-2.0-cm.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151963/1/jso25716.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151963/2/jso25716_am.pd

Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis

AbstractObjectivesCriteria for the selection of patients for adjuvant chemotherapy in intrahepatic cholangiocarcinoma (IHCC) are lacking. Some authors advocate treating patients with lymph node (LN) involvement; however, nodal assessment is often inadequate or not performed. This study aimed to identify surrogate criteria based on characteristics of the primary tumour.MethodsA total of 58 patients who underwent resection for IHCC between January 2000 and January 2010 at any of three institutions were identified. Primary outcome was overall survival (OS).ResultsMedian OS was 23.0months. Median tumour size was 6.5cm and the median number of lesions was one. Overall, 16% of patients had positive margins, 38% had perineural invasion (PNI), 40% had lymphovascular invasion (LVI) and 22% had LN involvement. A median of two LNs were removed and a median of zero were positive. Lymph nodes were not sampled in 34% of patients. Lymphovascular and perineural invasion were associated with reduced OS [9.6months vs. 32.7months (P= 0.020) and 10.7months vs. 32.7months (P= 0.008), respectively]. Lymph node involvement indicated a trend towards reduced OS (10.7months vs. 30.0months; P= 0.063). The presence of either LVI or PNI in node-negative patients was associated with a reduction in OS similar to that in node-positive patients (12.1months vs. 10.7months; P= 0.541). After accounting for adverse tumour factors, only LVI and PNI remained associated with decreased OS on multivariate analysis (hazard ratio4.07, 95% confidence interval 1.60–10.40; P= 0.003).ConclusionsLymphovascular and perineural invasion are separately associated with a reduction in OS similar to that in patients with LN-positive disease. As nodal dissection is often not performed and the number of nodes retrieved is frequently inadequate, these tumour-specific factors should be considered as criteria for selection for adjuvant chemotherapy

Abstract

BackgroundThe current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET).MethodsPatients who underwent curative resection for dNETs between 1997â 2016 were identified from 8 highâ volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cutâ off of TNLE relative to LNM was determined.ResultsAmong 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51â 68) years and median tumor size was 1.2â cm (IQR, 0.7â 2.0â cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (â ¤1â cm:52.2% vs 1â 2â cm:61.4% vs >2â cm:93.8%; Pâ 2â cm:80.0%; Pâ <â .05). TNLEâ â ¥â 8 had the highest discriminatory power relative to the incidence of LNM (area under the curveâ =â 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR]â =â 0.9; 95% confidence intervals [95%CI], 0.4â 2.3), G2/G3 tumor grade was (HRâ =â 1.5; 95%CI, 1.0â 2.1).ConclusionsWhile the incidence of LNM directly correlated with tumor size, patients with dNETsâ â ¤â 1â cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153174/1/jso25753.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153174/2/jso25753_am.pd

The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8â institution study from the US Neuroendocrine Tumor Study Group

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147162/1/jso25306_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147162/2/jso25306.pd

Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi‐institutional analysis

BackgroundThe benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.MethodsPatients undergoing surgery for pNET between 1997 and 2016 were identified using a multi‐institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.ResultsAmong 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4‐16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5‐year recurrence‐free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly‐differentiated pNET (21.5), Ki‐67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1‐7: 7.5; difference of index: 11.4).ConclusionLND was mostly beneficial among patients with pNETs >2 cm, Ki‐67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151957/1/jso25689_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151957/2/jso25689.pd

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

Benchmarks in Liver Resection for Intrahepatic Cholangiocarcinoma

Introduction: Benchmarking in surgery has been proposed as a means to compare results across institutions to establish best practices. We sought to define benchmark values for hepatectomy for intrahepatic cholangiocarcinoma (ICC) across an international population. Methods: Patients who underwent liver resection for ICC between 1990 and 2020 were identified from an international database, including 14 Eastern and Western institutions. Patients operated on at high-volume centers who had no preoperative jaundice, ASA class &lt;3, body mass index &lt;35 km/m2, without need for bile duct or vascular resection were chosen as the benchmark group. Results: Among 1193 patients who underwent curative-intent hepatectomy for ICC, 600 (50.3%) were included in the benchmark group. Among benchmark patients, median age was 58.0 years (interquartile range [IQR] 49.0–67.0), only 28 (4.7%) patients received neoadjuvant therapy, and most patients had a minor resection (n = 499, 83.2%). Benchmark values included ≥3 lymph nodes retrieved when lymphadenectomy was performed, blood loss ≤600 mL, perioperative blood transfusion rate ≤42.9%, and operative time ≤339 min. The postoperative benchmark values included TOO achievement ≥59.3%, positive resection margin ≤27.5%, 30-day readmission ≤3.6%, Clavien-Dindo III or more complications ≤14.3%, and 90-day mortality ≤4.8%, as well as hospital stay ≤14 days. Conclusions: Benchmark cutoffs targeting short-term perioperative outcomes can help to facilitate comparisons across hospitals performing liver resection for ICC, assess inter-institutional variation, and identify the highest-performing centers to improve surgical and oncologic outcomes.</p

APOLLO: A randomized phase II double-blind study of olaparib versus placebo following curative intent therapy in patients with resected pancreatic cancer and a pathogenic BRCA1, BRCA2 or PALB2 mutation-ECOG-ACRIN EA2192

Background: A meaningful subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with pathogenic variants in BRCA1, BRCA2 and PALB2. In the metastatic setting, PARP inhibitor maintenance provides a progression-free survival benefit after a period of platinum based chemotherapy1,2, but the role of PARP inhibitors in the curative intent setting is undefined. The OlympiA study established one year of olaparib as the standard of care for patients with BRCA-related, early stage breast cancer who completed all other curative-intent treatment3. Therefore, we have designed a randomized, phase II double-blind study of one year of olaparib vs placebo in patients with pancreatic cancer and a germline or somatic variant in BRCA or PALB2 who have completed all curative intent therapy. Methods: We have enrolled and treated 23 of 152 planned patients on study NCT 04858334/EA2192. Eligibility criteria include: a pathogenic germline or somatic variant in BRCA1, BRCA2 or PALB2 as determined by local laboratory (central review required); completion of curative-intent resection and ≥ three months of multi-agent chemotherapy; no evidence of recurrent disease. At enrollment, patients must be within 12 weeks of their last anti-cancer intervention. Patients are randomized 2:1 to receive oral olaparib 300 mg twice daily or placebo for 12 28-day cycles. The primary endpoint is relapse-free survival. Overall survival is a secondary endpoint. Tumor tissue, fecal material (for microbiome analysis) and serial ctDNA samples are being collected

Development and Validation of a Predictive Risk Score for Blood Transfusion in Patients Undergoing Curative-Intent Surgery for Intrahepatic Cholangiocarcinoma

Background and Objectives: Among patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC), perioperative bleeding requiring blood transfusion is a common complication, yet preoperative identification of patients at risk for transfusion remains challenging. The objective of this study was to develop a preoperative risk score for blood transfusion requirement during surgery for ICC. Methods: Patients undergoing curative-intent liver surgery for ICC (1990–2020) were identified from a multi-institutional database. A predictive model was developed and validated. An easy-to-use risk calculator was made available online. Results: Among 1420 patients, 300 (21.1%) received an intraoperative transfusion. Independent predictors of transfusion included severe preoperative anemia (OR = 1.65, 95% CI 1.10–2.47), T2 category or higher (OR = 2.00, 95% CI 1.36–3.02), positive lymph nodes (OR = 1.75, 95% CI 1.32–2.32) and major resection (OR = 2.56, 95%CI 1.85–3.58). Receipt of blood transfusion significantly correlated with worse outcomes. The model showed good discriminative ability in both training (AUC = 0.68, 95% CI 0.66–0.72) and bootstrapping validation (C-index = 0.67, 95% CI 0.65–0.70) cohorts. An online risk calculator of blood transfusion requirement was developed (https://catalano-giovanni.shinyapps.io/TransfusionRisk). Conclusions: Intraoperative blood transfusion was significantly associated with poor postoperative outcomes among patients undergoing surgery for ICC. The identification of patients at high risk of transfusion could improve perioperative patient care and blood resources allocation.</p