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

Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma

Background: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. Methods: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ. Results: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p < 0.001). Conclusion: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.info:eu-repo/semantics/publishedVersio

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

Proposed Modification of the Eighth Edition of the AJCC Staging System for Intrahepatic Cholangiocarcinoma

Background: To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Methods: Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (≥3 LNM). Results: The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p < 0.05), and SEER (Median OS, stage I 87.0 vs. II 29.3 vs. III 17.7 vs. IV 14.2 months, all p < 0.05) datasets, which was also verified among patients who had ≥6 lymph node harvested from both databases. Conclusion: The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.info:eu-repo/semantics/publishedVersio

Defining Long-Term Survivors Following Resection of Intrahepatic Cholangiocarcinoma

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). RESULTS: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived  5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. CONCLUSION: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.info:eu-repo/semantics/publishedVersio

Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma

Background: Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. Objective: The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. Methods: Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. Results: A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. Conclusions: Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.info:eu-repo/semantics/publishedVersio

Impact of Body Mass Index on Tumor Recurrence Among Patients Undergoing Curative - Intent Resection of Intrahepatic Cholangiocarcinoma - a Multi-institutional International Analysis

Background: The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category. Methods: Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI≥30 kg/m2) according to the World Health Organization (WHO) definition. Impact of clinico-pathological factors on recurrence-free survival (RFS) was assessed using Cox proportional hazards model among patients in the three BMI categories. Results: Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22; overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17; overweight: 6.9%, n = 19)(p 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase). Conclusion: Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.info:eu-repo/semantics/publishedVersio

Cytoreductive Debulking Surgery Among Patients with Neuroendocrine Liver Metastasis: a Multi-Institutional Analysis

BACKGROUND: Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM. METHODS: 612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2). RESULTS: 179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P < 0.001) or liver disease burden that was bilateral (R0/R1: 52.8% vs. R2: 75.6%; P < 0.001). After a median follow-up of 51 months, median (R0/R1: not reached vs. R2: 87 months; P < 0.001) and 5-year survival (R0/R1: 85.2% vs. R2: 60.7%; P < 0.001) was higher among patients who underwent an R0/R1 resection compared with patients who underwent a debulking operation. Among patients with ≥50% NELM liver involvement, median and 5-year survival following debulking was 55.4 months and 40.6%, respectively. CONCLUSION: Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit.info:eu-repo/semantics/publishedVersio

Perception Is Reality: quality metrics in pancreas surgery – a Central Pancreas Consortium (CPC) analysis of 1399 patients

Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established