Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

Cohort study of long-term survival and recurrence patterns following operative management of colorectal liver metastasis - is follow-up beyond 5 years warranted?

AIMS: To evaluate the patterns of overall survival (OS) and recurrence following surgical resection of colorectal liver metastases (CRLM). METHODS: In compliance with STROCSS guideline, a single-centre retrospective cohort study was conducted. All consecutive patients undergoing resection of CRLM between 2003 and 2019 were considered eligible for inclusion. The outcome measures included OS, recurrence-free survival (RFS), recurrence rate, time to recurrence (TTR) and longest TTR. Statistical analyses included simple descriptive statistics and Kaplan-Meier survival statistics. RESULTS: We included 486 liver resections in 472 patients. The estimated median OS and RFS were 5.1 years and 3.1 years, respectively. The probability of 1-year, 3-year, 5-year and 10-year OS was 93%, 69%, 50% and 34%, respectively. The probability of 1-year, 3-year, 5-year and 10-year RFS was 81%, 50%, 34% and 33%, respectively. Recurrence occurred in 56% (271/486) of patients, and the median TTR was 1.6 years (IQR: 0.8-2.7) with longest TTR of 4.8 years. Although there were no recurrences in the 66 patients that entered the 6th year, the 95% CI for true rate of recurrence in the population given these data is 0-5.4%. CONCLUSIONS: Our results suggest that recurrences that occur after operative management of CRLM are almost certain to occur within the first 5 years even for patients surviving longer than 5 years. This does not disprove the requirement for follow up beyond 5 years. However, based on this data, we have altered our follow up from 10 to 6 years. The need for the 6th year of follow up will be reassessed in light of further observations.

The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.

INTRODUCTION: The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK. METHODS: A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records. RESULTS: The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001). CONCLUSION: The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.

How successful is liver resection for colorectal cancer liver metastases in patients over 75 years old?

BACKGROUNDS/AIMS: As populations age, an increased incidence of colorectal cancer will generate an increase in colorectal cancer liver metastases (CRLM). In order to guide treatment decisions, this study aimed to identify the contemporary complication rates of elderly patients undergoing liver resection for CRLM in a, centralised, UK centre. METHODS: All patients undergoing operative procedures for CRLM between January 2013 and January 2019 were included. Patient, tumour and operative data were analysed, including the prognostic marker; tumour burden score. RESULTS: 339 operations were performed on 289 consecutive patients with CRLM (272 patients ＜75 years old, 67 patients ≥75 years old). Median age was 66 years (range 20-93). There was no difference in major complication rates between the two age cohorts (6.65 vs. 6.0%, p=0.847) or operative mortality (1.1% vs. 1.4%, p=0.794). Younger patients had higher R1 resection rates (20.4% vs. 4.5%, p=0.002) and post-operative chemotherapy rates (60.3% vs. 35.8%, p< 0.001). The 1, 3 and 5-year OS was 90.2%, 70.5% and 52.3% respectively, median 70 months, with no difference between age cohorts (p=0.772). Tumour Burden score and operation type were independent predictors of overall survival. CONCLUSIONS: Liver resection for CRLM in patients 75 years and older is feasible, safe and confers a similar 5-year survival rate to younger patients. The current outcomes from surgery are better than historical datasets.

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study.

OBJECTIVE: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. SUMMARY BACKGROUND DATA: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. METHODS: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Overall, 887 patients were included, with a mean age of 66 ±â€Š10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09-5.21]), perineural invasion (HR = 1.50 [1.01-2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48-0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65-4.27]). CONCLUSIONS: Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

The microbiology of infected pancreatic necrosis.

BACKGROUND: Acute pancreatitis (AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics. METHODS: Clinical data, including microbiology results, of consecutive patients with IPN undergoing minimally invasive necrosectomy at our institution between January 2009 and July 2016 were retrospectively reviewed. RESULTS: The results of 40 patients (22 males and 18 females, median age 60 years) with IPN were reviewed. The etiology of AP was gallstones, alcohol, dyslipidemia and unknown in 31, 2, 2 and 5 patients, respectively. The most frequently identified microbes in microbiology cultures were Enterococcus faecalis and faecium (22.5% and 20.0%) and Escherichia coli (20.0%). In 19 cases the cultures grew multiple organisms. The antibiotics with the least resistance amongst the microbiota were teicoplanin (5.0%), linezolid (5.6%), ertapenem (6.5%), and meropenem (7.4%). CONCLUSION: The carbapenem antibiotics, ertapenem and meropenem provide good antimicrobial cover against the common, mainly enteral, microorganisms causing IPN. Culture and sensitivity results of acquired samples should be regularly reviewed to adjust prescribing and monitor for emergence of resistance.

Can infected pancreatic necrosis really be managed conservatively?

OBJECTIVES: Guidelines advocate minimally invasive drainage rather than open surgery for infected pancreatic necrosis (IPN) after acute pancreatitis. We hypothesized that the conservative approach could be extended even further by treating patients using an antibiotics-only protocol. PATIENTS AND METHODS: Between June 2009 and July 2017, patients with IPN were selectively managed with carbapenem antibiotics for a minimum of 6 weeks. We compared these patients with patients who underwent minimal access retroperitoneal pancreatic necrosectomy (MARPN) for IPN to identify characteristics of this patient group. RESULTS: Of 33 patients with radiologically proven IPN, 13 patients received antibiotics without any surgical or radiological intervention and resulted in no disease-specific mortality and one case of pancreatic insufficiency. In comparison, 44 patients underwent MARPN with a mortality of 20%, and 81.8% developed pancreatic insufficiency. The modified Glasgow score and computed tomography severity score was less in the antibiotic-only group (P<0.001 and P=0.014, respectively). Patients who underwent MARPN had lower serum haemoglobin and albumin levels (P=0.030 and 0.001, respectively), and a higher C-reactive protein (P=0.027). CONCLUSION: Conservative treatment of IPN with antibiotics is a valid management option for haemodynamically stable patients experiencing less severe disease, requiring careful selection by experienced clinicians.

How to decide which patient-reported outcome measure to use? A practical guide for plastic surgeons.

The use of patient-reported outcome measures (PROMs) is increasing across all medical specialties, as their importance to patient care is validated. They are likely to play a particularly important role in plastic and reconstructive surgery where outcomes are often subjective, and the recent guidance from the Royal College of Surgeons of England advising their use in cosmetic surgery highlights this. To drive their routine use across our specialty, it is important that clinicians are capable of understanding the often complex and confusing language that surrounds their design and validation. In this article, we describe the process of PROM design and validation, and we attempt to 'demystify' the language used in the health outcome literature. We present the important steps that a well-designed PROM must go through and suggest a straightforward guide for selecting the most appropriate PROMs for use in clinical practice. We hope that this will encourage greater use of PROM data across plastic and reconstructive surgery and ultimately help improve outcomes for our patients.

A meta-analysis of the utility of the neutrophil-to-lymphocyte ratio in predicting survival after pancreatic cancer resection.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is thought to reflect cancer disease burden. To assess the prognostic ability of the NLR on overall survival in patients with resectable, pancreatic cancer a meta-analysis of published literature was undertaken. METHOD: A systematic review was performed independently by two authors using PubMed, Ovid MEDLINE and Embase databases. Included studies detailed the pre-operative NLR and overall survival of pancreatic cancer patients. RESULTS: Of the 214 studies retrieved using the search strategy, 8 studies involving 1519 patients were included in the meta-analysis. Only one study did not find a statistically significant association between a high NLR and OS. The pooled Hazard Ratio was 1.77 (95% CI [1.45-2.15]; p < 0.01). The NLR cut-off values ranged from 2 to 5. There was low to moderate inter-study heterogeneity (I2 = 31%; p = 0.17), a low risk of intra-study bias, and potentially 3 unpublished (negative) studies. CONCLUSIONS: A high pre-operative NLR indicates a worse prognosis than in patients with a low NLR. There is potential to use the NLR to direct therapies. A specific cut-off value has not been established from this study and so further research is required.

Surgical outcomes for duodenal adenoma and adenocarcinoma: a multicentre study in Australia and the United Kingdom.

BACKGROUND: Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection. METHODS: This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK. RESULTS: There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%. CONCLUSION: Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

Laparoscopic Left Pancreatectomy in the United Kingdom: Analysis of a Six-Year Experience in a Single Tertiary Center.

OBJECTIVES: Laparoscopic techniques have been slow to establish a role in pancreatic surgery. Worldwide, laparoscopic left pancreatectomy (LLP) is gaining in popularity; however, there remains little published data from the United Kingdom.We aimed to evaluate the results of LLP performed in a single UK pancreatic unit. METHODS: Patients undergoing LLP for lesions in the body and tail of the pancreas between April 2009 and April 2015 were identified. Patient records were reviewed retrospectively. RESULTS: Laparoscopic left pancreatectomy was performed on 46 patients, median age, 62 years (range, 19-84). The spleen was preserved in 27 patients (93% of planned), and 6 (13%) operations were converted to open. The overall morbidity rate was 39%; 28 patients had no complications. Significant complications were seen in 7 (15%) patients; this included 3 pancreatic fistula (6.5%) and 1 mortality (2%). Median length of stay was 6 days (range, 3-28). Histology revealed 15 neuroendocrine tumors, 8 adenocarcinomas, 4 mucinous cystadenomas, 1 intraductal papillary mucinous neoplasm, 2 metastases, and 16 other benign pathologies. CONCLUSIONS: Laparoscopic pancreatic surgery has a low risk of significant complications. Our results offer encouragement to identify LLP as the gold standard approach for premalignant lesions. Further work should clarify the outcomes for malignant lesions.

Is surgical smoke harmful to theater staff? a systematic review.

BACKGROUND: Smoke is generated by energy-based surgical instruments. The airborne byproducts may have potential health implications. This study aimed to evaluate the properties of surgical smoke and the evidence for the harmful effects to the theater staff. METHODS: Cochrane Database, MEDLINE, PubMed, Embase classic and Embase, and the metaRegister of Controlled Trials were searched for studies reporting the constituents found in the smoke plume created during surgical procedures, the methods used to analyze the smoke, the implications of exposure, and the type of surgical instrument that generated the smoke. Studies were excluded if they were animal based, preclinical experimental work, or opinion-based reports. The common end points were particle size and characteristics, infection risk, malignant spread, and mutagenesis. RESULTS: The inclusion criteria were fulfilled by 20 studies. In terms of particle size, 5 (25%) of the 20 studies showed that diathermy and laser can produce ultrafine particles (UFP) that are respirable in size. With regard to particle characterization, 7 (35%) of the 20 studies demonstrated that a variety of volatile hydrocarbons are present in diathermy-, ultrasonic-, and laser-derived surgical smoke. These are potentially carcinogenic, but no evidence exists to support a cause-effect relationship for those exposed. In terms of infection risk, 6 (30%) of the 20 studies assessed surgical smoke for the presence of viruses, with only 1 study (5%) positively identifying viral DNA in laser-derived smoke. One study (5%) demonstrated bacterial cell culture (Staphylococcus aureus) from a laser plume after surgery. Regarding mutagenesis and malignant spread, one study (5%) reported the mutagenic effect of smoke, and one study (5%) showed the presence of malignant cells in the smoke of a patient undergoing procedures for carcinomatosis. CONCLUSIONS: The potentially carcinogenic components of surgical smoke are sufficiently small to be respirable. Infective and malignant cells are found in the smoke plume, but the full risk of this to the theater staff is unproven. Future work could focus on the long-term consequences of smoke exposure.