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Surgical site infection is a major source of morbidity in patients undergoing pancreatic head resection and is often from organisms in intraoperative bile duct cultures. As such, many institutions use prolonged prophylactic antibiotics and tailor based on bile duct cultures. However, standard cultures take days, leaving many patients unnecessarily on prolonged antibiotics. Nanopore sequencing can provide data in hours and, thus, has the potential to improve antibiotic stewardship. The present study investigates the feasibility of nanopore sequencing in intraoperative bile samples.Patients undergoing pancreatic head resection were included. Intra-operative bile microbial profiles were determined with standard cultures and nanopore sequencing. Antibiotic recommendations were generated, and time-to-results determined for both methods. Organism yields, resistance patterns, antibiotic recommendations, and costs were compared.Out of 42 patients, 22 (52%) had samples resulting in positive standard cultures. All positive standard cultures had microbes detected using nanopore sequencing. All 20 patients with negative standard cultures had negative nanopore sequencing. Nanopore sequencing detected more bacterial species compared to standard cultures (10.5 vs 4.4, p0.05) and more resistance genotypes (10.3 vs 2.7, p0.05). Antimicrobial recommendations based on nanopore sequencing provided coverage for standard cultures in 27 out of 44 (61%) samples, with broader coverage recommended by nanopore sequencing in 13 out of 27 (48%) of these samples. Nanopore sequencing results were faster (8 vs 98 hours) than standard cultures but had higher associated costs ($165 vs $38.49).Rapid microbial profiling with nanopore sequencing is feasible with broader organism and resistance profiling compared to standard cultures. Nanopore sequencing has perfect negative predictive value and can potentially improve antibiotic stewardship; thus, a randomized control trial is under development.

Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates.To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS.This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021.Cytoreductive surgery.Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC).Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes.In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients.Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD.The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P 0.001).Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). The US HIPEC collaborative database (2000–2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. A total of 174 patients were identified. Median PCI was 16 (3–39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59–4.74; MOR-2+ : HR 0.77, 95% CI 0.22–2.69). MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

BACKGROUND. Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS. Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000–2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS. Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7–20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16–3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08–5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS. Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.

Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction.Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations.A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P .001; colorectal: r = 0.729; P .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071).In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.

Postoperative surgical site infection is a major source of morbidity after pancreatic head resections, and data suggest bacterobilia as a leading cause. Some centers use intraoperative bile duct cultures to guide postoperative antimicrobial prophylaxis. This prospective study evaluates culture differences between traditional bile duct swab versus bile duct aspiration intraoperative samples.Prospective patients undergoing pancreatic head resection with both bile duct swab and bile duct aspiration were included. Cultures were reviewed for organism characteristics. Any growth of organisms was considered a positive culture. Bile duct swab yield and characteristics were compared with bile duct aspiration. Postoperative surgical site infection complications were compared to bile duct culture results.Fifty patients were included. Bile duct aspiration resulted in a significantly higher median number of organisms compared to bile duct swab (6 vs 3; P.001). There were no differences in the number of patients (37 vs 33) having positive bile duct aspiration and bile duct swab cultures (P = .385). Anaerobic cultures (not possible with bile duct swab) were positive in 21 patients with bile duct aspiration. A total of 37 (74%) patients had preoperative biliary stenting, which highly associated (P.001) with positive cultures. Bile duct culture organisms correlated with postoperative surgical site infection in 12/17 (71%) patients.Use of bile duct aspiration improves intraoperative bile duct culture organism yield over bile duct swab and may improve tailoring of antibiotics in patients undergoing pancreatic head resection.

Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood.Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula).Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p 0.01), higher complication rate (90% vs 59%; p 0.01), higher reoperation rate (41% vs 9%; p 0.01), more 30-day readmissions (59% vs 22%; p 0.01), greater 30-day mortality (9% vs 1%; p 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p 0.01).Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Overall the incidence of gastric cancer is declining in the United States; however, the incidence of early-onset gastric cancer is increasing. We sought to elucidate clinical and genomic characteristics and risk factors for early-onset gastric cancer compared with late-onset gastric cancer.We utilized the Surveillance, Epidemiology, and End Results database (1973-2015), the Behavioral Risk Factor Surveillance Survey, and The Cancer Genome Atlas to characterize early-onset gastric cancer.The incidence of early-onset gastric cancer increased during the study period and now comprises30% of all gastric cancer in the United States. Early-onset gastric cancer was associated with higher grade (55.2 vs 46.9%), signet-ring cells (19.0 vs 10.4%), diffuse histology (25.7 vs 15.0%), and metastatic disease (49.5 vs 40.9%, all P.01) compared with late-onset gastric cancer. Early-onset gastric cancer was more likely to be Epstein-Barr virus (7.7 vs 5.1%) or genomically stable (22.5 vs 8.1%) subtype, whereas late-onset gastric cancer was more likely to be microsatellite instability subtype (18.6 vs 5.6%; all P.01). Risk factors for gastric cancer were less correlated with early-onset gastric cancer compared with late-onset gastric cancer.The incidence of early-onset gastric cancer has been steadily increasing in the United States, comprising30% of new gastric cancer cases today. Early-onset gastric cancer is genetically and clinically distinct from traditional gastric cancer. Additional investigations are warranted to better understand this alarming phenomenon.

Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC.The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed.Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA.While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6–15.3) versus 13.1 months (95% CI 9.5–16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5–36.6) versus 45.4 months (95% CI 35.9–54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19–2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09–2.73; p = 0.020). Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.

BackgroundPostoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on thesurvivalof patients withappendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.MethodsThe US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).ResultsOf the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p

BackgroundWhile emergent pancreatic resection for trauma has been previously described, no large contemporary investigations into the frequency, indications, and outcomes of emergent pancreatectomy (EP) secondary to complications of neoplastic disease exist. Modern perioperative outcomes data are currently unknown.MethodsACS-NSQIP was reviewed for all non-traumatic pancreatic resections (DP – distal pancreatectomy, PD - pancreaticoduodenectomy, or TP- total pancreatectomy) in patients with pancreatico-biliary or duodenal-ampullary neoplasms from 2005 to 2013. Patients treated for complications of pancreatitis were specifically excluded. Emergent operation was defined as NSQIP criteria for emergent case and one of the following: ASA Class 5, preoperative ventilator dependency, preoperative SIRS, sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Chi-square tests, Fisher’s exact tests were performed to compare postoperative outcomes between emergent and elective cases as well as between pancreatectomy types.ResultsOf 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients who underwent emergent resection. Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation. PD was performed in 409 (77%) patients, DP in 115 (21%), and TP in 10 (2%) patients. Overall major morbidity was significantly higher (46.1% vs. 25.6%,p p p p = 0.002), unplanned intubation (9.% vs. 4.1%,p p p p ConclusionEmergent pancreatic resection is markedly uncommon in the setting of neoplastic disease. Although these operations result in increased morbidity and mortality compared to elective resections, they can be life-saving in specific circumstances. The results of this large series of modern era national data may assist surgeons as well as patients and their families in making critical decisions in select cases of acutely complicated neoplastic disease.

While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM).All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay75th percentile, and non-home discharge.Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p 0.01).Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

BackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p

BACKGROUND Variations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers. METHODS Data from the US HIPEC Collaborative represents a retrospective multi-institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed-effects linear (continuous outcomes) or logistic (binary outcomes) regression models. RESULTS A total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8-70.9) and readmissions (overall 20.6%, range: 8.9-33.3) varied by institution (P

Background Elevated BNP is associated with adverse cardiac outcomes after noncardiac surgery. We assessed BNP values as markers of perioperative fluid status and their correlation with major/cardiopulmonary (CP) complications following CRS + HIPEC. Methods Fluid balance, BNP levels, and morbidity data were collected for all patients undergoing CRS + HIPEC between 6/2014 and 2/2016. Results One hundred and twenty-nine patients underwent CRS + HIPEC for appendiceal adenocarcinoma (n = 99), mesothelioma (n = 16), and colon cancer (n = 14). Less than 10% had CP comorbidities. The median PCI was 14 (range 4-39); 89% underwent CC0/1 resection (n = 115). Median blood loss (EBL) was 497 mL (50-2700). Major complications (Clavien III-V) occurred in 16 (12%), CP in 17 (13%), and major/CP in 24 (18%). Thirty-day mortality occurred in 2 (1.5%). Elevated BNP on POD1 correlated with increased risk of major/CP complications (OR 2.2, P = 0.052). This was most pronounced in the 25 patients receiving cisplatin: for each 100 unit increase in POD1 BNP the OR for major/CP complication was 7.4 versus 1.2 for the remaining patients, P = 0.083. Multivariate analysis identified increased EBL (OR 4.1 P = 0.011) and a trend toward increased BNP on POD1 (OR for each 100 unit increase 2.0, P = 0.10) as risk factors for major/CP complications. Conclusions Postoperative BNP measurement after CRS + HIPEC may guide postoperative fluid resuscitation and facilitate identification of patients at risk for major and/or cardiopulmonary complications.

Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure.Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0.Eighty-seven patients underwent a MILND. Seventy-seven cases (88.5%) were completed via a minimally invasive approach. The median total inguinal lymph nodes pathologically examined (SLN + MILND) was 12.0 (interquartile range 8.0, 14.0). Overall, 71% of patients suffered an adverse event (AE); the majority of these were grades 1 and 2, with 26% of patients experiencing a grade 3 AE. No grade 4 or 5 AEs were observed.After a structured training program, high-volume melanoma surgeons adopted a novel surgical technique with a lymph node retrieval rate that met or exceeded current oncologic guidelines and published benchmarks, and a favorable morbidity profile.

BACKGROUND National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community. METHODS Patients with stage II to III gastric adenocarcinoma undergoing curative-intent resection (National Cancer Data Base, 2006-2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan-Meier analysis was used to assess survival. RESULTS There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10-year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline-concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM). Methods The US HIPEC Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ± HIPEC between 2000 and 2012 (P1) versus 2013–2017 (P2). Results Among 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045). Conclusion CRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.

BACKGROUND. No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS. The U.S. HIPEC Collaborative database (2000–2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6–12mos or high-frequency surveillance (HFS) at q2–4mos. Primary outcome was overall survival (OS). RESULTS. Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for noninvasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two postoperative years would potentially save $13–19 M/year to the U.S. healthcare system. CONCLUSIONS. Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Background For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. Methods All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). Results Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. Conclusion The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

The differential diagnosis for ulcerating small bowel strictures is extensive and includes exposure to non-steroidal anti-inflammatory drugs (NSAIDs), Crohn’s disease, infections, gastrointestinal lymphoma and vasculopathy. It also encompasses the exceptionally rare and poorly understood diagnosis of cryptogenic multifocal ulcerative stenosing enterocolitis (CMUSE), often a diagnosis of exclusion and considerable difficulty. We present a case of persistent proximal jejunal ulcerating stenoses in a 75-year-old Caucasian man, which continued despite cessation of NSAIDs. After extensive clinical, radiographic, laboratory and ultimately surgical pathological appraisal—as well as failure to improve with both misoprostol and budesonide—he was diagnosed with CMUSE and managed with limited small bowel resection. In the presentation of this case, we aim to underscore the diagnostic challenges that clinicians face in differentiating CMUSE from other more common diagnoses, particularly NSAIDs-induced enteropathy.

Prognosis is markedly improved when melanoma is diagnosed early. Improved methods are needed for earlier detection and screening. We hypothesized that epigenetic analysis of blood samples could discriminate patients with melanoma from patients with other cutaneous lesions and from healthy volunteers. After institutional review board approval and consent, whole blood was obtained from 59 patients with melanoma, 20 patients with other skin cancers, 20 patients with benign skin conditions, and 20 healthy volunteers. Fifteen conformation biomarkers from five gene loci were analyzed on chromatin with the EpiSwitch technology using a modified chromatin conformation capture assay. Differentiation between patients with melanoma and those with nonmelanoma skin cancers was correct 85% of the time, resulting in a sensitivity of 88% and a specificity of 82%. Differentiation of patients with melanoma from healthy controls was correct 80% of the time, resulting in a sensitivity of 85% and a specificity of 75%. The noninvasive test was more accurate in early-stage melanoma (1/10 and 1/16 stage I and stage II patients were misclassified, respectively) and became less accurate with more advanced disease (3/14 and 4/19 stage III and IV patients were misclassified, respectively). We report the results of a noninvasive test using chromosomal aberrations and epigenetic changes identified in peripheral blood that, in this pilot study, distinguished patients with early-stage melanoma from other cohorts.

T1 melanomas, despite their favorable prognosis, account for 25% of melanoma deaths. The American Joint Committee on Cancer (AJCC) 7th edition melanoma staging, implemented in 2010, replaced the level of invasion with the mitotic rate for T1 substaging, on the basis of prognostic modeling, not prediction of occult lymph node metastasis. Previously, sentinel lymph node biopsy (SLNB) was recommended for T1b patients, whereas current guidelines suggest SLNB for select high-risk T1 melanomas. We investigated the effect of this staging change on the performance and outcomes of SLNB for T1 melanoma. Using 2004-2010 data from the Surveillance, Epidemiology, and End Results (SEER) Registry, we identified 32 527 cases of T1 melanoma and compared pre-2010 (N=27 170) with 2010 (N=5357) data. We used χ-tests, t-tests, and logistic regression models for analysis. After implementation of the 2010 AJCC staging system, SLNB for T1 patients increased from 12.1% (2004) to 14.4% (2010), despite a decrease for T1b melanomas (40.9 to 33.3%; both P values0.001), and there was no change in SLNB for melanomas that were 0.7 mm or thicker (38.3 and 39.3%). T-stage, thickness, level, ulceration, age, and geographic region were correlated with SLNB performance (all P values0.001). For T1 patients, overall SLN positivity rates were 6.1% pre-2010 and 7.8% in 2010 (P=0.12), while nearly doubling for T1a patients (3.6 to 6.6%, P=0.03). SLN-positive patients had diminished cancer-specific survival (P0.001). SLNB for T1b melanomas decreased after AJCC T1 reclassification, without changing for melanomas that were 0.7 mm or thicker. SLN positivity rates increased for T1a melanomas, and SLN status was prognostic for T1 patients. Improved strategies to identify high-risk T1 melanoma patients most likely to benefit from SLN surgery and to minimize clinical practice variation would be valuable.

Background The purpose of this study was to describe a single institution's experience with adult intussusception and determine how this was influenced by evolving computed tomography (CT) technology. Methods Adults treated between 1978 and 2013 for intussusception were reviewed. CT utilization and utilization of multislice technology over time were determined. Sensitivity of CT was calculated. Results A total of 318 patients were identified. CT utilization was 72% and it increased over time. The number of channels ranged from 1 to 128. CT sensitivity was greater than 85% for single and multislice scanners. A lead point was identified in 69% of patients and a malignancy in 40%. Surgical exploration was required in 60% of patients and 40% were managed nonoperatively. Conclusions The diagnosis of intussusception in adults is increasing over time, particularly idiopathic intussusception. This is associated with increased utilization of highly sensitive CT technology, which facilitates the safe nonoperative management in many patients.

Controversy exists regarding the predictive ability of a negative sentinel lymph node biopsy (SLNB) and the use of adjuvant radiation in Merkel cell carcinoma (MCC). Retrospective study of patients with MCC undergoing SLNB at Mayo Clinic from 1995 to 2011. Cumulative incidence (CI) of regional recurrence and death from MCC, respectively, were estimated taking into account the competing risk of death from other causes and compared between groups using Gray’s test. A total of 111 (74 %) of 150 SLNB were negative and comprised our study group. There were 15 regional recurrences, and the CI of a regional recurrence was 5.1, 15.0, and 16.6 % at 1, 3, and 5 years, respectively, after initial surgery. Nine patients (8 % of all patients) experienced a same nodal basin recurrence after a negative SLNB. Among 14 patients who received nodal radiation, the CI of a regional recurrence was 0 and 9.1 % at 1 and 3 years, respectively, compared to 5.8 and 15.5 %, respectively, among the 97 who did not receive nodal radiation (p = 0.45). Male sex was the only characteristic predictive of regional recurrence after a negative SLNB; the CI at 3 years was 21.3 versus 0 % in men and women, respectively (p = 0.007). Head and neck location was not associated with a higher risk of recurrence or an improvement in regional recurrences after radiation. Same nodal basin recurrences are uncommon after SLNB in MCC, and regional nodal irradiation can be avoided in the setting of successful sentinel lymph node mapping and a negative SLNB.

Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio [HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (p = 0.011). In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.

Background Merkel cell carcinoma (MCC) is a rare cutaneous malignancy of neuroendocrine origin with a high propensity for lymph node metastasis. Sentinel lymph node (SLN) status is important for accurate staging; however, the optimal treatment following SLN biopsy, regardless of nodal status, remains unclear. Methods 150 patients with MCC who underwent SLN biopsy from 1995 to 2011 at 3 Mayo Clinic sites were reviewed. Results Of 150 patients with MCC who underwent SLN biopsy, 39 (26%) were positive and 111 (74%) were negative. There was no significant difference between the sex, age, tumor location, or size of primary in the positive and negative SLN groups. While there was no difference in the cumulative incidence of any regional recurrence between SLN groups, the rate of in-transit recurrences was significantly higher in patients with a positive SLN (p = 0.022). The disease-specific survival for MCC was 97.0%, 82.4%, and 82.4% at 1, 3, and 5 years with a positive SLN and 99.0%, 94.9%, and 86.8% with a negative SLN (p = 0.31). Among those alive at last follow up, the median follow up was 3.8 years (IQR, 2.1–8.4) and 2.9 years (IQR, 1.8–6.1) for positive and negative SLN cohorts respectively. Conclusions Occult nodal metastasis is common in MCC(26%). No tumor or patient characteristics were identified to predict SLN positivity. Patients with a positive SLN have a higher risk of in-transit recurrence and may benefit from adjuvant radiation with inclusion of the in-transit field in amenable cases. When patients with a positive SLN receive additional treatment to the at-risk nodal basin, both OS and DSS are similar to patients with a negative SLN.

Stage III melanoma is associated with an increased risk of recurrence and death. Complete surgical resection remains the best chance for cure. Unfortunately, no adjuvant therapy has demonstrated a consistent improvement in melanoma-specific survival (MSS). We hypothesize that adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) may improve clinical outcomes.Retrospective cohort study of 317 surgically resected stage III melanoma patients managed with observation or adjuvant GM-CSF at a single institution from 2001 to 2010.Of the 317 stage III patients, 165 (52%) were observed and 152 (48%) were treated with GM-CSF, with a median follow-up of 34 months. Patients treated with GM-CSF tended to be younger (P0.0001), had more advanced stage disease (P = 0.002), and were more likely to have had a recurrence before initiation of adjuvant therapy than the observation group (P0.0001). Adjuvant GM-CSF seemed to be associated with improved MSS, but this did not reach statistical significance (P = 0.08). Patients with stage IIIC melanoma derived a substantial benefit from adjuvant GM-CSF, with a 52% risk reduction in melanoma-specific death (hazard ratio 0.48; 95% confidence interval, 0.27-0.87; P = 0.02).Despite selecting patients with more advanced stage and a higher incidence of regional relapse, adjuvant GM-CSF was associated with an improved MSS but not disease-free survival in patients with stage IIIC disease. In patients not otherwise eligible for clinical trials, adjuvant GM-CSF treatment is a reasonable option for individuals with resected high-risk melanoma.

Background Knowledge regarding behavior of and prognostic factors for Merkel cell carcinoma (MCC) is limited. Objective We sought to further understand the characteristics, behavior, prognostic factors, and optimal treatment of MCC. Methods A multicenter, retrospective, consecutive study of patients with known primary MCC was completed. Overall survival and survival free of locoregional recurrence were calculated and statistical analysis of characteristics and outcomes was performed. Results Among the 240 patients, the mean age at diagnosis was 70.1 years, 168 (70.0%) were male, and the majority was Caucasian. The most common location was head and neck (111, 46.3%). Immunosuppressed patients had significantly worse survival, with an overall 3-year survival of 43.4% compared with 68.1% in immunocompetent patients. In our study, patients with stage II disease had improved overall survival versus those with stage I disease, in a statistically significant manner. Patients with stage III disease had significantly worse survival compared with stage I and with stage II. Primary tumor size did not predict nodal involvement. Conclusion The data presented represent one of the largest series of primary MCC in the literature and confirm that MCC of all sizes has metastatic potential, supporting sentinel lymph node biopsy for all primary MCC. Because of the unpredictable natural history of MCC, we recommend individualization of care based on the details of each patient's tumor and clinical presentation.

The purpose of this study was to evaluate the accuracy of frozen section (FS) analysis of sentinel lymph nodes (SLN) in melanoma.Five hundred seventy-one patients underwent FS analysis of SLN between 1/2000 and12/2010. Surgical and pathological characteristics, recurrence, and survival were analyzed. Comparisons were made using χOne hundred thirty-three (23%) patients were SLN positive of which 63 (47.4%) were identified on FS. 16/70 SLN metastases not identified on FS (23%) were seen only on immunohistochemistry. FS analysis detected 84% of SLN metastasis2 mm. SLN FS false negative rate was 53%, positive predictive value 100%, negative predictive value 88%, and overall accuracy 89%. Among patients with a FS positive SLN, 17/63 (27%) had additional positive nodes on CLND, versus 1 of 70 (1.4%) with a positive SLN identified only on permanent section pathology (P 0.0001). The nodal recurrence rate following a negative SLN biopsy was 5%.FS analysis for SLNs spared approximately half of patients a second operation. Patients with a positive SLN detected on FS were more likely to have further nodal involvement. In our experience intraoperative pathologic analysis of melanoma SLNs does not impair our ability to detect SLN metastasis or lead to a high rate of false positive results or nodal recurrences. J. Surg. Oncol. 2016;114:879-883. © 2016 2016 Wiley Periodicals, Inc.

Regional lymph nodes are the most frequent site of spread of metastatic melanoma. Operative intervention remains the only potential for cure, but the reported morbidity rate associated with inguinal lymphadenectomy is approximately 50 %. Minimally invasive lymph node dissection (MILND) is an alternative approach to traditional, open inguinal lymph node dissection (OILND). The aim of this study is to evaluate our early experience with MILND and compare this with our OILND experience. We conducted a prospective study of 13 MILND cases performed for melanoma from 2010 to 2012 at two tertiary academic centers. We compared our outcomes with retrospective data collected on 28 OILND cases performed at the same institutions, by the same surgeons, between 2002 and 2011. Patient characteristics, operative outcomes, and 30-day morbidity were evaluated. Patient characteristics were similar in the two cohorts with no statistically significant differences in patient age, gender, body mass index, or smoking status. MILND required longer operative time (245 vs 138 min, p = 0.0003). The wound dehiscence rate (0 vs 14 %, p = 0.07), hospital readmission rate (7 vs 21 %, p = 0.25), and hospital length of stay (1 vs 2 days, p = 0.01) were all lower in the MILND group. The lymph node count was significantly higher (11 vs 8, p = 0.03) for MILND compared with OILND. MILND for melanoma is a novel alternative to OILND, and our preliminary data suggest that MILND provides an equivalent lymphadenectomy while minimizing the severity of postoperative complications. Further research will need to be conducted to determine if the oncologic outcomes are similar.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is the preferred treatment for selected patients with mucinous appendiceal adenocarcinoma. Frequently, the hemidiaphragms are infiltrated with tumor, requiring partial diaphragm resection (DR) in order to obtain complete cytoreduction (CC-0). The clinical significance of diaphragmatic invasion and the optimum management to prevent transmission of disease from abdomen to chest is largely unknown. This was a retrospective review of 78 patients with mucinous appendiceal adenocarcinoma undergoing cytoreduction and partial DR at a single institution between 2010 and 2014. Partial DR was necessary in 31 (39.7 %) patients in order to obtain CC-0. DR was not associated with increased morbidity or poor survival. Of the 31 patients who had a DR, 26 (83.9 %) were treated with thoracoabdominal chemoperfusion. The remaining five (16.1 %) patients had the diaphragm closed prior to HIPEC. Thoracoabdominal chemoperfusion was not associated with increased 30-day grade III/IV morbidity or respiratory complications. Overall, five (20 %) patients with a DR developed thoracic recurrence. There were two (8 %) thoracic recurrences in the 26 patients treated with thoracic chemoperfusion compared with three (60 %) in the five patients who had their diaphragm closed prior to HIPEC (p = 0.002). In univariate analysis histology, CC-0 and thoracoabdominal chemoperfusion were associated with thoracic disease-free survival; however, none of these were significant on multivariate analysis. DR is not associated with increased morbidity and should be performed, if needed, to obtain a CC-0. Following DR, patients remain at significant risk of developing thoracic recurrence. Thoracoabdominal chemoperfusion reduces this risk without increasing morbidity.

Because most adult intussusceptions are reportedly due to malignancy, operative treatment is recommended. With current availability of computed tomography, we questioned the role of mandatory operative exploration for all adult intussusceptions.This study is a retrospective review of all adults treated from 1983 to 2008 at a large tertiary referral center for intussusception.One hundred ninety-six patients had intussusception over the 25-year study period. Computed tomography was obtained in 60% of patients. Neoplasms [malignant, (21%); benign, (24%)] were the commonest etiology; 30% cases were idiopathic. One hundred twenty (61%) patients underwent operative treatment for intussusception. Six of the 58 idiopathic or asymptomatic cases were operated on with negative findings in all. Palpable mass (OR 4.56, p 0.035), obstructive symptoms (OR 9.13, p 0.001) or obstruction (OR 9.67, p 0.001), GI bleeding (OR 14.41, p 0.001), and a lead point on computed tomography (OR 10.08, p 0.001) were associated with the need for operation.In the current era of computed tomography, idiopathic or asymptomatic intussusception is being seen more commonly; however, the majority of adult intussusceptions still have pathologic lead points. From our experience, all patients with palpable mass, obstructive symptoms or obstruction, gastrointestinal bleeding, or a lead point on computed tomography should undergo operative exploration.

Published data have reported that components of the peripheral blood are significant prognostic factors in hematologic and solid malignancies. Thus, we sought to investigate if the preoperative absolute lymphocyte count (ALC) and absolute monocyte count (AMC) affects disease progression and survival after complete surgical resection of advanced malignant melanoma.We retrospectively reviewed records of 227 patients with resected advanced malignant melanoma (153 stage III and 74 stage IV) that were treated at the Mayo Clinic from 2000 to 2010. Survival analysis was performed using the Kaplan-Meier method, log-rank tests, and the Cox proportional hazards model for the univariate and multivariate analysis.Surgically resected stage III melanoma patients with a preoperative AMC0.6×10/L experienced a longer overall survival (OS) versus AMC≥0.6×10/L (median: 63.9 vs. 34.8 mo, respectively, P0.008). Multivariate analysis showed AMC to be an independent predictor for OS in stage III patients. Stage IV resected melanoma patients with an ALC≥1.9×10/L experienced a superior median relapse-free survival (RFS) compared with patients with an ALC1.9×10/L (median: 11.4 vs. 5.4 mo, respectively, P0.006). Multivariate analysis showed ALC to be an independent predictor for RFS in stage IV patients.These data showed that in surgically resected stage III melanoma, preoperative AMC is an independent prognostic factor for OS. In contrast, a higher preoperative ALC is an independent prognostic for longer RFS in surgically resected stage IV melanoma.

Background Among older melanoma patients, lymphatic mapping failure, lower rates of SLN positivity and poor prognosis are reported reasons for omission of sentinel lymph node biopsy (SLNB). We investigated reasons for non-compliance with guidelines, sensitivity and prognostic significance of SLNB and completion lymphadenectomy (CLND) for elderly melanoma patients. Methods Retrospective review of patients ≥65 years with ≥1 mm thick melanoma treated at a single Institution. Wilcoxon, chi-square and Fisher's exact tests were used for analysis as appropriate. Univariable and multivariable Cox regressions were used to analyze time-to-event variables. Results 72 of 358 patients (20%) did not undergo SLNB. Reasons for omission included selective neck dissection in 26 (7%), patient refusal in 11 (3%), physician recommendation in 15 (4%) and significant comorbidities in 8 (2%). Of the 286 patients undergoing SLNB, only 5 (1.7%) had lymphatic mapping failures. 76 patients (26.6%) were SLN-positive. The sensitivity of SLNB was 90.5%, the negative predictive value was 96.3% and the false negative rate was 3.8%. Sixty-seven (88%) SLN-positive patients underwent CLND and 10 (15%) had positive non-SLNs. Reasons for omission of CLND included patient refusal in 3 (4%), surgeon recommendation in 5 (7%) and postoperative complication in 1 (1%). SLN and non-SLN status were independently associated with disease-free survival. SLN status was independently associated with melanoma-specific survival. Conclusions SLNB was successful in 98.7% of elderly patients with high sensitivity and a low false negative rate. Only 2% of our elderly patients appeared too frail for SLNB. Age alone should not be a contraindication to SLNB and CLND for melanoma.

Pyogenic liver abscess in the pediatric population is a rare entity and can be difficult to manage. Surgical infections caused by Streptococcus anginosus are exceedingly rare. Here we present a case of pyogenic liver abscess caused by S anginosus in an adolescent presenting with fever, nausea, emesis, and right upper quadrant abdominal discomfort.

Stage III melanoma is currently stratified by number of lymph nodes (LNs) involved. However, given the variability of LN retrieval counts we hypothesize that lymph node ratio (LNR) may also provide prognostic information.Retrospective cohort study of 411 patients with stage III melanoma were divided into two groups based on LNR (0.15, n = 291 and ≥0.15, n = 120).In multivariate analysis N stage (N3 vs. N1, hazard ratio [HR] = 2.13, p0.001), extranodal extension (HR = 1.92, p = 0.002), macrometastasis (HR = 1.70, p = 0.005), non-SLN involvement (HR = 1.65, p = 0.005), risk of N2 disease exceeding 35 % (HR = 1.51, p = 0.03), and LNR ≥0.15 (HR = 1.46, p = 0.03) were associated with overall survival (OS). LNR failed to further stratify stage III melanoma; however, the number of LNs examined was an independent prognostic factor. Patients who had8 inguinal,15 axillary, or20 cervical LNs examined had fewer same nodal basin recurrences (26 [8 %] vs. 20 [20 %], p = 0.0009) and for N1 patients an improved OS (3-year OS 84 % vs. 76 %, 10-year OS 53 % vs. 34 %, p = 0.06) compared with N1 patients who had fewer LNs examined.LNR is an important prognostic factor in stage III melanoma; however, it was not independent over the current AJCC TNM staging system. Diligence by the surgeon and pathologist to retrieve and examine8 inguinal,15 axillary, or20 cervical LNs is associated with fewer same nodal basin recurrences and improved survival and is critical to reliable prognostication.

Tumor-infiltrating lymphocytes (TILs) and regression are manifestations of the host immune response to tumor, but their influence on outcome remains undefined. There is a paucity of data on the elderly who represent a growing proportion of melanoma patients. The aim of this study was to evaluate the influence of TILs and regression as an indirect measure of immunity on outcome in elderly patients with melanoma. From a prospective database, we identified 250 consecutive cutaneous melanoma patients aged at least 65 years at the time of diagnosis. Data were verified by record review. Within the primary melanoma, a brisk TIL response was present in 66 (31%), nonbrisk TILs in 36 (17%), and absent in 111 (52%). The presence of a brisk infiltrate conferred a three-fold increased risk of sentinel lymph node (SLN) metastasis (P=0.02). Despite this, nonbrisk or absent TILs were associated with a five-fold increased risk of recurrence (P=0.0001). In multivariate analysis, nonbrisk or absent TILs were independently associated with recurrence (P0.0001), diminished 5-year disease-free survival (76 vs. 91%, P=0.0006), and 5-year melanoma-specific survival (82 vs. 95%, P=0.0008). Regression was not an independent predictor of SLN metastasis, disease-free survival, or melanoma-specific survival. Our study demonstrates that an active antitumor immune response exists in elderly melanoma patients that, paradoxically, predicts both SLN metastasis and improved melanoma-specific outcomes. Further investigation to characterize this lymphocytic infiltrate and to confirm its clinical significance as a predictor of nodal status, patient outcome, and response to immunotherapy in elderly melanoma patients appears warranted.

Background Locoregional recurrence occurs in approximately 20% of patients with melanoma and is associated with a significantly worse prognosis. Standards are well established for peripheral margins; however, there is insufficient evidence regarding depth of resection. Methods Retrospective review of 964 patients undergoing excision of trunk or extremity melanoma ≥1 mm thick during a 29-year period at a tertiary academic center. Multivariate analysis and hazard ratios were used to determine the effect of excision of the deep muscular fascia on locoregional recurrence. Results A total of 278 (29%) patients underwent resection of the muscular fascia. Of these patients, 18 (6%) developed local, 33 (12%) developed in-transit, and 68 (24%) developed nodal recurrence within 5 years. A total of 686 (71%) patients underwent excision of their primary melanoma with preservation of the muscular fascia. Of these patients, 40 (6%) developed local, 30 (4%) developed in-transit, and 84 (12%) developed nodal recurrence at 5 years. In multivariate analysis excision of the deep muscular fascia was an independent predictor of locoregional recurrence in patients treated with sentinel lymph node biopsy. Specifically, fascia resection was associated with a 2.5-fold increased risk of nodal recurrence but not associated with local recurrence or overall survival. Conclusion On the basis of no demonstrated advantage for resection of the deep muscular fascia, but potential for increased risk of intralymphatic recurrences, we recommend preservation of the deep muscular fascia during resection of primary cutaneous melanoma.

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with an ill-defined natural history following locoregional recurrence.This is a retrospective review of patients with MCC diagnosed at the Mayo Clinic from 1981 to 2008. For each outcome (subsequent locoregional recurrence, distant recurrence, and death) the survival-free of the outcome was estimated using the Kaplan-Meier method. Associations of patient and clinical characteristics with the outcomes were assessed by fitting Cox proportional hazards regression models.Among the 240 patients diagnosed with MCC, 70 (29%) patients were identified who developed locoregional recurrence as the first site of recurrence. The median time from diagnosis to locoregional recurrence was 6 months. The pattern of first locoregional failure in this group includes 25 (10.4%) local, 18 (7.5%) in-transit, and 27 (11.3%) nodal recurrences. Recurrences were most commonly treated by surgery and radiation. At 3 years after the initial recurrence, locoregional recurrence-free survival was 75% and the distant recurrence-free survival was 56%. Locoregional recurrence is a poor prognostic sign associated with a 3-year overall survival of 39%. Nodal status at time of original surgery and time to first recurrence were important predictors of distant recurrence (P0.006) and overall survival following locoregional recurrence (P0.001).Locoregional recurrence is a substantial problem in patients with MCC and is a poor prognostic sign. In those patients who experience a locoregional recurrence, aggressive efforts to regain locoregional control appear warranted and may result in long-term survival.

In order to characterize the degree of immunosuppression in regional immunity in patients with melanoma, we used immunohistochemistry to analyze markers of T-cell subtype and polarity, costimulation, dendritic cell maturation, monocytes, lymphatic vasculature, and angiogenesis. Specifically, we analyzed expression of CD4, CD8, CD14, CD40, CD86, CD123, HLA-DR, IL-10, LYVE, VEGFR3, and VEGF-C in lymph nodes. We compared sentinel lymph nodes with and without metastasis from patients with melanoma with both infection inflamed (reactive) and dormant human lymph nodes. There were no differences demonstrated between sentinel lymph nodes with or without metastasis from patients with melanoma in any of the markers that were tested. Both groups of sentinel lymph nodes had fewer CD8(+) T cells than either set of control nodes. Whereas the infection inflamed lymph nodes demonstrated Th2 polarity, the dormant lymph nodes demonstrated Th1 polarity. In conclusion, changes in regional immunity appeared to precede metastasis in melanoma. Whether there was tumor present in sentinel lymph nodes or not, these nodes demonstrated a marked decrease in cytotoxic T cells compared with both sets of controls. Furthermore, the control lymph nodes used for comparison can significantly impact interpretation, as the dormant and reactive lymph nodes markedly varied in their immune profiles. These immunologic changes may explain the successful metastasis of melanoma in the midst of the immune environment of the sentinel lymph node, and lend insights into the mechanisms of lymphatic metastases in other solid malignancies.

BackgroundHepatic epithelioid haemangioendothelioma (HEH) is a rare vascular neoplasm with unpredictable clinical behaviour.AimTo compare overall survival (OS) and disease-free survival (DFS) between liver resection (LR) and orthotopic liver transplantation (OLT) for the treatment of HEH.MethodsRetrospective review of 30 patients with HEH treated at Mayo Clinic during 1984 and 2007.ResultsMedian age was 46 years with a female predominance of 2:1. Treatment included LR (n= 11), OLT (n= 11), chemotherapy (n= 5) and no treatment (n= 3). LR was associated with a 1-, 3- and 5-year OS of 100%, 86% and 86% and a DFS of 78%, 62% and 62%, respectively. OLT was associated with a 1-, 3- and 5-year OS of 91%, 73% and 73% and a DFS 64%, 46% and 46%, respectively. Metastases were present in 37% of patients but did not significantly affect OS. Important predictors of a favourable OS and DFS were largest tumour ≤ 10cm and multifocal disease with ≤10 nodules.ConclusionLR and OLT achieve comparable results in the treatment of HEH. LR is appropriate for patients with resectable disease and favourable prognostic factors. OLT is appropriate for patients with unresectable disease and possibly those with unfavourable prognostic factors. Metastases may not be a contraindication to surgical treatment.