Sentinel lymph node positivity in melanoma: Which risk prediction tool is most accurate?

BACKGROUND: Sentinel lymph node biopsy for melanoma determines treatment and prognostic factors and improves disease-specific survival. To risk-stratify patients for sentinel lymph node biopsy consideration, Memorial Sloan Kettering Cancer Center and Melanoma Institute Australia developed nomograms to predict sentinel lymph node positivity. We aimed to compare the accuracy of these 2 nomograms. METHODS: A multi-institutional study of patients with melanoma receiving sentinel lymph node biopsy between September 2018 and December 2022 was performed. The accuracy of the 2 risk prediction tools in determining a positive sentinel lymph node biopsy was analyzed using receiver operating characteristic curves and area under the curve. RESULTS: In total, 532 patients underwent sentinel lymph node biopsy for melanoma; 98 (18.4%) had positive sentinel lymph node. Increasing age was inversely related to sentinel lymph node positivity (P < .01); 35.7% of patients ≤30 years had positive sentinel lymph node compared with 9.7% of patients ≥75 years. When we analyzed the entire study population, accuracy of the 2 risk prediction tools was equal (area under the curveMemorial Sloan Kettering Cancer Center: 0.693; area under the curveMIA: 0.699). However, Memorial Sloan Kettering Cancer Center tool was a better predictor in patients aged ≥75 years (area under the curveMemorial Sloan Kettering Cancer Center: 0.801; area under the curveMelanoma Institute Australia: 0.712, P < .01) but Melanoma Institute Australia tool performed better in patients with a higher mitotic index (mitoses/mm2 ≥2; area under the curveMemorial Sloan Kettering Cancer Center: 0.659; area under the curveMelanoma Institute Australia: 0.717, P = .027). Both models were poor predictors of sentinel lymph node positivity in young patients (age ≤30 years; area under the curveMemorial Sloan Kettering Cancer Center: 0.456; area under the curveMelanoma Institute Australia: 0.589, P = .283). CONCLUSION: The current study suggests that the 2 risk stratification tools differ in their abilities to predict sentinel lymph node positivity in specific populations: Memorial Sloan Kettering Cancer Center tool is a better predictor for older patients, whereas Melanoma Institute Australia tool is more accurate in patients with a higher mitotic index. Both nomograms performed poorly in predicting sentinel lymph node positivity in young patients.

Revisiting the Value of Drains After Low Anterior Resection for Rectal Cancer: a Multi-institutional Analysis of 996 Patients.

BACKGROUND: Intraoperative pelvic drains are often placed during low anterior resection (LAR) to evacuate postoperative fluid collections and identify/control potential anastomotic leaks. Our aim was to assess the validity of this practice. METHODS: Patients from the US Rectal Cancer Consortium (2007-2017) who underwent curative-intent LAR for a primary rectal cancer were included. Patients were categorized as receiving a closed suction drain intraoperatively or not. Primary outcomes were superficial surgical site infection (SSI), deep SSI, intraabdominal abscess, anastomotic leak, and need for secondary drain placement. Three subgroup analyses were conducted in patients who received neoadjuvant chemoradiation, had a diverting loop ileostomy (DLI), and had low anastomoses < 6 cm from the anal verge. RESULTS: Of 996 patients 67% (n = 551) received a drain. Drain patients were more likely to be male (64 vs 54%), have a smoking history (25 vs 19%), have received neoadjuvant chemoradiation (73 vs 61%), have low tumors (56 vs 36%), and have received a DLI (80 vs 71%) (all p < 0.05). Drains were associated with an increased anastomotic leak rate (14 vs 8%, p = 0.041), although there was no difference in the need for a secondary drainage procedure to control the leak (82 vs 88%, p = 0.924). These findings persisted in all subset analyses. Drains were not associated with increased superficial SSI, deep SSI, or intraabdominal abscess in the entire cohort or each subset analysis. Reoperation (12 vs 10%, p = 0.478) and readmission rates (28 vs 31%, p = 0.511) were similar. CONCLUSIONS: Although not associated with increased infectious complications, intraoperatively placed pelvic drains after low anterior resection for rectal cancer are associated with an increase in anastomotic leak rate and no reduction in the need for secondary drain placement or reoperation. Routine drainage appears to be unnecessary.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

BACKGROUND: While 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. METHODS: Patients 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). RESULTS: A 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 < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS (2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%). CONCLUSIONS: As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown. METHODS: The 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). RESULTS: Of 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 < 0.001) and RFS (32% vs 42%; p < 0.001). Infectious POCs were the most common (35%; n = 196). In Multivariable analysis accounting for gender, peritoneal cancer index (PCI), and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared with no complication (hazard ratio [HR] 2.08; p < 0.01) or other types of complications (HR, 1.6; p < 0.01). Similarly, infectious POCs were independently associated with worse RFS (HR 1.61; p < 0.01). CONCLUSION: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease such as noninvasive appendiceal neoplasm, and this association is largely driven by infectious complications. The exact mechanism is unknown, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious postoperative complications.

Institutional variation in recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: An opportunity for enhanced recovery pathways.

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 < .001). Institution-level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%. CONCLUSIONS: Significant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.

The Intersection of Age and Tumor Biology with Postoperative Outcomes in Patients After Cytoreductive Surgery and HIPEC.

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.

Repeat Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Is Not Associated with Prohibitive Complications: Results of a Multiinstitutional Retrospective Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. PATIENTS AND METHODS: We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan-Meier and Cox estimates were used to assess survival. RESULTS: In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. CONCLUSIONS: Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000-2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

What is the Optimal Preoperative Imaging Modality for Assessing Peritoneal Cancer Index? An Analysis From the United States HIPEC Collaborative.

BACKGROUND: 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 AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

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.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Is Obesity Protective in Thoracoabdominal Penetrating Trauma?

The incidence of obesity has been increasing in the United States, and the medical care of obese patients after injury is complex. Obesity has been linked to increased morbidity after blunt trauma. Whether increased girth protects abdominal organs from penetrating injury or complicates management from obesity-associated medical comorbidities after penetrating injury has not been well defined. All patients admitted with penetrating injury between January 1, 2010, and December 31, 2013, at a university-affiliated Level I center trauma center were reviewed. Primary endpoints for analysis were the presence of significant injuries requiring operative intervention and outcomes, including inpatient complications. Logistic regression, chi-squared tests, and the Kruskal-Wallis test were used to compare groups. Five hundred patients were included in the study; 225 with stabs and 275 with gunshot wounds (GSWs). In each group, there was no major difference between obese and nonobese patients in regard to injury location, operative approach, or postoperative outcomes. Unadjusted odds ratios comparing both overweight and obese individuals to normal BMI patients did not suggest a decreased rate of therapeutic operations for either population after stabs or GSWs. In obese or overweight patients, there is no difference in the rate of operative intervention for significant injuries after penetrating axial trauma compared with a normal BMI population. On the other hand, obesity was not associated with prolonged length of stay, increased complications, or death after penetrating injuries.

Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection.

BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma.

BACKGROUND: Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. METHODS: Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). RESULTS: A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71). CONCLUSION: Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection.

The Cost of Failure: Assessing the Cost-Effectiveness of Rescuing Patients from Major Complications After Liver Resection Using the National Inpatient Sample.

OBJECTIVE: To estimate the cost of rescue and cost of failure and determine cost-effectiveness of rescue from major complications at high-volume (HV) and low-volume (LV) centers METHODS: Ninety-six thousand one hundred seven patients undergoing liver resection were identified from the Nationwide Inpatient Sample (NIS) between 2002 and 2011. The incremental cost of rescue and cost of FTR were calculated. Using propensity-matched cohorts, a cost-effectiveness analysis was performed to determine the incremental cost-effectiveness ratio (ICER) between HV and LV hospitals. RESULTS: Ninety-six thousand one hundred seven patients were identified in NIS. The overall mortality was 2.3% and was lowest in HV centers (HV 1.4% vs. MV 2.1% vs. LV 2.6%; p < 0.001). Major complications occurred in 14.9% of hepatectomies and were comparable regardless of volume (HV 14.2% vs. MV 14.3% vs. LV 15.4%; p < 0.001). The FTR rate was substantially lower among HV centers (HV 7.7%, MV 11%, LV 12%; p < 0.001). At a willingness to pay benchmark of $50,000 per year of life saved, both HV (ICER = $3296) and MV (ICER = $4182) centers were cost-effective at rescuing patients from a major complication compared to LV hospitals. CONCLUSION: Not only was FTR less common at HV hospitals, but the management of most major complications was cost-effective at higher volume centers.

Surgical approaches for the treatment of perihilar cholangiocarcinoma.

INTRODUCTION: Since their initial description, perihilar cholangiocarcinoma (pCCA) has remained one of the more clinically challenging scenarios encountered by hepatobiliary surgeons. Surgery remains the only potentially curative therapy, but requires complex, technically demanding operations with high associated morbidity and mortality. Over the last several decades, advances in surgical technique and perioperative management have improved patient outcomes. Areas covered: Achievement of optimal outcomes requires a multidisciplinary approach from a team of providers with expertise in hepatobiliary and oncologic surgery, medical oncology, radiation oncology, and advanced gastroenterology. We herein report a comprehensive review on pCCA with an emphasis on surgical strategies and perioperative management. Expert commentary: Despite incremental improvements from advances in surgical technique and perioperative management, outcomes remain poor due to the aggressive systemic nature of this disease and the tendency for locoregional and distant recurrence. The marginal benefit observed with traditional systemic therapies continues to be a key weakness in current management. However, improved understanding of the genetic alterations and pathways that drive tumorigenesis has the potential to dramatically alter the way in which we care for these patients.

Perioperative complications and the cost of rescue or failure to rescue in hepato-pancreato-biliary surgery.

BACKGROUND: It is unclear how either the successful or failed rescue of hepato-pancreato-biliary (HPB) patients from complications impacts costs. METHODS: A retrospective cohort study of HPB surgical patients was performed using claims data from 2013 to 2015 in the Medicare Provider Analysis and Review (MEDPAR) database. Patient demographics, characteristics, outcomes and risk-adjusted Medicare payments were compared. RESULTS: 11,596 patients were identified. Over half of the patients (n = 5,810, 50.1%) underwent liver surgery, while 42% (n = 4892) had pancreatic and 8% (n = 894) had biliary operations. The overall complication rate varied (liver: 19.6%; pancreas: 20.3%; biliary: 25.2%, p = 0.001). In general, both minor and serious complications resulted in higher Medicare payments. Failed rescue led to higher average Medicare payments during index hospitalization compared to successful rescue ($53,476 versus $44,636, p < 0.001). The reverse was true on readmission; successful rescue was associated with higher average Medicare payments ($25,746 versus $15,654, p < 0.001). Taken together (index plus readmission), total hospitalization payments were higher for failed compared to successful rescue ($66,604 versus $52,143, p < 0.001). CONCLUSION: Following HPB surgery, there is a significant cost associated with both rescue and failure-to-rescue from perioperative complications. Total hospitalization cost was highest for patients who experienced failure-to-rescue.

Unique Genes in Tumor-Positive Sentinel Lymph Nodes Associated with Nonsentinel Lymph Node Metastases in Melanoma.

BACKGROUND: Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy. METHODS: RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients. RESULTS: The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases. CONCLUSIONS: A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.