Interval Sentinel Lymph Nodes With the Use of Routine Lymphoscintigraphy in Extremity Melanoma.

INTRODUCTION: Lymphoscintigraphy (LS) helps identify drainage to interval (epitrochlear or popliteal) lymph node basins for extremity melanomas. This study evaluated how often routine LS evaluation identified an interval sentinel lymph node (SLN) and how often that node was found to have metastasis. METHODS: A single institution, retrospective study identified patients with an extremity melanoma who underwent routine LS and SLN biopsy over a 25-y period. Comparisons of factors associated with the identification of interval node drainage and tumor status were made. RESULTS: In 634 patients reviewed, 5.7% of patients drained to an interval SLN. Of those biopsied, 29.2% were positive for micrometastases. Among patients with biopsies of both the traditional and interval nodal basins, nearly 20% had positive interval nodes with negative SLNs in the traditional basin. Sex, age, thickness, ulceration, and the presence of mitotic figures were not predictive of identifying an interval node on LS, nor for having disease in an interval node. Anatomic location of the primary melanoma was the only identifiable risk factor, as no interval nodes were identified in melanomas of the thigh or upper arm (P ≤ 0.001). CONCLUSIONS: Distal extremity melanomas have a moderate risk of mapping to an interval SLN. Routine LS should be considered in these patients, especially as these may be the only tumor-positive nodes. However, primary extremity melanomas proximal to the epitrochlear or popliteal nodal basins do not map to interval nodes, and improved savings and workflow could be realized by selectively omitting routine LS in such patients.

Barriers to resection following neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma: A national and local perspective.

BACKGROUND: Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC. METHODS: Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy. RESULTS: Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%). CONCLUSIONS: Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion.

Combined pre-operative risk score predicts pancreatic leak after pancreatic resection.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a major complication following pancreatectomy and is currently difficult to predict pre-operatively. This study aims to validate pre-operative risk factors and develop a novel combined score for the prediction of POPF in the pre-operative setting. METHODS: Data were collected from 2016 to 2021 for radiologic main pancreatic duct diameter (MPD), body mass index (BMI), physical status classified by American Society of Anesthesiologists (ASA), polypharmacy, mean platelet ratio (MPR), comorbidity-polypharmacy score (CPS), and a novel Combined Pancreatic Leak Prediction Score (CPLPS) (derived from MPD diameter, BMI, and CPS) were obtained from pre-operative data and analyzed for their independent association with POPF occurrence. RESULTS: In total, 166 patients who underwent pancreatectomy with pancreatic leak (Grade A, B, and C) occurring in 51(30.7%) of patients. Pre-operative radiologic MPD diameter < 4 mm (p < 0.001), < 5 mm (p < 0.001), < 6 mm (p = 0.001), BMI ≥ 25 (p = 0.009), and ≥ 30 (p = 0.017) were independently associated with the occurrence of pancreatic leak. CPLPS was also predictive of pancreatic leak following pancreatectomy on univariate (p = 0.005) and multivariate analysis (p = 0.036). CONCLUSION: MPD and BMI were independent risk factors predictive for the development of pancreatic leak. CPLPS, was an independent predictor of pancreatic leak following pancreatectomy and could be used to help guide surgical decision making and patient counseling.

Impact of adjuvant therapy on outcomes after curative-intent resection for distal cholangiocarcinoma.

BACKGROUND: The benefit of adjuvant therapy (AT) after curative resection of distal cholangiocarcinoma (DCC) remains unclear. The objective of the current study was to investigate the impact of AT on long-term survival of patients who underwent curative-intent resection for DCC. METHODS: Patients who underwent curative-intent resection for DCC between 2000 and 2020 were identified from a multi-institutional database. The primary outcomes included overall (OS) and recurrence-free survival (RFS). RESULTS: Among 245 patients, 150 (61.2%) patients received AT (chemotherapy alone: n = 43; chemo- and radiotherapy: n = 107) after surgical resection, whereas 95 (38.8%) patients underwent surgery only. Patients who received AT were younger, and more likely to have an advanced tumor with the presence of perineural invasion (PNI), lymph node metastasis (LNM), lymph-vascular invasion, and higher T categories (all p < 0.05). Overall, there was no difference in OS (median, surgery + AT 25.5 vs. surgery alone 24.5 months, p = 0.27) or RFS (median, surgery + AT 15.8 vs. surgery alone 18.9 months, p = 0.24) among patients who did versus did not receive AT. In contrast, AT was associated with improved long-term survival among patients with PNI (median OS, surgery + AT 25.9 vs. surgery alone 17.8 months, p = 0.03; median RFS, surgery + AT 15.9 vs. surgery alone 11.9 months, p = 0.04) and LNM (median, surgery + AT 20.0 vs. surgery alone 17.8 months, p = 0.03), but not among patients with no PNI or LNM (all p > 0.1). CONCLUSIONS: AT was commonly utilized among patients with DCC. Patients with more advanced disease, including the presence of PNI or LNM, benefited the most from AT with improved long-term outcomes among this subset of patients.

Preventing Futile Liver Resection: A Risk-Based Approach to Surgical Selection in Major Hepatectomy for Colorectal Cancer.

BACKGROUND: Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. METHODS: Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). RESULTS: Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1-16.2) for the futile resection cohort versus 45.6 (95% CI 39.1-52.1) for non-futile hepatectomies (p < 0.001). CONCLUSIONS: Futile hepatic resection can be predicted based on preoperative factors and carries a poor prognosis. Improved risk stratification for futility will aid in patient selection and treatment discussions.

Drug-Eluting Bead, Irinotecan Therapy of Unresectable Intrahepatic Cholangiocarcinoma (DELTIC) with Concomitant Systemic Gemcitabine and Cisplatin.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, and currently there are moderately established chemotherapeutic [gemcitabine/cisplatin (Gem/Cis)] treatments to prolong survival. The purpose of this study was to assess the efficacy of irinotecan drug-eluting beads (DEBIRI) therapy by transarterial infusion in combination with systemic therapy in unresectable ICC. PATIENTS AND METHODS: This is a prospective, multicenter, open-label, randomized phase II study (Clin Trials: NCT01648023-DELTIC trial) of patients with ICC randomly assigned to Gem/Cis with DEBIRI or Gem/Cis alone. The primary endpoint was response rate. RESULTS: The intention-to-treat population comprised 48 patients: 24 treated with Gem/Cis and DEBIRI and 22 with Gem/Cis alone (2 screen failures). The two groups were similar with respect to the extent of liver involvement (35% versus 38%) and presence of extrahepatic disease (29% versus 14%, p = 0.12). Median numbers of chemotherapy cycles were similar (6 versus 6), as were rates of grade 3/4 adverse events (34% for the Gem/Cis-DEBIRI group versus 36% for the Gem/Cis group). The overall response rate was significantly greater in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm at 2 (p < 0.04), 4 (p < 0.03), and 6 months (p < 0.05). There was significantly more downsizing to resection/ablation in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm (25% versus 8%, p < 005), and there was improved median progression-free survival [31.9 (95% CI 8.5-75.3) months versus 10.1 (95% CI 5.3-13.5) months, p = 0.028] and improved overall survival [33.7 (95% CI 13.5-54.5) months versus 12.6 (95% CI 8.7-33.4) months, p = 0.048]. CONCLUSION: Combination Gem/Cis with DEBIRI is safe, and leads to significant improvement in downsizing to resection, improved progression-free survival, and overall survival.

Prognostic Utility of Systemic Immune-Inflammation Index After Resection of Extrahepatic Cholangiocarcinoma: Results from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: We sought to define the association of the systemic immune inflammation index (SII) with prognosis and adjuvant therapy benefit among patients undergoing resection of extrahepatic cholangiocarcinoma (eCCA). METHODS: The impact of SII on overall (OS) and recurrence-free survival (RFS) following resection of eCCA was assessed and compared with other inflammatory markers and traditional prognostic factors. Propensity score matching (PSM) was used to determine the impact of adjuvant therapy (AT) on OS and RFS relative to low versus high SII. RESULTS: Patients with high versus low SII had worse 5-year OS (15.9% vs. 27.9%) and RFS (12.4% vs. 20.9%) (both p < 0.01). On multivariate analysis, high SII remained associated with worse OS (HR = 1.50, 95% CI 1.20-1.87) and RFS (HR = 1.46, 95% CI 1.18-1.81). Patients with T1/2 disease and a high-SII had worse 5-year OS versus individuals with T3/4 disease and low-SII (5-year OS: T1/2 & low-SII 35.6%, T1/2 & high-SII 16.4%, T3/4 & low-SII 22.1%, T3/4 & high-SII 15.6%, p < 0.01). Similarly, 5-year OS was comparable among individuals with N0 and high-SII versus N1 and low-SII (5-year OS: N0 & high-SII 23.2%, N1 and low-SII 19.8%, p = 0.95). On PSM, AT improved OS and RFS among patients with high SII (5-year OS: 22.5% vs. 12.3%, p < 0.01, 5-year RFS: 19.0% vs. 12.5%; p = 0.01) but not individuals with low SII (5-year OS: 22.9% vs. 26.9%; p = 0.98, 5-year RFS: 18.5% vs. 19.9%; p = 0.94). CONCLUSIONS: SII was independently associated with postoperative OS and RFS following curative-intent resection of eCCA. High SII up-staged patients relative T- and N-categories and identified patients with high SII as the most likely to benefit from AT.

Locally advanced pancreatic cancer: a reliable contraindication to resection in the modern era?

BACKGROUND: The aim of this study is to present radiologically designated LAPC found to be resectable upon surgical exploration and evaluate the outcomes of such resections. METHODS: Sequential LAPC patients between 2013 and 2019 were staged and underwent resection were included in the analysis of both perioperative and long-term outcomes. RESULTS: Twenty-eight patients with radiologically-designated LAPC underwent surgical resection after chemotherapy with a median follow-up of 31.7 m,75% underwent pancreaticoduodenectomy. The margin positivity and local recurrence rates were 21.4% and 35.7%, respectively. When compared to the 30 BRPC controls, the LAPC group had a higher rates of an arterial resection (11vs.1; p = 0.002), but the groups were similar with regard to all other preoperative and intraoperative variables (p < 0.05). Perioperative morbidity rates were similar (25.9%vs21.4%; p = 0.53). The LAPC and BRPC groups were also equivalent with respect to median recurrence-free survival (9.0mo; 95%CI 6.3, 11.7vs.8.3mo; 95%CI 5.4, 11.2) and median overall survival (19.9mo; 95%CI 17.0, 22.7 vs. 19.9mo; 95%CI 14.8, 25.1), respectively. CONCLUSION: Despite a radiologic designation of locally advanced pancreatic cancer, certain subtypes of LAPC warrant surgical exploration provided the operative surgeon is prepared for major arterial and/or venous resection. Pancreatectomy in these patients has acceptable morbidity and oncologic outcomes, similar to patients who are radiologically borderline resectable.

Using machine learning to preoperatively stratify prognosis among patients with gallbladder cancer: a multi-institutional analysis.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy associated with a high risk of recurrence and mortality. We used a machine-based learning approach to stratify patients into distinct prognostic groups using preperative variables. METHODS: Patients undergoing curative-intent resection of GBC were identified using a multi-institutional database. A classification and regression tree (CART) was used to stratify patients relative to overall survival (OS) based on preoperative clinical factors. RESULTS: CART analysis identified tumor size, biliary drainage, carbohydrate antigen 19-9 (CA19-9) levels, and neutrophil-lymphocyte ratio (NLR) as the factors most strongly associated with OS. Machine learning cohorted patients into four prognostic groups: Group 1 (n = 109): NLR ≤1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 2 (n = 88): NLR >1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 3 (n = 46): CA19-9 >20, no drainage, tumor size <5.0 cm; Group 4 (n = 77): tumor size <5.0 cm with drainage OR tumor size ≥5.0 cm. Median OS decreased incrementally with CART group designation (59.5, 27.6, 20.6, and 12.1 months; p < 0.0001). CONCLUSIONS: A machine-based model was able to stratify GBC patients into four distinct prognostic groups based only on preoperative characteristics. Characterizing patient prognosis with machine learning tools may help physicians provide more patient-centered care.

Outcomes of Esophageal Stent Therapy for the Management of Anastomotic Leaks.

BACKGROUND: The purpose of this study was to present the optimal patient selection for esophageal stenting after esophageal resection to investigate possible factors leading to treatment success or treatment failure in these patients. METHODS: This was a prospective, observational study of patients from January 2005 to May 2019 with an esophageal anastomotic leak that were treated with a self-expandable stent (SES). RESULTS: A total of 34 patients were treated. All achieved technical success (100%); 33 (97%) achieved clinical success. No patient had to have reoperative surgery based on their leak management. The stenting in-hospital mortality was 0% with 1 patient (2%) with a 90-day mortality from possible leak-related death. Patients had their stents removed with a median of 106 days. CONCLUSIONS: Stenting for an anastomotic leak after resection offers a safe and effective method of treatment and is successful in the majority of cases. Critical to success is optimal patient selection, adequate leak drainage, and optimal stent selection and placement.

An Improved Staging System for Locally Advanced Pancreatic Cancer: A Critical Need in the Multidisciplinary Era.

BACKGROUND: Locally-advanced pancreatic cancer (LAPC) is traditionally considered stage III unresectable disease. Advances in induction systemic therapy regimens, surgical technique, and perioperative care have led to successful resection of an increasing number of these tumors with reasonable perioperative outcomes and disease-free intervals. Certain anatomic characteristics that meet criteria for locally-advanced disease, however, are more likely to result in a successful surgical outcome. METHODS: A practical and consistent system is needed to communicate such nuance between surgical and nonsurgical oncologists for optimal treatment planning and to improve recording for cancer registries and research studies. RESULTS: The present study proposes a novel subclassification system for stage III pancreatic cancers based on their pattern of vascular involvement and examines the current evidence for resection in each scenario. Introducing needed detail into the current catch-all stage III categorization will help to direct patient referrals and increase the body of knowledge about the variable presentations of this complex malignancy. CONCLUSION: This proposed staging revision for LAPC is designed to convey more actionable tumor descriptions for treating oncologists, clinical trial eligibility, and surgical patient selection in the era of effective induction systemic therapy.

Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer.

BACKGROUND: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We sought to develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC. PATIENTS AND METHODS: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortium database. A minimum p value approach in the log-rank test was used to define the optimal cutoff for ER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated. RESULTS: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1 months. The optimal cutoff for ER was defined at 12 months (p = 3.04 × 10-18). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumor differentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using ß-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk for ER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p < 0.001). The external validation demonstrated good model generalizability with good calibration (n = 102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p < 0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ . CONCLUSIONS: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.

Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma.

BACKGROUND: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. PATIENTS AND METHODS: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. RESULTS: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)]. CONCLUSIONS: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.

Identification of patients who may benefit the most from adjuvant chemotherapy following resection of incidental gallbladder carcinoma.

BACKGROUND: To develop a scoring system to identify the subset of patients who may benefit the most from adjuvant chemotherapy following curative-intent resection for incidental gallbladder cancer (IGBC). METHODS: A novel scoring system was utilized to stratify patients relative to overall survival (OS), as well as potential benefit from adjuvant chemotherapy following curative resection for IGBC. RESULTS: Among 266 patients with IGBC, a total of 99 (37.2%) patients received adjuvant chemotherapy. Five risk factors were used to develop an integer-based score to predict OS. Risk of death at 5-years incrementally increased among patients in the low (n = 42, 69.0%), medium (n = 64, 56.3%) and high-risk groups (n = 40, 30.0%) (median OS, 99.4 vs. 33.5 vs. 15.6 months, all p < .001). Use of adjuvant chemotherapy did not provide a survival benefit among patients in the low-risk group (median survival, 99.4 vs. 60.7 months, p = .56). In contrast, utilization of adjuvant chemotherapy was associated with an improvement in survival among medium- (median survival, 21.7 vs. 59.5 months, p = .04) and high-risk patients (median survival, 11.6 vs. 20.1 months, p = .01). CONCLUSIONS: While low-risk patients did not benefit from adjuvant chemotherapy, individuals with medium or high-risk scores had an improved survival with the utilization of adjuvant chemotherapy.

A literature-based treatment algorithm for low-grade neuroendocrine liver metastases.

BACKGROUND: The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM. METHODS: A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments. RESULTS: Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p < 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics. CONCLUSION: This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.

The Sunbelt Melanoma Trial.

The Sunbelt Melanoma Trial, a multicenter, prospective randomized clinical study, evaluated the role of high-dose interferon alfa-2b (HDI) therapy for patients with a single positive sentinel lymph node (SLN) metastasis treated with a completion lymph node dissection (CLND). A second protocol in the trial evaluated the prognostic significance of using molecular markers to identify submicroscopic metastases in sentinel lymph nodes that were negative by routine pathologic analysis. The role of CLND with or without adjuvant HDI was evaluated in this group of patients. The results of the study demonstrated that adjuvant HDI offered no survival benefit for patients with a single positive SLN in terms of disease-free or overall survival. Molecular staging using polymerase chain reaction (PCR) for melanoma markers did not identify a high-risk group of patients at increased risk of melanoma recurrence. Additional treatment of these patients who were PCR-positive with either CLND alone or CLND plus HDI did not improve their survival. Additional studies from the Sunbelt Melanoma Trial helped to validate the operational standards of the SLN biopsy procedure and defined the complication rates for both SLN biopsy and CLND. A prognostic risk calculator has been developed from trial data, and the importance of different micrometastatic tumor burden measurements was reported. Although the Sunbelt Melanoma Trial did not demonstrate an improvement in survival with HDI, it is an important trial that highlights the significance of surgeon-initiated randomized clinical trials that incorporate surgical techniques, molecular biomarkers, and adjuvant therapy.

Impact of Perfusate Glucose Concentration on Perioperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common treatment for peritoneal surface malignancies but no standard carrier solution currently exists for the procedure. This study compared a standard low-dextrose perfusate to a higher-dextrose dialysate that has previously shown favorable impact on perioperative patient outcomes in trauma settings. MATERIALS AND METHODS: A single-center retrospective study identified patients undergoing CRS/HIPEC from 2008 to 2019 with recorded dextrose concentration of administered perfusate. An institutional shift to a higher-dextrose solution was made in late 2015. Comparisons of preoperative factors, intraoperative and postoperative glucose levels, and postoperative outcomes were made using the chi-square test, Fisher's exact test, Wilcoxon rank sum test, or repeated measures analysis of variance. RESULTS: There were 97 patients in the study, 73 (75%) in the low-dextrose group and 24 (25%) in the high-dextrose group. There was no significant difference in peak intraoperative blood glucose levels between the 1.5% (mean 230 mg/dL) and the 2.5% group (mean 199 mg/dL, P = 0.15). Daily postoperative glucose values were also not statistically different (repeated measures analysis of variance, P = 0.18). Median length of stay was slightly lower for the high-dextrose group (10 d, interquartile range 8-15) than that for the low-dextrose group (12 d, interquartile range 9-17), but was not statistically significant (P = 0.29). Return of bowel function and resumption of diet were similar between the groups. The high-dextrose group had a lower rate of overall complications (20.8%) than the low-dextrose group (49.3%, P = 0.0143). Ninety-day mortality was equivalent between the two groups (2.7% low-dextrose, 4.2% high-dextrose, P = 1.0). CONCLUSIONS: Use of 2.5% dextrose-containing perfusate appears safe for CRS/HIPEC operations, does not negatively impact intraoperative or postoperative glucose levels, and may be associated with a decreased risk of complications.

Optimal perfusion chemotherapy: A prospective comparison of mitomycin C and oxaliplatin for hyperthermic intraperitoneal chemotherapy in metastatic colon cancer.

BACKGROUND: Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. METHODS: A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. RESULTS: Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. CONCLUSIONS: MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.

Primitive neuroectodermal tumor incidence, treatment patterns, and outcome: An analysis of the National Cancer Database.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS: The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS: White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P < .001), primary tumor resection (P < .001), and experienced increased 90-day mortality (P < .014). CONCLUSION: cPNET and pPNET are rare and aggressive malignancies that tend to arise in White males. Multimodal treatment including surgery, chemotherapy, and radiation is conventional. Patients with cPNET more often receive radiation and primary tumor resection with increased 90-day mortality.

Survival benefit of lymphadenectomy for gallbladder cancer based on the therapeutic index: An analysis of the US extrahepatic biliary malignancy consortium.

BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood. METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy. RESULTS: Among 449 patients, less than half had LNM (N = 183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200 UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease. CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200 UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.