Bile leak incidence, risk factors and associated outcomes in patients undergoing hepatectomy: a contemporary NSQIP propensity matched analysis.

BACKGROUND: Despite advances in surgical technique, bile leak remains a common complication following hepatectomy. We sought to identify incidence of, risk factors for, and outcomes associated with biliary leak. STUDY DESIGN: This is an ACS-NSQIP study. Distribution of bile leak stratified by surgical approach and hepatectomy type were identified. Univariate and multivariate factors associated with bile leak and outcomes were evaluated. RESULTS: Robotic hepatectomy was associated with less bile leak (5.4% vs. 11.4%; p < 0.001) compared to open. There were no significant differences in bile leak between robotic and laparoscopic hepatectomy (5.4% vs. 5.3%; p = 0.905, respectively). Operative factors risk factors for bile leak in patients undergoing robotic hepatectomy included right hepatectomy [OR 4.42 (95% CI 1.74-11.20); p = 0.002], conversion [OR 4.40 (95% CI 1.39-11.72); p = 0.010], pringle maneuver [OR 3.19 (95% CI 1.03-9.88); p = 0.044], and drain placement [OR 28.25 (95% CI 8.34-95.72); p < 0.001]. Bile leak was associated with increased reoperation (8.7% vs 1.7%, p < 0.001), 30-day readmission (26.6% vs 6.8%, p < 0.001), 30-day mortality (2% vs 0.9%, p < 0.001), and complications (67.2% vs 23.4%, p < 0.001) for patients undergoing MIS hepatectomy. CONCLUSION: While MIS confers less risk for bile leak than open hepatectomy, risk factors for bile leak in patients undergoing MIS hepatectomy were identified. Bile leaks were associated with multiple additional complications, and the robotic approach had an equal risk for bile leak than laparoscopic in this time period.

Combined mechanical and oral antibiotic bowel preparation is associated with prolonged recurrence-free survival following surgery for colorectal cancer.

BACKGROUND AND OBJECTIVES: Recent studies suggest that bacteria influence the pathogenesis of primary colorectal cancer (CRC), yet their role in recurrence after resection is largely unknown. We have discovered that collagenase-producing bacteria promote cancer recurrence in mice, and that antibiotic bowel decontamination decreases colonization of these same organisms in humans. We hypothesized that preoperative combined mechanical and oral antibiotic bowel preparation would improve disease-free survival (DFS) in patients undergoing surgery for CRC. METHODS: We reviewed a cancer registry of patients treated for CRC at a tertiary center. Patients who received bowel preparation were compared to those that did not via a 1:1-propensity score matched for follow-up, age, sex, BMI, stage, location, chemoradiation, infection, anastomotic leak, and blood transfusion. RESULTS: One thousand two hundred and seventy-nine patients met inclusion criteria. Following propensity score matching, 264 patients receiving bowel prep were matched to 264 patients who did not. Kaplan-Meier estimates showed that patients who received bowel prep had a significantly improved 5-year DFS compared to those that did not (76.3% vs. 64.2%; p < .01). Cox regression demonstrated that bowel prep was associated with improved DFS (HR, 0.57; 95% CI, 0.37-0.89; p < .01). CONCLUSION: Combined mechanical and oral antibiotic bowel preparation is independently associated with improved recurrence-free survival in patients undergoing surgery for CRC.

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy.

Programmed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.

Novel Application of Iterative Hyperthermic Intraperitoneal Chemotherapy for Unresectable Peritoneal Metastases from High-Grade Appendiceal Ex-Goblet Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PMs) from appendiceal ex-goblet adenocarcinoma (AEGA) are associated with a poor prognosis. While cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong survival, the majority of patients are ineligible for complete cytoreduction. We describe a novel approach to the management of such patients with iterative HIPEC (IHIPEC). METHODS: Patients with signet ring/poorly differentiated AEGA with high Peritoneal Cancer Index (PCI) and extensive bowel involvement underwent IHIPEC with mitomycin C at 6-week intervals for a total of three cycles. Survival outcomes for these patients were compared with patients with high-grade appendiceal tumors matched for tumor burden who were treated with other conventional approaches, i.e. systemic chemotherapy only (SCO) or complete CRS + HIPEC. RESULTS: Between 2016 and 2019, seven AEGA patients with high PCI (median 32.5 [range 21-36]) underwent 18 IHIPEC cycles (median cycles per patient 3 [2-3]) in combination with systemic chemotherapy (median 2 lines [1-3], 12 cycles [10-28]). IHIPEC was delivered laparoscopically in 14/18 cases. Postoperatively, the median length of stay was 1 day (1-8 days), no procedure-related complications were reported, and five (28%) 90-day readmissions for bowel obstruction were documented. Median overall survival after IHIPEC was better compared with a matched group of patients (n = 16) receiving SCO (24.6 vs. 7.9 months; p = 0.005), and similar to those (n = 7) who underwent CRS + HIPEC (24.6 vs. 16.5 months; p = 0.62). CONCLUSIONS: IHIPEC in combination with systemic chemotherapy is tolerable, safe, and may be associated with encouraging survival outcomes compared with SCO in selected patients with high-grade, high-burden AEGA PM.

Robotic pancreaticoduodenectomy decreases the risk of clinically relevant post-operative pancreatic fistula: a propensity score matched NSQIP analysis.

BACKGROUND: A single-institution study demonstrated robotic pancreaticoduodenectomy (RPD) was protective against clinically-relevant postoperative pancreatic fistula (CR-POPF) compared to open pancreaticoduodenectomy (OPD). We sought to compare the national rate of CR-POPF by approach. METHODS: Procedure-targeted pancreatectomy Participant User Data File was queried from 2014 to 2017 for all patients undergoing pancreaticoduodenectomy. A modified fistula risk score was calculated and patients were stratified into risk categories. Multivariate logistic regression and propensity score matching was used. RESULTS: The rate of CR-POPF (15.6% vs. 11.9%; p = 0.026) was higher in OPD compared to RPD. On subgroup analysis, OPD had higher CR-POPF in high risk patients (32.9% vs. 19.4%; p = 0.007). On multivariable analysis OPD was a predictor of increased CR-POPF (Odds Ratio [OR] = 1.61 [1.15-2.25]; p = 0.005). Other operative factors associated with increased CR-POPF included soft pancreatic texture (OR = 2.65 [2.27-3.09]; p < 0.001) and concomitant visceral resection (OR = 1.41 [1.03-1.93]; p = 0.031). Increased duct size (reference <3 mm) was predictive of decreased CR-POPF: 3-6 mm (OR = 0.70 [0.61-0.81]; p < 0.001) and ≥6 mm (OR = 0.47 [0.37-0.60]; p < 0.001). Following propensity score matching, RPD continued to be protective against the occurrence of CR-POPF (OR = 1.54 [1.09-2.17]; p = 0.013). CONCLUSIONS: This is the largest multicenter study to evaluate the impact of RPD on POPF. It suggests that RPD can be protective against POPF, especially for high risk patients.

Benchmarking Perioperative Outcomes of Cytoreductive Surgery for Cancer: Implications for Quality Measurement.

BACKGROUND: Understanding variation and heterogeneity in practice patterns allows programs to develop effective strategies to improve patient outcomes. Cytoreductive surgery is a potentially highly morbid operation that could benefit from systematic assessments directed towards quality improvement. We describe the hospital-level variation and benchmarks for programs performing cytoreductive surgery. PATIENTS AND METHODS: Cytoreductive and tumor debulking operations with or without hyperthermic intraperitoneal chemotherapy performed for cancer between January 1, 2013 and June 30, 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program registry. Risk-adjusted hospital-level variation in 30-day death, serious morbidity, reoperation, readmission, and a composite of death or serious morbidity (DSM) were evaluated using hierarchical models. National Cancer Institute (NCI)-designated cancer center (NCI-CC) status was also explored. RESULTS: A total of 6203 operations across 589 hospitals were included, of which 56 were at NCI-CCs. Unadjusted rates of death, serious morbidity, reoperation, readmission, and DSM were 1.4%, 12.9%, 3.6%, 8.6%, and 13.4%, respectively. The coefficients of variation for hospital-level performance were 4.7%, 2.1%, 4.6%, 14.4%, and 1.0% for DSM, death, serious morbidity, unplanned reoperation, and unplanned readmissions, respectively. When compared with other hospitals, NCI-CCs had better risk-adjusted 30-day mortality (median odds ratio 0.984 versus 0.998, p < 0.001), but not for the other outcomes studied. CONCLUSIONS: Hospital-level variation was modestly detected using the usual measures of perioperative outcomes. Given the increasing interest in cytoreductive surgery, we demonstrate a clear opportunity to not only improve the quality of our care but to also better improve the way quality is measured for these patients.

Adjuvant Therapy for Cutaneous Melanoma.

This article presents the current data supporting adjuvant therapy for patients with cutaneous melanoma. With the recent development of novel immunotherapy agents as well as targeted therapy, there are strong data to support the use of these therapies in patients at high risk of developing recurrent or metastatic disease.

Metastatic Colorectal Cancers with Mismatch Repair Deficiency Result in Worse Survival Regardless of Peritoneal Metastases.

BACKGROUND: Mismatch-repair deficiency (dMMR) predicts worse chemoresponsiveness but better survival in early-stage colorectal adenocarcinoma. This study examined metastatic colorectal and appendix cancers with and without peritoneal metastasis (PM) in the National Cancer Database (NCDB), hypothesizing that dMMR tumors show better survival. METHODS: Stage 4 colon, rectum, and appendix cancers (2010-2016) were identified in the NCDB (including goblet cell carcinoids, excluding neuroendocrine tumors). Stage 4 disease without liver, bone, brain, lung, or distant nodal metastases defined PM. Fisher's exact tests were used to compare proportions, and Kaplan-Meier analysis was used to evaluate survival. RESULTS: Of 130,125 stage 4 colon, rectum, and appendix cancers, 27,848 (21.4%) had PM. Appendix primary tumors had PM more commonly than colon or rectum cancer (83.6% vs. 20.6% and 12.1% of stage 4 cases; p < 0.0001). More PM patients had MMR testing than patients with other metastasis (OM) (21.4% vs. 16.1%), and testing increased from 9.6% in 2010 to 26.3% in 2016 (both p < 0.0001). Among the PM patients, MMR testing was least common for appendix cancers (9.0%). When tested, PM patients more often had dMMR (22.9% [1122/4900] vs. 15.4% [2532/16,495] of OM patients; p < 0.0001). Colon primary tumor had dMMR most frequently (25.0% vs. 14.6% and 14.5% for rectal and appendix tumor; p < 0.0001). Most PM patients received chemotherapy (66.2%). Immunotherapy use increased over time (1.1% of PM diagnoses in 2010 vs. 20.8% in 2016). For MMR-tested stage 4 patients, dMMR correlated with worse survival (median OM, 19.7 vs. 23.9 months, p < 0.0001; median PM, 19.9 vs. 24.6 months, p = 0.035). CONCLUSIONS: The NCDB showed dMMR predicting worse survival for stage 4 colorectal cancers with and without PM and dMMR existing in 14.5-25% of tested patients, suggesting that increased attention to MMR testing in stage 4 colorectal and appendix cancers can identify many patients who could potentially benefit from immunotherapy.

Virtual Surgical Fellowship Recruitment During COVID-19 and Its Implications for Resident/Fellow Recruitment in the Future.

BACKGROUND: The COVID-19 pandemic has overlapped with the scheduled interview periods of over 20 surgical subspecialty fellowships, including the Complex General Surgical Oncology (CGSO) fellowships in the National Resident Matching Program and the Society of Surgical Oncology's Breast Surgical Oncology fellowships. We outline the successful implementation of and processes behind a virtual interview day for CGSO fellowship recruitment after the start of the pandemic. METHODS: The virtual CGSO fellowship interview process at the University of Chicago Medicine and NorthShore University Health System was outlined and implemented. Separate voluntary, anonymous online secure feedback surveys were email distributed to interview applicants and faculty interviewers after the interview day concluded. RESULTS: Sixteen of 20 interview applicants (80.0%) and 12 of 13 faculty interviewers (92.3%) completed their respective feedback surveys. Seventy-five percent (12/16) of applicants and all faculty respondents (12/12) stated the interview process was 'very seamless' or 'seamless'. Applicants and faculty highlighted decreased cost, time savings, and increased efficiency as some of the benefits to virtual interviewing. CONCLUSIONS: Current circumstances related to the COVID-19 pandemic require fellowship programs to adapt and conduct virtual interviews. Our report describes the successful implementation of a virtual interview process. This report describes the technical steps and pitfalls of organizing such an interview and provides insights into the experience of the interviewer and interviewee.

Risk factors for complications in patients undergoing pancreaticoduodenectomy: A NSQIP analysis with propensity score matching.

BACKGROUND: Reports on the safety of minimally invasive pancreaticoduodenectomy compared to open pancreaticoduodenectomy (OPD) have demonstrated mixed results. One study comparing robotic pancreaticoduodenectomy (RPD) vs OPD demonstrated decreased complications associated with RPD. OBJECTIVES: To evaluate the morbidity of RPD vs OPD using a national data set. METHODS: This is a retrospective cohort study from 2014 to 2017. Factors associated with complications in patients undergoing pancreaticoduodenectomy were evaluated using multivariate logistic regression (MVA) and propensity score matching (PSM). RESULTS: Of 13 110 PDs performed over the study period, 12 612 (96.2%) were OPD and 498 (3.8%) were RPD. Patients who underwent RPD vs OPD were less likely to have any complications (46.8% vs 53.3%; P = .004), surgical complications (42.6% vs 48.6%; P = .008), wound complications (6.2% vs 9.1%; P = .029), clinically relevant postoperative pancreatic fistulas (11.9% vs 15.6%; P = .026), sepsis (6.2% vs 9.3%; P = .019), and pneumonia (1.6% vs 3.8%; P = .012). On MVA, OPD was associated with increased complications compared with RPD. On PSM analysis, OPD remained a significant predictor for any (OR, 1.29; 95% CI, 1.03-1.61; P = .029) and surgical (OR, 1.26; 95% CI, 1.00-1.58; P = .048) complications. CONCLUSIONS: This is the largest multicenter study to evaluate the impact of RPD on morbidity and suggests RPD is associated with decreased morbidity.

Robotic Distal Pancreatectomy and Splenectomy for an Intrapancreatic Hepatocellular Carcinoma: A Case Report and Review of the Literature.

Background: Liver parenchyma that resides outside of the normal hepatic confines is defined as accessory liver if in communication with the native biliary tree, or ectopic liver (EL) if it is not. EL can develop in a variety of tissues, including but not limited to the gallbladder, the hepatic ligaments, the pancreas, and retroperitoneum. EL has an increased propensity for malignant degeneration resulting in hepatocellular carcinoma (HCC). Presentation: A 67-year-old Korean male presented with epigastric discomfort and was found to have an elevation in his transaminases. Cross-sectional imaging demonstrated a 1.3 cm solid mass in the body of the pancreas with features concerning for either a pancreatic ductal adenocarcinoma or pancreatic neuroendocrine tumor. Subsequent endoscopic ultrasound and fine needle aspiration demonstrated cells of epithelial origin with hepatocellular differentiation. A robotic-assisted distal pancreatectomy and splenectomy was performed with final pathology demonstrating a well-differentiated HCC. Conclusions: EL with malignant degeneration resulting in HCC requires surgical excision. The majority of patients reported with EL resulting in HCC in the pancreas have had the tumors located in the body and tail. Therefore, definitive treatment requires distal pancreatectomy and splenectomy. Herein, we describe the presentation, workup, and definitive treatment of HCC arising in the pancreas.

Thirty Years of the Journal of Cancer Education: a Review.

Since its foundation in 1986, the Journal of Cancer Education (JCE) has served as an important outlet for myriad aspects of cancer education and currently serves as the official journal of the American and European Associations for Cancer Education. During its history, the JCE has been under the auspices of five publishers, with its first full year under the current publisher, Springer, in 2010. Print and distribution metrics from 2010 to present were obtained from Springer. These were compared to historical data including the first 10 years of the JCE, published by Dr. Bakemeier in 1995. Since its beginning, the JCE has consisted of four issues per year. The original contract for 256 pages per year has increased to an average of 858 pages from 2010 to 2014. In 2015, the JCE received a total of 344 submissions, up from 339 in 2014, and 262 the year before. This is a stark contrast to the roughly 44 submission received in 1994. Over this same period, the overall rejection rate has increased from 30% in 2010 to 45% in 2015. The number of online deals has increased from 347 in 2014 to 361 in 2015 and has been accompanied by a steady increase in the number of full-text article downloads: 19,000 in 2010 to 58,923 in 2015. Accordingly, the JCE has seen a pronounced and steady increase in impact factor, rising from 0.52 in 2009 to 1.368 in 2015. Since moving to Springer, the JCE has seen unprecedented growth, receiving increasing submissions yearly, an increasing number of subscription deals and online full-text downloads, and a corresponding increase in impact factor.

Impact of Gene Expression Profiling on Decision-Making in Clinically Node Negative Melanoma Patients after Surgical Staging.

INTRODUCTION: The surgeon's role in the follow-up of pathologic stage I and II melanoma patients has traditionally been minimal. Melanoma genetic expression profile (GEP) testing provides binary risk assessment (Class 1-low risk, Class 2-high risk), which can assist in predicting metastasis and formulating appropriate follow up. We sought to determine the impact of GEP results on the management of clinically node negative cutaneous melanoma patients staged with sentinel lymph node biopsy (SLNB). METHODS: A retrospective review of prospectively gathered data consisting of patients seen from September 2015 - August 2016 was performed to determine whether GEP class influenced follow-up recommendations. Patients were stratified into four groups based on recommended follow-up plan: Dermatology alone, Surgical Oncology, Surgical Oncology with recommendation for adjuvant clinical trial, or Medical and Surgical Oncology. RESULTS: Of ninety-one patients, 38 were pathologically stage I, 42 stage II, 10 stage III, and 1 stage IV. Combining all stages, GEP Class 1 patients were more likely to be followed by Dermatology alone and less like to be followed by Surgical Oncology with recommendation for adjuvant trial compared to Class 2 patients (P less than 0.001). Among stage 1 patients, Class 1 were more likely to follow up with Dermatology alone compared to Class 2 patients (82 vs. 0%; P less than 0.001). Among stage II patients, GEP Class 1 were more likely to follow up with Dermatology alone (21 vs 0%) and more Class 2 patients followed up with surgery and recommendations for adjuvant trial (36 vs 64%; P less than 0.05). There was no difference in follow up for stage III patients based on the GEP results (P=0.76). CONCLUSION: GEP results were significantly associated with the management of stage I-II melanoma patients after staging with SLNB. For node negative patients, Class 2 results led to more aggressive follow up and management. J Drugs Dermatol. 2018;17(2):196-199.

Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?

INTRODUCTION: Completion lymph node dissection (CLND) for melanoma after positive sentinel lymph node biopsy (SLNB) was recently shown to improve regional but not overall survival, likely due to the majority of patients harboring no further nodal disease. We sought to determine predictors of non-sentinel node (NSN) positivity. METHODS: Retrospective review of prospectively collected data on melanoma patients undergoing SLNB. RESULTS: 116 patients underwent 119 CLNDs. The incidence of NSN positivity was 17.6%; the average number of positive NSNs in those cases was 1.5. Cervical and inguinofemoral location were most likely to yield positive NSN(s) (40% each). Conversely, the axilla was least likely at 18% (p < 0.001). The average number of nodes harvested was 13 for NSN negative cases and 20 for NSN positive cases (p = 0.005). Tumor thickness increased the probability of positive NSN(s) (OR 1.2, p = 0.02). CONCLUSIONS: Tumor thickness and nodal basin were predictors of NSN metastasis, factors that could help determine which patients may benefit from CLND. Further, CLNDs with fewer nodes may inadequately clear residual nodal disease.

Is pelvic sentinel node biopsy necessary for lower extremity and trunk melanomas?

OBJECTIVE: There is currently no consensus regarding how to address pelvic sentinel lymph nodes (PSLNs) in melanoma. Thus, our objectives were to identify the incidence and clinical impact of PSLNs. METHODS: Retrospective review of a prospectively collected multi-institutional melanoma database. RESULTS: Of 2476 cases of lower extremity and trunk melanomas, 227 (9%) drained to PSLNs (181 to both PSLNs and superficial (inguinal or femoral) sentinel lymph nodes (SSLN) and 46 to PSLNs alone). Seventeen (7.5%) of 227 PSLN cases were positive for nodal metastasis, 8 of which drained to PSLNs only while 9 drained to both PSLNs and SSLNs. Complication rates between PSLN and SSLN biopsy were similar (15% vs. 14% respectively). In 181 cases with drainage to both SSLNs and PSLNs, PSLN biopsy upstaged one patient (0.6%), and completion dissection based on a positive PSLN did not upstage any. CONCLUSIONS: PSLN biopsy is safe, however in the setting of negative SSLNs there is minimal clinical impact. We therefore recommend PSLN biopsy when the SSLNs are positive or when the tumor drains to PSLNs alone.