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.

Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly.

BACKGROUND: Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS: SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS: Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION: Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.

Does Stage Migration Occur as a Consequence of Omitting Completion Lymph Node Dissection for Melanoma?

INTRODUCTION: Completion lymph node dissection (CLND) is no longer recommended routinely in the treatment of melanoma. CLND omission may understage patients for whom the distinction between stage IIIA and IIIB-C could alter adjuvant therapy recommendations. The aim of this study is to determine if stage migration has occurred with the declining use of CLND. METHODS: Patients with clinically node-negative ≥ T1b cutaneous melanoma were identified from the National Cancer Database (NCDB) from 2012 to 2018. CLND utilization and changes in AJCC staging were analyzed. Patients undergoing sentinel lymph node biopsy (SLNB) alone were compared with those undergoing SLNB + CLND. RESULTS: Overall, 68,933 patients met inclusion criteria and 60,536 underwent SLNB, of which 9031 (14.9%) were tumor positive. CLND was performed in 3776 (41.8%). Patients undergoing CLND were younger (58 versus 62 years, p < 0.0001) and more likely male (61.5% versus 57.9%, p = 0.0005). Patients were more likely to have an N classification >N1a if they received SLNB + CLND (36.8%) versus SLNB alone (19.3%), p < 0.0001. This translated to a small difference in stage IIIA patients between groups (SLNB alone 34.0%, SLNB + CLND 31.8%, p < 0.0001). Of the patients with T1b/T2a tumors who would be upstaged from IIIA to IIIC with identification of additional positive nodes, IIIC incidence was only slightly higher after SLNB + CLND compared with SLNB alone (4.4% versus 1.1%, p < 0.0001). CLND utilization dramatically decreased from 59% in 2012 to 12.6% in 2018, p < 0.0001. However, the incidence of stage IIIA disease for all patients remained stable over the 7-year study period. CONCLUSIONS: While the utilization of CLND after positive SLNB has declined dramatically in the last 7 years, stage migration that may affect adjuvant therapy decisions has not occurred to a clinically meaningful degree.

Neoadjuvant Radiotherapy Facility Type Affects Anastomotic Complications After Esophagectomy.

BACKGROUND: Esophagectomy is a complex oncologic surgery that results in lower perioperative morbidity and mortality when performed in high-volume hospitals by experienced surgeons; however, limited data exists evaluating the importance of neoadjuvant radiotherapy delivery at high- versus low-volume centers. We sought to compare postoperative toxicity among patients treated with preoperative radiotherapy delivered at an academic medical center (AMC) versus community medical centers (CMC). METHODS: Consecutive patients undergoing esophagectomy for locally advanced esophageal or gastroesophageal junction (GEJ) cancer at an academic medical center between 2008 and 2018 were reviewed. Associations between patient factors and treatment-related toxicities were calculated in univariate (UVA) and multivariable analyses (MVA). RESULTS: One hundred forty-seven consecutive patients were identified: 89 CMC and 58 AMC. Median follow-up was 30 months (0.33-124 months). Most patients were male (86%) with adenocarcinoma (90%) located in the distal esophagus or GEJ (95%). Median radiation dose was 50.4 Gy between groups. Radiotherapy at CMCs resulted in higher rates of re-operation after esophagectomy (18% vs 7%, p = 0.055) and increased rates of anastomotic leak (38% vs 17%, p < 0.01). On MVA, radiation at a CMC remained predictive of anastomotic leak (OR 6.13, p < 0.01). CONCLUSION: Esophageal cancer patients receiving preoperative radiotherapy had higher rates of anastomotic leaks when radiotherapy was completed at a community medical center versus academic medical center. Explanations for these differences are uncertain but further exploratory analyses regarding dosimetry and radiation field size are warranted.

Continuous manual agitation significantly improves temperature distribution during closed hyperthermic intraperitoneal chemotherapy: Results of a porcine model.

BACKGROUND: Debate persists regarding the need for shaking during hyperthermic intraperitoneal chemotherapy. Studies assessing the thermal behaviors of the perfusate throughout the abdomen during hyperthermic intraperitoneal chemotherapy are limited. METHODS: A closed hyperthermic intraperitoneal chemotherapy technique was performed in an institutional International Animal Care and Use Committee approved porcine model targeting a 41°C outflow temperature. Continuous temperature monitoring was conducted. Abdominal shaking was performed for 60 second intervals and temperatures were allowed to equilibrate without shaking between intervals. Temperature distributions and changes due to shaking were evaluated. These findings were validated against human subjects' data. RESULTS: The experimental procedure was conducted in 2 different animals and with 6 total shaking intervals assessed. Without shaking, temperatures were highly variable ranging between 38.0 to 42.2°C. Shaking the abdomen reduced the mean range of temperatures across all locations observed from 3.9°C to 0.8°C (P < .01). The locations of the most divergent temperatures varied based on perfusion cannula position. The point of minimum temperature heterogeneity was achieved in 28.3 (19.1-37.5) seconds. After shaking stopped, heterogeneity equal to the baseline measurements was seen on average within 25.7 (13.3-38.0) seconds. The outflow catheter differed from the system mean temperature by 1.4°C and from the coldest-reading probe by 2.8°C and outperformed the inflow catheter for all time points. With shaking these were significantly reduced to 0.4°C (P < .01) and 0.6°C (P < .01). The patient data mirrored that of the pig data. CONCLUSION: Shaking significantly reduces temperature variability within the abdomen during hyperthermic intraperitoneal chemotherapy, and significantly improves the ability of the outflow catheter to estimate internal temperatures.

Morbidity and mortality of synchronous hepatectomy with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

BACKGROUND: Liver resection in conjunction with partial colectomy for colon cancer is considered acceptable treatment for isolated metastasis to the liver. This method is unstudied in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for carcinomatosis due to colon cancer and high grade appendiceal cancer. METHODS: A retrospective chart review included patients from 2005 to 2016 undergoing CRS/HIPEC. Cancers other than colorectal adenocarcinoma and high grade appendiceal carcinoma were excluded. Patients were divided into hepatectomy and non-hepatectomy groups. Data was collected by chart review from electronic medical records to assess morbidity and mortality, as well as oncologic outcomes of included patients. RESULTS: The average patient age, length of stay, and sex were similar between groups. For those in the hepatectomy group, 80% underwent minor hepatectomy, and 20% underwent major hepatectomy. The comprehensive complication index (CCI) scores ranged from 0 (no complications), to 100 (death). The average CCI between study groups was similar (27.29 vs. 17.41, P=0.09). Hepatectomy was associated with a higher rate of Clavien-Dindo classifications (CDCs) of III or greater. Complications included pressor requirement, renal failure, blood transfusions, TPN, pleural effusions and leaks requiring drain placement, respiratory failure, UTI, new onset atrial fibrillation, wound infections, and death. CONCLUSIONS: Patients who underwent CRS/HIPEC and hepatectomy for colorectal and high grade appendiceal carcinomatosis had more severe complications at similar rates to non-hepatectomy patients. Complication rates should be considered when selecting patients for aggressive surgical intervention.

Discontinuation of surgical versus nonsurgical clinical trials: an analysis of 88,498 trials.

BACKGROUND: It has been previously reported that over 20% of surgical trials will be discontinued prematurely raising ethical and financial concerns. Previous studies have been limited in scope owing to the need for manual review of selected trials. To date, there has been no broad analysis comparing surgical and nonsurgical registered clinical trials. MATERIALS AND METHODS: ClinicalTrials.gov was queried October 7, 2017 for all US trials from 2005 to 2017. Trials were assigned to surgical or nonsurgical groups by automated sorting. The sorting algorithm was validated by comparison with manual assignments made by blinded investigators. Comparisons were made between trial status, funding sources, and trial design. The reasons for discontinuation were examined and tabulated. RESULTS: The database search yielded 82,719 nonsurgical and 5779 surgical trials after automatic assignment. The algorithm for assignments had an overall accuracy of 87.99% and a positive likelihood ratio of 6.09 and negative likelihood ratio of 0.093. Significant differences existed in trial status (nonsurgical versus surgical: completed: 55.51% versus 39.49%, P < 0.001 and discontinued: 11.07% versus 15.97%, P < 0.001). Discontinuation due to poor recruitment was more commonly cited by surgical trials (44.65% versus 34.74% P < 0.001). Industry funding predicted discontinuation for all trials (odds ratio 1.63 P < 0.001) and surgical trials independently (OR 1.25 P = 0.041). Patient enrollment, reporting results, and NIH funding were all protective against discontinuation. CONCLUSIONS: Surgical trials are more likely to prematurely discontinue than nonsurgical trials. Industry funding independently predicts trial discontinuation. Poor recruitment is a major cause of early trial discontinuation for all trials and is more pronounced in surgical trials.