Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

Association Between Biliary Pathogens, Surgical Site Infection, and Pancreatic Fistula: Results of a Randomized Trial of Perioperative Antibiotic Prophylaxis in Patients Undergoing Pancreatoduodenectomy.

OBJECTIVE: To establish the association between bactibilia and postoperative complications when stratified by perioperative antibiotic prophylaxis. BACKGROUND: Patients undergoing pancreatoduodenectomy experience high rates of surgical site infection (SSI) and clinically relevant postoperative pancreatic fistula (CR-POPF). Contaminated bile is known to be associated with SSI, but the role of antibiotic prophylaxis in mitigation of infectious risks is ill-defined. METHODS: Intraoperative bile cultures (IOBCs) were collected as an adjunct to a randomized phase 3 clinical trial comparing piperacillin-tazobactam with cefoxitin as perioperative prophylaxis in patients undergoing pancreatoduodenectomy. After compilation of IOBC data, associations between culture results, SSI, and CR-POPF were assessed using logistic regression stratified by the presence of a preoperative biliary stent. RESULTS: Of 778 participants in the clinical trial, IOBC were available for 247 participants. Overall, 68 (27.5%) grew no organisms, 37 (15.0%) grew 1 organism, and 142 (57.5%) were polymicrobial. Organisms resistant to cefoxitin but not piperacillin-tazobactam were present in 95 patients (45.2%). The presence of cefoxitin-resistant organisms, 92.6% of which contained either Enterobacter spp. or Enterococcus spp., was associated with the development of SSI in participants treated with cefoxitin [53.5% vs 25.0%; odds ratio (OR)=3.44, 95% CI: 1.50-7.91; P =0.004] but not those treated with piperacillin-tazobactam (13.5% vs 27.0%; OR=0.42, 95% CI: 0.14-1.29; P =0.128). Similarly, cefoxitin-resistant organisms were associated with CR-POPF in participants treated with cefoxitin (24.1% vs 5.8%; OR=3.45, 95% CI: 1.22-9.74; P =0.017) but not those treated with piperacillin-tazobactam (5.4% vs 4.8%; OR=0.92, 95% CI: 0.30-2.80; P =0.888). CONCLUSIONS: Previously observed reductions in SSI and CR-POPF in patients that received piperacillin-tazobactam antibiotic prophylaxis are potentially mediated by biliary pathogens that are cefoxitin resistant, specifically Enterobacter spp. and Enterococcus spp.

National Trends in Treatment for Retroperitoneal Soft Tissue Sarcoma: A Modern Appraisal of Variability in Therapeutic Strategies.

BACKGROUND: Little level 1 evidence exists to guide multimodality treatment in retroperitoneal soft tissue sarcoma (RPS), which may lead to significant variation in therapeutic approaches. This analysis aimed to describe national RPS treatment trends and explore potential variability among low-/high-volume hospitals (LVH/HVHs). PATIENTS AND METHODS: In total, 5992 patients who underwent resection for primary RPS were retrospectively identified in the National Cancer Database (2004-2017). Time trend analyses examined rates of multivisceral resection (MVR), radiation, and chemotherapy use. LVHs were defined as those carrying out fewer than ten resections per year (N = 5433), whereas HVHs were defined as those carrying out ten or more (N = 559). Descriptive statistics and logistic regression models compared trends between groups. RESULTS: MVR was more frequent at HVHs (63.7% versus 43.5%, p < 0.001). Use of radiation varied widely by hospital volume. HVHs more frequently employed preoperative radiation as compared with LVHs (14.7% versus 8.1%, p < 0.001). Throughout the study period, LVHs increased utilization of preoperative radiation (2.6% to 12.0%, p < 0.001) whereas rates at HVHs remained stable. Overall, LVHs utilized postoperative radiation significantly more frequently as compared with HVHs (14.7% versus 2.7%, respectively, p < 0.001). Postoperative radiation at LVHs remained stable until 2013 and sharply declined thereafter (16.7% to 6.9%, p < 0.001). Rates of postoperative radiation use at HVHs remained lower than those at LVHs at all time points. CONCLUSIONS: Strategies for resection and radiation use at LVHs have trended towards those of HVHs. Current national implementation of preoperative radiation, MVR, and chemotherapy remains heterogeneous. These findings inform future trial design and support standardization of care.

COVID-19 is Affecting the Presentation and Treatment of Melanoma Patients in the Northeastern United States.

BACKGROUND: Covid-19 significantly affected healthcare delivery over the past year, with a shift in focus away from nonurgent care. Emerging data are showing that screening for breast and colon cancer has dramatically decreased. It is unknown whether the same trend has affected patients with melanoma. METHODS: This is a retrospective cohort study of melanoma patients at two large-volume cancer centers. Patients were compared for 8 months before and after the lockdown. Outcomes focused on delay in treatment and possible resultant upstaging of melanoma. RESULTS: A total of 375 patients were treated pre-lockdown and 313 patients were treated post-lockdown (17% decrease). Fewer patients presented with in situ disease post-lockdown (15.3% vs. 17.9%), and a higher proportion presented with stage III-IV melanoma (11.2% vs. 9.9%). Comparing patients presenting 2 months before versus 2 months after the lockdown, there was an even more significant increase in Stage III-IV melanoma from 7.1% to 27.5% (p < 0.0001). Finally, in Stage IIIB-IIID patients, there was a decrease in patients receiving adjuvant therapy in the post lockdown period (20.0% vs. 15.2%). CONCLUSIONS: As a result of the recent pandemic, it appears there has been a shift away from melanoma in situ and toward more advanced disease, which may have significant downstream effects on prognosis and could be due to a delay in screening. Significantly patients have presented after the lockdown, and fewer patients are undergoing the recommended adjuvant therapies. Patient outreach efforts are essential to ensure that patients continue to receive preventative medical care and screening as the pandemic continues.

Rethinking Routine Intensive Care After Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy: The Fiscal Argument.

BACKGROUND: Patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) are frequently admitted to the intensive care unit (ICU) for mitigation of potential complications, although ICU length of stay (LOS) is a significant driver of cost. This study asked whether a fiscal argument could be made for the selective avoidance of ICU admission after CRS/HIPEC. METHODS: Prospective data for select low-risk patients (e.g., lower peritoneal cancer index [PCI]) admitted to the intermediate care unit (IMC) instead of the ICU after CRS/HIPEC were matched with a historic cohort routinely admitted to the ICU. Cohort comparisons and the impact of the intervention on cost were assessed. RESULTS: The study matched 81 CRS/HIPEC procedures to form a cohort of 49 pre- and 15 post-intervention procedures for patients with similar disease burdens (mean PCI, 8 ± 6.7 vs. 7 ± 5.1). The pre-intervention patients stayed a median of 1 day longer in the ICU (1 day [IQR, 1-1 day] vs. 0 days [IQR, 0-0 days]) and had a longer LOS (8 days [IQR, 7-11 days] vs. 6 days [IQR, 5.5-9 days]). Complications and complication severity did not differ statistically. The median total hospital cost was lower after intervention ($30,845 [IQR, $30,181-$37,725] vs. $41,477 [IQR, $33,303-$51,838]), driven by decreased indirect fixed cost ($8984 [IQR, $8643-$11,286] vs. $14,314 [IQR, $12,206-$18,266]). In a weighted multiple variable linear regression analysis, the intervention was associated with a savings of $2208.68 per patient. CONCLUSIONS: Selective admission to the IMC after CRS/HIPEC was associated with $2208.68 in savings per patient without added risk. In this era of cost-conscious practice of medicine, these data highlight an opportunity to decrease cost by more than 5% for patients undergoing CRS/HIPEC.

A Virtual Tumor Board Platform: A Way to Enhance Decision-Making for Complex Malignancies.

INTRODUCTION: Multidisciplinary tumor boards (TBs) are crucial for decision-making and management of patients diagnosed with complex malignancies. The social distancing conditions imposed by coronavirus disease 2019 presented an opportunity to compare virtual versus in-person TBs. METHODS: A retrospective analysis of attendance data from an National Cancer Institute-designated cancer center's gastrointestinal (GI) TB participant data from September 2019 to October 2020. In addition, an online survey assessing the virtual TB experience was sent to participants of all TBs. Interrupted time series analyses were performed to evaluate preintervention and postintervention GI TB attendance only. RESULTS: The overall mean attendance for GI TB was 30 participants; turnout was higher for virtual format compared to in-person (32 versus 23 attendees, P < 0.001). This increase was seen across all participant categories: attending physicians (15 versus 11 attendees, P < 0.001), trainees (11 versus 8, P < 0.001), and support staff (6 versus 3, P < 0.001). There was no significant difference in the mean number of cases discussed between TB formats. The majority of the 141 survey respondents (across all TB) were attending physicians with >20-year experience. Most supported a permanent virtual or hybrid TB format, 72.5% found this format to be more time efficient and with similar productivity, and 85.8% found it easier to attend. The majority (89.9%) felt confident that the decision-making process was not affected by virtual interactions. CONCLUSIONS: A virtual platform for multispecialty TBs allows for greater attendance without sacrificing the decision-making process. This survey supports continuing with a virtual or hybrid format, which may increase attendance and facilitate access to multidisciplinary discussions leading to improved patient care.

Initial Clinical Experience With Novel Directional Low-Dose Rate Brachytherapy for Retroperitoneal Sarcoma.

BACKGROUND: A novel Palladium-103 low-dose rate (LDR) brachytherapy device was developed to provide dose-escalation to the tumor bed after resection while shielding adjacent tissues. This multicenter report describes the initial experience with this device in patients with retroperitoneal sarcoma (RPS). MATERIALS AND METHODS: Patients with recurrent RPS, prior radiotherapy, and/or concern for positive margins were considered. An LDR brachytherapy dose of 20-60 Gy was administered, corresponding to biologically effective dose values of 15-53 Gy and equivalent dose values of 12-43 Gy. RESULTS: Six patients underwent implantation at four institutions. Of these, five had recurrent disease in the retroperitoneum or pelvic sidewall, one had untreated locally advanced leiomyosarcoma, two had prior external beam radiation therapy at the time of initial diagnosis, and four received neoadjuvant external beam radiation therapy plus brachytherapy. The device was easily implanted and conformed to the treatment area. Median follow-up was 16 mo; radiation was delivered to the at-risk margin with minimal irradiation of adjacent structures. No local recurrences at the site of implantation, device migration, or radiation-related toxicities were observed. CONCLUSIONS: The novel LDR directional brachytherapy device successfully delivered a targeted dose escalation to treat RPS high-risk margins. Lack of radiation-related toxicity demonstrates its safety.

Traveling to Receive Treatment for Extremity Soft Tissue Sarcomas: Is it worth the drive?

BACKGROUND: Regionalization of sarcoma care may improve outcomes. Concerns exist regarding the burdens of travel and its effects on care. We evaluate the presence of a "distance bias". METHODS: Retrospective cohort study of patients with extremity soft tissue sarcoma (stage I-III) within the NCDB. Travel distance (TD) and hospital volume (VOL) were categorized into quartiles. Alternating statistical models were used for analysis. RESULTS: 1,035 hospitals contributed 11,979 cases. Median and maximum VOL were 5 and 45 cases/year. VOL quartiles were "low-volume" (LV) (892 hospitals, < 3 cases/yr.), "intermediate low-volume" (ILV) (89, 3-5 cases/yr.), "intermediate high-volume" (IHV) (39, 6-12 cases/yr.), and "high-volume" (HV) (15, > 12 cases/yr.). TD quartiles: "short-travel" (ST) (< 8 mi), "intermediate-short travel" (IST) (8-17), "intermediate long-travel" (ILT) (18-49), and "long-travel" (LT) (> 50). VOL but not TD is associated with improved survival [HR 0.65 (CI 0.52-0.83)] and rate of R0 resection [1.87 (CI 1.4-2.5)] but has no effect on amputation rates. Matched analyses demonstrate similar results. CONCLUSIONS: Hospital volume but not distance traveled to treatment facility is associated with improved survival and R0 resections for extremity soft tissue sarcomas. Despite the inconveniences of travel, patients may benefit from treatment at high volume centers.

Upfront resection versus neoadjuvant therapy for T1/T2 pancreatic cancer.

BACKGROUND: The role of neoadjuvant therapy remains controversial for resectable pancreatic neoplasms. We evaluated treatment outcomes for T1/T2 tumors. METHODS: Retrospective study of patients with T1/T2 (Stage I-II) pancreatic cancer within the NCDB. Treatment-sequence variables were used for classification: "surgery + chemotherapy" (S+C), "chemotherapy + surgery" (C+S), "surgery only" (SO), and "chemotherapy only" (CO). RESULTS: 13 412 patients were included; the majority had T2 tumors. 8 490 received upfront surgery; 4 922 preoperative chemotherapy. In the surgery branch, 5 684 received surgery and chemotherapy (S+C); 2 806 did not receive chemotherapy (SO). Of those intended to receive preoperative chemotherapy, 3 804 received only chemotherapy (CO); 1 118 proceeded to surgery (C+S). Median survival for S+C and C+S groups was similar (25.9 vs 26.2) [HR 0.92, p= 0.41]. Compared to the CO group, the SO group had improved median survival (13.5 vs. 10.8) [HR 0.63, p<0.001]. Branched analyses demonstrated improved median and 5-year (20.8% vs 12.7%) survival for patients receiving upfront resection [HR 0.77, p<0.001]. CONCLUSION: Patients with T1/T2 pancreatic cancer have similar survival irrespective of the timing of chemotherapy and surgery, if they receive both. Upfront resection ensures surgery is delivered, increasing the possibility of long-term survival.

A retrospective cohort study of endoscopic therapy and esophagectomy for stage 1 esophageal cancer: less is more.

BACKGROUND AND AIMS: Current guidelines recommend consideration of endoscopic therapy (ET) when treating select stage I esophageal cancers. The proportion of esophageal cancers treated with ET compared with esophagectomy has increased over time. Overall and cancer-specific survival have not been shown to be superior with ET in prior population-based studies. We thus evaluated cancer-specific survival comparing patients treated with ET and esophagectomy. METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results database from 2004 to 2015 of patients with node-negative, superficial (T1a/T1b), esophageal cancer treated with ET or esophagectomy. Competing-risks models were used to compare cancer-specific survival. Cox proportional hazards models were used to assess overall survival. Subgroup analysis was performed comparing time periods 2004 to 2009 and 2010 to 2015. RESULTS: Of 2133 included individuals, 772 (36.2%) underwent ET and 1361 (63.8%) underwent esophagectomy. Unadjusted 5-year survival for cancer-specific death was 87.7% (95% confidence interval [CI], 84.2-90.5) for ET and 82.4% (95% CI, 80.0- 84.5) for esophagectomy (P = .002). Within the adjusted competing-risk model, cancer-specific survival was superior in patients treated with ET compared with esophagectomy (subdistribution hazard ratio [SHR], 1.92; 95% CI, 1.35-2.74; P < .001). From 2004 to 2009, the SHR for esophagectomy was 1.68 (95% CI, 1.07-2.66; P = .024); whereas from 2010 to 2015, the SHR for esophagectomy was 2.02 (95% CI, 1.08-3.76; P = .027). CONCLUSIONS: ET was associated with improved cancer-specific survival compared with esophagectomy in stage I esophageal cancer. This advantage was more pronounced for patients treated after 2009, potentially because of increasing clinician expertise in performing ET and patient selection.

Better Defining the Role of Total Neoadjuvant Radiation: Changing Paradigms in Locally Advanced Pancreatic Cancer.

BACKGROUND: This study was designed to better define the role of radiation (Neo-Rad) in addition to neoadjuvant multiagent chemotherapy (NAT) for the treatment of locally advanced pancreatic cancer. METHODS: Retrospective cohort study using the NCDB. Individuals with AJCC clinical T3/T4 pancreatic carcinoma who underwent resection and multiagent chemotherapy were included. Kaplan-Meier, logistic-regression, and Cox proportional-hazard models were used for analysis. RESULTS: A total of 2703 patients were included; 2039 had T3 and 664 had T4 tumors, and 1092 (40.4%) received Neo-Rad. Median follow-up was 22.5 months. During the study period, there was increased use of NAT and a decline in the use of Neo-Rad. Addition of Neo-Rad did not affect 30-day (2.51% vs. 3.24%, p = 0.272) or 90-day mortality (5.23% vs. 6.38%, p = 0.216). Neo-Rad was not associated with improved overall survival on univariable (25.95 vs. 24.7 months, p = 0.202), or multivariable analyses (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.85-1.05). Time from diagnosis to definitive surgery was increased by Neo-Rad (204 vs. 115 days, p < 0.001). Neo-Rad was associated with increased pathologic downstaging in T3 (32.8% vs. 14.4%) (odds ratio [OR] 2.90; 95% CI 2.30-3.66) and T4 tumors (88.9% vs. 77.8%) (OR 2.29; 95% CI 1.44-3.67); complete pathologic response (5.3% vs. 1.6%) (OR 2.89; 95% CI 1.73-4.83), and increased R0 resection rates (85.7% vs. 76.8%) (OR 1.79; 95% CI 1.44-2.23). CONCLUSIONS: The use of neoadjuvant therapy is increasing for the treatment of locally advanced pancreatic cancer. The addition of radiation to neoadjuvant chemotherapy is associated with improved antineoplastic effectiveness (downstaging, complete pathologic response), surgical resection (R0 rates), but has no effect on overall survival.

Can time to healing in pediatric blunt splenic injury be predicted?

BACKGROUND: Current consensus guidelines do not recommend routine follow-up imaging for blunt splenic injury (BSI) in children. However, repeat imaging is recommended based on persistent symptoms. Wide variation of practice continues to exist among surgeons. By defining the natural evolution of BSI, we sought to identify patients at higher risk for delayed healing who could benefit from outpatient imaging. METHODS: A retrospective review of all children with BSI at a Level 1 Pediatric Trauma Center was completed. Grade of injury, hospital course, laboratory values and follow-up imaging results were obtained. Injured spleens were classified as 'healed', 'healing' (with echogenic scar), or 'non-healing' with persistence of parenchymal abnormalities. RESULTS: Between 2000 and 2014, 222 patients with BSI were identified. Seven patients (3%) underwent immediate splenectomy. Packed red blood cell transfusion was required in 13 (6%) of the 222 patients, and 3 (2%) of 145 with isolated splenic injuries. Seventy-one percent of patients underwent additional imaging 2-74 weeks post-injury. A receiver operating characteristics (ROC) curve was used to establish the relationship between sensitivity and specificity of capturing non-healing spleens over time. Optimal timing for post-injury imaging for grades I-II was 7-8 weeks; healing of higher-grade injuries could not accurately be predicted. CONCLUSIONS: If return to full physical activity, in particular contact sports, is contingent upon documented healing of the splenic parenchyma after blunt trauma in the pediatric population, follow-up imaging for low-grade injuries is best obtained around 7-8 weeks. No such recommendations can be made for high-grade splenic injuries, as the exact time to healing cannot be predicted based on initial data. LEVEL OF EVIDENCE: IV. Diagnostic test.

Survival of the Hmong population diagnosed with colon and rectal cancers in the United States.

BACKGROUND: The Hmong population constitutes an independent ethnic group historically dispersed throughout Southeast Asia; fallout from the Vietnam War led to their forced migration to the United States as refugees. This study seeks to investigate characteristics of the Hmong population diagnosed with in colorectal cancer (CRC) as well as survival within this population. METHODS: Cases of colon and rectal adenocarcinoma diagnosed between 2004 and 2017 were identified from the National Cancer Database (NCDB). Summary statistics of demographic, clinical, socioeconomic, and treatment variables were generated with emphasis on age and stage at the time of diagnosis. Cox-proportional hazard models were constructed for survival analysis. RESULTS: Of 881,243 total CRC cases within the NCDB, 120 were classified as Hmong. The average age of Hmong individuals at diagnosis was 58.9 years compared 68.7 years for Non-Hispanic White (NHW) individuals (p < 0.01). The distribution of analytic stage differed between the Hmong population and the reference NHW population, with 61.8% of Hmong individuals compared to 45.8% of NHW individuals with known stage being diagnosed at stage III or IV CRC compared to 0, I, or II (p = 0.001). However, there was no difference in OS when adjusting for potential confounders (HR 1.00 [0.77-1.33]; p = 0.998). CONCLUSIONS: Hmong individuals are nearly a decade younger at the time of diagnosis of CRC compared to the NHW individuals. However, these data do not suggest an association between Hmong ethnicity and overall survival, when compared to the NHW population.

The Cost of Frailty in Complex Gastrointestinal Surgery.

BACKGROUND: Frailty is a syndrome characterized by decreased physiologic reserve related with aging; it has been associated with increased costs of health care. Factors driving its economic impact remain poorly understood. We examine the association between frailty, complications, and costs in complex gastrointestinal surgery. METHODS: Retrospective review of a prospective database encompassing elective complex gastrointestinal operations from 2017 to 2018 at a tertiary care hospital. Patients were categorized into non-frail (NF): MFI 0, pre-frail (PF): MFI 1-2, and frail (FR): MFI >2 based on the 5-Factor Modified Frailty Index. Linear regression models were applied. RESULTS: 612 patients were included; 268 (44%) were NF, 325 (53%) were PF, and 19 (3%) were FR. The FR group had a longer length of stay (7.26 days) compared to NF (5.05 days) or PF (5.67 days) (p = 0.031). The average total cost of care for all patients was $19,413.06 (CI 18,297.13-20,528.98). The cost for NF was $17,648.54 (CI 15,969.18-19,327.9), PF $20,435.70 (CI 18,911.01-21,960.4, p = .016), and FR patients was $26,809.36 (CI 20,511.9-33,106.81). A complication was observed in 91 patients (14.9%); of these, 76 (12.4%) were serious complications, as defined by NSQIP. There was no difference in incidence of complications (NF 14.93%, PF 14.46%, FR 21.05%, p = .734). On average, a complication added $12,656.67 regardless of frailty category. DISCUSSION: Frail patients are more costly and have a longer length of stay than their more robust counterparts. Complications were the major driver of costs after complex gastrointestinal surgery regardless of frailty status.

Real-world frequency of BRAF testing and utilization of therapies in patients with advanced melanoma.

Both BRAF/MEK targeted agents and immunotherapy are approved for the treatment of advanced melanoma. BRAF testing is recommended at the time of advanced melanoma diagnosis. In addition, little is known regarding the treatment trends for patients with BRAF mutated tumors. This investigation aims to assess the real-world prevalence of molecular testing and treatment trends for patients with BRAF mutated tumors. Using a de-identified database, patients of age ≥18 years with advanced melanoma from 2013 to 2018 were examined. Molecular testing performed within 3 months of advanced diagnosis was considered to have the test performed at the time of diagnosis. Test prevalence was calculated and compared in groups stratified by the patient, tumor and treatment factors. In total 4459 patients were included; 1936 (43.4%) stage III, 1191 (26.7%) stage IV and 1332 (29.9%) recurrent. Totally 50.4% of patients received systemic treatment; 76.4% stage IV, 71% recurrent patients and 26.7% stage III patients. However, 73.5% received first-line immunotherapy. In total 73.8% of patients had molecular testing, and 50.5% had tested at the time of advanced diagnosis. Of those tested 42% had a BRAF mutated tumor. In total 48% of these patients received first-line immunotherapy whereas 43% received a BRAF inhibitor, with increasing immunotherapy use seen over time. The majority of patients with advanced melanoma undergo molecular testing at the time of advanced diagnosis. Immunotherapy is the most commonly prescribed treatment regardless of BRAF mutational status. These results provide real-world data on the frequency of molecular testing and treatment trends for patients with advanced melanoma.

GSK-3: An important kinase in colon and pancreatic cancers.

In this review, the role of glycogen synthase kinase 3 (GSK-3) in pancreatic and colon cancers will be explored. GSK-3 plays a fundamental role in many metabolic processes, primarily as the final enzyme in glycogen synthesis. Active ß-catenin represents the final step for the transcription of Wnt target genes. Both GSK-3 and ß-catenin are key in the neoplastic transformation and tumorigenesis of human cells. Despite the advances in diagnosis and treatment of pancreatic malignancies, survival remains dismal. Continued poor outcomes are attributable to tumor cell resistance and high frequency of metastatic disease. Survival for patients diagnosed with colon cancer is often excellent, and many patients achieve long term remission. However, the incidence of colon cancers continues to increase, especially among the young. The future use of targeted therapy in pancreatic and colo-rectal cancer utilizing GSK-3 may be promising, pending a more thorough understanding of potential downstream effects. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.

Tumor mitotic rate is an independent predictor of survival for nonmetastatic melanoma.

BACKGROUND: Tumor mitotic rate is a known prognostic variable in Stage I melanoma; however, its importance is unclear in Stages II and III. METHODS: Patients diagnosed with nonmetastatic cutaneous melanoma from 2010 to 2014 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results registry. RESULTS: Of a total of 71,235 patients, the majority were white (94.7%), male (58.5%), and had a Stage I tumor (79.0%). On univariable analysis, 5-year disease-specific survival decreased with each increasing tumor mitotic rate category of 0-3, 4-10, and >10 mitoses/mm2 (Stage I 98.3%, 90.9%, 79.7%; Stage II 86.1%, 74.2%, 72.9%; and Stage III 72.5%, 58.6%, 49.7%). In multivariable models, tumor mitotic rate as both a continuous and categorical variable was associated with disease-specific survival for Stages I-III melanoma. Each unit increase in tumor mitotic rate increased the risk of death by 23% in Stage I, 5% in Stage II, and 3% in Stage III. Compared with the 0-3 tumor mitotic rate category, the risk of disease-specific mortality increased for tumors in the 4-10 and >10 categories for Stage I (RR 3.07 and 6.74, P < .0001), Stage II (RR 1.37 and 1.62, P = .0002), and Stage III (RR 1.24 and 1.35, P = .0004). CONCLUSION: In this cohort study, tumor mitotic rate is an independent predictor of survival for localized melanoma.

American College of Surgeons National Surgical Quality Improvement Program as a quality-measurement tool for advanced cancer patients.

BACKGROUND: Multiple studies have shown the significantly increased post-operative morbidity and mortality of patients undergoing palliative operations. It has been proposed by some authors that the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database can be used reliably to develop risk-calculators or as an aid for clinical decision-making in advanced cancer patients. ACS-NSQIP is a population-based database that by design only captures outcomes data for the first 30-day following an operation. We considered the suitability of these data as a tool for decision-making in the advanced cancer patient. METHODS: Six-year retrospective review of a single institution's ACS-NSQIP database for cases identified as "Disseminated Cancer". Procedures performed with palliative intent were identified and analyzed. RESULTS: Of 7,763 patients within the ACS-NSQIP database, 138 (1.8%) were identified as having "Disseminated Cancer". Of the remaining 7,625 entries only 4,486 contained complete survival data for analysis. Thirty-day mortality within the "Disseminated Cancer" group was higher when compared to all other surgical patients (7.9% vs. 0.9%, P<0.001). Explicit chart review of these 138 patients revealed that 32 (23.2%) had undergone operations with palliative intent. Overall survival for palliative and non-palliative operations was significantly different (104 vs. 709 days, P<0.001). When comparing palliative to non-palliative procedures using ACS-NSQIP data, we were unable to detect a difference in 30-day mortality (9.4% vs. 7.5%, P=0.72). CONCLUSIONS: Calculations utilizing ACS-NSQIP data fail to demonstrate the increased mortality associated with palliative operations. Patients diagnosed with advanced cancer are not adequately represented within the database due to the limited number of cases collected. Also, more suitable outcomes measures for palliative operations such as pain relief, functional status, and quality of life, are not captured. Therefore, the sole use of thirty-day morbidity and mortality data contained in the ACS-NSQIP database is insufficient to make sound decisions for surgical palliation.