CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.

Perioperative cyclooxygenase inhibition and postoperative pancreatic fistula after pancreatoduodenectomy: A systematic review and meta-analysis of comparative studies.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use has been investigated as a modifiable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). This study comprises a systematic review and meta-analysis examining the impact of perioperative NSAID use on rates of POPF after PD. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review was performed. Pooled mean differences (MD), odds ratios (OR), and risk ratios with 95% CIs were calculated. RESULTS: Seven studies published from 2015 to 2021 were included, reporting 2851 PDs (1372 receiving NSAIDs and 1479 not receiving NSAIDs). There were no differences regarding blood loss (MD -99.40 mL; 95% CI, -201.71 to 2.91; P = .06), overall morbidity (OR 1.05; 95% CI, 0.68-1.61; P = .83), hemorrhage (OR 2.35; 95% CI, 0.48-11.59; P = .29), delayed gastric emptying (OR 0.98; 95% CI, 0.60-1.60; P = .93), bile leak (OR 0.68; 95% CI, 0.12-3.89; P = .66), surgical site infection (OR 1.02; 95% CI, 0.33-3.22; P = .97), abscess (OR 0.99; 95% CI, 0.51-1.91; P = .97), clinically relevant POPF (OR 1.18; 95% CI, 0.84-1.64; P = .33), readmission (OR 0.94; 95% CI, 0.61-1.46; P = .78), or reoperation (OR 0.82; 95% CI, 0.33-2.06; P = .68). NSAID use was associated with a shorter hospital stay (MD -1.05 days; 95% CI, -1.39 to 0.71; P < .00001). CONCLUSION: The use of NSAIDs in the perioperative period for patients undergoing PD was not associated with increased rates of POPF.

Malignant Solid Pseudopapillary Neoplasm of the Pancreas: An Orthogonal Analysis.

BACKGROUND: Pancreatic solid pseudopapillary neoplasms (SPN) are generally indolent; however, some patients present with "malignant" SPN. An orthogonal analysis of multiple datasets was performed to investigate the utility of complete surgical resection (CSR) for malignant SPN. METHODS: A systematic review was performed for cases of malignant SPN, defined as T4, N1, and/or M1. Malignant SPN was analyzed within the National Cancer Database (NCDB) and compared with T1-3N0M0 SPN. Predictors of malignant SPN were assessed, and treatments were analyzed by using survival analysis. RESULTS: The systematic review yielded 164 cases of malignant SPN. Of 31 children, only one died due to malignant SPN. Among adults, CSR was associated with improved disease-specific survival (DSS) (P = 0.0002). Chemotherapy did not improve malignant SPN DSS, whether resected (P = 0.8485) or not (P = 0.2219). Of 692 adults with SPN within the NCDB, 93 (13.4%) had malignant SPN. Pancreatic head location (odds ratio [OR] 2.174; 95% confidence interval [CI] 1.136-4.166; P = 0.0186) and tumor size (OR 1.154; 95% CI 1.079-1.235; P < 0.0001) associated with the malignant phenotype. Malignant SPN predicted decreased overall survival (OS) compared with T1-3N0M0 disease (P < 0.0001). Resected malignant SPN demonstrated improved OS (P < 0.0001), including resected stage IV malignant SPN (P = 0.0003). Chemotherapy did not improve OS for malignant SPN, whether resected (P = 0.8633) or not (P = 0.5734). Within a multivariable model, resection was associated with decreased hazard of death (hazard ratio 0.090; 95% CI 0.030-0.261; P < 0.0001). CONCLUSIONS: Approximately 13% of patients with SPN present with a malignant phenotype. Pediatric cases may be less aggressive. Resection may improve survival for malignant SPN, which does not appear chemosensitive.

Pancreatic carcinosarcoma: An orthogonal analysis.

BACKGROUND: Pancreatic carcinosarcoma is a rare subtype of pancreatic cancer. There are no consensus guidelines regarding its treatment. The current study is an orthogonal analysis of multiple datasets to evaluate prognostic features. METHODS: A modified Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 systematic review was performed for reported cases of pancreatic carcinosarcoma. All cases of pancreatic carcinosarcoma in the National Cancer Database were identified for analysis. Analyses were compared to previously published data from the Surveillance, Epidemiology, and End Results database to increase validity. RESULTS: Seventy-one cases of pancreatic carcinosarcoma were reported in the literature. Reports of pancreatic carcinosarcoma increased over time (P = .0075). Tumor size >5.0 cm, metastatic disease, and relapse were associated with decreased disease-specific survival (all log-rank P < .05). Ninety-nine cases of pancreatic carcinosarcoma were analyzed within the National Cancer Database. Pancreatic carcinosarcoma incidence increased over time (P = .0371). Resection + chemotherapy, pathologic lymph node examination, and treatment at an academic center were associated with improved overall survival (all log-rank P < .05), whereas harboring ≥2 positive lymph nodes was associated with decreased overall survival (log-rank P = .0171). Within a multivariable model adjusting for age, sex, comorbid disease, and disease stage, resection + chemotherapy was associated with a decreased hazard of death (hazard ratio .036; confidence Interval .004-.298; P = .0022). Published data from the Surveillance, Epidemiology, and End Results database supported the current analysis regarding the incidence of pancreatic carcinosarcoma, resection, lymph node evaluation, and the impact of metastatic disease. CONCLUSION: Pancreatic carcinosarcoma is exceedingly rare, with a poor prognosis. Long-term survival is possible with curative resection in the absence of relapse. The number of positive lymph nodes appears to impact prognosis.

Segmental bile duct resection versus pancreatoduodenectomy for middle and distal third bile duct cancer. A systematic review and meta-analysis of comparative studies.

INTRODUCTION: Data regarding oncologic outcomes of segmental bile duct resection (SBDR) versus pancreatoduodenectomy (PD) for bile duct cancers (BDC) are conflicting. We compared SBDR and PD for BDC utilizing pooled data analysis. MATERIALS AND METHODS: A comprehensive PRISMA 2020 systematic review was performed. Studies comparing SBDR with PD for BDC were included. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Subgroup analyses were performed. Study quality, bias, heterogeneity, and certainty were analyzed. RESULTS: Twelve studies from 2004 to 2021 were included, comprising 533 SBDR and 1,313 PD. SBDR was associated with positive proximal duct margins (OR 1.56; CI 1.11-2.18; P = .01), and distal duct margins (OR 43.25; CI 10.38-180.16; P < .01). SBDR yielded fewer lymph nodes (MD -6.93 nodes; CI -9.72-4.15; P < .01) and detected fewer nodal metastases (OR 0.72; CI 0.55-0.94; P = .01). SBDR portended less perioperative morbidity (OR 0.31; CI 0.21-0.46; P < .01), but not mortality (OR 0.52; CI 0.20-1.32; P = .17). SBDR was associated with locoregional recurrences (OR 1.88; CI 1.01-3.53; P = .02), and lymph node recurrences (OR 2.13; CI 1.42-3.2; P = .04). SBDR yielded decreased 5-year OS (OR 0.75; CI 0.65-0.85; P < .01). CONCLUSIONS: Despite decreased perioperative morbidity, SBDR appears to provide inferior oncologic control for BDC.

Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Giant Paraesophageal Hernia With Obstructing Splenic Flexure Mass in the Left Hemithorax.

Giant paraesophageal hernias contain greater than fifty percent of the stomach above the diaphragm. Over fifty percent of large bowel obstructions are due to colorectal adenocarcinoma. Here, we present a rare case of a 69-year-old female patient who developed a closed loop colonic obstruction caused by a colonic mass in the distal transverse colon within a giant paraesophageal hernia. We successfully performed emergent paraesophageal hernia reduction and mesh repair with extended right hemicolectomy and ileocolonic anastomosis. Emergent hernia repair via an abdominal approach can be used in this setting.

Sugarbaker Versus Keyhole Repair for Parastomal Hernia: a Systematic Review and Meta-analysis of Comparative Studies.

INTRODUCTION: Parastomal hernia is a debilitating complication of stoma creation. Parastomal hernia repair with mesh reduces recurrence rates in open and laparoscopic settings. Recent comparative studies conflict with previously pooled data on optimal mesh repair technique. The objective of this study is to examine parastomal hernia recurrence rates after Sugarbaker and keyhole repairs by performing an updated systematic review and meta-analysis of comparative studies. METHODS: A systematic review of PubMed, MEDLINE, EMBASE, the Cochrane database, SCOPUS, and the PROSPERO registry was performed according to PRISMA 2020 guidelines (PROSPERO ID: CRD42021290483). Studies comparing parastomal hernia recurrences after Sugarbaker and keyhole repairs were included. Studies with overlapping patient cohorts (duplicate data), non-comparative studies, studies that did not report the primary outcome of interest, and studies not in the English language were excluded. Study bias was assessed using the Newcastle-Ottawa scale. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the I2 statistic. Forest plots and funnel plots were generated. Study quality was analyzed using MINORS. Additional subgroup analysis of modern studies was performed. RESULTS: Ten comparative studies published between 2005 and 2021 from 5 countries were included for analysis comprising 347 Sugarbaker repairs and 246 keyhole repairs. There were no differences in patient age, sex, or BMI between the groups. There was no difference between the groups regarding surgical site infection (OR 0.78; CI 0.31-1.98; P = 0.61) or post-operative bowel obstruction (OR 0.76; CI 0.23-2.56; P = 0.66). Sugarbaker repairs were significantly less often associated with parastomal hernia recurrence when compared to keyhole repairs (OR 0.38; CI 0.18-0.78; P = 0.008). There was no significant heterogeneity among the studies comparing parastomal hernia recurrence (I2 = 32%; P = 0.15). Quality analysis revealed a median MINORS score of 11 (range 6-16). Subgroup analysis of studies performed after the previously published pooled analysis (2015-2021) revealed no significant difference in parastomal hernia recurrence between the two groups (OR 0.58; CI 0.24-1.38; P = 0.22) with a significant subgroup effect (P = 0.05). CONCLUSIONS: Though there were lower rates of parastomal hernia recurrence with Sugarbaker repairs on overall analysis, this phenomenon disappeared on subgroup analysis of modern studies. Randomized controlled trials with contemporary cohorts would help further evaluate these repairs and minimize potential bias.

Tumor Location in the Pancreatic Tail Is Associated with Decreased Likelihood of Receiving Chemotherapy for Pancreatic Adenocarcinoma.

BACKGROUND: Chemotherapy (CTX) is associated with improved survival for patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). The current study evaluated the influence of tumor location on receipt of CTX. METHODS: The NCDB (2006-2017) was queried to identify patients with clinical stage I-III PDAC. Predictors of receipt of CTX, sequencing of CTX, and overall survival (OS) were analyzed. RESULTS: Among 14,557 patients who underwent resection for PDAC 3,453 (24%) did not receive CTX. On multivariable analysis, patients with tail tumors were 15% less likely to receive CTX (OR 0.85, 95% CI 0.747-0.968) and 58% less likely to receive neoadjuvant CTX (OR 0.42, 95% CI 0.351-0.509) relative to patients with head/neck tumors. For patients with body tumors, there was no difference in rates of administration or sequence of CTX. For patients with resected tail tumors, median OS was 29.9 vs 18.9 months (p < 0.001) between those who did and did not receive CTX. For patients with tail tumors, independent predictors of not receiving CTX, regardless of sequence, were increasing age (OR 0.95, 95% CI 0.935-0.965), increasing post-op length of stay (OR 0.95, 95% CI 0.932-0.968), and 30-day post-op readmission (OR 0.46, 95% CI 0.315-0.670). CONCLUSIONS: In patients with clinical stage I-III PDAC, tumor location within the tail was independently associated with not receiving CTX. Given the marked improvement in OS when CTX is administered, strategies aimed at increasing the number of these patients who receive CTX are necessary.

The Association of Race With Adequate Lymph Node Evaluation for Gastric Cancer.

BACKGROUND: National studies have reported racial and socioeconomic disparities in gastric cancer (GC) care. The current study evaluated adequate lymph node (LN) assessment (≥16 LNs) during resection for GC within a healthcare system servicing a socioeconomically disparate, mostly non-White population in the Southeast United States. METHODS: A retrospective cohort study of patients undergoing resection for GC between 2003-2019 was performed. Factors associated with adequate LN assessment including patient and tumor characteristics were analyzed. RESULTS: Among 202 patients, adequate LN assessment was performed in 97 (48%) patients. On univariable analysis, younger age, non-White race, lower Charlson Comorbidity Index (CCI), Medicaid or no insurance, D1+/D2 lymphadenectomy, clinical evidence of regional LN metastases, total gastrectomy, and receipt of neoadjuvant therapy were associated with adequate LN assessment. On multivariable analysis, non-White race (OR 2.79, 95% CI 1.38-5.65), CCI <4 (OR 2.14, 95% CI 1.15-3.96), and D1+/D2 lymphadenectomy (OR 3.63, 95% CI 1.96-6.74) were the only factors independently associated with adequate LN evaluation. CONCLUSIONS: In the current study, non-White race, independent of socioeconomics, was significantly associated with adequate LN assessment. Future work is necessary to improve standardization and achieve higher rates of adequate LN assessment for all patients during resection for GC.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

The Role of Perioperative Chemotherapy in the Management of Colloid Carcinoma of the Pancreas.

OBJECTIVES: Colloid carcinoma (CC) of the pancreas is associated with an improved prognosis compared with pancreatic ductal adenocarcinoma (PDAC), yet studies on the optimal management of these rare lesions are lacking. METHODS: Patients with CC or PDAC treated from 2004 to 2014 were identified in the National Cancer Database. Clinicopathologic characteristics were compared between groups and stratified by disease stage. Survival analysis evaluating the role of perioperative chemotherapy was performed. RESULTS: A total of 1295 CC patients (11%) and 10,855 PDAC patients (89%) were identified. Pancreatic ductal adenocarcinoma was associated with a higher likelihood of mortality compared with CC (hazard ratio, 1.35; 95% confidence interval, 1.25-1.45; P < 0.001). When stratifying by stage, perioperative chemoradiation improved overall survival in early stage (I/IIA) PDAC but had no effect in CC patients. However, for node-positive disease (stage IIB), median overall survival was improved with adjuvant chemoradiation for both CC patients (22 vs 13 months; P < 0.001) and PDAC patients (20 vs 11 months; P < 0.001) compared with surgery alone. CONCLUSIONS: Surgery alone may be sufficient for the management of node-negative (I/IIA) CC lesions in contrast to conventional PDAC, whereas CC patients with stage IIB disease have a survival benefit from perioperative chemoradiation.

The Usefulness of the Pretreatment Neutrophil/Lymphocyte Ratio as a Predictor of the 5-Year Survival in Stage 1-3 Triple Negative Breast Cancer Patients.

BACKGROUND: We have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC). METHODS: Patients with stage 1-3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS: The average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3-5.9, p < 0.001) and DFS (HR 2.3, CI 1.2-4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2-13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3-11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low) and nodal status (positive vs. negative) resulted in four groups with significantly different OS and DFS (log rank p < 0.0001). Significant improvements in OS (p < 0.001) and DFS (p < 0.001) were observed for patients who received chemotherapy and had high NLR but not for patients with low NLR (p = 0.65 and p = 0.07, respectively). CONCLUSION: High pretreatment NLR is an independent predictor of poor OS and DFS among TNBC patients. Combining NLR and pN provides better risk stratification for TNBC patients. Chemotherapy appears to be beneficial only in patients with high NLR. Larger prospective studies are needed to validate these findings.

Role of TGF-ß in pancreatic ductal adenocarcinoma progression and PD-L1 expression.

PURPOSE: The transforming growth factor-beta (TGF-ß) pathway plays a paradoxical, context-dependent role in pancreatic ductal adenocarcinoma (PDAC): a tumor-suppressive role in non-metastatic PDAC and a tumor-promotive role in metastatic PDAC. We hypothesize that non-SMAD-TGF-ß signaling induces PDAC progression. METHODS: We investigated the expression of non-SMAD-TGF-ß signaling proteins (pMAPK14, PD-L1, pAkt and c-Myc) in patient-derived tissues, cell lines and an immunocompetent mouse model. Experimental models were complemented by comparing the signaling proteins in PDAC specimens from patients with various survival intervals. We manipulated models with TGF-ß, gemcitabine (DNA synthesis inhibitor), galunisertib (TGF-ß receptor inhibitor) and MK-2206 (Akt inhibitor) to investigate their effects on NF-κB, ß-catenin, c-Myc and PD-L1 expression. PD-L1 expression was also investigated in cancer cells and tumor associated macrophages (TAMs) in a mouse model. RESULTS: We found that tumors from patients with aggressive PDAC had higher levels of the non-SMAD-TGF-ß signaling proteins pMAPK14, PD-L1, pAkt and c-Myc. In PDAC cells with high baseline ß-catenin expression, TGF-ß increased ß-catenin expression while gemcitabine increased PD-L1 expression. Gemcitabine plus galunisertib decreased c-Myc and NF-κB expression, but induced PD-L1 expression in some cancer models. In mice, gemcitabine plus galunisertib treatment decreased metastases (p = 0.018), whereas galunisertib increased PD-L1 expression (p < 0.0001). In the mice, liver metastases contained more TAMs compared to the primary pancreatic tumors (p = 0.001), and TGF-ß increased TAM PD-L1 expression (p < 0.05). CONCLUSIONS: In PDAC, the non-SMAD-TGF-ß signaling pathway leads to more aggressive phenotypes, TAM-induced immunosuppression and PD-L1 expression. The divergent effects of TGF-ß ligand versus receptor inhibition in tumor cells versus TAMs may explain the TGF-ß paradox. Further evaluation of each mechanism is expected to lead to the development of targeted therapies.

Traveling for Pancreatic Cancer Care Is Worth the Trip.

BACKGROUND: Centralized care for patients with pancreatic cancer is associated with longer survival. We hypothesized that increased travel distance from home is associated with increased survival for pancreatic cancer patients. METHODS: The National Cancer Database user file for all pancreatic cancer patients was investigated from 2004 through 2015. Distance from the patients' zip code to the treating facility was determined. Survival was investigated using the Kaplan-Meier method. Cox hazard ratios (CoxHRs) were determined based on stage of disease, distance traveled for care, and clinical factors. RESULTS: 340 780 patients were identified. In the average age of 68 ± 12 years, 51% were male and 83% were Caucasian. For all stages of cancer, longer survival was associated with traveling farther (P < .001). The survival advantage was longer for Caucasians than African Americans (3.7 months vs. 2.6 months, P < .001) Travel was associated with a 13% decrease in risk of death (P < .001). Even controlling for the pathologic stage, traveling farther was associated with decreased risk of death (CoxHR = .91, P < .001). DISCUSSION: Traveling for care is associated with improved survival for pancreatic cancer patients. While a selection bias may exist, the fact that all stages of patients investigated benefited suggests that this is a real phenomenon.

Analysis of the Survival Impact of Postoperative Chemotherapy After Preoperative Chemotherapy and Resection for Gastric Cancer.

BACKGROUND: Perioperative chemotherapy is a standard-of-care treatment for patients with gastric cancer. However, the impact of the postoperative chemotherapy (postCTX) component on overall survival (OS) is not well defined. METHODS: The National Cancer Database (NCDB) 2006-2014 was queried for patients who received preoperative chemotherapy (preCTX) and resection for gastric cancer. Analysis was performed to identify factors influencing receipt of postCTX. The impact of postCTX on OS was evaluated in propensity-matched groups. RESULTS: Among 3449 patients who received preCTX and resection for gastric cancer, 1091 (31.6%) received postCTX. Independent predictors of receiving postCTX were diagnosis after 2010 (odds ratio [OR] 1.985), distal tumor location (OR 1.348), and 15 or more lymph nodes examined (OR 1.214). Predictors of not receiving postCTX were older age (OR 0.985), comorbidity score higher than 1 (OR 0.592), and black race (OR 0.791). After propensity-matching (1091 per group), the median OS was 56.8 months for those who did receive postCTX versus 52.5 months for those who did not (p = 0.131). Subset analysis according to tumor grade, lymphovascular invasion, number of lymph nodes evaluated, T and N class, and AJCC stage identified an improvement in OS for the patients with N1 disease who received postCTX compared with those who did not (79.6 vs 41.3 months; p = 0.025). However, no other subgroup had a significant survival benefit. CONCLUSIONS: Additional postCTX was administered to a minority of patients who received preCTX and gastrectomy for gastric cancer, and its influence on OS appeared to be limited. Future trials should aim to define patients who will benefit from postCTX.

Implications of Conversion during Attempted Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma.

BACKGROUND: Although advocated by some, minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) is controversial. Moreover, the oncologic implications for patients requiring conversion to an open procedure during attempted MIA for ACC are not extensively reported. PATIENTS AND METHODS: The National Cancer Database was queried for patients undergoing resection for ACC. Overall survival (OS) for patients undergoing successful MIA was compared with those requiring conversion, and additionally evaluated with a multivariable Cox regression analysis including other factors associated with OS. After propensity matching, those experiencing conversion were further compared with patients who underwent planned open resection. RESULTS: Among 196 patients undergoing attempted MIA for ACC, 38 (19.4%) required conversion. Independent of 90-day postoperative mortality, conversion was associated with significantly reduced OS compared with successful MIA (median 27.9 months versus not reached, p = 0.002). Even for tumors confined to the adrenal, conversion was associated with worse median OS compared with successful MIA (median 34.2 months versus not reached, p = 0.003). After propensity matching for clinicopathologic covariates to establish well-balanced cohorts (N = 38 per group), patients requiring conversion during MIA had significantly worse OS than those having planned open resection (27.9 months versus 50.5 months, p = 0.020). On multivariable analysis for predictors of OS, conversion during MIA (HR 2.32, p = 0.003) was independently associated with mortality. CONCLUSIONS: ACC is a rare tumor for which adequate oncologic resection is the only chance for cure. Given the relatively high rate of conversion and its associated inferior survival, open resection should be considered standard of care for known or suspected ACC.