Adoptive Cellular Therapy for Metastatic Melanoma: The Road to Commercialization and Treatment Guidelines for Clinicians.

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has been gaining promise as a therapeutic option for metastatic melanoma. By harnessing the power of patients' tumor-resident lymphocytes, TIL therapy has shown promise in delivering durable, complete responses for patients who have progressed with other treatments, including checkpoint inhibition. This form of personalized medicine has traditionally been limited to select academic facilities with the infrastructure and resources to generate TIL cells and care for patients during the treatment phase. In this review, the authors discuss the role of TIL therapy for patients with metastatic melanoma, including the current state of therapeutic options, logistics of TIL harvest and infusion, management of infusion-specific toxicities, and foundational steps for surgeons and oncologists to establish cell-based therapies in individual hospitals and cancer centers.

What to do When Decompressive Gastrostomies and Jejunostomies are not Options? A Scoping Review of Transesophageal Gastrostomy Tubes for Advanced Malignancies.

BACKGROUND: In advanced malignant bowel obstruction, decompressive gastrostomy tubes (GTs) may not be feasible due to ascites, peritoneal carcinomatosis, and altered gastric anatomy. Whereas nasogastric tubes (NGTs) allow temporary decompression, percutaneous transesophageal gastrostomy tubes (PTEGs) are an alternative method for long-term palliative decompression. This study performed a scoping review to determine outcomes with PTEG in advanced malignancies. METHODS: A systematic literature search was performed to include all studies that reported the clinical results of PTEGs for malignancy. No language, national, or publication status restrictions were used. RESULTS: The analysis included 14 relevant studies with a total of 340 patients. In 11 studies, standard PTEGs were inserted with a rupture-free balloon's placement into the mouth or nose and esophageal puncture under fluoroscopy or ultrasound, followed by a guidewire into the stomach with placement of a single-lumen tube. Of 340 patients, 65 (19.1%) had minor complications, and 5 (2.1%) had significant complications, including bleeding and severe aspiration pneumonia. Of 171 patients, 169 with PTEGs (98.8%) reported relief of nasal discomfort from NGT and alleviation of obstructive symptoms. The one randomized controlled trial reported a significantly higher quality of life with PTEGs than with NGTs. CONCLUSIONS: When decompression for advanced malignancy is technically not feasible with a gastrostomy tube, the PTEG is a viable, safe option for palliation. The PTEG is associated with lower significant complication rates than the gastrostomy tube and significantly higher patient-derived outcomes than the NGT.

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

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

Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™).

BACKGROUND: Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC. METHODS: Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2-112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8-11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75-1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01-1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03-1.25, p = 0.018). CONCLUSION: Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Epigenetic modulation enhances immunotherapy for hepatocellular carcinoma.

BACKGROUND: Anti-PDL-1 immunotherapy for Hepatocellular Carcinoma (HCC) demonstrated a mixed response. Polycomb Repressor Complex 2(PRC2) contributes to the initiation and progression of HCC by suppressing tumor antigens and inhibiting an immune response. Two components of epigenetic modulation are Enhancer of Zeste Homolog 2 (EZH2, the catalytic component of PRC2) and DNA Methyltransferase 1 (DNMT1). We aim to investigate the potential role of epigenetic therapy targeting EZH2 and DNMT1 as a novel strategy to modulate immunotherapy response in HCC. METHODS: HepG2, Hep3B, and Hepa1-6 HCC cell lines were treated with EZH2 inhibitor (DZNep) and DNMT1 inhibitor (5-Azacytidine) with and without anti-PDL-1. Quantitative RT-PCR and immunohistochemistry were performed to evaluate the expression of tumor suppressors, tumor antigens, and Th1 chemokines. In-vivo C57/LJ immunocompetent mice model with subcutaneous tumor inoculation was performed with intraperitoneal drug injections. RESULTS: There was a significant upregulation of Th1 chemokines in HepG2 (CXCL9 5.5 ±â€¯0.2 relative fold change; CXCL10 1.44 × 103 ±â€¯37 relative fold change) and Hep3B (CXCL 9 6.85 × 103 ±â€¯1.3 × 103 relative fold change; CXCL 10 2.15 × 103 ±â€¯3.1 × 102 relative fold change). Additionally, there was a significant induction of cancer testis antigens NY-ESO-1 (3.6-3.7 ±â€¯0.3 relative fold change) and LAGE (8.3-11.7 ±â€¯1.9 relative fold change). In vivo model demonstrated statistically significant tumor regression in the combination treatment group (0.02 g ±â€¯0.02) compared to epigenetic therapy (0.63 g ±â€¯0.61) or immunotherapy alone (0.15 g ±â€¯0.21) with untreated control (2.4 g ±â€¯0.71). There was significantly increased trafficking of cytotoxic T- lymphocytes and associated apoptosis for the combination treatment group compared to epigenetic or immunotherapy alone. CONCLUSIONS: This study demonstrates that epigenetic modulation could be a novel potential strategy to augment immunotherapy for HCC by stimulating T cell trafficking into tumor microenvironment via activation of transcriptionally repressed chemokine genes responsible for T-cell trafficking, inducing previously silent neoantigens for immune targets, and allowing tumor regression as a result. A clinical trial of this feasible combination therapy of these clinically available agents is warranted.

Evaluating the Regulatory Immunomodulation Effect of Irreversible Electroporation (IRE) in Pancreatic Adenocarcinoma.

BACKGROUND: Irreversible electroporation (IRE) has been demonstrated as an effective local method for locally advanced (stage 3) pancreatic adenocarcinoma. Immune regulatory T cells (Tregs) induce immunosuppression of tumors by inhibiting patients' anti-tumor adaptive immune response. This study aimed to evaluate the immunomodulation effect of IRE to identify an ideal time point for potential adjuvant immunotherapy. METHODS: This study prospectively evaluated an institutional review board-approved study of patients undergoing either in situ IRE or pancreatectomy. Patient blood samples were collected at different time points (before surgery [preOP] and on postoperative day [POD] 1, POD3, and POD5). Peripheral blood mononuclear cells (PBMCs) were isolated and evaluated for three different CD4 + Treg subsets (CD25 + CD4 +, CD4 + CD25 + FoxP3 +, CD4 + CD25 + FoxP3 -) by flow cytometry and analyzed for median fold change (MFC) between each two consecutive time points (MFC = log2(T2/T1)). RESULTS: The study analyzed 15 patients with in situ IRE (n = 11) or pancreatectomy (PAN) (n = 4). In both groups, CD25 + CD4 + Tregs decreased on POD1 followed by a steady increase in pancreatectomy, whereas the trend in the IRE group reversed between D3 and D5 (MFC: IRE [- 0.01], PAN [+ 0.39]). For each period, CD4 + CD25 + FoxP3 + Tregs showed the most dramatic inverse effect, with D3 to D5 showing the most change (MFC: IRE [- 0.18], PAN [+ 0.39]). Also, CD4 + CD25 + FoxP3 - Tregs showed an inverse effect between D3 and D5 (MFC: IRE [- 0.25], PAN [+ 0.49]). Altogether, the Treg trend was inversely affected by the in situ IRE procedure, with the greatest cumulative significant change for all three Treg subsets between D3 and D5 (MFC ± SEM: IRE [- 0.24 ± 0.05], PAN [+ 0.37 ± 0.02]; p = 0.016). CONCLUSIONS: The study data suggest that in situ IRE procedure-mediated Treg attenuation between POD3 and POD5 can provide a clinical window of opportunity for potentiating clinical efficacy in combination with immunotherapy.

Approach to the surgical management of resectable gastric cancer.

The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases. The benefit of surgical therapy is enhanced by at least 13% when it is integrated with multimodal therapy: either surgery followed by adjuvant chemoradiotherapy or surgery with perioperative systemic therapy. This multidisciplinary approach to treatment will continue to be an evolving paradigm, especially with the emergence of systemic and targeted therapies.

Approach to the surgical management of resectable gastric cancer.

The rates of gastric cancer, which is the third leading cause of cancer-related deaths worldwide, vary depending on geographic location. Margin-negative gastrectomy and adequate lymphadenectomy (removal of ≥15 lymph nodes) are the cornerstones of multimodal treatment for operable gastric cancer. Diagnostic laparoscopy should be included in the armamentarium for newly diagnosed gastric cancer in order to overcome the limitations of cross-sectional imaging in identifying sub-radiographic hepatic or peritoneal metastases. The benefit of surgical therapy is enhanced by at least 13% when it is integrated with multimodal therapy: either surgery followed by adjuvant chemoradiotherapy or surgery with perioperative systemic therapy. This multidisciplinary approach to treatment will continue to be an evolving paradigm, especially with the emergence of systemic and targeted therapies.

Identification and Treatment of SMARCA4 Deficient Poorly Differentiated Gastric Carcinoma.

Loss of expression of the SMARCA4 gene, a subunit of the SWI/SNF complex, has been historically associated with thoracic sarcomas. This loss of expression is extremely rare in gastric cancers, and its role in gastrointestinal tract carcinomas has not been fully elucidated. We report a case of a 73-year-old male with poorly differentiated, SMARCA4-deficient gastric cancer, showing that this immunophenotype is not limited to thoracic sarcomas or advanced-stage tumors. These tumors are often resistant to conventional FLOT chemotherapy and have poor prognoses, necessitating the need for early identification and alternative therapeutic approaches. New therapies such as EZH2 inhibitors and etoposide should be considered in cases where standard treatments are ineffective.

Tyrosine kinase inhibitors versus radiation therapy in unresectable dermatofibrosarcoma protuberans (DFSP): A narrative systematic review.

BACKGROUND: In unresectable dermatofibrosarcoma protuberans (DFSP), no clear guideline exists regarding the use of tyrosine kinase inhibitors (TKI) versus radiotherapy. This study reviews current literature regarding TKI and radiotherapy in unresectable DFSP. METHODS: Following PROSPERO registration (CRD42021232508), a systematic literature search was performed including all studies reporting clinical results of TKI and/or radiotherapy in the treatment of unresectable DFSP. A narrative synthesis was used to compare patient characteristics, outcomes, and adverse effects. RESULTS: Of 1345 screened studies, 14 were included for review. Patient age ranged 18-77 years and 55% were male. Radiotherapy patients exhibited lower grade disease than TKI patients. Overall clinical benefit following TKI ranged from 70% to 96%. Radiotherapy patients exhibited control or resolution on last follow-up in 90% of cases. Radiotherapy adverse effects were mild, while TKI adverse effects were more severe and managed with dose reduction. CONCLUSION: TKI may be employed in unresectable DFSP of all histology types whereas radiation alone may be limited to low-grade and classic-type DFSP. TKI may cause more severe adverse effects compared to radiation alone.

Gastric Neuroendocrine Tumor Treatment and Survival Outcome Depends on Facility Type.

BACKGROUND: Gastric neuroendocrine tumors (gNETs) are rare cancers for which surgery may improve survival. We aim to determine if facility type affects treatment and survival outcomes. METHODS: The NCDB was queried for patients with gNET from 2004-2016 and stratified into Academic/Research Program (ARP), Community Cancer Program (CCP), Comprehensive Community Cancer Program (CCCP), or Integrated Network Cancer Program (INCP). Overall survival along with clinical and demographic features was compared. RESULTS: Median survival was improved in patients treated at an academic program: 137.3 months versus 88.0, 96.3, and 100.2 for CCP, CCCP, INCP, respectively (P < .0001). Patients treated at academic centers were more likely to have surgery (64.2% vs 59.1%, 57.5%, 51.4%, P < .0001). After propensity matching for age, race, grade, stage, insurance status, and comorbidity score, survival benefit from treatment at an academic center remained (P = .03), particularly for patients undergoing surgery (P < .0001) and chemotherapy (P = .04). CONCLUSION: Patients with gNET treated at an academic hospital had improved median survival after propensity matching and may benefit from treatment at academic rather than community medical centers.

Advance care planning for patients undergoing gastrostomy tube procedures; prevalence, outcomes, and disparities.

BACKGROUND: Advanced care planning (ACP) is the process of establishing goals for end-of-life care. We aimed to examine ACP's prevalence, associated factors, and impact in a cohort of patients undergoing gastrostomy tube procedures. METHODS: Adult patients who underwent gastrostomy tube placement from 2016 to 2021 â€‹at a tertiary center were identified. Variables evaluated included age, sex, race, comorbidities, and median income of patient home zip code. Primary outcomes included the presence of ACP, length of stay (LOS), and 90-day mortality. Analysis was performed using independent T tests, Mann Whitney U-tests, and Chi Square analysis. ACP, LOS, and 90-day mortality were analyzed with multivariate analysis. RESULTS: 877 patients underwent gastrostomy tube placement and 10.6 â€‹% had ACP. Black race was an isolated factor negatively associated with ACP (OR 0.423, p â€‹= â€‹0.013). There was no difference in the proportion of patients with or without ACP who died within 90 days of the procedure (17 â€‹% vs. 15 â€‹%, p â€‹= â€‹0.836). Average LOS was 6 days shorter for patients with ACP (p â€‹< â€‹0.001). CONCLUSION: This study highlights the significant underutilization and racial disparity in ACP, and found that ACP does not negatively impact outcomes or perioperative mortality for patients undergoing gastrostomy tube placement.

Cost-Benefit Analysis of Robotic vs. Laparoscopic Hepatectomy: A Propensity-Matched Retrospective Cohort Study of American College of Surgeons National Surgical Quality Improvement Program Database.

BACKGROUND: Robotic and laparoscopic hepatectomies having increased utilization as minimally invasive techniques are explored for hepatobiliary malignancies. Although the data on outcomes from these 2 approaches are emerging, the cost-benefit analysis of these approaches remains sparse. This study compares the costs associated with robotic vs. laparoscopic liver resections, taking into account 30-day complications. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, a propensity-matched cohort of patients with laparoscopic or robotic liver resections between 2014 and 2017 was identified. Costs were assigned to perioperative variables, including operating room (OR) time, length of stay, blood transfusions, and 30-day complications. Cost estimates were obtained from the Centers for Medicare and Medicaid Services billing data (2017), American Hospital Association data (2017), relevant literature, and local institutional cost data. RESULTS: In our matched cohort of 454 patients (227 per group), total costs associated with laparoscopic liver resections were estimated at $5.5 M ($24 K per patient) vs. $6.8 M ($29.8 K per patient) for robotic liver resections (21.3% difference, P < .001). The higher cost associated with robotic hepatectomies was related to blood transfusions ($22.0 K vs. $12.1 K, P = .02), length of stay ($2.05 M vs. $1.76 M, P = .046), and OR time ($4.01 M vs. $3.24 M, P < .0001). DISCUSSION: Robotic hepatectomies were associated with higher costs compared to laparoscopic hepatectomies. The 2 major contributors to the cost disparity were increased OR time and increased length of stay. Future studies are warranted to analyze high-volume Minimally Invasive Surgery surgeons' impact in specialty centers on potentially mitigating this current cost disparity.

Epigenetic modulation enhances immunotherapy for pancreatic ductal adenocarcinoma.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. PDAC has poor response to immunotherapy because of its unique tumour microenvironment (TME). In an attempt to stimulate immunologically silent pancreatic cancer, we investigated the role of epigenetic therapy in modulating the TME to improve immunogenicity. Methods: In vitro human PDAC cell lines MiaPaca2 and S2-013 were treated with 5µ m 3-Deazaneplanocin A (DZNep, an EZH2 inhibitor) and 5 µ m 5-Azacytidine (5-AZA, a DNMT1 inhibitor). In vivo orthotopic murine tumour models using both murine PAN02 cells and KPC cells inoculated in immunocompetent C56/BL7 mice were treated with anti-PD-L1 combined with DZNep and 5-AZA. Short hairpin knockdown (KD) of EZH2 and DNMT1 in PAN02 cells for the orthotopic murine tumour model was established to validate the drug treatment (DZNep and 5-AZA). qRT-PCR and microarray assays were performed for the evaluation of Th1-attracting chemokines and cancer-associated antigen induction. Results: Drug treatments induced significant upregulation of gene expressions of Th1-attracting chemokines, CXCL9 and CXCL10, and the cancer-testis antigens, NY-ESO-1, LAGE and SSX-4 (P < 0.05). In orthotopic tumour models, inoculation of PAN02 cells or KPC cells demonstrated significant tumour regression with corresponding increased apoptosis and infiltration of cytotoxic T lymphocytes in the combination treatment group. In the orthotopic Pan02-KD model, the anti-PD-L1 treatment also caused significant tumour regression. Conclusion: We demonstrate that immunotherapy for PDAC can be potentiated with epigenetic therapy by increasing cancer-associated antigen expression and increased T-cell trafficking across the immunosuppressive tumour microenvironment via upregulation of the repressed chemokines and increased apoptosis with subsequent tumour regression.

Role of metastasectomy for liver metastasis in stage IV anal cancer.

INTRODUCTION: There is a paucity of data on the role of metastasectomy for metastatic anal cancer on survival outcomes. We aim to define the role of metastasectomy in stage IV anal cancer. METHODS: National Cancer Database (NCDB) from 2004 to 2014 was accessed to include patients with metastatic anal cancer, excluding adenocarcinoma, neuroendocrine, and 'other' histologies. We compared patients undergoing metastasectomy (n = 165) to those who did not have metastasectomy (n = 2093) by age, sex, cancer grade, and site of metastasis, including metastasis to bone, liver, and lung, using chi-square analysis. The primary outcome was overall survival. RESULTS: Patients had equal distribution of metastatic sites between those who underwent metastasectomy versus no metastasectomy: bone (7.64% vs 4.85%, p = 0.22), brain (0.24% vs 0%, p = 1.0), liver (23.22% vs 29.70%, p = 0.07), and lung (11.85% vs 9.09%, p = 0.38). Survival following metastasectomy was increased at one year (71% vs. 61%, p = 0.016), two years (50% vs. 38%, p = 0.014), and five years (30% vs. 19%, p = 0.025). Median overall survival was increased (23 months vs. 16 months; p = 0.015) for patients with metastasectomy. Survival increases were demonstrated only in the group with liver metastasis undergoing metastasectomy. When stratifying for liver metastases only, median overall survival time was further increased (34 months vs. 16 months; p < 0.0001) following metastasectomy. CONCLUSION: These results demonstrate a survival benefit for hepatic metastasectomy in stage IV anal cancer. Our findings demonstrate a potential survival benefit in highly select patients with metastatic anal cancer to the liver. These findings support further investigation in a randomized clinical trial to delineate these findings.

Simple Versus Radical Resection for Duodenal Adenocarcinoma: A Propensity Score Matched Analysis of National Cancer Database.

BACKGROUND: Duodenal adenocarcinoma treatment consists of either simple or radical surgical resection. Existing evidence suggests similar survival outcomes between the two but is limited by small numbers and single-institution analysis. We aim to compare survival after partial versus radical resection for duodenal adenocarcinoma using the National Cancer Database (NCDB). METHODS: Using NCDB results from 2004 to 2014, we compared patients with duodenal adenocarcinoma undergoing partial resection (n = 1247) and radical resection (n = 1240) by age, sex, facility type, facility location, cancer stage, cancer grade, lymph node sampling, node status, tumor size, margin status, neoadjuvant therapy, and adjuvant therapy using chi-square analysis. Survival was compared using propensity matching. RESULTS: Patients undergoing partial resection had overall earlier cancer stage, more favorable tumor grade, and were less likely to undergo lymph node sampling and neoadjuvant therapy. When overall survival was compared between the 2 propensity-matched groups, the median survival was 46.7 months after partial resection and 43.2 months after radical resection (P = .329), and overall survival was similar between the 2 groups (P = .894). The use of adjuvant therapy demonstrated improved survival over either surgery alone (P < .0001, P = .0037). CONCLUSION: Partial resection did not demonstrate worse survival outcomes than radical resection for duodenal adenocarcinoma. The use of adjuvant therapy in addition to surgery demonstrated improved survival regardless of surgery type and played a larger role in survival than the type of surgery. Our findings provide evidence to support the continued use of both partial and radical surgical resections to treat duodenal malignancy.

The Role of Neoadjuvant Versus Adjuvant Therapy for Duodenal Adenocarcinoma: A National Cancer Database Propensity Score Matched Analysis.

INTRODUCTION: Adjuvant therapy is recommended in duodenal adenocarcinoma (DA), but the role of neoadjuvant therapy remains undefined. We compared the effect of neoadjuvant therapy to adjuvant therapy on overall survival, 30-day, and 90-day mortality following the resection of DA. METHODS: A retrospective review of the National Cancer Database was performed on patients with DA who received either adjuvant or neoadjuvant therapy in addition to surgical resection. Propensity score matching was done for patient, socioeconomic, and tumor characteristics. Overall survival, 30-day, and 90-day mortality were compared. RESULTS: A total of 112 patients were identified; 55 received adjuvant therapy; 57 received neoadjuvant therapy. There was no difference in 30-day (0% vs. 1.75%; P = 1.00), 90-day mortality (1.82% vs. 7.02%; P = .36), nor overall survival (1 yr: 86% vs. 76; 3 yr: 49% vs. 46%; 5 yr: 42% vs. 39%; P = .28). CONCLUSIONS: There was no difference in overall survival after propensity score matched analysis.

Omental patch versus gastric resection for perforated gastric ulcer: Systematic review and meta-analysis for an unresolved debate.

BACKGROUND: Perforated gastric ulcers are surgical emergencies with paucity of data on the preferred treatment modality of resection versus omental patch. We aim to compare outcomes with ulcer repair and gastric resection surgeries in perforated gastric ulcers after systematic review of literature. METHODS: A systematic literature search was performed for publications in PubMed Medline, Embase, and Cochrane Central Register of Controlled Trials. We included all studies which compared ulcer repair vesus gastric resection surgeries for perforated gastric ulcers. We excluded studies which did not separate outcomes gastric and duodenal ulcer perforations. RESULTS: The search included nine single-institution retrospective reviews comparing ulcer repair (449 patients) versus gastric resection surgeries (212 patients). Meta-analysis was restricted to perforated gastric ulcers and excluded perforated duodenal ulcers. The majority of these studies did not control for baseline characteristics, and surgical strategies were often chosen in a non-randomized manner. All of the studies included were at high risk of bias. The overall odds ratio of mortality in ulcer repair surgery compared to gastric resection surgery was 1.79, with 95% CI 0.72 to 4.43 and p-value 0.209. CONCLUSION: In this meta-analysis, there was no difference in mortality between the two surgical groups. The overall equivalence of clinical outcomes suggests that gastric resection is a potentially viable alternative to ulcer repair surgery and should not be considered a secondary strategy. We would recommend a multicenter randomized control trial to evaluate the surgical approach that yields superior outcomes. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level III.

Disparities in Treatment for Gallbladder Carcinoma: Does Treatment Site Matter?

BACKGROUND AND PURPOSE: Current treatment guidelines for gallbladder cancer range from simple cholecystectomy to regional hepatic resection. Treatment patterns for radical resection and adjuvant chemotherapy vary. We aim to determine if there is any disparity in treatment or difference in survival between academic versus community treatment centers. METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2014 for gallbladder carcinoma. Cases were stratified into treatment sites as "Community Cancer Center" (CCC) or "Academic Cancer Center" (ACC). Propensity score matching was performed for patient demographics, TNM stage, resection type, and administration of adjuvant chemotherapy. The primary outcome included 30-day mortality, 90-day mortality, and overall survival. RESULTS: There are similar frequencies of radical versus simple resection and administration of adjuvant chemotherapy between ACC and CCC. When propensity-matched for resection type, cases treated at ACC have lower 30-day mortality (4.1% vs. 6.9%) and 90-day mortality (13.2% vs. 18.5%) and increased 5-year overall survival (26.2% vs. 22.4%) (p < 0.01). After propensity matching for adjuvant chemotherapy, cases at ACC have lower 30-day mortality (4.12% vs. 7.71%) and 90-day mortality (13.22% vs. 19.19%) and increased overall survival (13.6% vs. 11.0%) (p < 0.01). DISCUSSION AND CONCLUSIONS: While treatment patterns for gallbladder cancer at ACC and CCC were similar, there was a decrease in 30-day and 90-day mortality and improved overall survival associated with patients treated at ACC. Treatment site may have an impact in the surgical outcomes of gallbladder cancer patients. This disparity warrants further research.