Association of negative pressure wound therapy and surgical site infections in patients undergoing cytoreductive surgery: An entropy balanced analysis.

BACKGROUND AND OBJECTIVES: Surgical site infections (SSIs) after cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) are a major cause of potentially avoidable morbidity. We explored the association of negative pressure wound therapy (NPWT) with SSI in patients undergoing CRS/HIPEC. METHODS: Retrospective analysis of consecutive patients undergoing CRS/HIPEC for non-gynecologic cancers. Exposure was the receipt of NPWT versus traditional skin closure. Primary outcome was SSI within 90 days of surgery. We performed multivariable logistic regression (before and after entropy balancing) to evaluate the association of exposure with outcomes. RESULTS: A total of 251 patients were included, of which 43 (17%) received NPWT and 26 (10.4%) developed SSIs. Baseline demographics and clinicopathologic characteristics were similar between the two groups with some exceptions: Patients who received NPWT had a higher Peritoneal Carcinomatosis Index (median 19 vs. 11, p = 0.002) and operative time (10 vs. 8.2 h, p = 0.003) but were less likely to undergo HIPEC (84% vs. 95%, p < 0.05). After entropy balancing, on multivariable logistic regression, NPWT was not associated with 90-day SSI (odds ratio = 0.90; 95% confidence interval = 0.21-3.80; p = 0.89). CONCLUSION: NPWT was not associated with a reduction in SSIs. These findings prompt a reevaluation of the routine use of NPWT in CRS/HIPEC.

Pilot study of a telehealth intervention for personalized self-management for eating symptoms after gastroesophageal cancer surgery.

BACKGROUND AND OBJECTIVES: Following gastric and esophageal cancer surgery, patients often experience significant, prolonged eating-related symptoms. One promising approach to help patients improve their eating-related quality of life (QOL) is through self-management coaching to aid in diet modification. We performed a randomized pilot study of a nutritionist-led telehealth intervention for the self-management of eating after gastroesophageal cancer surgery. METHODS: Patients who were within 30 days of resuming oral intake after undergoing surgery for gastric and/or esophageal cancer were consented and then randomized to the intervention or usual care. The intervention was performed by a nutritionist trained in self-management coaching and delivered in four telehealth sessions over 4 months. The following outcomes were measured at baseline and at 6 months after baseline: QOL (EORTC QLQC30), weight, body mass index, and sarcopenia. RESULTS: Fifty-three patients were enrolled. 22/27 usual care and 21/26 intervention patients completed the study for a retention rate of 81%. Differences between the intervention and control groups were not statistically significant, but the intervention group had indications of greater improvements in overall QOL as measured by EORTC QLQC30 Summary Score (8.7 vs. 2.3, p = 0.17) as well as greater improvements in 4/5 functional domains (p > 0.3). The intervention group also had slightly more weight gain (6 kg vs. 3 kg, p = 0.3) and less sarcopenia (3/16 vs. 9/18, p = 0.07). CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a telehealth intervention for self-management of eating symptoms after gastroesophageal cancer surgery. There were trends toward improved overall QOL in the intervention group. A larger study is needed to validate the results.

Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer.

A spectrum of immune states resulting from tumor resident macrophages and T-lymphocytes in the solid tumor microenvironment correlates with patient outcomes. We hypothesized that in gastric cancer (GC), macrophages in a polarized immunosuppressive transcriptional state would be prognostic of poor survival. We derived transcriptomic signatures for M2 (M2TS, MRC1; MS4A4A; CD36; CCL13; CCL18; CCL23; SLC38A6; FGL2; FN1; MAF) and M1 (M1TS, CCR7; IL2RA; CXCL11; CCL19; CXCL10; PLA1A; PTX3) macrophages, and cytolytic T-lymphocytes (CTLTS, GZMA; GZMB; GZMH; GZMM; PRF1). Primary GC in a TCGA stomach cancer dataset was evaluated for signature expressions, and a log-rank test determined overall survival (OS) and the disease-free interval (DFI). In 341 TCGA GC entries, high M2TS expression was associated with histological types and later stages. Low M2TS expression was associated with significantly better 5-year OS and DFI. We validated M2TS in prospectively collected peritoneal fluid of a GC patient cohort (n = 28). Single-cell RNA sequencing was used for signature expression in CD68+CD163+ cells and the log-rank test compared OS. GC patients with high M2TS in CD68+CD163+ cells in their peritoneal fluid had significantly worse OS than those with low expression. Multivariate analyses confirmed M2TS was significantly and independently associated with survival. As an independent predictor of poor survival, M2TS may be prognostic in primary tumors and peritoneal fluid of GC patients.

Different Methods of Minimally Invasive Esophagojejunostomy After Total Gastrectomy for Gastric Cancer: Outcomes from Two Experienced Centers.

BACKGROUND: Esophagojejunostomy after minimally invasive total gastrectomy (MITG) for gastric cancer (GC) is technically challenging. Failure of the esophagojejunal anastomosis can lead to significant morbidity, leading to short- and long-term quality of life (QoL) impairment or mortality. The optimal reconstruction method following MITG remains controversial. We evaluated outcomes of minimally invasive esophagojejunostomy after laparoscopic or robotic total gastrectomies. METHODS: We retrospectively reviewed MITG patients between 2015 and 2020 at two high-volume centers in China and the United States. Eligible patients were divided into groups by different reconstruction methods. We compared clinicopathologic characteristics, postoperative outcomes, including complication rates, overall survival rate (OS), disease-free survival rate (DFS), and patient-reported QoL. RESULTS: GC patients (n = 105) were divided into intracorporeal esophagojejunostomy (IEJ, n = 60) and extracorporeal esophagojejunostomy (EEJ, n = 45) groups. EEJ had higher incidence of wound infection (8.3% vs 13.3%, P = 0.044) and pneumonia (21.7% vs 40.0%, P = 0.042) than IEJ. The linear stapler (LS) group was inferior to the circular stapler (CS) group in reflux [50.0 (11.1-77.8) vs 44.4 (0.0-66.7), P = 0.041] and diarrhea [33.3 (0.0-66.7) vs 0.0 (0.0-66.7), P = 0.045] while LS was better than CS for dysphagia [22.2 (0.0-33.3) vs 11.1 (0.0-33.3), P = 0.049] and eating restrictions [33.3 (16.7-58.3) vs 41.7 (16.7-66.7), P = 0.029] at 1 year. OS and DFS did not differ significantly between LS and CS. CONCLUSIONS: IEJ anastomosis generated better results than EEJ. LS was associated with a better patient eating experience, but more diarrhea and reflux compared with CS. Clinical and patient-reported outcomes show the superiority of IEJ with the LS reconstruction method in MITG for GC.

Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA.

BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a laparoscopic locoregional treatment for peritoneal metastases (PM) from colorectal cancer (CRC) or appendiceal cancer (AC) in patients who cannot undergo cytoreductive surgery (CRS). While PIPAC has been studied in Europe and Asia, it has not been investigated in the USA. PATIENTS AND METHODS: We evaluated PIPAC with 90 mg/m2 oxaliplatin alone (cycle 1) and preceded by systemic chemotherapy with fluorouracil (5-FU) and leucovorin (LV) (cycle 2-3) as a multicenter prospective phase I clinical trial (NCT04329494). The primary endpoint was treatment-related adverse events (AEs). Secondary endpoints included survival and laparoscopic, histologic, and radiographic response. RESULTS: 12 patients were included: 8 with CRC and 4 with AC. Median prior chemotherapy cycles was 2 (interquartile range (IQR) 2-3). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median peritoneal carcinomatosis index (PCI) was 28 (IQR 19-32). Six (50%) of twelve patients completed three PIPAC cycles. No surgical complications or dose-limiting toxicities were observed. Two patients developed grade 3 treatment-related toxicities (one abdominal pain and one anemia). Median overall survival (OS) was 12.0 months, and median progression-free survival (PFS) was 2.9 months. OS was correlated with stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria but not with laparoscopic response by PCI or histologic response by peritoneal regression grading system (PRGS). CONCLUSIONS: This phase I trial in the USA demonstrated safety, feasibility, and early efficacy signal of PIPAC with oxaliplatin and chemotherapy in patients with PM from AC or CRC who are refractory to standard lines of systemic chemotherapy.

Anti-Tumor Immunogenicity of the Oncolytic Virus CF33-hNIS-antiPDL1 against Ex Vivo Peritoneal Cells from Gastric Cancer Patients.

We studied the immunotherapeutic potential of CF33-hNIS-antiPDL1 oncolytic virus (OV) against gastric cancer with peritoneal metastasis (GCPM). We collected fresh malignant ascites (MA) or peritoneal washings (PW) during routine paracenteses and diagnostic laparoscopies from GC patients (n = 27). Cells were analyzed for cancer cell markers and T cells, or treated with PBS, CF33-GFP, or CF33-hNIS-antiPDL1 (MOI = 3). We analyzed infectivity, replication, cytotoxicity, CD107α upregulation of CD8+ and CD4+ T cells, CD274 (PD-L1) blockade of cancer cells by virus-encoded anti-PD-L1 scFv, and the release of growth factors and cytokines. We observed higher CD45-/large-size cells and lower CD8+ T cell percentages in MA than PW. CD45-/large-size cells were morphologically malignant and expressed CD274 (PD-L1), CD252 (OX40L), and EGFR. CD4+ and CD8+ T cells did not express cell surface exhaustion markers. Virus infection and replication increased cancer cell death at 15 h and 48 h. CF33-hNIS-antiPDL1 treatment produced functional anti-PD-L1 scFv, which blocked surface PD-L1 binding of live cancer cells and increased CD8+CD107α+ and CD4+CD107α+ T cell percentages while decreasing EGF, PDGF, soluble anti-PD-L1, and IL-10. CF33-OVs infect, replicate in, express functional proteins, and kill ex vivo GCPM cells with immune-activating effects. CF33-hNIS-antiPDL1 displays real potential for intraperitoneal GCPM therapy.

Emotional Distress and Financial Toxicity in Younger Adult Patients Undergoing Oncologic Surgery.

BACKGROUND: There has been an alarming increase in the number of young adults (YA) diagnosed with cancer. The emotional, psychosocial, and financial distress experienced by newly diagnosed YA undergoing cancer surgery remains largely unknown. METHODS: A validated biopsychosocial distress screening tool (SupportScreen) was administered to patients diagnosed with cancer before surgery between 2009 and 2017 in a National Cancer Institute Comprehensive Cancer Center. Patients were stratified into YA less than or equal to 45 years and older adults (OA) above 45 years. Descriptive statistics and logistic regression were used to analyze distress outcomes. RESULTS: In total, 4297 patients were identified, with YA comprising 13.3% (n=573) of the cohort. YA reported higher emotional distress, including increased anxiety (33.8% vs 27.4%, P =0.002), greater fear of procedures (26.7% vs 22%, P =0.018), and difficulty managing emotions (26% vs 20.7%, P =0.006). YA struggled more frequently to manage work/school (29.5% vs 19.3%, P <0.001), finding resources (17.8% vs 11.8%, P <0.001), changes in physical appearance (22.2% vs 13.4%, P <0.001), fatigue (36% vs 27.3%, P <0.001), and ability to have children (18.4% vs 3%, P <0.001). Financial toxicity was significantly higher in the YA group (40.5% vs 28%, P <0.001). While income level was strongly protective against emotional distress and financial toxicity in OAs, it was less protective against the risk of financial toxicity in YA. Younger age was an independent predictor of financial toxicity in a model adjusted to income (odds ratio=1.52, P =0.020). CONCLUSIONS: YA in the prime of their personal and professional years of productivity require special attention when undergoing surgical evaluation for cancer. Resource allocation and counseling interventions should be integrated as part of their routine care to expedite their return to optimal physical and holistic health and mitigate psychosocial distress and financial toxicity.

An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS: On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS: The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS: There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.

PIPAC for the Treatment of Gynecologic and Gastrointestinal Peritoneal Metastases: Technical and Logistic Considerations of a Phase 1 Trial.

BACKGROUND: Peritoneal metastases (PM) from ovarian, gastric, appendiceal, or colorectal origin can be treated via cytoreductive surgery with or without the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) for selected patients. Unfortunately, not all patients are candidates for aggressive surgical debulking. For these patients, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as an alternative method for intraperitoneal (IP) chemotherapy administration. This report presents the design and implementation of the first phase 1 trial to evaluate the safety and efficacy of PIPAC in the United States. METHODS: This is an ongoing prospective phase 1 clinical trial of PIPAC for patients who have histologically confirmed ovarian, uterine, gastric, appendiceal, or colorectal cancer with PM and have progressed to at least one evidence-based chemotherapeutic regimen. The trial has two clinical arms. The patients in arm 1 have gynecologic and gastric malignancies treated with IP cisplatin and doxorubicin, and the arm 2 patients have colorectal and appendiceal malignancies treated with intravenous fluorouracil and leucovorin followed by IP oxaliplatin. All the patients are monitored for dose-limiting toxicities and adverse events. RESULTS: Practical and technical considerations for the phase 1 PIPAC trial are presented. These considerations include patient selection, operating room setup, and technical details for successful aerosolized chemotherapy delivery. The phase 1 study results will be reported separately at completion of the trial. CONCLUSIONS: The PIPAC treatment is a feasible, minimally invasive approach that permits IP delivery of chemotherapy. Once completed, the ongoing phase 1 trial will help to provide safety and initial efficacy data.

Immunotherapy-Based Neoadjuvant Treatment of Advanced Microsatellite Instability-High Gastric Cancer: A Case Series.

Despite the use of first-line therapies like fluoropyrimidine and platinum-based cytotoxic chemotherapy, gastric cancer (GC) continues to carry a poor prognosis. Recent subgroup analyses of first-line phase III trials have demonstrated that patients with microsatellite instability-high (MSI-H) metastatic GC derive significant improvement in survival rates when immune checkpoint inhibitors (ICIs) are combined with chemotherapy compared with chemotherapy alone. However, it remains to be seen whether the success of ICIs in the metastatic setting can be translated into earlier stages of GC with resectable disease. We report 6 cases of locally advanced, nonmetastatic MSI-H GC that all demonstrated favorable response following treatment with pembrolizumab in addition to neoadjuvant chemotherapy. With the exception of immune-related colitis in one patient, pembrolizumab was well-tolerated. To our knowledge, this is the first reported US case series of patients treated with an ICI in combination with neoadjuvant chemotherapy for advanced, nonmetastatic, resectable or unresectable MSI-H GC.

Impact of Neoadjuvant Therapy on Minimally Invasive Surgical Outcomes in Advanced Gastric Cancer: An International Propensity Score-Matched Study.

BACKGROUND: No international consensus on the treatment of advanced gastric cancer (AGC) exists. In the absence of well-designed, comparative studies between neoadjuvant versus adjuvant strategies, concerns about increased risk of postoperative complications remain barriers to neoadjuvant chemotherapy (NAC) for AGC. We evaluated surgical outcomes of AGC patients who received minimally invasive radical gastrectomy with D2 lymphadenectomy after NAC. METHODS: We collected data from two high-volume gastric cancer programs in the United States and China between January 2015 and December 2019 with the last follow-up in February 2020. AGC patients undergoing minimally invasive radical surgery were included. After propensity score-matching, surgical outcomes were analyzed. Risk-factor of complications was analyzed in the whole cohort. RESULTS: After 1:1 propensity score-matching, 97 patients were included in each cohort. NAC + surgery cohort was younger (58.2 ± 10.3 vs. 61.3 ± 9.6, P = 0.036) with lower preoperative WBC count (5.7 ± 2.8 vs. 6.9 ± 2.1 × 109/ml) than the surgery upfront cohort. NAC was not a risk-factor for postoperative complications (odds ratio [OR], 0.859; 95% confidence interval [CI], 0.46-1.60; P = 0.633). Overall risk-factors of postoperative complications included age ≥ 60 years (OR, 21.338; 95% CI, 5.00-91.05; P < 0.001), tumor size ≥ 5 cm (OR, 1.24; 95% CI, 1.08-1.83; P < 0.001), operation time ≥ 240 min (OR, 5.53; 95% CI, 1.26-24.26; P = 0.012), and ASA classification ≥ II (OR, 13.14; 95% CI, 4.12-24.73; P < 0.001). CONCLUSIONS: NAC before minimally invasive radical gastrectomy with D2 lymphadenectomy does not increase postoperative complications, and these findings support broader application of NAC and MIS for AGC. Additional studies are required to determine the effect of NAC on long-term survival.

Disparate and Alarming Impact of Gastrointestinal Cancers in Young Adult Patients.

BACKGROUND: The rise in the incidence of gastric cancer (GC) and colorectal cancer (CRC) in young adults (YA) remains unexplained. We aim to identify differences in these malignancies between YA and older patients. PATIENTS AND METHODS: We retrospectively analyzed the California Cancer Registry for all GC and CRC cases from 2000 to 2012. Pearson's Chi square analysis and stepwise regression model with backward elimination were used to analyze differences in demographic, clinical, and histopathologic features, and log-rank test to compare survival between young (≤ 40 years) and older adults (41-90 years) with GC or CRC, separately. RESULTS: We analyzed 19,368 cases of GC and 117,415 cases of CRC. YA accounted for 4.6% of GC (n = 883) and 2.8% of CRC (n = 3273) patients. Compared with older patients, YA were more likely to be Hispanic (P < 0.0001) and have poorly differentiated (P < 0.0001), higher histologic grade (P < 0.0001), and signet ring features (P < 0.0001). Synchronous peritoneal metastases were more common in YA patients (32.1% vs. 14.1% GC, 8.8% vs. 5.4% CRC, P < 0.0001). The 5-year overall survival (OS) of YA with CRC or GC was longer than that of older patients with the same stage of malignancy; except YA with stage I GC, who demonstrated poor OS and disease-specific survival (DSS) (65.1% and 67.9%, respectively) which were significantly worse than those of adults aged 41-49 years (70.7% and 76.2%, respectively) and 50-64 years (69.1% and 78.1%, respectively). CONCLUSIONS: YA with GC or CRC have distinctly worse clinical and histopathologic features compared with older patients and are disproportionately of Hispanic ethnicity. These results contribute to improving understanding of younger versus older GI cancer patients.

Functional Impairments and Quality of Life in Older Adults With Upper Gastrointestinal Cancers.

BACKGROUND: Functional impairments (measured by activities of daily living [ADLs]) and health-related quality of life (HRQOL) may complicate outcomes in older adults diagnosed with cancer. In this retrospective cohort analysis, we characterized ADLs and HRQOL in adults older than 65 y with upper gastrointestinal (UGI) cancers and evaluated for an association to cancer-specific survival. MATERIALS AND METHODS: Patients with UGI cancers aged 65 y or older were selected from the Surveillance, Epidemiology and End Results and the Medicare Health Outcomes Survey-linked database. Demographics, comorbidities, stage, ADLs, and HRQOL were summarized by patients managed with and without surgery. Because of the wide variety of cancers, we subdivided patients into cohorts of esophagogastric [EG; n = 88] or hepatobiliary/pancreatic [n = 68]. Cancer-specific survival curves were modeled for changes in ADL and HRQOL scores after diagnosis. Risk factors for cancer-specific survival were assessed with hazard ratios (HRs) and adjusted for demographics, stage, comorbidities, and disease cohorts. RESULTS: HRQOL scores declined after diagnosis, with a sharper decline in nonsurgery patients. On multivariate analysis, inability to perform specific ADLs was associated with worse survival in multiple cohorts: hepatobiliary/pancreatic nonsurgery patients unable to eat (HR 3.3 95% confidence interval (CI) 1.7-6.5); all patients with EG unable to use the toilet (HR 3.3 95% CI 1.5-7.9); EG nonsurgery cohort unable to dress or use the toilet (dress HR 14.1 95% CI 4.0-49.0; toilet HR 4.7 95% CI 1.8-12.3). CONCLUSIONS: Older survivors with UGI cancers report declines in HRQOL, especially those not undergoing surgery. The ability to perform ADLs may be linked to survival in this population.

Trends and outcomes of robotic surgery for gastrointestinal (GI) cancers in the USA: maintaining perioperative and oncologic safety.

OBJECTIVE: Minimally invasive surgery (MIS) continues to gain traction as a feasible approach for the operative management of gastrointestinal (GI) malignancies. The aim of this study is to quantify national trends, perioperative and oncologic outcomes of MIS for the most common GI malignancies including the esophagus, stomach, pancreas, colon, and rectum. We hypothesize that with more widespread use of MIS techniques, perioperative outcomes and oncologic resection quality will remain preserved. METHODS: The National Cancer Database (2010-2014) was utilized to assess perioperative outcomes and pathologic quality of MIS (robotic and laparoscopic) compared to open, in patients who underwent resection for cancers of the esophagus, stomach, pancreas, colon, and rectum. Multilevel logistic regression models were constructed to identify independent factors associated with postoperative and long-term outcomes. RESULTS: Data from 11,023 esophageal, 30,664 gastric, 30,689 pancreas, 260,669 colon, and 52,239 rectal resections were analyzed. Although laparoscopy is the most prevalent MIS approach, the number of robotic resections increased nearly fourfold from 2010 to 2014 in all organ sites (increase by factor: esophagus: 3.8, stomach: 4.4, pancreas: 4.4, colon: 3.8 and rectum: 4). The number of laparoscopic resections increased at a slower rate (factor: 1.3-1.9), whereas the number of open resections decreased (factor: 0.67-0.77). Patients who underwent robotic-assisted resections were younger for stomach and colorectal resections and with lower Charlson Comorbidity Index across all sites. Patients who underwent robotic or laparoscopic resections had shorter hospitalizations, fewer readmissions (with the exception of rectal resections) and lower postoperative mortality at 90 days. Robotic-assisted resections had comparable negative margin resections and number of lymph nodes to laparoscopic and open resections across all sites. CONCLUSION: The utilization of robotic-assisted resections of GI cancers is rapidly increasing with more frequent use in younger and healthier patients. This study demonstrates that with the rising utilization of robotic-assisted resections, perioperative outcomes and oncologic safety have not been compromised.

Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models.

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers.

Robotic Versus Open Minor Liver Resections of the Posterosuperior Segments: A Multinational, Propensity Score-Matched Study.

BACKGROUND: Minor liver resections of posterosuperior segments (1, 4A, 7, 8) are challenging to perform laparoscopically and are mainly performed using an open approach. We determined the feasibility of robotic resections of posterosuperior segments and compared short-term outcomes with the open approach. METHODS: Data on open and robotic minor (≤ 3 segments) liver resections including the posterosuperior segments, performed between 2009 and 2016, were collected retrospectively from four hospitals. Robotic and open liver resections were compared, before and after propensity score matching. RESULTS: In total, 51 robotic and 145 open resections were included. After matching, 31 robotic resections were compared with 31 open resections. Median hospital stay was 4 days (interquartile range [IQR] 3-7) for the robotic group, versus 8 days (IQR 6-10) for the open group (p < 0.001). Median operative time was 222 min (IQR 164-505) for robotic cases versus 231 min (IQR 190-301) for open cases (p = 0.668). Median estimated blood loss was 200 mL (IQR 100-400) versus 300 mL (IQR 125-750), respectively (p = 0.212). In the robotic group, one patient (3%) had a major complication, versus three patients (10%) in the open group (p = 0.612). Readmissions were similar-10% in the robotic group versus 6% in the open group (p > 0.99). There was no mortality in either group. CONCLUSION: Minor robotic liver resections of the posterosuperior segments are safe and feasible and display a shorter length of stay than open resections in selected patients at expert centers.

Multi-institutional validation of the 8th AJCC TNM staging system for gastric cancer: Analysis of survival data from high-volume Eastern centers and the SEER database.

BACKGROUND: The clinical relevance and general applicability of the 8th American Joint Committee on Cancer TNM gastric cancer staging system vs the 7th version have not been examined using datasets from both the East and West. METHODS: Patients (n = 29 984) treated for gastric adenocarcinoma at two high-volume centers (Severance Hospital [SH] and Gangnam Severance Hospital [GSH]) in Korea and data from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival curves, the performance of tumor staging, and the homogeneity of modified subgroups were compared. RESULTS: Minute changes were noted in the stage IIB subgroup; most changes were noted in stage III. Applying the 8th staging system facilitated better prediction of survival than applying the 7th version for SH data according to the log-rank test, C-index, and AIC (8444.5 vs 9263.8, 0.796 vs 0.798, and 104152 vs 103909, respectively). Its performance was also superior for GSH and SEER data. In a subgroup analysis of stages IIB to IIIC in SH, GSH, and SEER data, the 8th staging system showed similar or more homogeneous survival for each sub-classification than the 7th version. CONCLUSION: Compared with the 7th gastric cancer staging system, the newer version more accurately predicted prognosis and stratified subgroups more homogeneously.

Robotic surgery trends in general surgical oncology from the National Inpatient Sample.

BACKGROUND: Robotic surgery is offered at most major medical institutions. The extent of its use within general surgical oncology, however, is poorly understood. We hypothesized that robotic surgery adoption in surgical oncology is increasing annually, that is occurring in all surgical sites, and all regions of the US. STUDY DESIGN: We identified patients with site-specific malignancies treated with surgical resection from the National Inpatient Sample 2010-2014 databases. Operations were considered robotic if any ICD-9-CM robotic procedure code was used. RESULTS: We identified 147,259 patients representing the following sites: esophageal (3%), stomach (5%), small bowel (5%), pancreas (7%), liver (5%), and colorectal (75%). Most operations were open (71%), followed by laparoscopic (26%), and robotic (3%). In 2010, only 1.1% of operations were robotic; over the 5-year study period, there was a 5.0-fold increase in robotic surgery, compared to 1.1-fold increase in laparoscopy and 1.2-fold decrease in open surgery (< 0.001). These trends were observed for all surgical sites and in all regions of the US, they were strongest for esophageal and colorectal operations, and in the Northeast. Adjusting for age and comorbidities, odds of having a robotic operation increased annually (5.6 times more likely by 2014), with similar length of stay (6.9 ± 6.5 vs 7.0 ± 6.5, p = 0.52) and rate of complications (OR 0.91, 95% CI 0.83-1.01, p = 0.08) compared to laparoscopy. CONCLUSIONS: Robotic surgery as a platform for minimally invasive surgery is increasing over time for oncologic operations. The growing use of robotic surgery will affect surgical oncology practice in the future, warranting further study of its impact on cost, outcomes, and surgical training.

Prophylactic Pancreatectomies Carry Prohibitive Mortality at Low-Volume Centers: A California Cancer Registry Study.

BACKGROUND: Pancreatectomy for malignancy is associated with improved outcomes when performed at high-volume centers. The goal of this study was to assess pancreatectomy outcomes for premalignant cystic lesions as a function of hospital volume. METHODS: The Healthcare Cost and Utilization Project (HCUP) was queried for all pancreatectomies performed in California from 2003 to 2011. Cases were stratified, separating benign versus malignant disease. Hospitals were categorized as low-volume (≤25 pancreatectomies/year; LV) or high-volume (>25; HV) centers. Perioperative morbidity, mortality, and length of stay were compared in HV vs. LV centers. RESULTS: There were 7554 pancreatectomies performed in 201 hospitals during the study period, where 5652 (75%) procedures were performed for malignancy, 338 (4%) for chronic pancreatitis, and 1564 (21%) for benign/premalignant cysts. The majority of pancreatectomies for cystic disease were performed at LV centers (65%). There were no significant differences in length of stay (7 vs. 8 days; p = 0.6) or 90-day readmission rates (12.8% vs. 12.9%; p = 1.0) in HV versus LV centers. However, there were higher surgical (46.2% LV vs. 41.1% HV, p = 0.05) and medical (13.3% LV vs. 9.2% HV; p = 0.017) complications at LV centers. Most importantly, there was a fourfold higher in-hospital mortality at LV centers (2.36% vs. 0.55%; p = 0.007). CONCLUSION: Pancreatic resection for benign lesions at HV hospitals is associated with significantly lower morbidity and mortality, suggesting that when feasible, patients should seek care at high-volume centers for these semi-elective surgeries.

Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer. METHODS: After chimerization and high-throughput screening, CF33 was chosen from 100 new chimeric orthopoxvirus isolates for its ability to kill pancreatic cancer cells. In vitro cytotoxicity was assayed in six pancreatic cancer cell lines. In vivo efficacy and toxicity were evaluated in PANC-1 and MIA PaCa-2 xenograft models. RESULTS: CF33 caused rapid killing of six pancreatic cancer cells lines in vitro, releasing damage-associated molecular patterns, and regression of PANC-1 injected and non-injected distant xenografts in vivo after a single low intratumoral dose of 103 plaque-forming units. Using luciferase imaging, CF33 was noted to preferentially replicate in tumors which corresponds to the low viral titers found in solid organs. CONCLUSION: The low dose of CF33 required to treat pancreatic cancer in this preclinical study may ease the manufacturing and dosing challenges currently facing oncolytic viral therapy.