The impact of minimally-invasive esophagectomy operative duration on post-operative outcomes.

Background: Esophagectomy, an esophageal cancer treatment mainstay, is a highly morbid procedure. Prolonged operative time, only partially predetermined by case complexity, may be uniquely harmful to minimally-invasive esophagectomy (MIE) patients for numerous reasons, including anastomotic leak, tenuous conduit perfusion and protracted single-lung ventilation, but the impact is unknown. This multi-center retrospective cohort study sought to characterize the relationship between MIE operative time and post-operative outcomes. Methods: We abstracted multi-center data on esophageal cancer patients who underwent MIE from 2010 to 2021. Predictor variables included age, sex, comorbidities, body mass index, prior cardiothoracic surgery, stage, and neoadjuvant therapy. Outcomes included complications, readmissions, and mortality. Association analysis evaluated the relationship between predictor variables and operative time. Multivariate logistic regression characterized the influence of potential predictor variables and operative time on post-operative outcomes. Subgroup analysis evaluated the association between MIE >4 h vs. ≤4 h and complications, readmissions and survival. Results: For the 297 esophageal cancer patients who underwent MIE between 2010 and 2021, the median operative duration was 4.8 h [IQR: 3.7-6.3]. For patients with anastomotic leak (5.1%) and 1-year mortality, operative duration was elevated above the median at 6.3 h [IQR: 4.8-8.6], p = 0.008) and 5.3 h [IQR: 4.4-6.8], p = 0.04), respectively. In multivariate logistic regression, each additional hour of operative time increased the odds of anastomotic leak and 1-year mortality by 39% and 19%, respectively. Conclusions: Esophageal cancer is a poor prognosis disease, even with optimal treatment. Operative efficiency, a modifiable surgical variable, may be an important target to improve MIE patient outcomes.

Tyrosine Kinase Inhibition Activates Intratumoral γδ T Cells in Gastrointestinal Stromal Tumor.

γδ T cells are a rare but potent subset of T cells with pleiotropic functions. They commonly reside within tumors but the response of γδ T cells to tyrosine kinase inhibition is unknown. To address this, we studied a genetically engineered mouse model of gastrointestinal stromal tumor (GIST) driven by oncogenic Kit signaling that responds to the Kit inhibitor imatinib. At baseline, γδ T cells were antitumoral, as blockade of either γδ T-cell receptor or IL17A increased tumor weight and decreased antitumor immunity. However, imatinib therapy further stimulated intratumoral γδ T cells, as determined by flow cytometry and single-cell RNA sequencing (scRNA-seq). Imatinib expanded a highly activated γδ T-cell subset with increased IL17A production and higher expression of immune checkpoints and cytolytic effector molecules. Consistent with the mouse model, γδ T cells produced IL17A in fresh human GIST specimens, and imatinib treatment increased γδ T-cell gene signatures, as measured by bulk tumor RNA-seq. Furthermore, tumor γδ T cells correlated with survival in patients with GIST. Our findings highlight the interplay between tumor cell oncogene signaling and antitumor immune responses and identify γδ T cells as targets for immunotherapy in GIST.

Adjuvant Immunotherapy in Curative Intent Esophageal Cancer Resection Patients: Real-World Experience within an Integrated Health System.

BACKGROUND: Adjuvant immunotherapy has been shown in clinical trials to prolong the survival of patients with esophageal cancer. We report our initial experience with immunotherapy within an integrated health system. METHODS: A retrospective cohort study was performed reviewing patients undergoing minimally invasive esophagectomy at our institution between 2017 and 2021. The immunotherapy cohort was assessed for completion of treatment, adverse effects, and disease progression, with emphasis on patients who received surgery in 2021 and their eligibility to receive nivolumab. RESULTS: There were 39 patients who received immunotherapy and 137 patients who did not. In logistic regression, immunotherapy was not found to have a statistically significant impact on 1-year overall survival after adjusting for age and receipt of adjuvant chemoradiation. Only seven patients out of 39 who received immunotherapy successfully completed treatment (18%), with the majority failing therapy due to disease progression or side effects. Of the 17 patients eligible for nivolumab, 13 patients received it (76.4%), and three patients completed a full course of treatment. CONCLUSIONS: Despite promising findings of adjuvant immunotherapy improving the survival of patients with esophageal cancer, real-life practice varies greatly from clinical trials. We found that the majority of patients were unable to complete immunotherapy regimens with no improvement in overall 1-year survival.

Survival of Elderly Patients Undergoing Pancreatoduodenectomy in an Integrated Health System.

INTRODUCTION: The purpose of this study is to examine pancreatoduodenectomy (PD) perioperative outcomes and consider how age may be related to overall survival in an integrated health system. MATERIALS AND METHODS: A retrospective review was performed of 309 patients who underwent PD between December 2008 and December 2019. Patients were divided into two groups: aged 75 y or less and more than 75 y, defined as senior surgical patients. Univariate and multivariable analyses of predictive clinicopathologic factors associated with overall survival at 5 y were performed. RESULTS: In both groups, the majority underwent PD for malignant disease. The proportion of senior surgical patients alive at 5 y was 33.3% compared to 53.6% of younger patients (P = 0.003). There were also statistically significant differences between the two groups with respect to body mass index, cancer antigen 19-9, Eastern Cooperative Oncology Group performance status, and Charlson comorbidity index. On multivariable analysis, disease type, cancer antigen 19-9, hemoglobin A1c, length of surgery, length of stay, Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status were found to be statistically significant factors for overall survival. Age was not significantly related to overall survival on multivariable logistic regression and when the analysis was limited to pancreatic cancer patients. CONCLUSIONS: Although the difference in overall survival between patients aged less than and more than 75 years was significant, age was not an independent risk factor for overall survival on multivariable analysis. Rather than a patient's chronological age, his/her physiologic age including medical comorbidities and functional status may be more correlated to overall survival.

Surgical Management of Germline Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and usually results from a sporadic mutation in KIT or, less frequently, platelet-derived growth factor alpha (PDGFRA). Rarely, a germline mutation in the KIT, PDGFRA, succinate dehydrogenase (SDH), or neurofibromatosis 1 (NF1) gene is responsible for GIST. These tumors are found in the stomach (PDGFRA and SDH), small bowel (NF1), or a combination of both (KIT). There is a need to improve care for these patients regarding genetic testing, screening, and surveillance. Since most GISTs due to a germline mutation do not respond to tyrosine kinase inhibitors, the role of surgery is critical, especially when considering germline gastric GIST. However, in contrast to the established recommendation for prophylactic total gastrectomy in cadherin 1 (CDH1) mutation carriers once they reach adulthood, there are no formal guidelines as to the timing or extent of surgical resection for patients who are either carriers of a germline GIST mutation causing gastric GIST or have already developed gastric GIST(s). Surgeons must balance treating what is often multicentric, yet initially indolent disease with the chance of cure and the complications associated with total gastrectomy. Here, we consider the major issues in performing surgery in patients with germline GIST and illustrate the principles with a previously unreported patient harboring a germline KIT 579 deletion.

Utilization and Outcomes of Observation for Spontaneous Pneumothorax at an Integrated Health System.

INTRODUCTION: Though limited, recent evidence supports observation rather than intervention for spontaneous pneumothorax management. We sought to compare the utilization and outcomes between observation and intervention for patients with primary and secondary spontaneous pneumothoraces. METHODS: A retrospective cohort study of all adults presenting to Kaiser Permanente Northern California emergency rooms with spontaneous pneumothorax from 2016 to 2020 was performed. Those with prior pneumothoraces, tension physiology, bilateral pneumothoraces, effusions, and prior thoracic procedures or surgery on the affected side were excluded. Groups included observation versus intervention. Baseline clinicodemographic variables and outcomes were compared. Treatment was considered successful if further interventions were not required for pneumothorax resolution. Wilcoxon rank-sum tests, chi-square tests, Fischer exact tests, and multivariable logistic regression models were performed. RESULTS: Of the 386 patients with primary spontaneous pneumothorax, age, race/ethnicity, body mass index, smoking status, and the Charlson comorbidity index were not different between treatment groups. Of 86 patients with secondary spontaneous pneumothorax, age, gender, and smoking status were not different between treatment groups. Among patients with primary pneumothoraces, 83 underwent observation while 303 underwent intervention. The success rate was 92.8% for observation and 60.4% for intervention (P < 0.0001). Among patients with secondary pneumothoraces, 15 underwent observation while 71 underwent intervention, with a successful rate of 73.3% for observation and 32.4% for intervention (P = 0.003). CONCLUSIONS: Given the high success rates for observation of both small and moderate primary and secondary pneumothoraces, observation should be considered for clinically stable patients. Observation may be the superior choice for decreasing morbidity and healthcare costs.

Pancreatic Adenosquamous Carcinoma: Experience Within an Integrated Health Care System.

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.

A Multicenter Virtual Multidisciplinary Sarcoma Case Conference Improves Outcome for a Rare Soft Tissue Sarcoma (Dermatofibrosarcoma Protuberans).

INTRODUCTION: The purpose of this study is to analyze the impact of a virtual multidisciplinary sarcoma case conference (VMSCC) on the outcomes of dermatofibrosarcoma protuberans (DFSP). METHODS: We compared margin status after surgery and disease-free survival (DFS) on two cohorts of patients with DFSP, one diagnosed from 2010 to 2015 and one from 2016 to 2020 (before and after virtual multidisciplinary sarcoma case conference (VMSCC) within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: There was no significant difference between the two cohorts on demographics, tumor location, type of surgery, receipt of radiation, receipt of imatinib, or size of tumor. However, the percent of patients with positive margin after final surgery and the percent of local recurrence were significantly different: 6.5% and 6.3% for the 2010-2015 cohort, and .8% and 0% for the 2016-2020 cohort, respectively. CONCLUSION: Our data suggest that the outcomes of DFSP improved significantly after the implementation of VMSCC.

Incidental paratracheal lymph node lung adenocarcinoma in a patient with goiter: a case report.

Background: Paratracheal lymph nodes can be sites of metastasis for a variety of malignancies, but these metastases are treated differently depending on the tissue of origin. We describe a patient who underwent combined thoracoscopic and cervical resection of a multinodular goiter who was found to have incidental lung adenocarcinoma in an adjacent paratracheal lymph node despite having no pulmonary nodules. Case Description: A 62-year-old male with longstanding substernal multinodular goiter presented to his primary care doctor with continued growth of his goiter. After repeatedly declining surgery, he became amenable to resection and underwent right video-assisted thoracoscopic and cervical approaches. An incidentally found separate large right paratracheal lymph node was also discovered and completely resected. Final pathology of the thyroid mass revealed hyperplastic thyroid nodules consistent with a benign goiter. However, the separate right paratracheal lymph node revealed a thyroid transcription factor 1-positive (TTF-1) specimen concerning for lung adenocarcinoma in the absence of pulmonary nodules on imaging. Conclusions: Noteworthy to this case is the minimally invasive thoracoscopic approach preventing the need for median sternotomy and preventing any increased morbidity for the patient's incidentally found TxN3M0 lung adenocarcinoma. The patient could have been spared resection of the lymph node given its pulmonary origin as the standard of care for stage IIIB non-small cell lung cancer is definitive chemoradiation and adjuvant immunotherapy.

Isolated adrenal metastasis for hepatocellular carcinoma: a case report and literature review.

Background: We report one of the few cases in the United States of an isolated contralateral adrenal gland metastasis found 2 years after resection of a primary right hepatic lobe hepatocellular carcinoma (HCC). Case Description: The patient is a 60-year-old male with chronic hepatitis B and C who was found on imaging to have a 5.5 cm mass in segment 7 of the liver. He underwent transarterial chemoembolization of the right hepatic artery while awaiting liver transplantation evaluation. After his mass decreased in size, the patient declined transplantation and pursued resection. He underwent partial hepatectomy with cholecystectomy with final pathology showing a 6.5 cm well differentiated HCC with no vascular invasion and clear margins. After completion of treatment for hepatitis B and C, his surveillance magnetic resonance imaging (MRI) 2 years later showed a 2 cm left adrenal nodule but no local recurrence. The patient declined resection and elected for serial short term interval imaging. His next MRI was 14 months later showing the left adrenal nodule had increased in size to 4 cm. He underwent a laparoscopic left adrenalectomy with final pathology consistent with metastatic HCC. Surveillance MRI 21 months after surgery showed no evidence of recurrent disease. Conclusions: In this report, we describe one of the rare cases in the United States of a patient with primary HCC who underwent liver resection and was subsequently found to have an isolated metachronous contralateral adrenal metastasis. This case highlights the need for further work in developing the optimal treatment of isolated extra-hepatic metastases and targeted systemic therapies.

Predicting early discharge and readmission following pancreaticoduodenectomy [S079].

INTRODUCTION: Implementing enhanced recovery after surgery (ERAS) protocols for major abdominal surgery has been shown to decrease length of stay (LOS) and postoperative complications, including mortality and readmission. Little is known to guide which patients undergoing pancreaticoduodenectomy (PD) should be eligible for ERAS protocols. METHODS AND PROCEDURES: A retrospective chart review of all PD performed from 2010 to 2018 within an integrated healthcare system was conducted. A predictive score that ranges from 0 to 4 was developed, with one point assigned to each of the following: obesity (BMI > 30), operating time > 400 min, estimated blood loss (EBL) > 400 mL, low- or high-risk pancreatic remnant (based on the presence of soft gland or small duct). Chi-squared tests and ANOVA were used to assess the relationship between this score and LOS, discharge before postoperative day 7, readmission, mortality, delayed gastric emptying (DGE), and pancreatic leak/fistula. RESULTS: 291 patients were identified. Mean length of stay was 8.5 days in those patients who scored 0 compared to 16.2 days for those who scored 4 (p = 0.001). 30% of patients who scored 0 were discharged before postoperative day 7 compared to 0% of those who scored 4 (p = 0.019). Readmission rates for patients who scored 0 and 4 were 12% and 33%, respectively (p = 0.017). Similarly, postoperative pancreatic fistula occurred in 2% versus 25% in these groups (p = 0.007). CONCLUSION: A simple scoring system using BMI, operating time, EBL, and pancreatic remnant quality can help risk-stratify postoperative PD patients. Those with lower scores could potentially be managed via an ERAS protocol. Patients with higher scores required longer hospitalizations, and adjunctive therapy such as medication and surgical technique to decrease risk of delayed gastric emptying and pancreatic fistula could be considered.

An Epidemic Within the Pandemic: The Rising Tide of Trauma During COVID-19.

BACKGROUND: In the age of COVID-19 and enforced social distancing, changes in patterns of trauma were observed but poorly understood. Our aim was to characterize traumatic injury mechanisms and acuities in 2020 and compare them with previous years at our level I trauma center. MATERIAL AND METHODS: Patients with trauma triaged in 2016 through 2020 from January to May were reviewed. Patient demographics, level of activation (1 versus 2), injury severity score, and mechanism of injury were collected. Data from 2016 through 2019 were combined, averaged by month, and compared with data from 2020 using chi-squared analysis. RESULTS: During the months of interest, 992 patients with trauma were triaged in 2020 and 4311 in 2016-2019. The numbers of penetrating and level I trauma activations in January-March of 2020 were similar to average numbers for the same months during 2016 through 2019. In April 2020, there was a significant increase in the incidence of penetrating trauma compared with the prior 4-year average (27% versus 16%, P < 0.002). Level I trauma activations in April 2020 also increased, rising from 17% in 2016 through 2019 to 32% in 2020 (P < 0.003). These findings persisted through May 2020 with similarly significant increases in penetrating and high-level trauma. CONCLUSIONS: In the months after the initial spread of COVID-19, there was a perceptible shift in patterns of trauma. The significant increase in penetrating and high-acuity trauma may implicate a change in population dynamics, demanding a need for thoughtful resource allocation at trauma centers nationwide in the context of a global pandemic.

Pancreatic Neuroendocrine Tumor: Rationale for Centralization in an Integrated Health Care System.

OBJECTIVES: Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival. METHODS: Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS). RESULTS: Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001). CONCLUSIONS: Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.

Outcomes following interventions to sustain body weight in esophageal cancer patients starting preoperative therapy: a retrospective cohort study.

BACKGROUND: To improve nutritional status and dysphagia, esophageal cancer patients starting neoadjuvant therapy in advance of curative-intent surgery may receive a jejunostomy tube (J-tube) or esophageal stent, or they may be managed without a feeding modality. We examined percent total weight loss (%TWL), reinterventions, and progression to surgery in relation to these options. METHODS: The retrospective cohort study included stage II-III esophageal cancer patients diagnosed during 2010-2017 who received J-tube, stent, or nutritional counseling only, without a procedure, when starting chemotherapy or combined modality chemoradiation. Data were obtained from the electronic medical record and chart review. We compared median %TWL between intervention groups and reinterventions using Chi-square and Kruskal-Wallis tests. RESULTS: Among the 366 patients, median %TWL reached a nadir at 120 days, when it was 7% for patients with no procedure (N=307), 4% for J-tube (N=39), and 16% for stent (N=20) (P=0.01). Individual case analysis revealed 72-80% of the patients in the three groups started chemotherapy or chemoradiation as neoadjuvant curative-intent therapy (P difference =0.79). In J-tube patients, the reasons for intervention was anticipation of weight loss in 49% and mitigation of actual weight loss in 15%, whereas 95% of stent patients received the stent for dysphagia (P<0.001). A complication of the procedure was recorded in 85% of stent patients and 74% of J-tube patients (P<0.001). Among those who received no procedure initially, 25% received one later, compared with 15% of J-tube patients and 70% of stent patients who received a second procedure (P<0.001). Progression to surgery was observed in 65% of patients with no procedure, 51% of patients with J-tube, and 40% of stent patients, P=0.28). CONCLUSIONS: For stage II-III esophageal cancer patients starting chemotherapy, this study gives evidence that stents were associated with significant %TWL and risk of reintervention. Although J-tube patients returned to baseline weight sooner than those with no procedure, they experienced complications from their J-tubes. For esophageal cancer patients undergoing curative-intent treatment and with acceptable levels of weight loss, no procedure at all may be superior to placing a J-tube in terms of complications, weight loss, and progression to curative-intent surgery.

Impact of Race, Insurance Status, and Primary Language on Presentation, Treatment, and Outcomes of Patients with Pancreatic Adenocarcinoma at a Safety-Net Hospital.

BACKGROUND: Social determinants of health impact the delivery of care and outcomes in patients with pancreatic cancer. We explored the relationship between social determinants of health and presentation, treatment, and outcomes of patients with pancreatic adenocarcinoma at an urban safety-net medical center. DESIGN: A single-institution retrospective chart review of patients with pancreatic adenocarcinoma was conducted. Demographic, tumor, and treatment characteristics were obtained. Median overall survival, stage-specific survival, receipt of curative operation, and receipt of perioperative therapy were analyzed. Chi-square tests were used for categorical variables. Survival was determined by the Kaplan-Meier method. RESULTS: We identified 240 patients with pancreatic adenocarcinoma treated between January 2006 and December 2017. Median age was 66 years, 51% were female, 48% were non-white, 22% were non-English-speaking, 16% were Hispanic, and 40% were Medicaid/uninsured. There were 74 (31%) patients with early-stage (I/II) disease. There were no statistically significant differences between race, primary language, or ethnicity and receipt of surgical therapy or receipt of perioperative therapy. Relatively more patients with private insurance (100%) received perioperative therapy compared with Medicaid/uninsured (64%) and Medicare-insured (50%) patients (p = 0.018). Nearly 30% of patients with operable disease either declined having an intervention or were found to be too frail to undergo surgical intervention. CONCLUSIONS: There were no statistically significant relationships between examined social determinants of health and use of operation or perioperative therapy. Patients treated at an urban safety-net hospital with a focus on vulnerable patient populations are able to provide outcomes similar to national averages. Additional exploration of factors affecting outcomes for pancreatic cancer in these patients will be important, as many centers absorb higher immigrant and indigent populations.