Dual Stromal Targeting Sensitizes Pancreatic Adenocarcinoma for Anti-Programmed Cell Death Protein 1 Therapy.

BACKGROUND & AIMS: The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms. METHODS: A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations. RESULTS: The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi leads to improved survival in PDAC-bearing mice treated with anti-PD-1 antibody. HA degradation in combination with FAKi and anti-PD-1 antibody increases T-cell infiltration and alters T-cell phenotype toward effector memory T cells. FAKi alters the expression of T-cell modulating cytokines and leads to changes in T-cell metabolism and increases in effector T-cell signatures. HA degradation in combination with anti-PD-1 antibody and FAKi treatments reduces granulocytes, including granulocytic- myeloid-derived suppressor cells and decreases C-X-C chemokine receptor type 4 (CXCR4)-expressing myeloid cells, particularly the CXCR4-expressing granulocytes. Anti-CXCR4 antibody combined with FAKi and anti-PD-1 antibody significantly decreases metastatic rates in the PDAC liver metastasis model. CONCLUSIONS: This represents the first preclinical study to identify synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma and supports testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.

Anatomic Criteria Determine Resectability in Locally Advanced Pancreatic Cancer.

BACKGROUND: The introduction of multi-agent chemotherapy and radiation therapy has facilitated potential resection with curative intent in selected locally advanced pancreatic cancer (LAPC) patients with excellent outcomes. Nevertheless, there remains a remarkable lack of consensus on the management of LAPC. We sought to describe the outcomes of patients with LAPC and objectively define the multidisciplinary selection process for operative exploration based on anatomical factors. METHODS: Consecutive patients with LAPC were evaluated for pancreatic surgery in the multidisciplinary clinic of a high-volume institution, between 2013 and 2018. Prospective stratification (LAPC-1, LAPC-2, and LAPC-3), based on the involvement of regional anatomical structures, was performed at the time of presentation prior to the initiation of treatment. Resection rates and patient outcomes were evaluated and correlated with the initial anatomic stratification system. RESULTS: Overall, 415 patients with LAPC were included in the study, of whom 84 (20%) were successfully resected, with a median overall survival of 35.3 months. The likelihood of operative exploration was associated with the pretreatment anatomic LAPC score, with a resection rate of 49% in patients classified as LAPC-1, 32% in LAPC-2, and 11% in LAPC-3 (p < 0.001). Resected patients with improvement of the LAPC score at the time of exploration had significantly longer median overall survival compared with those with no change or progression of LAPC score (60.7 vs. 29.8 months, p = 0.006). CONCLUSIONS: Selected patients with LAPC can undergo curative-intent surgery with excellent outcomes. The proposed Johns Hopkins anatomic LAPC score provides an objective system to anticipate the probability of eventual surgical resection after induction therapy.

Should non-invasive diffuse main-duct intraductal papillary mucinous neoplasms be treated with total pancreatectomy?

BACKGROUND: Main-duct (MD) intraductal papillary mucinous neoplasm (IPMN) is associated with malignancy risk. There is a lack of consensus on treatment (partial or total pancreatectomy) when the MD is diffusely involved. We sought to characterize the pancreatic remnant fate after partial pancreatectomy for non-invasive diffuse MD-IPMN. METHODS: Consecutive patients with partial pancreatectomy for non-invasive MD-IPMN from 2004 to 2016 were analyzed. Diffuse MD-IPMN was defined by preoperative imaging as dilation of the MD in the head of the pancreas more than 5 mm and involving the whole gland. RESULTS: Of 127 patients with resected non-invasive MD-IPMN, 47 (37%) had diffuse MD involvement. Eleven of 47(23%) patients developed imaging evidence of progression or new cystic disease in the pancreatic remnant. Patients with diffuse MD-IPMN were older (73yrs vs 67yrs, p = 0.009), more likely to receive a pancreaticoduodenectomy (96% vs 56%, p < 0.001) and have high-grade dysplasia (51% vs 31%, p = 0.025) than those with focal MD involvement. Diffuse MD involvement was not associated with shorter PFS following partial pancreatectomy (p = 0.613). CONCLUSION: Partial pancreatectomy is an appropriate surgical approach for diffuse MD-IPMN, and is not associated with earlier progression after surgery as compared to partial pancreatectomy for focal dilation.

Management of Locally Advanced Pancreatic Cancer: Results of an International Survey of Current Practice.

OBJECTIVE: The aim of this study was to investigate surgeon preferences for the management of patients with locally advanced pancreatic cancer (LAPC). BACKGROUND: Select patients with LAPC may become candidates for curative resection following neoadjuvant therapy, and recent reports of survival are encouraging. Yet the optimal management approach remains unclear. METHODS: An extensive electronic survey was systematically distributed by email to an international cohort of pancreas surgeons. Data collected included practice characteristics, management preferences, attitudes regarding contraindications to surgery, and 6 clinical vignettes of patients that ultimately received a margin negative resection (with detailed videos of post-neoadjuvant imaging) to assess propensity for surgical exploration if resection status is not known. RESULTS: A total of 153 eligible responses were received from 4 continents. Median duration of practice is 12 years (interquartile range 6-20) and 77% work in a university setting. Most surgeons (86%) are considered high volume (>10 resections/yr), 33% offer a minimally-invasive approach, and 50% offer arterial resections in select patients. Most (72%) always recommend neoadjuvant chemotherapy, and 65% prefer FOLFIRINOX. Preferences for the duration of chemotherapy varied widely: 39% prefer ≥2 months, 43% prefer ≥4 months, and 11% prefer ≥6 months. Forty-one percent frequently recommend neoadjuvant radiotherapy, and 53% prefer 5 to 6 weeks of chemoradiation. The proportion of surgeons favoring exploration following neoadjuvant varied extensively across 5 vignettes of LAPC, from 14% to 53%. In a vignette of oligometastatic liver metastases, 31% would offer exploration if a favorable therapy response is observed. CONCLUSIONS: In an international cohort of pancreas surgeons, there is substantial variation in management preferences, perceived contraindications to surgery, and the propensity to consider exploration in LAPC. These results emphasize the importance of a robust and nuanced multidisciplinary discussion for each patient, and suggest an evolving concept of "resectability."

Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.

OBJECTIVE: The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC). SUMMARY OF BACKGROUND DATA: A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients. METHODS: Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model. RESULTS: Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy. CONCLUSIONS: A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.

CT Radiomics-Based Preoperative Survival Prediction in Patients With Pancreatic Ductal Adenocarcinoma.

OBJECTIVE. Pancreatic ductal adenocarcinoma (PDAC) is often a lethal malignancy with limited preoperative predictors of long-term survival. The purpose of this study was to evaluate the prognostic utility of preoperative CT radiomics features in predicting postoperative survival of patients with PDAC. MATERIALS AND METHODS. A total of 153 patients with surgically resected PDAC who underwent preoperative CT between 2011 and 2017 were retrospectively identified. Demographic, clinical, and survival information was collected from the medical records. Survival time after the surgical resection was used to stratify patients into a low-risk group (survival time > 3 years) and a high-risk group (survival time < 1 year). The 3D volume of the whole pancreatic tumor and background pancreas were manually segmented. A total of 478 radiomics features were extracted from tumors and 11 extra features were computed from pancreas boundaries. The 10 most relevant features were selected by feature reduction. Survival analysis was performed on the basis of clinical parameters both with and without the addition of the selected features. Survival status and time were estimated by a random survival forest algorithm. Concordance index (C-index) was used to evaluate performance of the survival prediction model. RESULTS. The mean age of patients with PDAC was 67 ± 11 (SD) years. The mean tumor size was 3.31 ± 2.55 cm. The 10 most relevant radiomics features showed 82.2% accuracy in the classification of high-risk versus low-risk groups. The C-index of survival prediction with clinical parameters alone was 0.6785. The addition of CT radiomics features improved the C-index to 0.7414. CONCLUSION. Addition of CT radiomics features to standard clinical factors improves survival prediction in patients with PDAC.

Total Gastrectomy for CDH-1 Mutation Carriers: An Institutional Experience.

BACKGROUND: Gastric cancer is a leading cause of cancer-related death across the world. A subset of gastric cancers demonstrates an inherited genetic predisposition. Individuals with germline mutations in the CDH1 gene incur a lifetime risk for diffuse gastric cancer and benefit from prophylactic gastrectomy. The results for this operative intervention remain relatively undescribed in the literature, despite guidelines supporting its use. METHODS: We present a single-institution series of patients with confirmed CDH1 mutations who underwent gastrectomy. We describe their presenting symptoms, preoperative screening, clinicopathologic features, and outcomes. Focal outcomes of interest are weight loss and postoperative morbidity. RESULTS: Between 2010 and 2018, ten patients with a confirmed CDH1 mutation underwent total gastrectomy with intestinal pouch reconstruction at our institution. Two patients had clinical gastric cancer at the time of their operation at 21 and 60 y of age. Eight patients had prophylactic gastrectomy. All prophylactic patients had undergone prior endoscopic screening without detection of cancer; however, three had occult gastric cancer on pathological examination. Median weight loss after gastrectomy was 10 kg at 6 mo and 11 kg at 1 y. Postoperative morbidity was limited to one anastomotic leak, one hematoma, and one case of pneumonia. All patients remain disease-free with median follow-up of 19 mo. CONCLUSIONS: Total gastrectomy for patients with a CDH1 mutation is a cancer-preventing operation for a high-risk population. For this series, jejunal pouch reconstruction was performed with encouragingly low postoperative morbidity, weight loss, and good subjective function.

A Roadmap for Aspiring Surgeon-Scientists in Today's Healthcare Environment.

OBJECTIVE: Surgeon-scientists are an essential component of the field of academic surgery, contributing to the fundamental understanding of disease and the discovery of innovative therapies. Despite this recognized value, the current landscape of academic medicine presents significant barriers to establishing and maintaining a successful career as a surgeon performing basic/translational research. Our objective is to define these barriers to academic success for surgeons, and to provide a consensus strategy for optimizing the chances of success. SUMMARY BACKGROUND DATA: There is a significant decline in the proportion of academic surgeons who are pursuing basic science/translational research, which represents a potential threat to the very identify of the translational surgeon-scientist. METHODS: Based on published literature and expert opinion, the Basic Science Committee of the Society of University of Surgeons prepared this roadmap to encourage and guide the next generation of surgeon-scientists as they embark on their academic careers. RESULTS: This roadmap highlights key elements to consider in choosing an initial job and the importance of identifying a team of committed mentors. Expectations and guidelines for the first several years in practice are offered. CONCLUSIONS: With guidance and mentorship, aspiring surgeonscientists can overcome the challenges inherent in choosing this career path and sustain the important legacy of those before them.

Survival in Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy and Surgical Resection.

OBJECTIVE: The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient outcomes. BACKGROUND: An increasing number of LAPC patients who respond favorably to neoadjuvant therapy undergo surgical resection. The impact of surgery on patient survival is largely unknown. MATERIALS AND METHODS: All LAPC patients who presented to the institutional pancreatic multidisciplinary clinic (PMDC) from January 2013 to September 2017 were included in the study. Demographics and clinical data on neoadjuvant treatment and surgical resection were documented. Primary tumor resection rates after neoadjuvant therapy and overall survival (OS) were the primary study endpoints. RESULTS: A total of 415 LAPC patients were included in the study. Stratification of neoadjuvant therapy in FOLFIRINOX-based, gemcitabine-based, and combination of the two, and subsequent outcome comparison did not demonstrate significant differences in OS of 331 non-resected LAPC patients (P = 0.134). Eighty-four patients underwent resection of the primary tumor (20%), after a median duration of 5 months of neoadjuvant therapy. FOLFIRINOX-based therapy and stereotactic body radiation therapy correlated with increased probability of resection (P = 0.006). Resected patients had better performance status, smaller median tumor size (P = 0.029), and lower median CA19-9 values (P < 0.001) at PMDC. Patients who underwent surgical resection had significant higher median OS compared with those who did not (35.3 vs 16.3 mo, P < 0.001). The difference remained significant when non-resected patients were matched for time of neoadjuvant therapy (19.9 mo, P < 0.001). CONCLUSIONS: Surgical resection of LAPC after neoadjuvant therapy is feasible in a highly selected cohort of patients (20%) and is associated with significantly longer median overall survival.

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. SUMMARY BACKGROUND DATA: A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking. METHODS: Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models. RESULTS: Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. CONCLUSION: A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

Isolated pulmonary recurrence after resection of pancreatic cancer: the effect of patient factors and treatment modalities on survival.

BACKGROUND: The literature suggests favorable survival for patients with isolated pulmonary recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) as compared to other recurrence patterns. Within this cohort, it remains unclear what factors are associated with improved survival. METHODS: Patients who developed pulmonary recurrence after pancreatectomy were selected from a prospective database. Predictors for post-recurrence survival (PRS) were analyzed using a multivariable Cox regression model. RESULTS: Ninety-six patients were included. Median recurrence-free survival (RFS), PRS and overall survival (OS) were 16.3, 18.8 and 39.6 months, respectively. Further systemic treatment and/or metastasectomy (n = 64, 67%) was associated with significantly improved PRS and OS when compared to best supportive care (n = 35, 22%) (26.3 vs. 5.3 and 48.1 vs. 18.4, respectively; both P < 0.001). Patients who were able to undergo metastasectomy (n = 19) achieved a PRS and OS of 35.0 and 68.9 months, respectively. More than 5 pulmonary lesions, symptoms and CA 19-9 ≥100 U/mL at time of recurrence were predictive of decreased PRS. A recurrence-free interval of >16 months and treatment for recurrence were independently associated with improved PRS. CONCLUSIONS: Isolated pulmonary recurrence occurs in 13% of patients with recurrent PDAC and is associated with a median OS of 40 months. Aggressive treatment in highly selected patients was correlated with improved survival.

Is a Pathological Complete Response Following Neoadjuvant Chemoradiation Associated With Prolonged Survival in Patients With Pancreatic Cancer?

OBJECTIVES: To describe the survival outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) who have a pathologic complete response (pCR) following neoadjuvant chemoradiation. BACKGROUND: Patients with BR/LA-PDAC are often treated with neoadjuvant chemoradiation in an attempt to downstage the tumor. Uncommonly, a pCR may result. METHODS: A retrospective review of a prospectively maintained database was performed at a single institution. pCR was defined as no viable tumor identified in the pancreas or lymph nodes by pathology. A near complete response (nCR) was defined as a primary tumor less than 1 cm, without nodal metastasis. Overall survival (OS) and disease-free survival (DFS) were reported. RESULTS: One hundred eighty-six patients with BR/LA-PDAC underwent neoadjuvant chemoradiation and subsequent pancreatectomy. Nineteen patients (10%) had a pCR, 29 (16%) had an nCR, and the remaining 138 (74%) had a limited response. Median DFS was 26 months in patients with pCR, which was superior to nCR (12 months, P = 0.019) and limited response (12 months, P < 0.001). The median OS of nCR (27 months, P = 0.003) or limited response (26 months, P = 0.001) was less than that of pCR (more than 60 months). In multivariable analyses pCR was an independent prognostic factor for DFS (HR = 0.45; 0.22-0.93, P = 0.030) and OS (HR=0.41; 0.17-0.97, P = 0.044). Neoadjuvant FOLFIRINOX (HR=0.47; 0.26-0.87, P = 0.015) and negative lymph node status (HR=0.57; 0.36-0.90, P = 0.018) were also associated with improved survival. CONCLUSIONS: Patients with BR/LA-PDAC who had a pCR after neoadjuvant chemoradiation had a significantly prolonged survival compared with those who had nCR or a limited response.

Minimally Invasive Versus Open Primary Resection for Retroperitoneal Soft Tissue Sarcoma: A Propensity-Matched Study From the National Cancer Database.

BACKGROUND: Although well described for gastrointestinal and pelvic cancers, use of minimally invasive surgery (MIS) for the management of retroperitoneal soft tissue sarcoma (RPS) remains unknown. The current study aimed to describe patterns of MIS use and assess the association between MIS and clinical outcomes among patients undergoing surgery for RPS. METHODS: Patients undergoing a primary resection for RPS between 2010 and 2014 were identified using the National Cancer Database. Multivariable logistic and Cox proportional hazards models were used to assess the association between use of MIS and clinical outcomes. Sensitivity analysis was performed using propensity score-matching (PSM). RESULTS: This study identified 3844 patients who met the inclusion criteria. Of these patients, 89.3% (n = 3432) underwent an open surgery, whereas 10.7% (n = 412) underwent MIS. The patients undergoing MIS were more likely to present with smaller tumors (open vs MIS: median tumor size, 17 cm; interquartile range [IQR, 9.8-26.0] vs 10.5 cm [IQR, 6.5-18.0]) and to undergo surgery at community hospitals (26.8% vs 36.1%; both P < 0.001). Although MIS was associated with a shorter hospital length of stay [LOS] (median LOS, 6 days [IQR, 5-9 days] vs 4 days [IQR, 2-7]; P < 0.001), postoperative mortality and overall survival were comparable between the two treatment groups (all P > 0.05). These findings were confirmed using PSM. CONCLUSIONS: MIS was associated with a shorter LOS, however, postoperative mortality and overall survival were comparable by operative approach. Future research is required to evaluate the use of MIS for the management of RPS. Policies are required to ensure that patients receive care in accordance with best practices and recommended guidelines.

Implications of the Pattern of Disease Recurrence on Survival Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: After radical resection of pancreatic ductal adenocarcinoma (PDAC), approximately 80% of patients will develop disease recurrence. It remains unclear to what extent the location of recurrence carries prognostic significance. Additionally, stratifying the pattern of recurrence may lead to a deeper understanding of the heterogeneous biological behavior of PDAC. OBJECTIVE: The aim of this study was to characterize the relationship of recurrence patterns with survival in patients with resected PDAC. METHODS: This single-center cohort study included patients undergoing pancreatectomy at the Johns Hopkins Hospital between 2000 and 2013. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. Sites of first recurrence were stratified into five groups and survival outcomes were estimated using Kaplan-Meier curves. The association of specific recurrence locations with overall survival (OS) was analyzed using Cox proportional-hazards models with and without landmark analysis. RESULTS: Accurate follow-up data were available for 877 patients, 662 (75.5%) of whom had documented recurrence at last follow-up. Patients with multiple-site (n = 227, 4.7 months) or liver-only recurrence (n = 166, 7.2 months) had significantly worse median survival after recurrence when compared with lung- (n = 93) or local-only (n = 158) recurrence (15.4 and 9.7 months, respectively). On multivariable analysis, the unique recurrence patterns had variable predictive values for OS. Landmark analyses, with landmarks set at 12, 18, and 24 months, confirmed these findings. CONCLUSIONS: This study demonstrates that specific patterns of PDAC recurrence result in different survival outcomes. Furthermore, distinct first recurrence locations have unique independent predictive values for OS, which could help with prognostic stratification and decisions regarding treatment after the diagnosis of recurrence.

Resection of retroperitoneal sarcoma en-bloc with inferior vena cava: 20 year outcomes of a single institution.

BACKGROUND: Margin negative resection offers the best chance of long-term survival in retroperitoneal sarcoma (RPS). En-bloc resection of adjacent structures, including the inferior vena cava (IVC), is often required to achieve negative margins. We review our 20-year experience of en-bloc IVC and RPS resection. METHODS: Retrospective review of patients with RPS resection involving the IVC were matched 1:3 by age and histology to RPS without IVC resection. Prognostic factors for overall survival (OS) and disease free survival (DFS) were assessed. RESULTS: Thirty-two patients underwent RPS resection en-bloc with IVC. They were matched with 96 cases of RPS without IVC resection. Median OS of 59 months and DFS 18 months in IVC resection group was comparable to RPS resection without vascular involvement: median OS 65 months, DFS 18 months (P = 0.519, P = 0.604). On multivariate analyses, R2 margin (OS: HR = 6.52 [95%CI: 1.18-36.09], P = 0.032) was associated with inferior OS. R2 margin and increased number of organs resected (DFS: HR = 5.07, [1.15-22.27], P = 0.031, HR = 1.28 [1.01-1.62], P = 0.014) were associated with inferior DFS. Reconstructions included graft (n = 19, 59%), patch (n = 4, 13%), primary repair (n = 6, 19%), and ligation (n = 4, 13%). CONCLUSIONS: RPS resection en-bloc with IVC can achieve equivalent rates of DFS and OS to patients without vascular involvement.

Incidence and risk factors for abdominal occult metastatic disease in patients with pancreatic adenocarcinoma.

BACKGROUND: The incidence of occult metastatic disease (OMD) in pancreatic ductal adenocarcinoma (PDAC) and associated risk factors are largely unknown. METHODS: We identified all patients with PDAC, who had an aborted oncologic operation due to OMD within a 10-year period. The cases were matched to a cohort of resected PDAC patients on a 1:3 ratio, based on age and sex, for comparison of preoperative clinical characteristics and potential risk factors for OMD. RESULTS: In the studied period, 117 patients with OMD were identified in 1423 pancreatectomies performed for PDAC (8%). Liver metastases were the most common finding (79%) followed by peritoneal implants (16%). When compared with non-OMD cases, patients with OMD presented more often with abdominal pain (P < 0.001), and higher preoperative carbohydrate antigen 19-9 (CA 19-9) values ( P = 0.007). Additionally, indeterminate liver lesions on preoperative computed tomography (CT) were identified in 40% of OMD versus 17% of non-OMD patients ( P < 0.001). Multivariable analysis distinguished four independent predictors for OMD: indeterminate lesions on preoperative CT, tumor size > 30 mm, abdominal pain, and preoperative CA 19-9 > 192 U/mL. CONCLUSIONS: Occurrence of OMD in PDAC accounts for 8% of cases. Preoperative CA 19-9 > 192 U/mL, primary tumor size > 30 mm, and identification of indeterminate lesions in preoperative CT may indicate the need for diagnostic laparoscopy.

Emergency department utilization and predictors of mortality for inpatient inguinal hernia repairs.

BACKGROUND: Although inguinal hernias are common surgical diagnoses, minimally symptomatic patients are often not scheduled for repairs and are asked to seek medical attention if they develop symptoms. We investigated factors associated with emergency department (ED) utilization for inguinal hernia repairs and determined whether ED utilization affected mortality for this otherwise electively treated condition. METHODS: We performed a retrospective analysis of the 2009-2013 Nationwide Inpatient Sample to identify patients who presented through the ED and were then admitted for unilateral inguinal hernia repairs. Multivariable logistic regressions that adjusted for several patient and hospital characteristics determined predictors of both ED admission and postoperative mortality. RESULTS: There were 116,357 inpatient hospitalizations. The majority (57%) resulted from ED admissions, of which most (85%) had a diagnosis of obstruction or gangrene. Notable predictors of ED admission from the multivariable analysis included obstruction (odds ratio, 9.77 [95% confidence interval: 9.05-10.55]), gangrene (18.24 [13.00-25.59]), Black race (1.47 [1.29-1.69]), Hispanic ethnicity (1.35 [1.18-1.54]), self-pay (2.29 [1.97-2.66]) and Medicaid insurance (1.76 [1.50-2.06]). While overall mortality decreased from 2.03% in 2009 to 1.36% in 2013, admission through the ED was independently associated with higher mortality compared with elective repair (1.67 [1.21-2.29]), even after adjusting for the diagnosis of obstruction and gangrene. Other predictors of mortality included patient age and comorbidities. CONCLUSIONS: In our study, Black, Hispanic, and self-pay patients were more likely to present through the ED. After adjusting for obstruction or gangrene, simply presenting through the ED was independently associated with a 67% higher postoperative mortality rate compared with that of an elective operation. Our findings suggest both a difference in ED utilization and subsequent difference in mortality by patient race and ethnicity and insurance for this common surgical condition.

Long-term survival after resection of sarcomatoid carcinoma of the pancreas: an updated experience.

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) is a rare histologic subtype of undifferentiated pancreatic carcinoma. Historically, this has been associated with a worse overall prognosis than adenocarcinoma. However, the clinical course and surgical outcomes of SCP remain poorly characterized owing to its rarity. METHODS: A single-institution, prospectively maintained database was queried for patients who underwent pancreatic resection with a final diagnosis of SCP. We describe their histology, clinicopathologic features, and perioperative outcomes. Survival data are highlighted, and common traits of long-term survivors are examined. RESULTS: Over a 25-year period, 7009 patents underwent pancreatic resection at our institution. Eight (0.11%) were diagnosed with SCP on final histopathology. R0 resection was achieved in six patients (75%). Four patients had early recurrence leading to death (<3 months). Two (25%) experienced long-term survival (>5 years), with the longest surviving nearly 16 years despite the presence of lymph node metastasis. There were no deaths attributed to perioperative complications. Both long-term survivors had disease in the body/tail of the pancreas and received adjuvant radiotherapy. One also received adjuvant gemcitabine-based chemotherapy. CONCLUSIONS: SCP is a rarely appreciated subset of pancreatic malignancy that does not necessarily portend to a uniformly dismal prognosis. Although some have rapid recurrence and an early demise, long-term survival may be possible. Future studies are needed to better define the cohort with potential for long-term survival so that aggressive therapies may be tailored appropriately in this patient subset.

A unifying theory of tonsillitis, intratonsillar abscess and peritonsillar abscess.

We review existing models of the pathogenesis of peritonsillar abscess (PTA) and intra-tonsillar abscess (ITA) and present a novel pathophysiologic model based upon observed histopathology in 2 ITAs and 10 PTAs and acute tonsillitis cases. ITA is rare, and prevailing models are only able to account for a minority of cases. The tonsillar lymphatic ultrastucture and the rapid nature of intratonsillar lymphatic transit, offer the framework for a unifying model of the development and progression of tonsillitis, PTA and ITA.