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Background: Surgical resection remains the mainstay of treatment for tumors of the gastroesophageal junction (GEJ). However, contemporary analyses of the Western experience for GEJ adenocarcinoma are sparsely reported., Methods: Patients with GEJ adenocarcinoma undergoing resection between 2012 and 2022 at a single institution were grouped based on Siewert subtype and analyzed. Pathologic and treatment related variables were assessed with relation to outcomes., Results: A total of 302 patients underwent resection: 161 (53.3%) with type I, 116 (38.4%) with type II, and 25 (8.3%) with type III tumors. Most patients received neoadjuvant therapy (86.4%); 86% of cases were performed in a minimally invasive fashion. Anastomotic leak occurred in 6.0% and 30-day mortality in only 0.7%. The rate of grade 3+ morbidity was lower for the last 5 years of the study than for the first 5 years (27.5% vs 49.3%, P < .001), as was median length of stay (7 vs 8 days, P < .001). There was a significantly greater number of signet ring type tumors among type III tumors (44.0%) than type I/II tumors (11.2/12.9%, P < .001). Otherwise, there was no difference in the distribution of pathologic features among Siewert subtypes. Notably, there was a significant difference in 3-year overall survival based on Siewert classification: type I 60.0%, type II 77.2%, and type III 86.3% (P = .011). Siewert type I remained independently associated with worse survival on multivariable analysis (hazard ratio, 4.5; P = .023)., Conclusions: In this large, single-institutional series, operative outcomes for patients with resected GEJ adenocarcinoma improved over time. On multivariable analysis, type I tumors were an independent predictor of poor survival., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST., Methods: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM., Results: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02)., Conclusions: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST., (© 2023 Wiley Periodicals LLC.)

Background: Utilization of minimally-invasive distal pancreatectomy (MIDP) for pancreatic adenocarcinoma has increased. While unplanned conversion to an open procedure during MIDP is associated with inferior short-term outcomes, the long-term consequences of conversion have not been adequately examined., Methods: Patients with pancreatic adenocarcinoma undergoing MIDP were selected from the National Cancer Database (2010-2015) and subdivided based on the occurrence of unplanned conversion. Post-operative outcomes and overall survival (OS) were examined. Conversion was additionally compared to a matched group of planned open resections., Results: Among 592 patients undergoing attempted MIDP, unplanned conversion occurred in 23.1%. Despite increased 90-day mortality among patients experiencing conversion, there was no difference in median OS between groups (25.0 vs 27.8 months, p = 0.095). For patients undergoing conversion, post-operative outcomes and long-term survival were similar when compared to a propensity-matched group of patients undergoing planned open resection. On multivariable analysis, treatment at an academic facility (OR 0.63) and a robotic approach (OR 0.50) were both significantly associated with completed MIDP., Conclusion: Despite inferior post-operative outcomes compared to successful MIDP, unplanned conversion did not result in significantly reduced long term survival. MIDP can be attempted selectively but treatment at experienced centers via a robotic approach should be considered., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Reported rates of subcarinal lymph node (LN) metastases for esophageal carcinoma vary from 20% to 25% and the relevance of subcarinal lymph node dissection (LND) for gastroesophageal junction (GEJ) adenocarcinoma is poorly defined. This study aimed to evaluate rates of subcarinal LN metastasis in GEJ carcinoma and determine their prognostic significance., Methods: Patients with GEJ adenocarcinoma undergoing robotic minimally invasive esophagectomy from 2019 to 2021 were retrospectively assessed within a prospectively maintained database. Baseline characteristics and outcomes were examined with attention to subcarinal LND and LN metastases., Results: Among 53 consecutive patients, the median age was 62, 83.0% were male, and all had Siewert type I/II tumors (49.1% and 50.9%, respectively). Most patients (79.2%) received neoadjuvant therapy. Three patients had subcarinal LN metastases (5.7%) and all had Siewert type I tumors. Two had clinical evidence of LN metastases preoperatively and all three additionally had non-subcarinal nodal disease. A greater proportion of patients with subcarinal LN disease had more advanced (T3) tumors compared to patients without subcarinal metastases (100.0% versus 26.0%; P = 0.025). No patient with subcarinal nodal metastases remained disease free at 3 y after surgery., Conclusions: In this consecutive series of patients with GEJ adenocarcinoma undergoing minimally invasive esophagectomy, subcarinal LN metastases were found only in patients with type I tumors and were noted in just 5.7% of patients, which is lower than historical controls. Subcarinal nodal disease was associated with more advanced primary tumors. Further study is warranted to determine the relevance of routine subcarinal LND, especially for type 2 tumors., (Copyright © 2023. Published by Elsevier Inc.)

Background: Gracilis flap reconstruction (GFR) following abdominoperineal resection (APR) or proctocolectomy (PC) can reduce pelvic wound complications but has not been adequately assessed in the setting of immunosuppression, fistulous disease, and neoadjuvant chemoradiation., Methods: Patients undergoing APR/PC with GFR were retrospectively analyzed with regard to perioperative characteristics, and morbidity was assessed., Results: Patients underwent GFR for rectal cancer ( n = 28), anal cancer ( n = 3), inflammatory bowel disease ( n = 13), or benign fistulizing disease ( n = 1). 22.2% were chronically immunosuppressed, and 66.7% underwent preoperative chemoradiation. Twenty (44.4%) patients had minor wound complications, all treated nonoperatively. Nine patients had major complications with 4 patients requiring reoperation. The 4 threatened flaps were unilateral, and all were salvaged. Donor site morbidity was minimal. Patients with major complications were older (56 vs. 71 years, P = .030), and less likely to have pelvic drains ( P = .018)., Conclusion: In high-risk perineal wounds, GFR offers durable reconstruction with acceptably low morbidity.

Background: Lymph node (LN) metastases are uncommon among gastrointestinal stromal tumors (GISTs), and their presence has not been utilized in disease prognostication. This study was designed to examine factors associated with GIST nodal metastases and their impact on survival., Patients and Methods: Patients undergoing surgical resection of GIST with nodal evaluation were selected from the National Cancer Database. Logistic regression was utilized to evaluate factors associated with LN metastases. Survival was assessed for patients with and without nodal involvement and Cox regression was used to evaluate the impact of LN metastases while adjusting for other prognostic factors., Results: Out of 5018 patients, 301 (6.0%) had LN involvement. Nodal metastases occurred most frequently among tumors of the stomach (49.5%), followed by the small bowel (43.2%), colorectum (6.0%), and esophagus (1.3%). On multivariable analysis, male sex (OR 1.34), high mitotic rate (OR 2.10), tumor size (OR 1.02), and a primary tumor located in the small bowel (OR 1.36) were all significantly associated with nodal metastases. LN metastases were significantly associated with decreased overall survival (OS) for tumors arising in the small bowel (log-rank p < 0.01) and the colorectum (log-rank p < 0.01). Within a multivariable model adjusting for established prognostic factors, LN metastases remained independently associated with decreased survival (HR 1.60, p < 0.001)., Conclusions: For GISTs, LN metastases occur more often in males and were associated with tumor size and mitotic activity. Nodal involvement is associated with decreased survival, independent of other well-established prognostic factors., (© 2022. Society of Surgical Oncology.)

Surgical wide resection is the mainstay of treatment of sarcomas, but the advent of multimodality therapy has improved outcomes and the rates of limb-sparing resection. Often, wounds are unable to be closed primarily and require plastic surgical reconstruction. Following adequate oncologic resection, reconstruction should focus on maintaining functional and esthetic outcomes with minimal postoperative complications. Reconstruction methods range from simple techniques such as skin grafting and local rotational flaps all the way to more complex procedures such as free flaps. The reconstructive surgeon is an integral member of the multidisciplinary team and should be actively involved in treatment planning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Data is scarce regarding the need for early re-amputation to a higher anatomic level. This study seeks to define outcomes and risk factors for re-amputation., Methods: Patients undergoing primary major lower extremity amputation were identified within the 2012-2016 ACS-NSQIP database. Demographics, outcomes, and peri-operative characteristics were compared, and multivariable logistic regression model was used to determine association with early re-amputation., Results: Over a 4-year period, 8306 below knee amputations and 6367 above knee amputations were identified. Thirty-day re-amputation occurred in 262 patients (1.8%) and was associated with increased length of stay (12.9 vs. 7.3 days, P < 0.001), higher rates of readmission (64.9% vs. 13.6%, P < 0.001), and overall complications (69.5% vs. 39.3%, P < 0.01). On multivariable analysis, advanced age (OR 1.02, CI 1.01-1.03), smoking (OR 1.75, CI 1.32-2.33), dialysis dependence (OR 1.67, CI 1.23-2.26), preoperative septic shock (OR 2.53, CI 1.29-4.97), and bleeding disorders (OR 1.72, CI 1.34-2.22) were associated with early re-amputation., Conclusions: Thirty-day re-amputation rates are low, but are associated with significant morbidity, prolonged hospitalization, and frequent readmissions., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To measure the survival among comparable neonates with CDH supported with and without ECLS., Summary of Background Data: Despite widespread use in the management of newborns with CDH, ECLS has not been consistently associated with improved survival., Methods: A retrospective cohort study was performed using ECLS-eligible CDH Study Group registry patients born between 2007 and 2019. The primary outcome was in-hospital mortality. Neonates who did and did not receive ECLS were matched based on variables affecting risk for the primary outcome. Iterative propensity score-matched, survival (Cox regression and Kaplan-Meier), and center effects analyses were performed to examine the association of ECLS use and mortality., Results: Of 5855 ECLS-eligible CDH patients, 1701 (29.1%) received ECLS. "High-risk" patients were best defined as those with a lowest achievable first-day arterial partial pressure of CO2 of ≥60 mm Hg. After propensity score matching, mortality was higher with ECLS (47.8% vs 21.8%, odds ratio 3.3, 95% confidence interval 2.7-4.0, hazard ratio 2.3, P < 0.0001). For the subgroup of high-risk patients, there was lower mortality observed with ECLS (64.2% vs 84.4%, odds ratio 0.33, 95% confidence interval 0.17-0.65, hazard ratio 0.33, P = 0.001). This survival advantage was persistent using multiple matching approaches. However, this ECLS survival advantage was found to occur primarily at high CDH volume centers that offer frequent ECLS for the high-risk subgroup., Conclusions: Use of ECLS is associated with excess mortality for low- and intermediate-risk neonates with CDH. It is associated with a significant survival advantage among high-risk infants, and this advantage is strongly influenced by center CDH volume and ECLS experience., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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

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

Background: Forefoot transmetatarsal amputation is performed commonly to achieve limb salvage, but transmetatarsal amputations have a high rate of failure, requiring more proximal amputations. Few contemporary studies have examined the incidence of major amputation (transtibial or transfemoral) after transmetatarsal amputation. The goal of this study is to determine risk factors and outcomes for a more proximal amputation after forefoot amputation., Methods: We queried the 2012 to 2016 database of the American College of Surgeons National Quality Improvement Program for patients undergoing a complete transmetatarsal amputation with wound closure by Current Procedural Terminology code. Patients requiring early (within 30 days) more proximal amputation after transmetatarsal amputation were compared with those who did not need further amputation. Characteristics of patients requiring more proximal amputation were examined, and a multivariable logistic regression model was created to identity risk factors for early more proximal amputation., Results: In the study, 1,582 transmetatarsal amputation were identified. Most patients were male (70%), white (59%), and diabetic (74%), with a median age of 63 years. More proximal amputation occurred in 4.2% of patients within the first 30 days postoperatively. This early failure was associated with greater hospital stays postoperatively (10 days vs 7 days), more wound complications (29% vs 11%), pneumonia (8% vs 2%), stroke (3% vs 0.1%), and overall complications (50% vs 28%; P ≤ .025 each). Although there was no difference in 30-day mortality (P = .27), there was a marked increase in unplanned readmission (59% vs 14%; P < .0001) for those undergoing reamputation. On multivariable analysis, preoperative systemic inflammatory response, sepsis, or septic shock (odds ratio 2.1; 95% confidence interval, 1.2-3.6) were independent predictors of more proximal amputation., Conclusion: Early below-knee or above-knee amputation early after transmetatarsal amputation leads to increased morbidity. Because patients with preoperative sepsis may be at increased risk of failure after transmetatarsal amputation, the level of amputation should be considered carefully in these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adrenocortical carcinoma (ACC) is a rare tumor and the role of lymph node dissection remains ill-defined. This study evaluates the effect of nodal examination on prognosis and survival in patients undergoing curative-intent resection of ACC., Methods: The National Cancer Database (2004-2015) was queried for patients undergoing margin-negative resection for ACC. Patients with distant metastases, neoadjuvant therapy, multivisceral resection and T4 tumors were excluded., Results: Among 897 patients, 147 (16.4%) had lymph nodes examined. Factors associated with lymph node examination included increasing tumor size (P < .001), extra-adrenal extension (P < .001), open operation (P < .001), and resection at an academic facility (P = .003). Lymph node metastasis was significantly associated with extra-adrenal tumor extension (P = .04). Lymph node harvest, regardless of the number of nodes examined, was not associated with a survival benefit. Median overall survival was incrementally worse with increasing number of positive lymph nodes (88.2 months for N0, 34.9 months for 1-3 positive nodes, and 15.6 months for ≥4 positive nodes, P < .001)., Conclusions: Lymph node harvest and lymph node metastasis were associated with more advanced tumors. Although nodal harvest did not offer a survival advantage, stratifying the nodal staging classification may provide important prognostic information., (© 2020 Wiley Periodicals LLC.)

Background: Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined., Methods: The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated., Results: Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005)., Conclusion: This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection., Competing Interests: Conflicts of interest None to declare., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Socioeconomic disparities in gastric cancer have been associated with differences in care and inferior outcomes. We evaluated the presentation, treatment, and survival for patients with gastric cancer (GC) in a metropolitan setting with a large African American population., Methods: Retrospective cohort analysis of patients with GC (2003-2018) across a multi-hospital system was performed. Associations between socioeconomic and clinicopathologic data with the presentation, treatment, and survival were examined., Results: Of 359 patients, 255 (71%) were African American and 104 (29%) Caucasian. African Americans were more likely to present at a younger age (64.0 vs 72.5, P < .001), have state-sponsored or no insurance (19.7% vs 6.9%, P = .02), reside within the lowest 2 quintiles for median income (67.4% vs 32.7%, P < .001), and have higher rates of Helicobacter pylori (14.9% vs 4.8%, P = .02). Receipt of multi-modality therapy was not impacted by race or insurance status. On multivariable analysis, only AJCC T class (HR 1.68) and node positivity (HR 2.43) remained significant predictors of disease-specific survival., Conclusion: Despite socioeconomic disparities, African Americans, and Caucasians with GC had similar treatment and outcomes. African Americans presented at a younger age with higher rates of H. pylori positivity, warranting further investigation into differences in risk factors and tumor biology., (© 2020 Wiley Periodicals, Inc.)

Background: Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT., Methods: A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed., Results: Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2)., Conclusions: Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.

Background: The "classic" CT appearance of pancreatic neuroendocrine tumors (PNETs) is a solid, hypervascular lesion; however, non-PNET diagnoses may appear similar. In addition, some PNETs have a "non-classic" appearance., Methods: Demographic, imaging, endoscopic ultrasound-fine needle aspiration (EUS/FNA) results, and pathology data were analyzed for patients who underwent pancreatectomy for suspected or confirmed diagnosis of PNET from our institutional database., Results: Forty-three patients with a hypervascular lesion on CT had pancreatectomy for a pre-operative diagnosis of PNET. Final pathology revealed PNET in 30 (70%) and non-PNET diagnoses in 13 (30%). EUS/FNA had a sensitivity of 82% for the pre-operative diagnosis of PNET in patients with "classic" CT. Of 13 non-PNET diagnoses, 7 were benign. Among a total of 41 patients with a final diagnosis of PNET, 11 (27%) had "non-classic" CT (5 hypodense solid lesions, 3 isodense solid lesions, and 3 cystic lesions). Among these patients, EUS/FNA had a sensitivity of 100% in diagnosing PNET., Conclusions: Consideration of non-PNET diagnoses is important for patients with hypervascular lesions on CT. Appropriate pre-operative evaluation will optimize treatment plans., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pancreatic cancer is a complex disease accounting for fibrotic tumors and an aggressive phenotype. Gemcitabine (GEM) is used as a standard therapy, which develops chemoresistance leading to poor patient outcome. We have recently developed a superparamagnetic iron oxide nanoparticle (SPION) formulation of curcumin (SP-CUR), which is a nontoxic, bioactive anti-inflammatory/anti-cancer agent for its enhanced delivery in tumors. In this study, we demonstrate that SP-CUR effectively delivers bioactive curcumin to pancreatic tumors, simultaneously enhances GEM uptake and its efficacy. Mechanistic revelations suggest that SP-CUR targets tumor microenvironment via suppression of sonic hedgehog (SHH) pathway and an oncogenic CXCR4/CXCL12 signaling axis that inhibits bidirectional tumor-stromal cells interaction. Increased GEM uptake was observed due to upregulation of the human nucleoside transporter genes (DCK, hCNT) and blocking ribonucleotide reductase subunits (RRM1/RRM2). Additionally, co-treatment of SP-CUR and GEM targets cancer stem cells by regulating pluripotency maintaining stemness factors (Nanog, Sox2, c-Myc and Oct-4), and restricting tumor sphere formation. In an orthotopic mouse model, an enhanced accumulation of SP-CUR was found in pancreas, which potentiated GEM to reduce tumor growth and metastasis. Analysis of tumor tissues suggest that the treatment inhibits tumor stroma (α-SMA, Desmin and Hyluronic Acid) and induces changes in cell stiffness, as measured via Atomic Force Microscopy. This was accompanied by alteration of key cellular proteins of SHH signaling such as SHH, Gli-1, Gli-2, Sufu, and NFĸB-65 as indicated by Immunoblotting and Immunohistochemistry. These results suggest that SP-CUR has a great potential for future clinical use in the management of pancreatic cancer., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival., Methods: A retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed., Results: The review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days)., Conclusion: Cytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.

Background: Intraductal papillary mucinous neoplasms (IPMN) are currently managed based on imaging characteristics and cyst fluid sampling. This study was designed to determine if MUC13, a glycoprotein aberrantly overexpressed in pancreatic adenocarcinoma, might aid in distinguishing high-risk lesions (high grade dysplasia/invasive disease) from low-grade lesions., Methods: MUC13 immunohistochemical staining was performed on surgically resected formalin-fixed tissue specimens from 49 IPMNs and 23 non-mucinous cysts. Membranous MUC13 expression was measured by H-score, which quantifies staining intensity and the percentage of cells involved (range 0-300)., Results: MUC13 expression was detected in all IPMNs and was significantly greater than in non-mucinous cysts (median 210 vs 40, p < 0.001). MUC13 expression was similar among main (n = 26), branch (n = 15), and mixed (n = 8) duct lesions (median 210, 200, 225, respectively). The highest expression was observed in tumors with intestinal and pancreatobiliary histologic features (both median 225) and the lowest in gastric type lesions (median 200). MUC13 expression was significantly greater in high-risk lesions (n = 21) compared to those with low-grade dysplasia (n = 28) (median 250 vs 195, p < 0.001)., Conclusion: MUC13 expression was significantly greater in high-risk IPMNs in this analysis. The preoperative assessment of MUC13 in cyst fluid samples warrants further investigation., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Laparoscopic liver resection (LLR) is increasingly utilized for patients with hepatocellular carcinoma (HCC). However, long-term outcomes for patients requiring conversion to an open procedure during LLR have not been examined., Methods: Patients undergoing attempted LLR for HCC were identified within the National Cancer Database. Patients undergoing successful LLR were compared with those who required unplanned conversion with regard to perioperative outcomes and overall survival (OS). Those experiencing conversion were further compared with patients who underwent planned open resection after propensity score matching., Results: Unplanned conversion occurred in 228 (18.0%) of 1270 patients undergoing LLR. Compared with successful LLR, conversion was associated with greater length of stay (6 vs. 4 days, p < 0.001), higher readmission rates (7.8% vs. 2.6%, p = 0.001), and reduced OS (55.1 vs. 67.6 months, p = 0.074). Unplanned conversion during major hepatectomy was associated with significantly worse OS (median 35.7 months) compared with successful major and minor LLR (median not reached and 67.6 months, respectively, p = 0.004). Compared with planned open resection, similar results were noted as conversion during major LLR was associated with worse OS (median 27.3 months) compared with open major hepatectomy (median not reached; p = 0.002). Unplanned conversion was independently associated with increased mortality (hazard ratio 1.38) after adjustment in a multivariable model. Tumor size was the strongest predictor of conversion on logistic regression analysis., Conclusions: Unplanned conversion during LLR for HCC is associated with inferior OS. This difference is most pronounced for major hepatectomy. LLR should be considered cautiously in patients with larger, more advanced tumors likely to require major resection.

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) offers a potential cure for peritoneal carcinomatosis (PC), whereas aborted cytoreduction is associated with a poor outcome. We evaluate factors associated with aborted CRS procedures., Methods: An IRB approved retrospective review was performed from 12/2011 to 2/2016. Clinicopathologic variables and outcomes are described., Results: Seventy-four patients underwent attempted CRS/HIPEC which was completed in 51 (69%) and aborted in 23 (31%). There was no difference in age, race, gender or prior treatment between groups. Patients who underwent aborted procedures had a higher peritoneal cancer index (PCI, 26.1±9.9 vs . 16.2±10.5, P=0.001). Overall survival (OS) was significantly improved for patients who underwent completed CRS/HIPEC (41.0±10.4 vs. 6.0±2.3 months, P<0.0001). Patients with an appendiceal and colorectal primary who underwent CRS/HIPEC had a significantly better outcome (median not reached vs. 6±5.4 months, P<0.0001, and 28.0±7.5 vs. 8.0±4.0 months, P<0.0001, respectively). Colorectal pathology (P=0.014) and PCI score (<0.0001) were independent predictors of aborted CRS procedures., Conclusions: One-third of patients with PC had significant disease which prevented successful completion of CRS/HIPEC. PCI and colorectal primary tumor pathology were associated with a greater likelihood of aborted CRS procedures., Competing Interests: Conflicts of Interest: This work was presented in part at the 11th Annual Regional Therapies Meeting, February 13–15, 2016, Phoenix, AZ, and the American College of Surgeons Clinical Congress, October 17–20, 2016, Washington, DC, USA.

Background: Minimally invasive pancreatic resection (MIPR) is being increasingly utilized. Outcomes for patients experiencing unplanned conversion to an open procedure during MIPR have been incompletely assessed. We sought to determine the short-term outcomes and factors associated with unplanned conversion during MIPR., Methods: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program pancreatectomy-targeted data set was conducted. Successful MIPR was compared with unplanned conversion. Propensity matching was used to separately compare unplanned conversion during MIPR with planned open pancreatectomy., Results: Unplanned conversion occurred in 24.6% of 350 attempted minimally invasive pancreatoduodenectomy (MIPD) and 19.6% of 1174 attempted minimally invasive distal pancreatectomy (MIDP). Conversion was associated with greater overall morbidity and 30-day mortality compared with successful MIPR for both MIPD and MIDP. After matching, unplanned conversion resulted in outcomes equivalent or inferior to open pancreatectomy. Factors significantly associated with unplanned conversion during MIPD included intermediate gland texture, vascular resection, hypertension, disseminated cancer, and chronic steroid use. For MIDP, male sex, hard gland texture, vascular resection, smoking, and recent weight loss were independently associated with conversion. A robotic approach was inversely associated with conversion for MIPD and MIDP., Conclusions: Unplanned conversion during MIPR is associated with greater morbidity and 30-day mortality. Conversion resulted in outcomes that, at best, mimicked those of open pancreatectomy. Several risk factors including the need for vascular resection are associated with unplanned conversion and should be acknowledged when planning an operative approach., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has improved outcomes for selected patients with peritoneal carcinomatosis and often requires ostomy creation. We examined the impact of ostomy creation in a newly established peritoneal malignancy program. A retrospective review was performed of CRS-HIPEC procedures from 2011 to 2016. Those who did and did not receive an ostomy were compared. Fifty-eight patients underwent CRS-HIPEC and an ostomy was created in 25.9 per cent. Median peritoneal cancer index (14 vs 16, P = 0.63) and multivisceral resection rates (87.9 vs 100.0%, P = 0.17) were similar between groups. Multivariable analysis revealed that bowel resection (OR 210.65, P = 0.02) was significantly associated with ostomy creation. Advanced age was noted to be inversely associated with stoma formation (OR 0.04, P = 0.04). Progression-free survival was significantly lower in the ostomy group (18 vs 23 months, P = 0.03). Those with an ostomy experienced prolonged length of stay (13.3 ± 7.4 vs 9.5 ± 3.7, P = 0.01). At follow-up, 6/10 temporary ostomies had undergone reversal and three patients experienced morbidity after reversal. Ostomy creation may occur during CRS-HIPEC and carries potential for morbidity. Ostomy creation may contribute to postoperative length of stay. Patients should be counseled preoperatively on the potential impact of ostomy placement during CRS-HIPEC.

Background and Objectives: Outcomes and recommendations regarding adjuvant therapy (AT) for stage I ampullary adenocarcinoma (AAC) are inadequately described. We sought to determine factors associated with survival and better define the impact of AT., Methods: The NCDB was queried for stage I AAC patients undergoing resection. We evaluated variables influencing the administration of AT and affecting survival, including the receipt of AT., Results: Five hundred thirty-seven patients were identified. 1, 3, and 5-year OS were 91.3%, 78.8%, and 67.4%, respectively. 103 received AT: 101 chemotherapy, 31 radiation, and 29 a combination of both. AT was more commonly utilized in patients with poorly differentiated and T2 tumors. Comorbid disease was inversely associated with use of AT. Age ≥65 was associated with decreased survival for stage IA and IB, while positive resection margins and sampling of <12 LNs were associated with decreased OS for stage IA and IB, respectively. After propensity matching key covariates, no significant difference in OS was observed between those receiving and not receiving AT (P = 0.449)., Conclusion: This analysis revealed a modest 5-year OS for stage I AAC. Age, positive resection margins, and evaluation of <12 LNs negatively influenced OS and AT did not convey a survival benefit., (© 2018 Wiley Periodicals, Inc.)

Background: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa., Methods: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses., Results: MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P < 0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC) samples (MCS = 9.7, P < 0.0001) as compared to low expression in tumor adjacent tissues (MCS = 4, P < 0.001) along with faint or no expression in normal pancreatic tissues (MCS = 0.8; AUC >0.8; P < 0.0001). Nuclear MUC13 expression positively correlated with nodal metastasis (P < 0.05), invasion of cancer to peripheral tissues (P < 0.5) and poor patient survival (P < 0.05; prognostic AUC = 0.9). Submicron scale mass density and artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival., Conclusion: This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Desmoplastic small round cell tumor (DSRCT) is a rare peritoneal surface malignancy. Current research is limited by the scarcity of this disease., Methods: Patients with DSRCT were identified in the 2004-2014 NCDB. Factors affecting overall survival (OS) were assessed. Additionally, trends were examined based on the volume of cases treated at individual facilities., Results: A total of 125 patients were identified with a median age of 21 (IQR 15-27). Six had extra-abdominal disease and 15 (12%) had liver involvement. Median OS was 28 months. Systemic chemotherapy (HR 0.4, P = 0.015) and surgery (HR 0.6, P = 0.047) were associated with reduced mortality. For the 74 patients undergoing surgery, absence of liver involvement and receipt of postoperative chemotherapy were associated with improved OS on univariate analysis. On multivariable analysis, two factors approached significance: adjuvant chemotherapy was associated with a reduced risk of mortality (HR 0.3, P = 0.073) and residual macroscopic disease after resection correlated with increased risk of mortality (HR 5.3, P = 0.071). High-volume facilities (≥5 cases) experienced improved OS (median 59.1 vs 28.8 months), albeit not significantly (P = 0.135), compared to low-volume centers., Conclusion: Despite multimodal treatment, DSRCT is associated with dismal outcomes. Facilities familiar with treating this uncommon disease may experience superior outcomes., (© 2018 Wiley Periodicals, Inc.)

Background: Minimally-invasive hepatectomy (MIH) is increasingly utilized; however, predictors and outcomes for patients requiring conversion to an open procedure have not been adequately studied., Methods: The 2014-15 ACS-NSQIP database was analyzed. Unplanned conversion was compared to successful MIH and elective open hepatectomy., Results: Among 6918 hepatectomies, 1062 (15.4%) underwent attempted MIH: 989 laparoscopic, 73 robotic. Conversion occurred in 203 (19.1%). Compared to successful MIH, patients requiring unplanned conversion experienced higher rates of complications (34.5% vs 14.6%, p<0.001), including bile leaks (7.4% vs 2.8%, p=0.002), organ space infection (6.4% vs 2.9%, p=0.016), UTI (4.9% vs 1.2%, p=0.002), perioperative bleeding (21.2% vs 6.1%, p<0.001), DVT (3.0% vs 0.8%, p=0.024), and sepsis (5.9% vs 1.9%, p=0.001). Conversion led to greater LOS (5 days vs 3 days, p<0.001) and 30-day mortality (3.0% vs 0.5%, p=0.005). Compared to elective open hepatectomy, conversion was associated with greater perioperative bleeding (21.2% vs 15.3%, p = 0.037). On multivariate analysis, major hepatectomy (OR 2.21, p<0.001), concurrent ablation (OR 1.79, p=0.020), and laparoscopic approach (vs. robotic) (OR 3.22, p=0.014) were associated with conversion., Conclusion: Analysis of this national database revealed unplanned conversion during MIH is associated with greater morbidity and mortality. MIH should be approached cautiously in patients requiring major hepatectomy., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Potentially curative treatment for gastrointestinal stromal tumors (GIST) involves resection with selective utilization of tyrosine kinase inhibitors. A potential association between obesity and GIST has been postulated as GIST is among the most common incidental findings during gastric resection for bariatric procedures. The purpose of this study is to investigate the relationship and impact of obesity on the pathologic and short-term outcomes in patients with GIST., Methods: We performed a retrospective review of patients with resected GIST. The impact of obesity, defined as body mass index (BMI) ≥30 kg/m 2 , on pathologic results and short-term outcomes was evaluated., Results: Sixty-one patients underwent resection with a median follow-up of 26 mo (1-129 mo). Disease involved the stomach (74%), small intestine (18%), or colon/rectum (5%). Median tumor size was 6 cm, and 13 patients (21%) underwent multivisceral resection. Median BMI for the cohort was 27.2 kg/m 2 , and 24 patients (39%) were classified as obese based on BMI. Nonobese patients were noted to have larger primary tumors (median: 7 cm versus 5 cm, P = 0.02) and undergo multivisceral resection more frequently (32.4% versus 4.2%, P < 0.01). Short-term outcomes were similar between the groups, with a slight trend toward more postoperative complications among the obese patients., Conclusions: In this study, obese patients tended to have more favorable pathologic features. GISTs may represent another example of the "obesity paradox" in which obesity seemingly provides a protective effect. Larger studies are warranted to verify the impact of obesity on outcomes and to elucidate any underlying clinicopathologic/biologic factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)