Phase 2 study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma.

BACKGROUND: Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins. METHODS: A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. RESULTS: Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. CONCLUSION: Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer.

Socioeconomic and Geographic Disparities in the Referral and Treatment of Pancreatic Cancer at High-Volume Centers.

Importance: Treatment at high-volume centers (HVCs) has been associated with improved overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC); however, it is unclear how patterns of referral affect these findings. Objective: To understand the relative contributions of treatment site and selection bias in driving differences in outcomes in patients with PDAC and to characterize socioeconomic factors associated with referral to HVCs. Design, Setting, Participants: A population-based retrospective review of the Oregon State Cancer Registry was performed from 1997 to 2019 with a median 4.3 months of follow-up. Study participants were all patients diagnosed with PDAC in Oregon from 1997 to 2018 (n = 8026). Exposures: The primary exposures studied were diagnosis and treatment at HVCs (20 or more pancreatectomies for PDAC per year), low-volume centers ([LVCs] less than 20 per year), or both. Main Outcomes and Measures: OS and treatment patterns (eg, receipt of chemotherapy and primary site surgery) were evaluated with Kaplan-Meier analysis and logistic regression, respectively. Results: Eight thousand twenty-six patients (male, 4142 [52%]; mean age, 71 years) were identified (n = 3419 locoregional, n = 4607 metastatic). Patients receiving first-course treatment at a combination of HVCs and LVCs demonstrated improved median OS for locoregional and metastatic disease (16.6 [95% CI, 15.3-17.9] and 6.1 [95% CI, 4.9-7.3] months, respectively) vs patients receiving HVC only (11.5 [95% CI, 10.7-12.3] and 3.9 [95% CI, 3.5-4.3] months, respectively) or LVC-only treatment (8.2 [95% CI, 7.7-8.7] and 2.1 [95% CI, 1.9-2.3] months, respectively; all P < .001). No differences existed in disease burden by volume status of diagnosing institution. When stratifying by site of diagnosis, HVC-associated improvements in median OS were smaller (locoregional: 10.4 [95% CI, 9.5-11.2] vs 9.9 [95% CI, 9.4-10.4] months; P = .03; metastatic: 3.6 vs 2.7 months, P < .001) than when stratifying by the volume status of treating centers, indicating selection bias during referral. A total of 94% (n = 1103) of patients diagnosed at an HVC received HVC treatment vs 18% (n = 985) of LVC diagnoses. Among patients diagnosed at LVCs, later year of diagnosis and higher estimated income were independently associated with higher odds of subsequent HVC treatment, while older age, metastatic disease, and farther distance from HVC were independently associated with lower odds. Conclusions and Relevance: LVC-to-HVC referrals for PDAC experienced improved OS vs HVC- or LVC-only care. While disease-related features prompting referral may partially account for this finding, socioeconomic and geographic disparities in referral worsen OS for disadvantaged patients. Measures to improve access to HVCs are encouraged.

Complications in Distal Pancreatectomy versus Radical Antegrade Modular Pancreatosplenectomy: A Disease Risk Score Analysis Utilizing National Surgical Quality Improvement Project Data.

INTRODUCTION: Radical antegrade modular pancreatosplenectomy (RAMPS) was developed to improve R0 resections and lymph node harvests versus distal pancreatectomy (DP) in pancreatic adenocarcinoma (PDAC); relative complication rates are understudied. METHODS: Patients undergoing distal pancreas resections from 2006 to 2020 were identified from our institutional NSQIP database, grouped by resection method, and evaluated for the following outcomes: postoperative pancreatic fistula (POPF), clinically relevant POPF (crPOPF), incisional surgical site infection (iSSI), organ space SSI (osSSI), and Clavien-Dindo grade ≥ 3 (CD ≥ 3) complications using logistic regression. Patients were matched 1:1 based on disease risk score. RESULTS: Two-hundred-thirty-six and 117 patients underwent DP and RAMPS, respectively. POPF, crPOPF, CD ≥ 3 complications, iSSI, and osSSIs occurred in 105 (30%), 43 (12%), 74 (21%), 34 (10%) and 52 (15%) patients, respectively. Disease risk score matching yielded 89 similar patients per group. On multivariable analysis, patients undergoing RAMPS were not significantly more likely to experience POPF (OR 0.69, P = 0.26), crPOPF (OR 0.41, P = 0.72), CD ≥ 3 complication (OR 0.78, P = 0.44), iSSI (OR 0.58, P = 0.27), or osSSI (OR 0.93, P = 0.86). Of patients with PDAC (n = 108) mean nodal harvest were 14.8 (SD 11.30) and 19.4 (SD 7.19) nodes for patients undergoing DP and RAMPS, respectively (P = 0.01). Six patients (20%) undergoing DP had positive margins versus 12 (15%) undergoing RAMPS (P = 0.56). At a median follow-up of 17 months, there was no difference in locoregional recurrence-free survival (P = 0.32) or overall survival (P = 0.92) on Kaplan-Meier analysis. CONCLUSION: RAMPS does not result in increased complications compared to DP and routine use is encouraged in pancreatic malignancies.

Similar Outcomes in Minimally Invasive versus Open Management of Primary Pancreatic Neuroendocrine Tumors: A Regional, Multi-Institutional Collaborative Analysis.

In pancreatic neuroendocrine tumors (PNETs), the impact of minimally invasive (MI) versus open resection on outcomes remains poorly studied. We queried a multi-institutional pancreatic cancer registry for patients with resected non-metastatic PNET from 1996−2020. Recurrence-free (RFS), disease-specific survival (DSS), and operative complications were evaluated. Two hundred and eighty-two patients were identified. Operations were open in 139 (49%) and MI in 143 (51%). Pancreaticoduodenectomy was performed in 77 (27%, n = 23 MI), distal pancreatectomy in 184 (65%, n = 109 MI), enucleation in 13 (5%), and total pancreatectomy in eight (3%). Median follow-up was 50 months. Thirty-six recurrences and 13 deaths from recurrent disease yielded 5-year RFS and DSS of 85% and 95%, respectively. On multivariable analysis, grade 1 (HR 0.07, p < 0.001) and grade 2 (HR 0.20, p = 0.002) tumors were associated with improved RFS, while T3/T4 tumors were associated with worse RFS (OR 2.78, p = 0.04). MI resection was not associated with RFS (HR 0.53, p = 0.14). There was insufficient mortality to evaluate DSS with multivariable analysis. Of 159 patients with available NSQIP data, incisional surgical site infections (SSIs), organ space SSIs, Grade B/C pancreatic fistulas, reoperations, and need for percutaneous drainage did not differ by operative approach (all p > 0.2). Nodal harvest was similar for MI versus open distal pancreatectomies (p = 0.16) and pancreaticoduodenectomies (p = 0.28). Minimally invasive surgical management of PNETs is equivalent for oncologic and postoperative outcomes.

Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications.

The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection.

Risk factors for postoperative pancreatic fistula in the Era of pasireotide.

INTRODUCTION: Postoperative pancreatic fistulas (POPFs) remain common; POPFs frequently require intervention, termed clinically-relevant POPFs (crPOPFs). Pasireotide is increasingly used to prevent POPF, however, risk factors for POPF in this population remain unexplored. METHODS: Patients undergoing pancreatectomy with perioperative pasireotide from 2013 to 2020 were identified from our institutional National Surgical Quality Improvement Project database. Logistic regression was utilized to identify risk factors associated with POPF. RESULTS: One-hundred patients were identified; 26 (26%) underwent distal pancreatectomy with the remainder undergoing pancreaticoduodenectomy. Thirty (30%) experienced POPF, with 21 crPOPFs. Only current smoking was significantly associated with crPOPF (OR 3.79, p = 0.04). Of 30 patients with a firm gland, none experienced crPOPF. Twenty-five received a partial course of pasireotide; 7/25 (28%) crPOPFs occurred versus 14/75 (19%) in patients receiving a full course (p = 0.38). CONCLUSION: Shortened courses of pasireotide do not increase crPOPF risk; selective discontinuation may be suitable in low-risk patients. Smoking cessation should be encouraged.

Intensive care unit observation after pancreatectomy: Treating the patient or the surgeon?

BACKGROUND: Routine intensive care unit admission (ICUA) is commonplace following pancreatectomy, particularly pancreaticoduodenectomy. The value of this practice in avoiding failure-to-rescue is poorly studied. METHODS: We queried our institutional National Surgical Quality Improvement Project database for patients undergoing pancreatectomy from 2013 to 2020. Postoperative dispositions, ICU courses, and hospital cost data in United States Dollars (USD) were captured. Data were analyzed with multivariable logistic regression. RESULTS: Six-hundred-thirty-seven patients were identified; 404 (63%) underwent pancreaticoduodenectomy. Postoperatively, 398 (99%) pancreaticoduodenectomies and 110 (47%) distal pancreatectomies had ICUA; two-thirds (n = 318, 63%) did not require immediate postoperative ICU-level interventions at ICUA. Of these, 17 (5.3%) subsequently required ICU-level interventions during initial ICUA, most commonly antiarrhythmic infusion (n = 12). Thirty-day and 90-day mortality in patients requiring immediate ICU-level interventions was 5% (n = 10) and 8% (n = 16) versus 0.3% (n = 1) and 1.2% (n = 4) in those without, respectively. Hospital length of stay was significantly longer with initial ICU-level interventions (median 11 vs. 9 days, p < 0.001), as were total ICU costs (mean 8683 vs. 14611 USD, p < 0.001). CONCLUSION: At high-volume pancreas centers, patients without immediate postoperative ICU-level interventions are very low risk for failure-to-rescue. Ward admission with a low threshold for care escalation presents a significant opportunity for cost-savings and un-burdening ICUs.

Intraoperative Bile Culture in Pancreaticoduodenectomy: Teaching Old Dogma New Tricks.

INTRODUCTION: Biliary stents increase surgical site infections (SSIs) following pancreaticoduodenectomy due to bactibilia and contaminated intraoperative bile spillage. Intraoperative bile culture (IOBC) is performed to guide empiric therapy for SSIs; however, its utility is poorly studied. We sought to evaluate IOBC and the interplay between stenting, bactibilia, and SSI following pancreaticoduodenectomy. METHODS: Patients undergoing pancreaticoduodenectomy from January 2008 to April 2020 were identified through our institutional National Surgical Quality Improvement Project (NSQIP) database; patients without IOBC were excluded. Odds of SSI were analyzed with multivariable logistic regression. RESULTS: Four-hundred-eighty-three patients were identified. One-hundred-eighty-nine (39%) patients had plastic stents and 154 (32%) had metal stents. Three-hundred-twenty-nine (96%) patients with stents had bactibilia versus 18 (13%) without stents (P < 0.001). The biliary microbiome and antibiotic resistance patterns in patients with metal and plastic stents were nearly identical. Of 159 NSQIP-defined SSIs, most were incisional (n = 92, 58%). Bactibilia and stent presence were associated with incisional (OR 3.69 and 3.39, both P < 0.001) but not organ space SSI (P > 0.1); however, stent type was not (P > 0.5). Of the 73 speciated SSI cultures, an IOBC-identified organism was present in 42 (58%), while at least one organism not found in the IOBC was present in 49 (67%). CONCLUSION: Bactibilia is associated with incisional but not organ space SSI following pancreaticoduodenectomy and is strongly associated with stent presence. Stent type does not independently influence the biliary microbiome or SSI risk. IOBC has a poor ability to predict causative organisms in SSIs following pancreaticoduodenectomy and is not recommended for routine use.

Appendiceal cancer masked as inflammatory appendicitis in the elderly, not an uncommon presentation (Surveillance Epidemiology and End Results (SEER)-Medicare Analysis).

BACKGROUND: The misdiagnosis of appendiceal cancer as inflammatory appendicitis is becoming of greater clinical concern because of the rise of nonoperative management especially in the elder population. To quantify this rate of misdiagnosis, we retrospectively reviewed SEER-Medicare data. METHODS: The SEER-Medicare database was reviewed from 2000 to 2014. We identified patients older than 65 years old who were diagnosed with appendiceal cancer and then cross-referenced them for a diagnosis of inflammatory appendicitis. Demographic data and oncologic stage were collected. RESULTS: Our results showed that 28.6% of appendiceal cancer patients received an incorrect initial diagnosis of inflammatory appendicitis. Patients older than 75 years of age were more likely to be misdiagnosed than those between ages 65 and 75 (risk ratio [RR]: 0.81; 95% confidence interval: 0.70-0.93; P = .003). We found that 42% of patients within the misdiagnosis group presented with an earlier stage of disease (stage 1 or 2) compared to 26% of those primarily diagnosed with appendiceal cancer (P < .001). CONCLUSION: A significant proportion of patients older than 65 years old with appendiceal cancer were initially misdiagnosed with acute appendicitis. We suggest caution when considering a nonoperative approach for appendicitis in the elderly and follow-up imaging or an interval appendectomy should be part of the treatment plan.

Cyclin-Dependent Kinase-9 Is a Therapeutic Target in MYC-Expressing Diffuse Large B-Cell Lymphoma.

Deregulation of the MYC transcription factor is a key driver in lymphomagenesis. MYC induces global changes in gene expression that contribute to cell growth, proliferation, and oncogenesis by stimulating the activity of RNA polymerases. A key feature in its ability to stimulate RNA Pol II activity is recruitment of pTEFb, an elongation factor whose catalytic core comprises CDK9/cyclin T complexes. Hence, MYC expression and function may be susceptible to CDK9 inhibition. We conducted a pre-clinical assessment of AZ5576, a selective CDK9 inhibitor, in diffuse large B-cell lymphoma (DLBCL). The in vitro and in vivo effects of AZ5576 on apoptosis, cell cycle, Mcl-1, and MYC expression were assessed by flow cytometry, immunoblotting, qPCR and RNA-Seq. We demonstrate that, in addition to depleting Mcl-1, targeting CDK9 disrupts MYC oncogenic function. Treatment with AZ5576 inhibited growth of DLBCL cell lines in vitro and in vivo, independent of cell-of-origin. CDK9 inhibition downregulated Mcl-1 and MYC mRNA transcript and protein in a dose-dependent manner. MYC-expressing cell lines demonstrated enhanced susceptibility to AZ5576. CDK9 inhibition promoted turnover of MYC protein, and decreased MYC phosphorylation at the stabilizing Ser62 residue and downregulated MYC transcriptional targets in DLBCL cells, a finding confirmed in a functional reporter assay, suggesting that CDK9 may govern MYC protein turnover, thus regulating its expression through multiple mechanisms. Our data suggest that targeting CDK9 is poised to disrupt MYC oncogenic activity in DLBCL and provide rationale for clinical development of selective CDK9 inhibitors.

Pheochromocytoma: 20 years of improving surgical care.

BACKGROUND: Laparoscopic adrenalectomy is now the standard for pheochromocytoma. We report two decades of institutional experience with pheochromocytoma adrenalectomy. METHODS: A retrospective review was undertaken of pheochromocytoma adrenalectomy patients between 1997 and 2017. Clinical variables and postoperative complications were recorded. Patients were divided into quartiles for analysis: group 1 from 1997 to 2001, group 2 from 2002 to 2006, group 3 from 2007 to 2011, and group 4 from 2012 to 2017. RESULTS: Eighty-two pheochromocytoma adrenalectomies were identified. The percentage of laparoscopic adrenalectomies increased over time: 60% in group 1-87.5% in group 4 (p = 0.03). The average tumor size decreased: 6.4 cm (2.8-14.3 cm) in group 1-4.6 cm (1.2-7.8 cm) in group 4 (p = 0.03). ICU utilization decreased from 80% to 40.6% (p = 0.03) and length of stay decreased from 7.2 days to 2.7 days (p = 0.005). Clavien-Dindo grade>3 complications did not differ between the quartiles (p = 0.08). CONCLUSION: Pheochromocytoma care has evolved from more open procedures with standard postoperative ICU stay to a laparoscopic resection with targeted ICU care and decreased length of stay. As experience with laparoscopic adrenalectomy increases, patient outcomes improve.

Who Undergoes Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Appendiceal Cancer? An Analysis of the National Cancer Database.

BACKGROUND: We sought to identify patterns of care for patients with appendiceal cancer and identify clinical factors associated with patient selection for multimodality treatment, including cytoreductive surgery and perioperative intraperitoneal chemotherapy (CRS/PIC). MATERIALS AND METHODS: National Cancer Database (NCDB) data from 2004 to 2014 of all diagnoses of appendiceal cancers were examined. We examined treatment modalities, as well as demographic, tumor-specific, and survival data. A multivariate logistic regression analysis was performed to determine the patient cohort most likely to receive CRS/PIC. Kaplan-Meier was used to estimate survival for all treatment groups. Significance was evaluated at P ≤ 0.05. RESULTS: We analyzed data on 18,055 patients. Nine thousand nine hundred ninety-two (55.3%) were treated with surgery only, 5848 (32.4%) received surgery and systemic chemotherapy, 1393 (7.71%) received CRS/PIC, 520 (2.88%) received chemotherapy alone, and 302 (1.67%) received neither surgery nor chemotherapy. Significant predictors of receiving CRS/PIC included male sex (OR 1.33, 95% CI: 1.11-1.59), white race (OR 2.00, 95% CI 1.40-2.86), non-Hispanic ethnicity (OR 1.92, 95% CI 1.21-3.05), private insurance (OR 1.52, 95% CI 1.26-1.84), and well-differentiated tumors (OR 4.25, CI: 3.39-5.32) (P < 0.05). Treatment with CRS/PIC was associated with a higher 5-year survival for mucinous malignancies, when compared to surgery alone (65.6% versus 62.4%, P < 0.01). Treatment with CRS/PIC was also associated with higher 5-year survival for well-differentiated malignancies, when compared to all other treatment modalities (74.9% versus 65.4%, P < 0.01). CONCLUSIONS: Patients were more likely to undergo CRS/PIC if they were male, white, privately insured, and with well-differentiated tumors. CRS/PIC was associated with improved survival in patients with mucinous and low-grade tumors.

Laparoscopic vagal nerve blocking device explantation: case series and report of operative technique.

BACKGROUND: Vagal nerve blockade with the vBloc device (ReShape Lifesciences, St. Paul, MN) has been shown to provide durable 2-year weight loss in patients with moderate obesity. These devices may require removal. We present a series of patients and report our technique for laparoscopic removal of this device. METHODS: From December 2009 to December 2016, the medical records of patients who underwent laparoscopic explantation of a vagal blocking device at our institution were retrospectively reviewed. All patients initially underwent device placement as part of a multi-center, randomized, controlled trial. The device leads were removed with the application of firm traction in order to safely dissect them away from the stomach and esophagus as the body tended to form a fibrotic capsule surrounding the leads. Operative details, length of stay, 30-day post-operative complications, demographics and reasons for device removal were reported. RESULTS: Thirty patients were identified. Median age was 54 (37-65) years. Average operative time was 227.63 (± 100.21) min. Median time from implantation to removal was 41 (11-96) months. Removal reasons included device malfunction (7 patients, 23.3%), pain at the neuroregulator site (5 patients, 16.7%), retrosternal or epigastric pain (11 patients, 36.7%), weight regain or dissatisfaction with weight loss (15 patients, 50%), and severe nausea (2 patients, 6.7%). Two patients (6.7%) had Clavien-Dindo grade II complications following explantation. Thirteen patients (43.3%) had dense adhesions noted at the time of operation. Seroma formation at the neuroregulator site was the most common complication (7 patients, 23.3%). CONCLUSION: The vagal nerve blocking device can be safely removed laparoscopically with a low 30-day complication rate. Surgeons should be familiar with the details of the device appearance, the typical lead location, and should anticipate dense adhesions surrounding the leads. In addition, experience operating in the region of the gastroesophageal junction is imperative.

Low-Dose Radiation Therapy is an Effective Treatment for Refractory Postoperative Chylous Ascites: A Case Report.

PURPOSE: When lymphatic pathways are disrupted via obstruction or traumatic injury, a temporary or chronic chyle leak may result, which is defined as the presence of chyle that collects outside of the lymphatic vessels within the thoracic or abdominal cavities. For a chyle leak that is refractory to surgical repair, no good options exist. Radiation therapy (RT) can result in scarring and fibrosis of the lymphatic fistula. We report on the first clinical case in the United States with the successful use of low-dose (LD) RT in the management of refractory chylous ascites. METHODS AND MATERIALS: A 74-year-old man developed significant chylous ascites after a laparoscopic Nissen fundoplication. After failure of numerous conservative and surgical interventions, he was referred for radiation medicine. We delivered a dose of 10 Gy in daily 1 Gy fractions to the para-aortic region, including the cisterna chyli and thoracic duct from T12 to L2. RESULTS: The patient tolerated LD-RT well with no toxicity. By the time of the 8-month post-RT follow-up visit, he had decreased chylous ascite levels and required no paracentesis or peritoneovenous shunting. There was no evidence of chylous ascites or recurrent chyle leak at the time of the 18-month follow-up visit. CONCLUSIONS: LD-RT for refractory postoperative chylous ascites is a safe and reasonable option that can provide temporary relief in addition to other conservative methods. This is the first reported case of refractory chylous ascites in the United States that was successfully treated with LD-RT.

Appendiceal Neoplasms.

Appendiceal neoplasms are identified in 0.9 to 1.4% of appendiceal specimens, and the incidence is increasing. It has long been professed that neuroendocrine tumors (formerly carcinoids) are the most common neoplastic process of the appendix; recent data, however, has suggested a shift in epidemiology. Our intent is to distill the complex into an algorithm, and, in doing so, enable the surgeon to seamlessly maneuver through operative decisions, treatment strategies, and patient counseling. The algorithm for evaluation and treatment is complex, often starts from the nonspecific presenting complaint of appendicitis, and relies heavily on often subtle histopathologic differences.

Evolution in the Treatment of Esophageal Disease at a Single Academic Institution: 2004-2013.

INTRODUCTION: Management of benign and malignant esophageal disease has changed rapidly over the past decade. The aim of this study was to analyze evolution in surgical management of esophageal disease at a single academic medical center during this period. MATERIALS AND METHODS: We reviewed a retrospective cohort of patients who underwent esophagectomy between 2004 and 2013. Patient, institutional, treatment, and outcomes variables were reviewed. RESULTS: 317 patients were analyzed. Median age was 63.5 years; 80% were male. Average inhospital mortality rate was 3.8%. Operative indications changed significantly from 2004 to 2013, with more operations performed for invasive malignancy (77% vs. 95%) and fewer for high-grade dysplasia (12% vs. 3%, P = .008). In 2004, Ivor Lewis esophagectomy was the most common surgical technique, but the three-field technique was the operation of choice in 2013. A minimally invasive approach was used in 19% of cases in 2004 and 100% of cases in 2013 (P < .001). Anastomotic leak ranged from 0% to 21% with no significant difference over the study period (P = .18). Median lymph node harvest increased from seven to 18 nodes from 2004 to 2013 (P = .001). Hospital length of stay decreased from 15 to 8 days (P = .001). In 2013, 79% of patients were discharged to home, compared to 73% in 2004 (P = .04). DISCUSSION: Over the last decade, our treatment of esophageal disease has evolved from a predominantly open Ivor Lewis to a minimally invasive three-field approach. Operations for malignancy have also increased dramatically. Postoperative complications and mortality were not significantly changed, but were consistently low during the latter years of the study.

Characteristics predicting clinical improvement and cure following laparoscopic adrenalectomy for primary aldosteronism in a large cohort.

BACKGROUND: Surgical resection is the standard of care for unilateral adrenal adenomas and hyperplasia resulting in primary aldosteronism (PA). Resolution of PA following surgery is variable and some patients continue to require some or all of their antihypertensives. Prior studies have investigated factors contributing to "cure" of PA (defined as no hypertension [HTN] medications required postoperatively). These models are a tool in patient selection, yet fail to consider the benefit of some reduction in medications, resolution of hypokalemia, or reduction in blood pressure which may improve long-term cardiovascular and renal outcomes. We sought to investigate factors contributing to postoperative improvement or complete resolution following surgery. METHODS: This is a retrospective review of prospectively collected data on 58 adrenalectomies performed for PA from December 1999 to April 2013 at a single center. Patient demographics, PA characteristics, labs, and imaging studies were evaluated, as well as operative characteristics. Mean systolic and diastolic blood pressures were calculated over several visits after discharge, and postoperative antihypertensive regimen was recorded. Patients were stratified by cured vs not cured and then again by improved vs not improved based on differences in pre- and postoperative values. Aldosteronoma Resolution Score was also calculated for each patient. RESULTS: Median age was 52.6 years, with 44.8% women and an average duration of HTN of 13.5 years. Average body mass index (BMI) was 31.5 kg/m(2); 74% of the lesions were adenomas. Patients with complications had higher BMIs than those without (36.9 vs 28.7 kg/m(2), P = .02). In comparing improved (n = 42, 72%) vs not improved (n = 16, 28%) patients, preoperative systolic blood pressure (147.5 vs 159.7 mm Hg, P = .047) and serum creatinine (.94 vs 1.32 mg/dL, P = .016) were higher in the not improved group. Cured (n = 13) vs not cured (n = 45) patients differed in terms of BMI (27.4 vs 32.7, P = .009), duration of HTN (9.1 vs 14.9 years, P = .020), and number of preoperative antihypertensives (2.1 vs 3.7, P = .002). Aldosteronoma Resolution Score was significantly higher in cured patients (3.2 vs 1.0, P < .01). CONCLUSIONS: A significant number of patients who are not cured by adrenalectomy for PA will still benefit from surgery. Obesity, duration of HTN, and number of medications may predict cure, yet fail to detect a population of patients with overall improvement. Attention to serum creatinine may help in distinguishing this population of patients.

Biliary dyskinesia: a surgical disease rarely found outside the United States.

BACKGROUND: Our objective was to determine if cholecystectomy for biliary dyskinesia (BD) was performed more commonly in the United States than in 4 comparator countries around the world. METHODS: Using the Nationwide Inpatient Sample, we extracted and analyzed data for cholecystectomy from 1991 to 2011 using ICD-9 (International Classification of Diseases 9th Revision) procedure codes. To derive the number of cholecystectomies performed for BD, we used the ICD-9 code 575.8, greater than 80% of which are patients with BD. The same or equivalent code was used for the international comparator group. Through a SURGINET query we obtained data from verifiable national databases in 4 developed countries including the Swedish quality registry for surgical treatments of gallstone-related conditions (GallRiks), the Norwegian Cholecystectomy Registry, the Australian Bureau of Statistics, and the Polish National Health Insurance Agency. RESULTS: In the years ranging from 2008 to 2011, the number of cholecystectomies for BD per 1,000,000 population per year was less than 25 in the 4 comparator countries and greater than 85 in the United States (P < .01). From 1991 to 2011, the number of cholecystectomies for BD in the United States significantly increased from 43.3 to 89.1 per 1,000,000 population (P < .01). CONCLUSIONS: These data strongly suggest that cholecystectomy for BD is over utilized in the United States. In addition, this trend continues to increase in frequency.

The adrenal psoas sign: surgical outcomes following a simple technique to maximize removal of extracortical adrenal tissue during bilateral laparoscopic adrenalectomy.

BACKGROUND: Bilateral laparoscopic adrenalectomy (BLA) is an effective therapy for the management of persistent hypercortisolism in patients after failed transphenoidal pituitary tumor resection for Cushing's disease. Extracortical adrenal tissue has been identified as a source of persistent hypercortisolism and, if not resected along with both adrenal glands, may lead to treatment failure. We report a reliable and reproducible technique called the "psoas sign" for BLA in patients with Cushing's disease which reduces the likelihood of retained extra-adrenal cortical rests and may reduce intraoperative complications. METHODS: A 16-year retrospective review of all consecutive patients who underwent transabdominal BLA at a single tertiary care center was performed. All patients underwent BLA utilizing the psoas sign technique and all procedures were performed replicating these predetermined surgical steps: (1) Identification of the inferior pole of the gland. (2) Identification of the inferior aspect of the adreno-caval groove on the right or the adrenal vein/renal vein confluence on the left. (3) Division of the adrenal vein. (4) Dissection and removal of the adrenal gland with clearance of all retroperitoneal fat overlying the psoas muscle. RESULTS: Between October 1996 and December 2012, 92 patients underwent BLA for refractory Cushing's disease. Patients were predominantly female (90 %) with a median age of 40 years (17-71). There were 3 intraoperative complications (3.2 %), 2 conversions (2.2 %), and 1 death (1.09 %). Four patients were identified as having extracortical rests of adrenal tissue within the retroperitoneal fat (4.3 %). Mean operative time was 272 min (±79.25, n = 68) and median estimated blood loss was 50 mL (10-800 mL). CONCLUSIONS: The psoas sign technique provides a clear view of the adrenal fossa and facilitates careful dissection of the anatomic planes around the adrenal gland. This technique is feasible, reproducible and in our experience allows for safe removal of both adrenal glands and all surrounding extracortical adrenal tissue.