Case example of a jail-based cancer prevention clinical trial: Social determinants of health framework, novel experimental design, and retention strategies to facilitate long-term follow-up of clinical trial participants.

Clinical trials conducted with incarcerated populations are rare. We present a case example of one such jail-based cancer prevention clinical trial to demonstrate the importance of including a theory-driven approach to intervention framing, novel experimental designs to boost access to low-risk trials, and retention strategies for long-term follow-up of hard-to-reach populations. As such we offer a social determinant of health framework to ensure cancer prevention research is conducted through the lenses of health promotion and health equity. Deviations from the gold-standard randomized control design, transparent systematic allotment, and street-based outreach retention strategies contribute to the feasibility of conducting clinical trials in carceral settings and after people leave jail. Best practices presented can be used in design and conduct of future clinical trials with criminal legal system-involved populations.

Developing a Cancer Prevention Health Education Resource: a Primer of Process and Evaluation.

Limited women's health and cancer prevention materials are available that have been validated for vulnerable populations. Such materials are especially important for groups, which have intermittent and typically low-quality healthcare access and are at greatest risk for missing out on women's health and cancer prevention screening. Health education materials are developed from heterogeneous sources. Clinical and research teams have minimal guidance in terms of sources, timelines, outputs, and evaluation in the development of such materials. The goal of this paper is to share our process in developing and evaluating an up-to-date women's health and cancer prevention learning guide appropriate for a target population of women involved in the criminal justice system. A ten-page learning guide was drafted using the current evidence-based data, with the objective of providing educational material on four topics: cervical cancer, breast cancer, sexually transmitted infection, and unintended pregnancy prevention. The learning guide was then tested on a convenience sample of 33 women at a local county jail. Feedback was organized into three parts in which the participants Responded to open-ended question, "What is missing?" Rated each of the four topics for design and content Completed a usability assessment Common themes were participants' interest in learning about side effects of birth control and wanting more information on testing and treatment, specifically for sexually transmitted infections (STIs). Women were satisfied with the cancer prevention information presented to them. This report provides a framework for cancer prevention researchers who are developing health education materials for vulnerable populations.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Features of synchronous versus metachronous metastasectomy in adrenal cortical carcinoma: Analysis from the US adrenocortical carcinoma database.

BACKGROUND: Adrenocortical carcinoma is a rare, aggressive cancer. We compared features of patients who underwent synchronous versus metachronous metastasectomy. METHODS: Adult patients who underwent resection for metastatic adrenocortical carcinoma from 1993 to 2014 at 13 institutions of the US adrenocortical carcinoma group were analyzed retrospectively. Patients were categorized as synchronous if they underwent metastasectomy at the index adrenalectomy or metachronous if they underwent resection after recurrence of the disease. Factors associated with overall survival were assessed by univariate analysis. RESULTS: In the study, 84 patients with adrenocortical carcinoma underwent metastasectomy; 26 (31%) were synchronous and 58 (69%) were metachronous. Demographics were similar between groups. The synchronous group had more T4 tumors at the index resection (42 vs 3%, P < .001). The metachronous group had prolonged median survival after the index resection (86.3 vs 17.3 months, P < .001) and metastasectomy (36.9 vs 17.3 months, P = .007). Synchronous patients with R0 resections had improved survival compared to patients with R1/2 resections (P = .008). Margin status at metachronous metastasectomy was not associated with survival (P = .452). CONCLUSION: Select patients with metastatic adrenocortical carcinoma may benefit from metastasectomy. Patients with metachronous metastasectomy have a more durable survival benefit than those undergoing synchronous metastasectomy. This study highlights need for future studies examining differences in tumor biology that could explain outcome disparities in these distinct patient populations.

Longitudinal patterns of recurrence in patients with adrenocortical carcinoma.

BACKGROUND: Patterns and prognostic implications of recurrent adrenocortical carcinoma are poorly understood. In this study, we aim to describe temporal and spatial patterns of adrenocortical carcinoma recurrence. METHODS: This is a retrospective review of 576 patients with adrenocortical carcinoma evaluated at a single institution. Clinicopathologic and follow-up data were collected longitudinally. RESULTS: A total of 354 patients underwent resection of stage I-III adrenocortical carcinoma. We found that 249 (70%) patients developed disease recurrence. The median recurrence-free interval after primary resection was 11 months. The most common sites of initial recurrence were lung and tumor bed. The shortest time to recurrence was associated with lung or multiple site metastases. We found that 142 of 249 patients developed one or more additional sites of recurrence (median 5 months), most commonly involving the lungs. A total of 20 patients developed a third site of recurrence. We found that 100 patients underwent one or more reoperations or metastasectomies and 79 recurred again after reoperation. Same organ or site recurrence was common after reoperation (67%). Although lung metastases occurred early, recurrences to the peritoneal cavity or to multiple sites were associated with worse survival. Metastasectomy beyond three total operations did not improve overall survival. CONCLUSION: Survival varies according to site of recurrence and other clinicopathologic factors. Knowledge of patterns of recurrence may assist in anticipating disease course and lead to better informed selection of treatment.

Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer. This report describes factors and outcomes associated with resection of extra-adrenal organs en bloc during index adrenalectomy. METHODS: Patients who underwent ACC resection for non-metastatic disease from 1993 to 2014 at 13 participating institutions of the US-ACC Group were included in the study. Factors associated with en bloc resection were assessed by uni- and multivariate analysis. The primary end point was overall survival. RESULTS: In this study, 167 patients were included and categorized as adrenalectomy with en bloc resection (AdEBR) if they had extra-adrenal organs removed or adrenalectomy (Ad) if they did not. The demographics were similar between the AdEBR (n = 68, 40.7%) and Ad groups, including age, gender, race, American Society of Anesthesiology (ASA) class, and body mass index (BMI). The AdEBR group had larger tumors (13 vs. 10 cm), more open operations (97.1 vs. 63.6%), and more lymph node dissections (LNDs) (36.8 vs. 12.1%). The most common organs removed were kidney (55.9%), liver (27.9%), and spleen (23.5%). Multiple organs were removed in 38.2% (n = 26) of the patients. Margin-negative resections were similar between the two groups. In the multivariate Cox regression adjusted for T and N stages, LND, margin, size, and hormone hypersecretion, en bloc resection was not associated with improved survival (hazard ratio [HR], 1.42; p = 0.323). CONCLUSION: The study findings validated current practice by showing that en bloc resection should occur at index adrenalectomy for ACC when a T4 lesion is suspected pre- or intraoperatively, or when it is necessary to avoid tumor rupture. However, in this study, when a negative margin resection was otherwise achieved, removal of extra-adrenal organs en bloc was not associated with additional survival benefit.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P < 0.001), inferior vena cava involvement (24.6% vs 5.4%, P = 0.002), additional organ resection (78.9% vs 36.3%, P < 0.001), and major complications (29% vs 2%, P < 0.001). Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P < 0.001). On univariate Cox regression, transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P < 0.001), and hormonal hypersecretion (HR = 2.6, 95% CI = 1.5-4.2, P < 0.001) were associated with worse RFS. When applying this model to OS, similar associations were seen (transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P < 0.001; hormonal hypersecretion HR = 3.5, 95% CI = 1.9-6.4, P < 0.001). There was no difference in outcomes between patients who received 1 to 2 units versus >2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%). CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

Actual 10-year survivors following resection of adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited therapeutic options beyond surgical resection. The characteristics of actual long-term survivors following surgical resection for ACC have not been previously reported. METHOD: Patients who underwent resection for ACC at one of 13 academic institutions participating in the US Adrenocortical Carcinoma Group from 1993 to 2014 were analyzed. Patients were stratified into four groups: early mortality (died within 2 years), late mortality (died within 2-5 years), actual 5-year survivor (survived at least 5 years), and actual 10-year survivor (survived at least 10 years). Patients with less than 5 years of follow-up were excluded. RESULTS: Among the 180 patients available for analysis, there were 49 actual 5-year survivors (27%) and 12 actual 10-year survivors (7%). Patients who experienced early mortality had higher rates of cortisol-secreting tumors, nodal metastasis, synchronous distant metastasis, and R1 or R2 resections (all P < 0.05). The need for multi-visceral resection, perioperative blood transfusion, and adjuvant therapy correlated with early mortality. However, nodal involvement, distant metastasis, and R1 resection did not preclude patients from becoming actual 10-year survivors. Ten of twelve actual 10-year survivors were women, and of the seven 10-year survivors who experienced disease recurrence, five had undergone repeat surgery to resect the recurrence. CONCLUSION: Surgery for ACC can offer a 1 in 4 chance of actual 5-year survival and a 1 in 15 chance of actual 10-year survival. Long-term survival was often achieved with repeat resection for local or distant recurrence, further underscoring the important role of surgery in managing patients with ACC. J. Surg. Oncol. 2016;114:971-976. © 2016 Wiley Periodicals, Inc.

Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit?

BACKGROUND: Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear. METHODS: Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon's effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups. RESULTS: Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p < .001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p = .72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection. CONCLUSIONS: In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon's effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.

Outcomes after resection of cortisol-secreting adrenocortical carcinoma.

BACKGROUND: We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC). METHODS: The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed. RESULTS: The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01). CONCLUSIONS: Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important.

Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group.

BACKGROUND: Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. STUDY DESIGN: Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. CONCLUSIONS: When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

Management of suspected adrenal metastases at 2 academic medical centers.

BACKGROUND: The optimal management of suspected adrenal metastases remains controversial. METHODS: This is a retrospective bi-institutional review of 37 patients who underwent adrenalectomy for suspected adrenal metastasis between 2001 and 2014. RESULTS: Three (8%) patients had benign adenomas on final pathology. At a median follow-up of 21 months, 7 (32%) patients were alive with no evidence of disease and 7 (32%) were alive with recurrent disease. Recurrence-free survival (RFS) was 8 months; decreased RFS was associated with positive margins and size ≥6 cm. Overall survival (OS) was 29 months; decreased OS was associated with capsular disruption. There were no differences in RFS or OS by surgical approach. CONCLUSIONS: The favorable OS supports adrenalectomy in select patients with suspected adrenal metastases. Minimally invasive adrenalectomy is safe and effective, but the surgical approach should be based on the ability to achieve a margin-negative resection with avoidance of capsular disruption.

Incidence and Risk Factors Associated with Readmission After Surgical Treatment for Adrenocortical Carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Given the lack of data on readmission after resection of ACC, the objective of the current study was to define the incidence of readmission, as well as identify risk factors associated with readmission among patients with ACC who underwent surgical resection. METHODS: Two hundred nine patients who underwent resection of ACC between January 1993 and December 2014 at 1 of 13 major centers in the USA were identified. Demographic and clinicopathological data were collected and analyzed relative to readmission. RESULTS: Median patient age was 52 years, and 62 % of the patients were female. Median tumor size was 12 cm, and the majority of patients had an American Society of Anesthesiologists (ASA) class of 3-4 (n = 85, 56 %). The overall incidence of readmission within 90 days from surgery was 18 % (n = 38). Factors associated with readmission included high ASA class (odds ratio (OR), 4.88 (95 % confidence interval (CI), 1.75-13.61); P = 0.002), metastatic disease on presentation (OR, 2.98 (95 % CI, 1.37-6.46); P = 0.006), EBL (>700 mL: OR, 2.75 (95 % CI, 1.16-6.51); P = 0.02), complication (OR, 1.91 (95 % CI, 1.20-3.05); P = 0.007), and prolonged length of stay (LOS; ≥9 days: OR, 4.12 (95 % CI, 1.88-9.01); P < 0.001). On multivariate logistic regression, a high ASA class (OR, 4.01 (95 % CI, 1.44-11.17); P = 0.008) and metastatic disease on presentation (OR, 3.44 (95 % CI, 1.34-8.84); P = 0.01) remained independently associated with higher odds of readmission. CONCLUSION: Readmission following surgery for ACC was common as one in five patients experienced a readmission. Patients with a high ASA class and metastatic disease on presentation were over four and three times more likely to be readmitted after surgical treatment for ACC, respectively.

Institutional experience with lateral neck dissections for thyroid cancer.

INTRODUCTION: Compartment-oriented neck dissection is recommended for patients with evidence of thyroid cancer metastases to lateral compartment lymph nodes. This study reviews the outcomes of patients who underwent lateral neck dissections (LND) at a high-volume institution. METHODS: This is a retrospective review of patients who underwent LND for metastatic thyroid cancer from January 2009 to June 2014. Preoperative evaluation, operative findings, and postoperative outcomes were analyzed. RESULTS: Ninety-six patients underwent 127 LNDs. Fine-needle aspiration (FNA) confirmed metastases in 82 lateral necks (65%). The remaining 45 LNDs (35%) were performed based on clinical suspicion of metastases; 29 (64%) had metastases on final pathology. Twenty patients had 26 complications, which included chyle leak (7 [6%]), spinal accessory nerve dysfunction (7 [6%]), neck seroma requiring drainage (2 [2%]), and surgical site infection (10 [8%]). CONCLUSION: LND is associated with a risk of early postoperative morbidity, but long-term complications are uncommon in the hands of experienced surgeons. In patients with thyroid cancer, a comprehensive preoperative evaluation of the lateral neck with physical examination, ultrasonography, and possible FNA should be performed. For those with suspicion of metastases, LND can be an important therapeutic option, but discussion with the patient regarding potential risks and benefits is essential.

Minimally invasive gastrectomy for cancer: current utilization in US academic medical centers.

BACKGROUND: Internationally, the utilization of minimally invasive techniques for gastric cancer resection has been increasing since first introduced in 1994. In the USA, the feasibility and safety of these techniques for cancer have not yet been demonstrated. METHODS: The University HealthSystem Consortium database was queried for gastrectomies performed between 2008 and 2013. Any adult patient with an abdominal visceral malignancy that necessitated gastric resection was included in the cohort. Clinicopathological and in-hospital outcome metrics were collected for open, laparoscopic, and robotic procedures. RESULTS: Open gastrectomies comprised 89.5% of the total study group, while 8.2% of procedures were performed laparoscopically, and 2.3% were performed with robotic assistance. When accounting for disparities in patient severity of illness and risk of mortality subclass designations, there were no significant differences in mean length of stay, 30-day readmission, and in-hospital mortality between the three groups; however, mean total cost was highest in the robotic-assisted group (P = 0.017). Overall, complication rates were also similar; however, there was a higher incidence of superficial infection in the laparoscopic group (P = 0.013) and a higher incidence of venous thromboembolism in the robotic group (P = 0.038). CONCLUSION: Despite widespread adoption for benign indications, minimally invasive gastrectomy for cancer remains underutilized in the USA. In these patients, laparoscopic and robot-assisted gastrectomies appear to be comparable to open resection with respect to overall complications, length of stay, 30-day readmission, and in-hospital mortality. However, when employing minimally invasive techniques, infection and thromboembolism risk reduction strategies should be emphasized in the operative and postoperative periods.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis.

BACKGROUND: Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature. METHODS: The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots. RESULTS: Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival. CONCLUSIONS: While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.

Leptin signaling in adipose tissue: role in lipid accumulation and weight gain.

RATIONALE: The link between obesity, hyperleptinemia, and development of cardiovascular disease is not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1-dependent mechanisms. However, the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known. OBJECTIVE: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans. METHODS AND RESULTS: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent 8 weeks of overfeeding, during which they gained an average weight of 4.1±1.4 kg, with leptin increases from 7±3.8 to 12±5.7 ng/mL. Weight gain also resulted in changes in adipose tissue caveolin-1 expression, which correlated with increases in leptin (rho=0.79, P=0.01). In cultured human white preadipocytes, leptin increased caveolin-1 expression, which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating human white preadipocytes, which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis. CONCLUSIONS: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intracellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism that may be essential to facilitate adipocyte lipid storage during weight gain.

Gastric prolapse with pseudocysts following laparoscopic adjustable gastric banding.

INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) is a reversible method of surgical gastric restriction. Following LAGB, the adverse event most commonly necessitating subsequent reoperation is prolapse of the gastric corpus or fundus above the band. A review of the medical literature reveals no reports of nonpancreatic pseudocysts being associated with this adverse event. Nonpancreatic pseudocysts, encountered during revisional bariatric surgery should be considered a cause of irreducible gastric prolapse. CASE REPORT: We report the case of a 41-year-old Caucasian female who underwent laparoscopic surgery to revise an adjustable gastric band and to repair an anterior gastric prolapse. Intraoperatively, 2 pseudocysts were found on the gastric fundus above the band in association with the gastric prolapse. The pseudocysts were resected, the gastric prolapse was reduced, and the band was left in place. The patient recovered uneventfully. CONCLUSION: Nonpancreatic pseudocysts may be associated with gastric prolapse in patients who have undergone LAGB. These pseudocysts can often be excised laparoscopically without violating the gastric lumen. This atypical presentation of gastric prolapse may pose a diagnostic and therapeutic challenge as these patients may.