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.

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.

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.

Association between body mass index and multigland primary hyperparathyroidism.

INTRODUCTION: Multigland disease (MGD) accounts for 15% of sporadic primary hyperparathyroidism (pHPT). Several studies have reported a link between obesity and calcium metabolism (e.g., increased incidence of pHPT, higher levels of parathyroid hormone, lower vitamin D levels, and larger parathyroid glands). Obese patients have also been shown to require reoperation for persistent/recurrent pHPT more often than nonobese controls. We hypothesize that obese patients may have a higher prevalence of MGD. METHODS: This was a retrospective review of a prospectively collected parathyroid database that included adult patients with sporadic pHPT, who underwent initial parathyroidectomy between 1999 and 2013. Demographic, clinicopathologic, operative, and laboratory data were assessed for associations with MGD. RESULTS: Of 1305 consecutive patients, 200 (15%) had MGD. Median age was 59 y. Univariate analyses demonstrated that MGD was associated with age > 60 y, higher body mass index (BMI), history of lithium therapy, lower 24-h urine calcium excretion, higher serum alkaline phosphatase levels, and smaller size of the first excised parathyroid gland. On multivariate analyses, predictors of MGD were BMI 30-39.9 kg/m(2) (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.2-2.5), BMI ≥ 40 kg/m(2) (OR 1.8; 95% CI 1.3-3.1), and smaller size of the first excised parathyroid (OR 0.7; 95% CI 0.6-0.8). CONCLUSIONS: This study demonstrates a higher incidence of MGD in obese and morbidly obese patients. Due to a higher risk of MGD, surgeons should have a lower threshold to perform bilateral exploration in obese patients, especially if the first excised parathyroid gland is relatively small.

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.

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.