Hypercalcemia and cancer: Differential diagnosis and treatment.

Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone-related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.

Differences in Clinicopathologic Behavior of Oncocytic Adrenocortical Neoplasms and Conventional Adrenocortical Carcinomas.

BACKGROUND: Oncocytic adrenocortical neoplasms (OANs) are rare endocrine tumors that present as a spectrum from benign to malignant. The outcomes after surgical resection of the oncocytic variant of adrenocortical carcinoma remain poorly understood. We sought to characterize the clinicopathologic features of OAN and compare oncocytic adrenocortical carcinoma (OAC) with conventional adrenocortical carcinoma (ACC). PATIENTS AND METHODS: Adult patients who underwent adrenalectomy for OAN or ACC between January 1990 and September 2020 were identified. Demographics, clinicopathologic factors, American Joint Committee on Cancer stage, and cancer-related outcomes were reviewed. A matched cohort analysis of disease-free survival (DFS) and overall survival (OS) was performed between patients with OACs and those with ACCs. RESULTS: Forty-one patients with OAN and 214 patients with ACC were included. The OAN cohort median age was 45.2 years [interquartile ratio (IQR) 38.5-54.0 years], and 61.0% were female. OANs were benign (n = 11), of uncertain malignant potential (UMP, n = 9), or OAC (n = 21). Disease recurrence occurred in 12 (57.1%) patients with OAC compared with 1 (11.1%) and 0 patients with UMP or benign OAN, respectively (p < 0.001). Seven (33.3%) patients with OAC died during follow-up compared with 0 patients with UMP or benign OAN (p = 0.020). Kaplan-Meier survival analysis found no difference in DFS between ACC and OAC groups before (p = 0.218) and after 2:1 matching (p = 0.417). Overall survival was shorter for patients who had ACC compared with those who had OAC (p = 0.031), but the difference was not evident with matched analysis (p = 0.200). CONCLUSIONS: OAN presents as a spectrum from benign indolent tumors to aggressive carcinomas. OACs demonstrate similar clinicopathologic behavior and recurrence-free and overall survival when matched to conventional ACCs.

Thyroid cancer is more likely to be detected incidentally on imaging in private hospital patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing. Patients with higher socioeconomic status have higher rates of WDTC, possibly due to increased imaging and overdiagnosis. We compared methods of WDTC diagnosis in patients treated at a public and an adjacent private university hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between 2004 and 2010 were included. Patients were categorized into having their WDTC discovered on physical examination or on unrelated imaging. Demographic and pathologic data were collected. T-test was used for quantitative variables, and chi-squared test was used for categorical values. Binomial logistic regression was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were from the university hospital, and 71 (15%) were from the public hospital. Patients from the university hospital were older (mean age: 49 versus 44, P = 0.02) and had a different racial composition compared to those from the public hospital. The patients at the public hospital had larger tumors (23 versus 18 mm, P = 0.04). Patients from the university hospital were more likely to have WDTC detected by imaging than patients in the public hospital (46% versus 28%, P < 0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients with WDTC treated at a university hospital are more likely to have their tumor detected on unrelated imaging than those treated at a public hospital. These data may support the hypothesis that patients with improved insurance are more likely to have WDTC detected by imaging.

Intraoperative leak testing has no correlation with leak after laparoscopic sleeve gastrectomy.

BACKGROUND: Staple line leak is a serious complication of sleeve gastrectomy. Intraoperative methylene blue and air leak tests are routinely used to evaluate for leak; however, the utility of these tests is controversial. We hypothesize that the practice of routine intraoperative leak testing is unnecessary during sleeve gastrectomy. METHODS: A retrospective cohort study was designed using a prospectively collected database of seven bariatric surgeons from two institutions. All patients who underwent sleeve gastrectomy from March 2012 to November 2014 were included. The performance of intraoperative leak testing and the type of test (air or methylene blue) were based on surgeon preference. Data obtained included BMI, demographics, comorbidity, presence of intraoperative leak test, result of test, and type of test. The primary outcome was leak rate between the leak test (LT) and no leak test (NLT) groups. SAS version 9.4 was used for univariate and multivariate analyses. RESULTS: A total of 1550 sleeve gastrectomies were included; most were laparoscopic (99.8%), except for one converted and two open cases. Routine intraoperative leak tests were performed in 1329 (85.7%) cases, while 221 (14.3%) did not have LTs. Of the 1329 cases with LTs, there were no positive intraoperative results. Fifteen (1%) patients developed leaks, with no difference in leak rate between the LT and NLT groups (1 vs. 1%, p = 0.999). After adjusting for baseline differences between the groups with a propensity analysis, the observed lack of association between leak and intraoperative leak test remained. In this cohort, leaks presented at a mean of 17.3 days postoperatively (range 1-67 days). Two patients with staple line leaks underwent repeat intraoperative leak testing at leak presentation, and the tests remained negative. CONCLUSION: Intraoperative leak testing has no correlation with leak due to laparoscopic sleeve gastrectomy and is not predictive of the later development of staple line leak.

Does adding a lesser-curvature gastrogastric plication suture reduce the need for revision after laparoscopic adjustable gastric band placement?

BACKGROUND: The need for revision after laparoscopic adjustable gastric band (LAGB) surgery has been reduced over the past 10 years with the introduction of the pars flaccida technique, delicate band tightening, and concurrent hiatal hernia repairs. However, band revision still occurs for as many as 5% of patients. Placement of a lesser-curvature gastrogastric suture distal to the band is one newer technique suggested to lower band slippage. To evaluate the worth of this technique, the authors have investigated two groups of patients in their practice: one group with the plication stitch and one group without it. METHODS: This retrospective review examined data for 1,365 LAGB patients collected prospectively by an institutional review board-approved database between July 2007 and May 2010. One surgeon did not perform the plication stitch (n = 776) and one did (n = 589). The surgical techniques were very similar. The majority of the patients had crural repair at the primary operation. Band revision rates were assessed. RESULTS: For 1,365 patients, LAGB was performed safely. The mean follow-up period was 22 months. The two groups were similar. The no-stitch group consisted of 776 patients (496 women, 64%) with a mean age of 42 years, a mean weight of 278 lb, and a mean body mass index (BMI) of 44.6 kg/m(2). The stitch group consisted of 589 patients (426 woman, 72%) with a mean age of 40 years, a mean weight of 278 lb, and a mean BMI of 44.8 kg/m(2). The no-stitch group had an estimated weight loss (EWL) of 44% at 12 months and 50% EWL at 2 years. The stitch group had 37% EWL at 12 months and 45% EWL at 2 years. Both groups had very low revision rates. The no-stitch group had 4 revisions in 776 patients (0.26%), and the stitch group had 9 revisions in 589 patients (1.5%). CONCLUSION: Adding gastrogastric plication sutures offers no benefit of reducing the rate of revision after LAGB surgery.

Surgical relief of small bowel obstruction by migrated biliary stent: extraction without enterotomy.

BACKGROUND: Distal stent migration is a well-known complication following insertion of biliary stents. Most such cases can be managed expectantly, because the stents pass through the gastrointestinal tract. However, small bowel obstruction as a result of the stent mandates surgical intervention. METHODS: We report the case of a patient who had distal stent migration causing a small bowel obstruction. We successfully retrieved the stent without an enterotomy, by using a combination of laparoscopy, endoscopy, and fluoroscopy. Our unique technique greatly decreased the risk of bacterial peritonitis in this patient with decompensated cirrhosis and associated ascites, which in this patient population results in a high mortality. RESULTS: Management of small bowel obstruction secondary to biliary stent migration necessitates operative intervention. Retrieval of a dislodged stent can be performed safely without subjecting the patient to an enterotomy or a small bowel resection. Postoperative morbidity should be significantly reduced by this approach. CONCLUSION: Retrieval of biliary stents in cases of small bowel obstruction without perforation may be successfully performed without enterotomy or bowel resection. A similar approach may be applied to other foreign bodies dislodged in the small bowel.

High prevalence of chronic kidney disease in patients with multiple endocrine neoplasia type 1 and improved kidney function after parathyroidectomy.

BACKGROUND: Because chronic kidney disease is an important comorbidity associated with primary hyperparathyroidism, we sought to evaluate the prevalence of chronic kidney disease and effects of parathyroidectomy on kidney function in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. METHODS: We performed a retrospective analysis of 112 patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism who had at least 1 operation for primary hyperparathyroidism at 2 tertiary referral centers. The preoperative and postoperative estimated glomerular filtration rates were compared. The prevalence of chronic kidney disease stage 3 or worse (estimated glomerular filtration rates less than 60 mL/min/1.73m2) in this cohort was compared to the rates in the US population reported by the Centers for Disease Control and Prevention. RESULTS: The median age at the time of parathyroidectomy was 36.5 years (range: 12-76 years). A total of 99 patients had biochemical remission. The rate of chronic kidney disease stage 3 or worse in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism was greater than that observed in the US population for ages 20-39 and 40-59 (5% [n = 2/44] vs 0.39% [n = 18/4565], P = .015 and 10% [n = 4/40] vs 2.31% (n = 89/3848), P = .015, respectively). We observed improved estimated glomerular filtration rates in those with chronic kidney disease stage 3 or worse postoperatively (48 vs 57 mL/min/1.73m2, P = .047). A successful parathyroidectomy normalized all 24-hour urine calcium excretion. CONCLUSION: An indication for early parathyroidectomy should include estimated glomerular filtration rates less than 60mL/min/1.73m2 in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism.

Intraoperative Decision-Making and Technical Aspects of Parathyroidectomy in Young Patients With MEN1 Related Hyperparathyroidism.

One in 5,000 to 1 in 50,000 births have multiple endocrine neoplasia type 1 (MEN1). MEN1 is a hereditary syndrome clinically defined by the presence of two of the following endocrine tumors in the same patient: parathyroid adenomas, entero-pancreatic endocrine tumors and pituitary tumors. Most commonly, patients with MEN1 manifest primarily with signs and symptoms linked to primary hyperparathyroidism. By age 50, it is estimated that 100% of patients with MEN1 will have been diagnosed with primary hyperparathyroidism. These patients will need to undergo resection of their hyperfunctioning glands, however there is no clear consensus on which procedure to perform and when to perform it in these patients. In this original study we describe and explain the rational of our peri-operative approach and management at MD Anderson Cancer Center of MEN1 patients with hyperparathyroidism. This protocol includes preoperative evaluation, intraoperative decision-making and detailed surgical technique adopted for these patients' care. Additionally we review follow-up and disease management in instances of recurrent primary hyperparathyroidism in patients with MEN1 syndrome.

Lack of Diagnosis of Pneumoperitoneum in Perforated Duodenal Ulcer After RYGB: a Short Case Series and Review of the Literature.

Perforated duodenal ulcer following RYGB is an unusual clinical situation that may be a diagnostic challenge. Only 23 cases have previously been reported. We present five cases. The hallmark of visceral perforation, namely pneumoperitoneum, was not seen in three of the four cases that underwent cross sectional imaging. This is perhaps due to the altered anatomy of the RYGB that excludes air from the duodenum. Our cases had more free fluid than expected. The bariatric surgeon should not wait for free intraperitoneal air to suspect duodenal perforation after RYGB.

Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2) have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients. METHODS: The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2) and Obese (BMI≥30 kg/m2) groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups. RESULTS: The final study group contained 270 patients, 181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group. In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were found by imaging, and 28(16%) were found incidentally. In the Obese group, 40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were found incidentally. These differences were not statistically significant (p-value 0.769). CONCLUSION: We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an increasingly obese population and that any association of WDTC and obesity is not related to the way in which these tumors are detected.

Thirty-Day Readmission After Laparoscopic Sleeve Gastrectomy­a Predictable Event?

BACKGROUND: Thirty-day readmission post-bariatric surgery is used as a metric for surgical quality and patient care. We sought to examine factors driving 30-day readmissions after laparoscopic sleeve gastrectomy (LSG). METHODS: We reviewed 1257 LSG performed between March 2012 and June 2014. Readmitted and nonreadmitted patients were compared in their demographics, medical histories, and index hospitalizations. Multivariable regression was used to identify risk factors for readmission. RESULTS: Forty-five (3.6 %) patients required 30-day readmissions. Forty-seven percent were readmitted with malaise (emesis, dehydration, abdominal pain) and 42 % with technical complications (leak, bleed, mesenteric vein thrombosis). Factors independently associated with 30-day readmission include index admission length of stay (LOS) ≥3 days (OR 2.54, CI = [1.19, 5.40]), intraoperative drain placement (OR 3.11, CI = [1.58, 6.13]), postoperative complications (OR 8.21, CI = [2.33, 28.97]), and pain at discharge (OR 8.49, CI = [2.37, 30.44]). Patients requiring 30-day readmissions were 72 times more likely to have additional readmissions by 6 months (OR 72.4, CI = [15.8, 330.5]). CONCLUSIONS: The 30-day readmission rate after LSG is 3.6 %, with near equal contributions from malaise and technical complications. LOS, postoperative complications, drain placement, and pain score can aid in identifying patients at increased risk for 30-day readmissions. Patients should be educated on postoperative hydration and pain management, so readmissions can be limited to technical complications requiring acute inpatient management.

Thyroid cancers detected by imaging are not necessarily small or early stage.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) in the United States is increasing rapidly. Much of this increase is due to the detection by imaging of small, nonpalpable tumors. The incidence of advanced WDTC is also increasing, suggesting a true increase in the incidence of WDTC. This study was performed to determine how WDTCs of all sizes and stages are initially detected. METHODS: A retrospective chart review of 519 patients who underwent surgery for WDTC from January 1, 2007, through August 31, 2010, was performed. A total of 473 patients suitable for inclusion in this study were divided into three groups based upon the method by which the tumor was initially detected: tumors detected by an imaging study (184 patients-39%), those detected because a mass was felt in the neck (218 patients-46%), and those detected incidentally on pathological study of the surgical specimen (71 patients-15%). Method of detection was correlated with age and sex of the patient, and size, stage, and nodal status of the tumor. RESULTS: Patients in the Palpation group were more likely to be female (79% vs. 67% vs. 74%), younger (46 vs. 51 vs. 52), and to have larger tumors than those in the Imaging or Incidental groups. In the Imaging group, the tumor was detected on thyroid sonogram in 98 (53%), computed tomography in 38 (21%), magnetic resonance imaging in 19 (10%), carotid duplex scan in 14 (8%), and positron-emission tomography or other imaging studies in 15 (8%). Thirty-three percent of tumors <1 cm, 51% 1-2 cm, 29% 2-4 cm, and 38% >4 cm were first detected on an imaging study. Forty-seven percent of Stage III and IV cancers in patients aged ≥45 years and 39% of patients with positive central nodes were in the Imaging group. CONCLUSION: This study demonstrates that while most tumors discovered by imaging were small and early stage, almost half of advanced (Stage III and IV) WDTCs were initially discovered by imaging studies. These findings are consistent with the hypothesis that the frequent use of imaging studies may explain not only the increasing incidence of early WDTC, but more advanced thyroid cancers as well.

Laparoscopic gastric banding resolves the metabolic syndrome and improves lipid profile over five years in obese patients with body mass index 30-40 kg/m(2.).

BACKGROUND: Obesity, metabolic syndrome (MS) and dyslipidemia are independent risk factors for cardiovascular disease. Bariatric surgery is increasingly recognized as an effective intervention for improving each of these risk factors. There are sparse data on the long-term durability of metabolic changes associated with bariatric surgery, in particular with laparoscopic gastric banding (LGB). Our objective was to evaluate the durability of metabolic changes associated with LGB in nonmorbid obesity. METHODS: Fifty obese patients (BMI 30-40) with ≥1 obesity-related comorbidity were prospectively followed for five years. At follow-up, subjects underwent fasting blood measures, including lipid NMR spectroscopy and standard lipid profile. RESULTS: Forty-seven patients (45 female, mean age 43.8 years) completed four years follow-up (46 completed five years). Baseline BMI was 35.1 ± 2.6. Subjects exhibited mean weight loss of 22.3 ± 7.9 kg (22.9 ± 7.4%) at year one and maintained this (19.8 ± 10.2%) over five years. At baseline, 43% (20/47) of subjects met criteria for MS. This was reduced to 15% (7/47) at year one and remained reduced over five years (13%, 6/46) (p < 0.001). There were reductions in triglycerides (p < 0.001) and increases in HDL cholesterol (HDL-C, p < 0.001) and HDL particle concentration (p = 0.02), with a trend toward increased HDL particle size (p = 0.06) at year five. Changes in triglycerides and HDL-C were more prominent in patients with MS at baseline, but unassociated with weight loss or waist circumference. Changes in HDL particle size and concentration were not associated with MS status, weight loss, waist circumference, or statin use. CONCLUSIONS: LGB produces significant weight loss, resolution of MS and changes in lipid profile suggestive of beneficial HDL remodeling. These changes persist five years following LGB.

Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma.

BACKGROUND: BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS: Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS: A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION: IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.