Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis,Management, and Literature Review

Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation.     

Impact of Delta Hemoglobin on Provider Transfusion Practices and Post-operative Morbidity Among Patients Undergoing Liver and Pancreatic Surgery

Background

Delta hemoglobin (ΔHb) is defined as the difference between the preoperative Hb and the lowest post-operative Hb level. We sought to define the impact of ΔHb relative to nadir Hb levels on the likelihood of transfusion, as well as characterize the impact of ΔHb and nadir Hb on morbidity among a large cohort of patients undergoing complex hepatopancreatobiliary (HPB) surgery.

Methods

Patients who underwent pancreatic or hepatic resection between January 1, 2009 and June 30, 2015 at Johns Hopkins Hospital were identified. Data on the perioperative ΔHb, nadir Hb, as well as blood utilization were obtained and analyzed. Multivariable logistic regression models were used to identify the factors associated with ΔHb and the impact of ΔHb on perioperative morbidity. A Bayesian model was used to evaluate the correlation of ΔHb and nadir Hb with the likelihood of transfusion, as well as the impact on morbidity.

Results

A total of 4363 patients who underwent hepatobiliary (n?=?2200, 50.4 %) or pancreatic (n?=?2163, 49.6 %) surgery were identified. More than one quarter of patients received at least one unit of packed red blood cells (PRBC) (n?=?1187, 27.2 %). The median nadir Hb was 9.2 (IQR 7.9–10.5)?g/dL resulting in an average ΔHb of 3.4 mg/dL (IQR 2.2–4.7) corresponding to 26.3 %. Both ΔHb and nadir Hb strongly influenced provider behavior with regards to use of transfusion. Among patients with the same nadir Hb, ΔHb was strongly associated with use of transfusion; among patients who had a nadir Hb ≤6 g/dL, the use of transfusion was only 17.9 % when the ΔHb?=?10 % versus 49.1 and 80.9 % when the ΔHb was 30 or 50 %, respectively. Perioperative complications occurred in 584 patients (13.4 %) and were more common among patients with a higher value of ΔHb, as well as patients who received PRBC (both P?<?0.001).

Conclusions

The combination of the Hb trigger with ΔHb was associated with transfusion practices among providers. Larger ΔHb values, as well as receipt of transfusion, were strongly associated with risk of perioperative complication following HPB surgery.

     

Imaging Surveillance of Hypervascular Liver Lesions in Non-Cirrhotic Patients

A consensus surveillance protocol is lacking for non-cirrhotic patients with hypervascular liver lesions presumed to represent hepatocellular adenomas. Patients with hypervascular liver lesions <5 cm not meeting criteria for focal nodular hyperplasia or hepatocellular carcinoma underwent surveillance with contrast-enhanced magnetic resonance imaging (MRI) 6, 12, and 24 months after baseline imaging. If lesions remained stable or decreased in size, then surveillance imaging was discontinued. Between 2011 and 2014, 116 patients with hypervascular liver lesions were evaluated. Seventy-nine patients were eligible for the surveillance protocol. Median follow-up was 24 months (range, 1–144 months). One patient (1 %) continued oral contraceptive pill (OCP) use and presented with hemorrhage requiring embolization 5 months after initial diagnosis. Ten patients (13 %) underwent elective embolization or surgical resection for size ≥5 cm. The remaining 68 patients (86 %) continued surveillance without hemorrhage or malignant transformation. Risk factors for requiring intervention during the surveillance period included younger age, larger lesion size, and estrogen use (all p?<?0.05). Patients with hepatocellular adenomas <5 cm can safely be observed after discontinuing OCP with serial imaging 6, 12, and 24 months after diagnosis. If lesions remain stable or decrease in size, then longer-term surveillance is unlikely to identify patients at risk for complications.     

Readmission Following Gastric Cancer Resection: Risk Factors and Survival

Background

This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival.

Methods

Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted.

Results

Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p?<?0.0128), American Society of Anesthesiology status ≥3 (p?=?0.0045), preexisting cardiac disease (p?<?0.0001), hypertension (p?=?0.0142), history of smoking (p?=?0.0254), increased preoperative blood urea nitrogen (BUN; p?=?0.0426), concomitant pancreatectomy (p?=?0.0056), increased operation time (p?=?0.0384), estimated blood loss (p?=?0.0196), 25th percentile length of stay (<7 days, p?=?0.0166), 75th percentile length of stay (>12 days, p?=?0.0256), postoperative complication (p?<?0.0001), and total gastrectomy (p?=?0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6–3.3, p?<?0.0001), postoperative complication (OR 2.3, 95 % CI 1.6–5.4, p?<?0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1–4.1, p?=?0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p?=?0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p?=?0.0002).

Conclusions

Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.

     

CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer

Background

Compared to the widely adopted 2–4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival.

Methods

Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992–2014 were reviewed.

Results

After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P?=?0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P?=?0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P?=?0.930).

Conclusions

Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.