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Background: Diagnosis of depression may be associated with adverse outcomes following surgery. The aim of this study is to investigate whether depression is associated with an increased readmission rate following elective pancreatectomy, which is currently unknown. Methods: The 2014 Nationwide Readmissions Database was used to evaluate whether diagnosis of depression was associated with 30-day readmission following elective pancreatectomy in adult patients. Univariate and multivariate logistic regression models were adjusted for clustering by facility. A secondary analysis was performed to evaluate whether the risk of diagnosis of depression on 30-day readmission rates was modified by length of stay (median 8 days). All multivariate models were adjusted for patient-level characteristics. Results: There were an estimated 11,992 patients who underwent elective pancreatectomy. Mean age was 63 years, and 48.9% were male. Approximately 10.2% (n = 1223) had diagnosis of depression. Depression was associated with higher odds of 30-day readmission following elective pancreatectomy on univariate [odds ratio (OR) 1.26, 95% confidence interval (CI) 1.01–1.59; P = 0.043] and multivariate analyses (OR 1.29, 95% CI 1.01–1.65; P = 0.039). Although length of stay > 8 days was independently associated with higher odds of 30-day readmission (P = 0.005), length of stay did not alter the association between diagnosis of depression and odds of readmission (P = 0.90). Conclusions: Diagnosis of depression was associated with higher odds of 30-day readmission following pancreatectomy, regardless of length of stay. Enhanced focus on evaluation and optimization of perioperative mental health is warranted to identify patients at high risk for readmission and reduce the burden related to readmission following pancreatic surgery. [ABSTRACT FROM AUTHOR]

Background: Dexamethasone is administered intraoperatively to prevent anesthesia-related nausea and vomiting and to reduce postoperative opioid administration. However, the adverse effects of corticosteroids on anastomotic healing and wound infection as well as oncologic outcomes remain unclear. We analyzed the effect of intraoperative dexamethasone administration on surgical outcomes after pancreaticoduodenectomy and on long-term survival in pancreatic cancer patients.Methods: A total of 679 pancreaticoduodenectomies from a prospectively maintained database were analyzed. Surgical outcomes were compared between patients who received intraoperative dexamethasone and those who did not. Kaplan-Meier curves and Cox-regression survival analysis were performed in patients with pancreatic cancer. A propensity analysis was done to reduce the inherent bias of retrospective design.Results: Patients who received dexamethasone (117, 17.2%) were younger and more likely to be female than those who did not (p = 0.001). Overall and 30-day major morbidity were similar among all resected patients, although there were fewer infectious complications in the dexamethasone group (18.8% vs. 28.5%, p = 0.032). In pancreatic cancer patients, dexamethasone was associated with significantly improved median overall survival (46 vs. 22 months, p = 0.017). This effect occurred independently of stage, pathologic characteristics, or adjuvant therapy, with adjusted hazard ratios, derived from pre-propensity and post-propensity analysis, of 0.67 (0.47-0.97) and 0.57 (0.37-0.87), respectively.Conclusions: A single intraoperative dose of dexamethasone did not increase morbidity after pancreaticoduodenectomy and, in fact, was associated with a decrease in infectious complications. The treatment was independently associated with improved overall survival in patients with pancreatic adenocarcinoma, an effect that cannot be explained and needs further validation in a prospective setting. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the use of chest imaging in pancreatic ductal adenocarcinoma (PDAC) patients. Among PDAC patients, we examined the use of chest computed tomography (CT) over time and determined whether the use of chest CT led to a survival difference or change in management via identification of indeterminate lung nodules (ILNs).Methods: Retrospective clinical data was collected for patients diagnosed with PDAC from 1998 to 2014. We examined the proportion of patients undergoing staging chest CT scan and those who had ILN, defined as ≥ 1 well-defined, noncalcified lung nodule(s) ≤ 1 cm in diameter. We determined time to overall survival (OS) using multivariate Cox regression. We also assessed changes in management of PDAC patients who later developed lung metastasis only.Results: Of the 2710 patients diagnosed with PDAC, 632 (23%) had greater than one chest CT. Of those patients, 451 (71%) patients had ILNs, whereas 181 (29%) had no ILNs. There was no difference in median overall survival in patients without ILNs (16.4 [13.6, 19.0] months) versus those with ILN (14.8 [13.6, 15.8] months, P = 0.18). Examining patients who developed isolated lung metastases (3.3%), we found that staging chest CTs did not lead to changes in management of the primary abdominal tumor.Conclusions: Survival did not differ for PDAC patients with ILNs identified on staging chest CTs compared with those without ILNs. Furthermore, ILN identification did not lead to changes in management of the primary abdominal tumor, questioning the utility of staging chest CTs for PDAC patients. [ABSTRACT FROM AUTHOR]

Background: Recent advances in imaging and the increasing use of neoadjuvant therapy puts the contemporary utility of staging laparoscopy for patients with pancreatic adenocarcinoma (PDAC) into question. This study aimed to develop a prognostic score to optimize prevention of an unnecessary laparotomy and minimize the rate for unnecessary laparoscopy. Methods: Clinicopathologic data were evaluated for all patients undergoing surgical intervention for PDAC between 2001 and 2015, who were stratified into group 1 (2001-2008) and group 2 (2009-2014). Results: The study identified 1001 patients eligible for analysis, 331 (33%) of whom underwent a staging laparoscopy before exploration. An unnecessary laparotomy was prevented for 44.4% of the patients in period 1 and for 24% of the patients in period 2 ( p < 0.001). Male gender [odds ratio (OR), 1.8; p < 0.05], preoperative resectability (borderline resectable OR 2.1; p < 0.019; locally advanced OR 7.6; p < 0.001), CA 19-9 levels higher than 394 U/L (OR 3.1; p < 0.001), no neoadjuvant chemotherapy (OR 2.7; p = 0.012), and pancreatic body or tail lesions (OR 1.8; p = 0.063) were predictive of occult metastatic disease. The developed scoring index demonstrated a c-statistic of 0.729. The observed-to-expected ratio for the index at every score level validated the index's model. A score cutoff at 4 was able to detect 76.1% of radiographically occult metastatic disease. Conclusion: The rate for unnecessary laparotomy among patients with PDAC has decreased in contemporary times, but unnecessary laparotomy still occurs for 1 in 4 patients. Using our scoring system, a cutoff of 4 allows 76% of radiographically occult metastases to be predicted, thereby selecting high-risk patients for laparoscopic biopsy and potentially avoiding a non-therapeutic laparotomy. [ABSTRACT FROM AUTHOR]

Background: The staging of pancreatic neuroendocrine tumors (PNETs) is continuously evolving. Mitotic count, as measured by hematoxylin and eosin (H&E) or Ki67 labeling index (Ki67LI), is the best predictor of disease biology. However, both of these methods have several limitations. Phosphorylated histone H3 (PHH3), a novel mitotic marker, is potentially more accurate and easier to evaluate. This study aimed to evaluate the prognostic impact of PHH3 on patients with PNETs. Methods: Clinicopathologic data and paraffin-embedded tissue were evaluated for 100 of the 247 PNET patients whose tumors were resected between 1998 and 2010. Mitotic counts were analyzed on H&E-, Ki67-, and PHH3-stained slides by two independent pathologists. Kaplan-Meier curves, log-rank tests, Cox regression models, and time-dependent receiver operative characteristics (ROC) curves were used to evaluate the prognostic power of these markers. An internal data cross-validation was performed to select the best cutoff. Results: Of the 100 PNET patients resected, 53 were men. The median age of the patients was 59 years (range 19-96 years). The median follow-up period was 68 months (range 3-186 months). The median time for evaluation of an H&E- or PHH3-stained slide was 3 min, relative to 15 min for Ki67. The findings showed H&E, Ki67, and PHH3 all to be excellent predictors of disease-specific survival (DSS). However, PHH3 was superior to H&E and Ki67 in predicting both disease-free survival (DFS) ( p = 0.006) and DSS ( p = 0.001). Evaluation of the PHH3 mitotic count showed 7 mitoses per 10 high-power fields (HPFs) to be the optimal cutoff for differentiating between low- and high-risk PNET patients. Conclusions: PHH3 is a better predictor of both DFS and DSS than H&E or Ki67 in PNET. In addition, PHH3 appears to be both easier to interpret and more accurate when compared to current prognostic markers. [ABSTRACT FROM AUTHOR]

High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/μl was used to define high platelet count. Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2–178) months. The median survival of the high platelet group was 18 (2–137) months, and that of the low platelet group was 15 (2–178) months ( p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19–9 > 200 U/ml were all significantly associated with poor survival. There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19–9 are predictors of poor survival in resected pancreatic cancer. [ABSTRACT FROM AUTHOR]

Hedgehog signalling-an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer-may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis. [ABSTRACT FROM AUTHOR]

The testosterone:dihydrotestosterone ratio (T:DHT) and the antigenic marker CA 19-9 were studied in the serum of 21 male patients with pancreatic cancer and 62 controls with other gastrointestinal malignancies or benign pancreatobiliary disease. Specificity of the T:DHT ratio was 98%, significantly better than the specificity of CA 19-9 at both a 37 U/ml cutoff level (61%) and at 100 U/ml (79%). Sensitivity+ of the T:DHT ratio was 67%, and that of CA 19-9, 71% and 90% at the upper and lower cutoff levels, respectively. False-negative results of the T:DHT ratio were found predominantly in cases of advanced pancreatic cancer, whereas all four stage I patients had an abnormal (< 5) T:DHT ratio. These results suggest that the T:DHT ratio is a useful marker for pancreatic cancer in males. It can be used alone or in combination with CA 19-9, and should be further evaluated in the differential diagnosis of patients with the early stages of this disease. [ABSTRACT FROM AUTHOR]

Background: Possible mass lesions identified on ultrasound (US) of the gallbladder may prompt an aggressive surgical intervention due to the possibility of a malignant neoplasm. Aim: This study aims to utilize a large modern series of patients with gallbladder lesions identified on US to evaluate imaging characteristics consistent with malignancy. Methods: A retrospective review was conducted of gallbladder ultrasound reports and clinicopathologic data of patients with a mass identified on US. Results: Approximately 59,271 abdominal ultrasounds and 9,117 cholecystectomies were performed between February 2000 and February 2010. We identified 213 patients with a questionable gallbladder neoplasm on ultrasonography who underwent surgical exploration. Median age was 52 years (range = 11–87 years) and 147 (69%) were females. Final pathology demonstrated no neoplasm in 130 patients (61%), while 32 patients (15%) had a wall adenomyoma, 36 (17%) had a polyp (five of which were malignant), 14 (7%) had an adenocarcinoma not arising from a polyp, and one patient had a cystic papillary neoplasm. The smaller the lesion, the more likely it was to be a pseudo-mass. For lesions measuring <5 mm on US, 83% had no lesion found on final pathology. Significant predictors of malignancy were age >52 years (p < 0.001), presence of gallstones on US (p = 0.004), size >9 mm (p < 0.001), evidence of invasion at the liver interface (p < 0.001), and wall thickening >5 mm (p < 0.001). Shape (sessile or penduculated), echogenicity (echogenic or isoechoic), or presence of flow on Doppler were not predictors of malignancy. An US size of ≤9 mm had a negative predictive value of 100% for malignancy. Conclusions: Despite improvements in imaging, most apparent lesions measuring <5 mm on US are not identified in the surgical specimen. US size >9 mm, age >52 years, US suggestion of invasion at the liver interface, and wall thickening >5 mm, especially in the presence of gallstones, should raise the suspicion of malignancy.

Portal hypertension often leads to collateralization of blood flow via variceal vessels that shunt blood from the portal to the systemic circulation. Rupture of an intra-abdominal varix is an unusual complication of portal hypertension that can lead to life-threatening hemoperitaneum. We describe a patient with portal hypertension secondary to liver cirrhosis who presented with acute Intra-abdominal hemorrhage. At loparotomy, she was found to have a rupture of the umbilical vein. The vessel was ligated, and the patient recovered uneventfully. The causes of hemoperitoneum in cirrhosis are discussed, and the previously reported cases of intra-abdominal variceal bleeding are reviewed. [ABSTRACT FROM AUTHOR]