Yasir Akmal

Prediction of malignancy in cystic neoplasms of the pancreas: A population-based cohort study

OBJECTIVES:Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN.METHODS:We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features.RESULTS:We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1–5%), and high (9–14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing).CONCLUSIONS:Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.

Ganglioneuroma of the adrenal gland and retroperitoneum: A case report

Context: Ganglioneuromas are benign tumors of the sympathetic nervous system that rarely arise in the adrenal gland. Majority of cases are detected incidentally since they are usually asymptomatic. Up to the current era of laparoscopic adrenal mass excision, this unusual entity has not been adequately reported in the surgical literature. Case Report: A 51 year old male with history of hypertension was found to have abdominal bruit during a regular physical examination. A 4 cm right adrenal mass with upper pole calcification and a 6 cm retro-pancreatic mass were subsequently found on a computed tomography scan. Endoscopic ultrasound-guided needle biopsy was indeterminate. Preoperative endocrine evaluation showed mildly elevated vanillyl mandelic acid with normal 24-hour cathecolamine, metanephrine and cortisol levels. Histopathologic examination after an uneventful laparoscopic excision was consistent with ganglioneuroma. Conclusions: Ganglioneuroma occurs rarely in adrenal gland and preoperative diagnosis is difficult since symptoms are usually nonspecific. Due to widespread utilization of abdominal imaging, however, it should be included in differential diagnosis of adrenal or retroperitoneal mass. Histopathologic examination is currently the mainstay of diagnosis.

Identification of a Natural Compound by Cell-Based Screening That Enhances Interferon Regulatory Factor-1 Activity and Causes Tumor Suppression

The transcription factor interferon regulatory factor-1 (IRF-1) is induced by many tumor-suppressive stimuli and can mediate antiproliferative and proapoptotic effects in cancer cells. Thus, identifying agents that enhance IRF-1 activity may be an effective approach to cancer therapy. A cell-based screening assay was developed to identify extracts and compounds that could enhance IRF-1 activity, using an IRF-1–dependent luciferase reporter cell line. Through this approach, we identified a natural product extract and a known active component of this extract, baicalein, which causes a marked increase in IRF-1–dependent reporter gene expression and IRF-1 protein, with modulation of known IRF-1 targets PUMA and cyclin D1. Baicalein causes suppression of growth in vitro in multiple cancer cell lines in the low micromolar range. IRF-1 plays a role in this growth suppression as shown by significant resistance to growth suppression in a breast cancer cell line stably transfected with short hairpin RNA against IRF-1. Finally, intraperitoneal administration of baicalein by repeated injection causes inhibition of growth in both xenogeneic and syngeneic mouse models of cancer without toxicity to the animals. These findings indicate that identifying enhancers of IRF-1 activity may have utility in anticancer therapies and that cell-based screening for activation of transcription factors can be a useful approach for drug discovery. Mol Cancer Ther; 10(10); 1774–83. ©2011 AACR.

Spontaneous massive hemoperitoneum: A potentially life threatening presentation of the wandering spleen

Context: Wandering spleen is an unusual condition characterized by the absence or maldevelopment of one or all of the ligaments securing the spleen in its normal position in the left upper abdomen. Pedicular tortion with a complete vascular disruption is a rare but known potential complication of this mostly congenital disorder. Spontaneous hemoperitoneum with acute abdomen however, is a life threatening situation that has not been adequately reported in the adult literature. Case Report: A forty four year old man presented to the emergency department with an acutely distended and rigid abdomen. His past medical history was only significant for mild mental retardation. The patient denies prior abdominal operation or recent trauma. On initial examination, he appeared to be anxious, pale, and tachycardic. Fullness in the midpelvic region was easily appreciated on palpation. An enlarged pelvic spleen and free intraperitoneal fluid consistent with blood were seen on a CT scan. The patient was promptly taken for an exploratory laparotomy where a large rush of blood was encountered upon entering the abdomen. A volvulus of the splenic pedicle with an infarcted spleen was found mandating a splenectomy. Conclusions: Abnormally located spleen, splenomegaly, and finding of hemoperitoneum are highly suggestive of wandering spleen with tortioned pedicle. Despite its life threatening presentation, immediate laparotomy and splenectomy invariably result in good outcome.