Pancreatic cancer is one of the deadliest cancers due to early rapid metastasis and chemoresistance. Recently, epithelial to mesenchymal transition (EMT) was shown to play a key role in the pathogenesis of pancreatic cancer. To understand the role of caveolin-1 (Cav-1) in EMT, we overexpressed Cav-1 in a pancreatic cancer cell line, Panc 10.05, that does not normally express Cav-1. Here, we show that Cav-1 expression in pancreatic cancer cells induces an epithelial phenotype and promotes cell-cell contact, with increased expression of plasma membrane bound E-cadherin and β-catenin. Mechanistically, Cav-1 induces Snail downregulation and decreased activation of AKT, MAPK and TGFβ-Smad signaling pathways. In vitro, Cav-1 expression reduces cell migration and invasion, and attenuates doxorubicin-chemoresistance of pancreatic cancer cells. Importantly, in vivo studies revealed that Cav-1 expression greatly suppresses tumor formation in a xenograft model. Most interestingly, Panc/Cav-1 tumors displayed organized nests of differentiated cells that were totally absent in control tumors. Confirming our in vitro results, these nests of differentiated cells showed reexpression of E-cadherin and β-catenin at the cell membrane. Thus, we provide evidence that Cav-1 functions as a crucial modulator of EMT and cell differentiation in pancreatic cancer.

The study determines the effects of palm vitamin E on the gene expression of bone-formation-related genes in nicotine-treated rats. Male rats were divided into three groups: normal saline olive oil (NSO), nicotine olive oil (NO), and nicotine palm vitamin E (NE). The treatment was carried out in 2 phases. During the first 2 months, the NSO group received normal saline while the NO and NE groups received nicotine 7 mg/kg, 6 days a week, intraperitoneally. The following 2 months, normal saline and nicotine administration was stopped and was replaced with oral supplementation of olive oil for the NSO and NO groups and oral supplementation of palm vitamin E (60 mg/kg) for the NE group. Both femurs were harvested to determine the gene expression of bone morphogenetic protein-2 (BMP-2), Osterix (OSX), and Runt-related transcription factor 2 (RUNX2). Nicotine significantly downregulated the gene expression. This effect was reversed by palm vitamin E treatment. In conclusion, palm vitamin E may play a role in osteoblast differentiation and can be considered as an anabolic agent to treat nicotine-induced osteoporosis.

Background

The aim of this report is to address treatment outcomes of patients with early-stage seminoma in a single institution with special reference to patients with history of surgical violation of the scrotum.

Methods

Seventy four patients with pure seminoma were treated at King Hussein Cancer Center (Amman, Jordan) between 2003 and 2010. All patients underwent orchiectomy. All but 3 patients received adjuvant radiotherapy. Patients who underwent surgical violation of the scrotum prior to referral were managed by further excision or irradiation of the scrotal scar. The follow-up ranged from 1 to 200 months (mean, 33 months).

Results

At the time of follow-up; all but one patient remain alive. The 3-year relapse-free survival for the entire cohort was 95.9%. Three patients developed relapse, all of whom received adjuvant irradiation following inguinal orchiectomy and initially harbored tumors larger than 4 cm upon pathological examination. Median time to relapse was 14 months (range, 8–25 months). None were associated with elevated tumor markers prior to detection of relapse. All but one patient were successfully salvaged by chemotherapy.

Conclusions

Our results confirm the excellent prognosis of patients with early-stage seminoma treated by orchiectomy and adjuvant radiotherapy in a developing country. Although all patients who developed relapse demonstrated adverse pathological findings upon initial assessment, no consistent predictor of relapse was found. Scrotal scar re-excision or irradiation in patients with prior history of surgical violation of the scrotum are effective measures in preventing local failure.

Strongyloides stercoralis is an intestinal nematode that is able to infect the host tissue and persist asymptomatic for many years through autoinfection. It causes life-threatening hyperinfection in immunocompromised hosts. This report describes a rare case of strongyloidiasis in a 40-year-old male following renal transplant, which was diagnosed by colonoscopic biopsy. The literature on the subject is also reviewed.

Background

The optimal time sequences for chemotherapy and radiation therapy after breast surgery for patients with breast cancer remains unknown. Most of published studies were done for early breast cancer patients. However, in Egypt advanced stages were the common presentation. This retrospective analysis aimed to assess the optimum sequence for our population.

Methods

267 eligible patients planned to receive adjuvant chemotherapy [FAC] and radiotherapy. Majority of patients (87.6%) underwent modified radical mastectomy while, 12.4% had conservative surgery.

We divided the patients into 3 groups according to the sequence of chemotherapy and radiotherapy. Sixty-seven patients (25.1%) received postoperative radiotherapy before chemotherapy [group A]. One hundred and fifty patients (56.2%) were treated in a sandwich scheme (group B), which means that 3 chemotherapy cycles were given prior to radiotherapy followed by 3 further chemotherapy cycles. A group of 50 patients (18.7%) was treated sequentially (group C), which means that radiotherapy was supplied after finishing the last chemotherapy cycle. Patients' characteristics are balanced between different groups.

Results

Disease free survival was estimated at 2.5 years, and it was 83.5%, 82.3% and 80% for patient receiving radiation before chemotherapy [group A], sandwich [group B] and after finishing chemotherapy [group C] respectively (p > 0.5). Grade 2 pneumonitis, which necessitates treatment with steroid, was detected in 3.4% of our patients, while grade 2 radiation dermatitis was 17.6%. There are no clinical significant differences between different groups regarded pulmonary or skin toxicities.

Conclusion

Regarding disease free survival and treatment toxicities, in our study, we did not find any significant difference between the different radiotherapy and chemotherapy sequences.

Introduction

Cigarette smoke and nicotine are among the leading environmental risk factors for developing pancreatic ductal adenocarcinoma (PDA). We showed recently that nicotine induces osteopontin (OPN), a protein that plays critical roles in inflammation and tumor metastasis. We identified an OPN isoform, OPNc, that is selectively inducible by nicotine and highly expressed in PDA tissue from smokers. In this study, we explored the potential proinflammatory role of nicotine in PDA through studying its effect on the expression of monocyte chemoattractant protein- (MCP)-1 and evaluated the role of OPN in mediating these effects.

Methods

MCP-1 mRNA and protein in PDA cells treated with or without nicotine (3–300 nM) or OPN (0.15–15 nM) were analyzed by real time PCR and ELISA. Luciferase-labeled promoter studies evaluated the effects of nicotine and OPN on MCP-1 transcription. Intracellular and tissue colocalization of OPN and MCP-1 were examined by immunofluorescence and immunohistochemistry.

Results

Nicotine treatment significantly increased MCP-1 expression in PDA cells. Interestingly, blocking OPN with siRNA or OPN antibody abolished these effects. Transient transfection of the OPNc gene in PDA cells or their treatment with recombinant OPN protein significantly (P<0.05) increased MCP-1 mRNA and protein and induced its promoter activity. MCP-1 was found in 60% of invasive PDA lesions, of which 66% were smokers. MCP-1 colocalized with OPN in PDA cells and in the malignant ducts, and correlated well with higher expression levels of OPN in the tissue from patients with invasive PDA.

Conclusions

Our data suggest that cigarette smoking and nicotine may contribute to PDA inflammation through inducing MCP-1 and provide a novel insight into a unique role for OPN in mediating these effects.

Objectives. Adhesive intestinal obstruction (AIO) is rare in the pediatric age group and its treatment is still controversial. This is a retrospective review of our experience in infants and children with AIO. Patients and Methods. The records of infants and children with AIO between January 2001 and December 2010 were retrospectively reviewed for age at diagnosis, sex, initial operation, interval between initial operation and presentation, diagnosis, treatment and outcome. Results. 44 infants and children were admitted with AIO. There were 28 males and 16 females who had 46 episodes. Their ages at presentation ranged from 1 month to 12 years (mean 5.4 years), while their ages at initial operation ranged from 2 days to 12 years (mean 4.15 years). Time elapsed from initial operation to presentation ranged from 7 days to 8 years (mean 1.5 years), and 66% developed AIO within 1 year from initial operation. Appenedecectomy was the commonest operation (29.5%). Four (9%) responded to conservative treatment. The other 40 (91%) required surgical intervention. Twenty-nine had release of adhesions only, while 10 (25%) had resection of small intestines and one underwent stricturoplasty. Two developed recurrence and one died. Conclusions. AIO is rare in the pediatric age group and the majority becomes symptomatic within 1 year of operation. Appendecectomy is the commonest operation leading to AIO. The place of conservative treatment is limited and to obviate delay and decrease the chance of intestinal ischemia, they should be treated early with surgical adhesiolysis.

Swallowed foreign bodies are common in the pediatric age group, but fortunately, the majority of them pass spontaneously without any adverse effects. Tube gastrostomy is an excellent method to provide prolonged enteral feeding. It is, however, associated with complications, namely, intraperitoneal leak and distal migration of the gastrostomy tube causing gastric outlet obstruction. This paper describes two unusual gastrointestinal foreign bodies, one was swallowed, while the other one was a complication of a tube gastrostomy.

Congenital paraesophageal hernia is rare in infants and children. This paper describes our experience with seven infants and children with congenital paraesophageal hernia with emphasis on two sisters who presented with unusually large paraesophageal hernias and herniation of most of the stomach resulting in intrathoracic gastric volvolus. The literature on the subject is also reviewed.

AIM: To evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis in patients with sickle cell anemia (SCA) in the era of laparoscopic cholecystectomy (LC).

METHODS: Two hundred and twenty four patients (144 male, 80 female; mean age, 22.4 years; range, 5-70 years) with SCA underwent ERCP as part of their evaluation for cholestatic jaundice (CJ). The indications for ERCP were: CJ only in 97, CJ and dilated bile ducts on ultrasound in 103, and CJ and common bile duct (CBD) stones on ultrasound in 42.

RESULTS: In total, CBD stones were found in 88 (39.3%) patients and there was evidence of recent stone passage in 16. Fifteen were post-LC patients. These had endoscopic sphincterotomy and stone extraction. The remaining 73 had endoscopic sphincterotomy and stone extraction followed by LC without an intraoperative cholangiogram.

CONCLUSION: In patients with SCA and cholelithiasis, ERCP is valuable whether preoperative or postoperative, and in none was there a need to perform intraoperative cholangiography. Sequential endoscopic sphincterotomy and stone extraction followed by LC is beneficial in these patients. Endoscopic sphincterotomy may also prove to be useful in these patients as it may prevent the future development of biliary sludge and bile duct stones.

Thromboembolism (TE) is a serious but under-recognized complication of inflammatory bowel disease (IBD). This is specially so in developing countries where the incidence of IBD is low. In Saudi Arabia, IBD is considered to be rare, but the incidence is increasing. Where the clinical manifestations resemble those of developed countries, TE as a complication of IBD is considered to be very rare. This report describes six IBD patients with TE. This importance of the complication of TE is stressed, and physicians caring for these patients should be aware of it in order to obviate potential morbidity and mortality.

Sickle cell disease is one of the common hemoglobinopathies in the world. It can affect any part of the body and one of the most common and an early organ to be affected in SCA is the spleen. It is commonly enlarged during the first decade of life but then undergoes progressive atrophy leading to autosplenectomy. This however is not the case always and sometimes splenomegaly persist necessitating splenectomy for a variety of reasons including acute splenic sequestration crisis, hypersplenism, massive splenic infarction and splenic abscess. Splenic complications of SCA are known to be associated with an increased morbidity and in some it may lead to mortality. To obviate this, splenectomy becomes an essential part of their management. This review is based on our experience in the management of 173 children with various splenic complications of SCA necessitating splenectomy.

Roux-en-Y gastric bypass is a common surgical procedure used to treat patients with morbid obesity. One of the rare, but potentially fatal complications of gastric bypass is upper gastrointestinal bleeding, which can pose diagnostic and therapeutic dilemmas. This report describes a 39-year-old male with morbid obesity who underwent a Roux-en-Y gastric bypass. Three months postoperatively, he sustained repeated and severe upper attacks of upper gastrointestinal bleeding. He received multiple blood transfusions, and had repeated upper and lower endoscopies with no diagnostic yield. Finally, he underwent laparoscopic endoscopy which revealed a bleeding duodenal ulcer. About 5 ml of saline with adrenaline was injected, followed by electrocoagulation to seal the overlying cleft and blood vessel. He was also treated with a course of a proton pump inhibitor and given treatment for H pylori eradication with no further attacks of bleeding. Taking in consideration the difficulties in accessing the bypassed stomach endoscopically, laparoscopic endoscopy is a feasible and valuable diagnostic and therapeutic procedure in patients who had gastric bypass.

AIM: To evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) in patients with sickle cell disease (SCD).

METHODS: Two hundred and twenty four SCD patients with cholestatic jaundice (CJ) had ERCP. The indications for ERCP were based on clinical and biochemical evidence of CJ and ultrasound findings.

RESULTS: Two hundred and forty ERCPs were performed. The indications for ERCP were: CJ only in 79, CJ and dilated bile ducts without stones in 103, and CJ and bile duct stones in 42. For those with CJ only, ERCP was normal in 42 (53.2%), and 13 (16.5%) had dilated bile ducts without an obstructive cause. In the remaining 22, there were bile duct stones with or without dilation. For those with CJ, dilated bile ducts and no stones, ERCP was normal in 17 (16.5%), and 28 (27.2%) had dilated bile ducts without an obstructive cause. In the remaining 58, there were bile ducts stones with or without dilation. For those with CJ and bile duct stones, ERCP was normal in two (4.8%), and 14 (33.3%) had dilated bile ducts without an obstructive cause. In the remaining 26, there were bile duct stones with or without dilatation.

CONCLUSION: Considering the high frequency of biliary sludge and bile duct stones in SCD, endoscopic sphincterotomy might prove helpful in these patients.

Background

This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection.

Methods

PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stimulation. PBMC from five healthy subjects were cultured for 7 days, flow cytometric analysis of DNA content was used to assess the mitogenic effect of SEA on PBMC proliferation compared to phytoheamaglutinine (PHA).

Results

Quantification of the intracellular viral load showed increased copy number/cell of both or either viral strands after induction with SEA in 18 of 26 patients (69.2%) thus indicating stimulation of viral replication. Flow cytometric analysis showed that mean ± S.D. of percent values of cell proliferation was induced from 3.2 ± 1.5% in un-stimulated cells to 16.7 ± 2.5 % and 16.84 ± 1.7 % in cells stimulated with PHA and SEA respectively.

Conclusion

the present study supports earlier reports on SEA proliferative activity on PBMC and provides a strong evidence that the higher morbidity observed in patients co-infected with schistosomiasis and HCV is related, at least in part, to direct stimulation of viral replication by SEA.