Pancreatico-gastric fistula arising from IPMN associated with ductal adenocarcinoma of the pancreas: a case report and a literature review.

Introduction: An intraductal papillary mucinous neoplasm (IPMN) is a potentially malignant cystic tumor that is characterized by an excessive papillary proliferation of mucin-producing epithelial cells. The IPMN usually exhibits different degrees of dysplasia and is accompanied by cystic dilation of the main pancreatic duct (MPD) or side branch. We report a case of an IPMN that has penetrated the stomach and has differentiated into an adenocarcinoma. Case presentation: A 69-year-old female, suffering from chronic pancreatitis of unknown etiology, visited our outpatient clinic with complaints of sudden weight loss, diarrhea, and abdominal pain. She underwent several examinations to evaluate the reasons for her sudden onset of symptoms. A gastroscopy showed an ulcerated lesion covered with mucus. CT and magnetic resonance cholangiopancreatography images revealed that the MPD was dilated to 1.3 cm with a fistula formation between the MPD and the stomach. After a multidisciplinary discussion of this case, a total pancreatectomy was proposed. An en bloc total pancreatectomy with gastric wedge resection including the fistula together with splenectomy was carried out. A Roux-en-Y choledochojejunostomy and gastrojejunostomy were performed. Histology results revealed the association of IPMN with invasive carcinoma. Discussion: Many reports on IPMN of the pancreas have been published recently. Fistula formation between IPMN and adjacent organs is possible. Given the CT and endoscopic ultrasonography findings, it shows that in our case a main duct IPMN (MD-IPMN) formed a pancreatico-gastric fistula. We point out that the adherence of invasive cancer cells contributed to the fistula formation between the pancreas and the stomach. Conclusion: This case report provides evidence for the possibility of IPMN becoming complicated with pancreatico-gastric fistula. Thus, we suggest that surgical resection should be considered in the case of MD-IPMN because of its high propensity for malignant transformation.

Symptomatic ileocolic pseudoaneurysm following laparoscopic ileocecectomy for Crohn's disease: A case report.

INTRODUCTION: Crohn's disease is prevalent worldwide. It is an idiopathic, chronic and relapsing disease, characterized by chronic inflammation of any part of the gastrointestinal tract. Vascular involvement rarely occurs in Crohn's patients. However, the chronic inflammatory process leads to structural and functional changes in the vascular endothelium. We present a case of ileocolic artery pseudoaneurysm after laparoscopic ileocecectomy in a Crohn's patient. CASE PRESENTATION: We report a case of a 26-years-old male diagnosed with Crohn's disease 4 months prior to an elective laparoscopic ileocecectomy. Before the operation, the patient suffered from severe terminal ileitis and typhlitis with signs of micro perforation. 3 weeks following his discharge, the patient arrived at the ER complaining of severe right lower abdominal pain. Computerized Tomography (CT) scans revealed a 35 mm ileocolic pseudoaneurysm that was treated urgently with coil-embolization via angiography. DISCUSSION: Until recently, few reports regarding the involvement of pseudoaneurysm of mesenteric arteries in relation to bowel resection surgeries have been reported. It is believed that the chronic inflammatory process induces a potent effect on the vascular endothelium, leading to thick, inflamed and highly friable mesenteric vessel walls. We propose that the pseudoaneurysm occurred as a result of surgical intervention on a thickened and diseased mesentery artery branch. CONCLUSION: Inclusion of mesenteric resection in Crohn patients' undergoing bowel resection may be an innovative way to avoid this complication and to reduce recurrence.

Treatment of large incisional abdominal wall hernias, using a modified preperitoneal prosthetic mesh repair.

Very large and complex incisional hernias, especially those with loss of abdominal wall, can be a very interesting and perplexing problem, which present a particular challenge to the surgeon. The reported technique was developed and refined by one of our surgeons, between 1998 and 1999 for the repair of incisional hernias in a selected group of patients with large defects, often with a major loss of abdominal wall, overweight and previous attempts for incisional hernia repair. The technique involves a modified preperitoneal approach and was used on 43 eligible patients between 1999 and 2002. There were 30 females and 13 males at a mean age of 61 years. The median ASA score of the group was 2, with a mean BMI of 30.4 and a mean hernia surface area of 162 cm(2). One-third of the patients had one or more previous incisional hernia repair. Mean operating time was 190 min with an average hospital stay of 5.7 days. Postoperative complications occurred in 28% of the patients, most of which were minor and did not necessitate admission to the intensive care unit. None of the patients died. Wound infections occurred in 9.3%, was associated with an increased risk for cutaneous sinus formation, but not for mesh removal or hernia recurrence. A recurrence rate of 12.5% was found after a mean follow-up period of 46 months. We advocate this procedure for the repair of large, complex incisional hernias with loss of abdominal domain in patients with significant risk factors for recurrence.

Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101.

Adenosine is a purine nucleoside that acts as a regulatory molecule by binding to specific G-protein-coupled A1, A(2A), A(2B), and A3 cell surface receptors. We have recently demonstrated that adenosine inhibits tumour cell growth and concomitantly stimulates bone marrow cell proliferation via activation of the A3 adenosine receptor (A3AR). In the present study, we show that a synthetic agonist to the A3AR, CF101, at the low nanomolar concentration range, inhibits HCT-116 human colon carcinoma cell growth. This effect was reversed by the selective A3AR antagonist MRS1523, demonstrating the specificity of the response. CF101 (given orally) was efficacious in inhibiting the development of primary tumours in xenograft and syngeneic models in which mice were inoculated subcutaneously with human HCT-116 or murine CT-26 colon carcinoma cells, respectively. Moreover, CF101 suppressed (50%, P<0.01) colon cancer liver metastases in syngeneic mice inoculated to the spleen with CT-26 cells. The mechanism of action entailed upregulation of interleukin-12 production in the CF101-treated groups and potentiation of NK cell activity. In the HCT-116 xenograft model in which a combined therapy of CF101 and 5-fluorouracyl (5-FU) was examined, an additive antitumour effect was demonstrated. Moreover, CF101 prevented the 5-FU-induced myelotoxicity, resulting in normal values of white blood cell and neutrophil counts. We conclude that the A3AR agonist CF101, a small orally bioavailable molecule, exerts systemic anticancer, antimetastatic, and myeloprotective effects in colon carcinoma-bearing mice, and may serve as an adjuvant treatment to enhance the chemotherapeutic index and prevent myelotoxicity.

Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor.

Adenosine is an ubiquitous nucleoside present in all body cells. It is released from metabolically active or stressed cells and subsequently acts as a regulatory molecule through binding to specific A1, A2A, A2B and A3 cell surface receptors. The synthesis of agonists and antagonists to the adenosine receptors and their cloning enabled the exploration of their physiological functions. As nearly all cells express specific adenosine receptors, adenosine serves as a physiological regulator and acts as a cardioprotector, neuroprotector, chemoprotector, and as an immunomodulator. At the cellular level, activation of the receptors by adenosine initiates signal transduction mechanisms through G-protein associated receptors. Adenosine's unique characteristic is to differentially modulate normal and transformed cell growth, depending upon its extracellular concentration, the expression of adenosine cell surface receptors, and the physiological state of the target cell. Stimulation of cell proliferation following incubation with adenosine has been demonstrated in a variety of normal cells in the range of low micromolar concentrations, including mesangial and thymocyte cells, Swiss mouse 3T3 fibroblasts, and bone marrow cells. Induction of apoptosis in tumor or normal cells was shown at higher adenosine concentrations (>100 microM) such as in leukemia HL-60, lymphoma U-937, A431 epidermoid cells, and GH3 tumor pituitary cell lines. It was further noted that the A3 adenosine receptor (A3AR) plays a key role in the inhibitory and stimulatory growth activities of adenosine. Modulation of the A3AR was found to affect cell growth either positively or negatively depending on the concentration of the agonist, similar to the effect described for adenosine. At nanomolar concentrations, the A3AR agonists possess dual activity, i.e., antiproliferative activity toward tumor cells and stimulatory effect on bone marrow cells. In vivo, these agonists exerted anti-cancer effects, and when given in combination with chemotherapy, they enhanced the chemotherapeutic index and acted as chemoprotective agents. Taken together, activation of the A3AR, by minute concentrations of its natural ligand or synthetic agonists, may serve as a new approach for cancer therapy.

Interruptions to the physician-patient encounter: an intervention program.

BACKGROUND: Israeli physicians are very familiar with the problem of interruptions during encounters with patients. However, a thorough search of the medical literature revealed only one report of this problem from Israel, and none from other countries. OBJECTIVES: To characterize the phenomenon of interruptions to the patient-physician encounter in a clinic in Dimona and to assess the effect of an intervention program designed to reduce the magnitude of this problem. METHODS: During an 8 day work period in March 1997 all patient-physician encounters were recorded and characterized. An intervention program was then designed and implemented to reduce the number of interruptions. Data were again collected a year after the initial data collection. RESULTS: During the 8 day study period prior to the intervention program there were 528 interruptions to 379 encounters (mean of 1.39 per encounter). The main causes of interruptions were entrance of uninvited patients to the examination room (31%) and telephone calls (27%). Most of the interruptions occurred during the morning hours between 8 and 10 a.m. (45%) and at the beginning of the week (Sunday 30%). After the intervention program there were 402 interruptions to 355 encounters (mean of 1.13 per appointment, P = 0.21). CONCLUSIONS: There was no statistically significant improvement in the number of interruptions following the intervention program. This finding is either the result of a local cultural phenomenon, or it indicates a national primary care health system problem that may require a long-term educational program to resolve it. Further research is needed on the magnitude, causes and consequences of interruptions in family practice and, if warranted, methods will have to devised to cope with this serious problem.

Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor.

In this study, we demonstrated several mechanisms exploring the inhibitory effect of low-dose adenosine on lymphoma cell growth. Adenosine, a purine nucleoside present in plasma and other extracellular fluids, acts as a regulatory molecule, by binding to G-protein associated cell-surface receptors, A1, A2 and A3. Recently we showed that low-dose adenosine released by muscle cells, inhibits tumour cell growth and thus attributes to the rarity of muscle metastases. In the present work, a cytostatic effect of adenosine on the proliferation of the Nb2-11C rat lymphoma cell line was demonstrated. This effect was mediated through the induction of cell cycle arrest in the G0/G1 phase and by decreasing the telomeric signal in these cells. Adenosine was found to exert its antiproliferative effect mainly through binding to its A3 receptor. The cytostatic anticancer activity, mediated through the A3 adenosine receptor, turns it into a potential target for the development of anticancer therapies.

The value of early and double phase 99Tcm-sestamibi scintimammography in the diagnosis of breast cancer.

The aim of this study was to assess the additional value of early and double phase scintimammography (SMM) with 99Tcm-sestamibi in the detection of breast cancer following initial evaluation by palpation and mammography. Altogether, 322 women with breast lesions evaluated prospectively by palpation, fine-needle aspiration and mammography were assigned a malignancy risk according to the results. Scintimammography was performed in all patients in the prone breast dependent position. Immediate and delayed views were obtained. Acquisition of immediate tracer uptake was termed 'early phase' SMM, whereas a combination of both immediate and delayed phase images was termed 'double phase' SMM. All patients underwent breast biopsy. Both early phase and double phase SMM detected eight of nine tumours in the low-risk group (88.8% sensitivity). In the uncertain cases (moderate-risk group), early phase SMM detected all malignant tumours, but double phase SMM missed one (92.3% sensitivity). In the high-risk group, early phase SMM missed two breast cancers (94.6% sensitivity) and double phase SMM missed four (89.2% sensitivity). Overall, early phase SMM had a sensitivity of 94.9% and a specificity of 80.2% in detecting breast cancer, whereas double phase SMM had a sensitivity of 89.8% and a specificity of 94.3%. Both methods had 100% sensitivity for tumours larger than 1 cm. In conclusion, SMM detected additional breast cancers following an initial evaluation by palpation, fine-needle aspiration and mammography. Our results suggest that double phase SMM is more specific than early phase SMM, although early phase SMM is more sensitive. Whether the interpretation of SMM results should rely on both early and delayed images, or early images alone, should be based on the relative risk of malignancy of the breast lesion as estimated by the initial evaluation.

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: a role for A1 and A3 adenosine receptors.

Adenosine, a ubiquitous nucleoside, is released into the extracellular environment from metabolically active or stressed cells. It binds to cells through specific A1, A(2A), A(2B), and A3 G-protein-associated cell-surface receptors, thus acting as a signal-transduction molecule by regulating the levels of adenylyl cyclase and phospholipase C. In this study, we showed that adenosine stimulates the proliferation of murine bone marrow cells in vitro. Pharmacological studies, using antagonists to the adenosine receptors, revealed that this activity was mediated through the binding of adenosine to its A1 and A3 receptors. This result was further corroborated by showing that the two selective A1 and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) respectively, induced bone marrow cell proliferation in a manner similar to adenosine. Adenosine's interaction with its A1 and A3 receptors induced G-CSF production, which led to its stimulatory effect on bone marrow cells. These results were confirmed in vivo when we demonstrated that low-dose adenosine (0.25 mg/kg) acted as a chemoprotective agent. When administered after chemotherapy, it restored the number of leukocytes and neutrophils to normal levels, compared with the decline in these parameters after chemotherapy alone. It is suggested that low-dose adenosine, already in clinical use, may also be applied as a chemoprotective agent.

Double-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing breast cancer.

UNLABELLED: The goal of our study was to assess the value of both scintimammography with 99mTc-sestamibi (SMM) and trans-scan (T-scan) in detecting breast cancer. METHODS: A total of 121 women were evaluated by palpation, mammography, SMM and T-scan. SMM was performed in the prone, breast dependent position. Immediate and delayed views (double-phase) were obtained. T-scan is a new breast imaging method that maps noninvasively the distribution of tissue electrical impedance and capacitance. RESULTS: SMM had 88.9% sensitivity, 88.4% specificity and 88.4% accuracy in detecting breast cancer. SMM had 100% sensitivity in detecting breast tumors >1 cm and only 66% sensitivity in detecting tumors <1 cm. T-scan had 72.2% sensitivity and 67% specificity in detecting breast cancer. It detected one more breast cancer than SMM, at the expense of 27 additional false-positive results. CONCLUSION: Double-phase SMM was sensitive and specific in detecting breast cancer. This method may reduce the rate of negative breast biopsies in tumors >1 cm. T-scan was only moderately accurate in detecting breast cancer. Its addition to SMM did not improve significantly the rate of breast cancer detection. However, because of its complete noninvasiveness, large-scale applicability and low cost, T-scan deserves further refining.

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice.

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (< 1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16-F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread.

Comparative study of the early postoperative course and complications in patients undergoing Billroth I and Billroth II gastrectomy.

Distal gastric resection can be followed by reconstruction according to the Billroth I (BI) or Billroth II (BII) techniques. The aim of this study was to compare the early postoperative results and complications of patients undergoing BI and those undergoing BII resection. Eighty-eight patients operated during the years 1991 to 1994 underwent distal gastric resection (41 had BI, and 43 had BII resections). The indications for BI resections were gastric tumors in 39 patients (95%) and duodenal ulcer in 2 (5%). The indications for BII resection were malignancy in 28 patients (65%) and duodenal ulcer disease in 15 (35%). The average duration of the procedure was 147 +/- 28 minutes for the BI resection and 175 +/- 38 minutes for the BII resection (p < 0.05). No patient in the BI group developed anastomic leakage. Two patients who underwent BII resection developed duodenal stump leakage (4.7%). Relaparotomy was indicated in five patients, two from the BI group (malignant cells in the resection margins) and three from the BII group (one due to duodenal stump leakage and two for bleeding). There was no postoperative mortality in the BI group. The postoperative mortality in the BII group was 7.1% (p < 0.05). The average proximal gastric resection margins were significantly smaller in the BI group than in the BII group (3.65 +/- 2.83 cm and 5.18 +/- 2.57 cm, respectively; p < 0. 05). The number of lymph nodes found in the resected specimen did not differ significantly between the two groups. Recurrent tumor at the gastric remnant developed in two patients in the BI group but not in the BII group. The results of our study revealed that the BI procedure is accompanied by significantly lower postoperative complication and mortality rates than the BII procedure in cases of gastric malignancy. BI resection performed for malignancy seems to achieve smaller proximal gastric resection margins, which may influence the recurrence rate.