Acute pancreatitis as a rare initial manifestation of Wegener's granulomatosis. A case based review of literature.

CONTEXT: Vasculitis is a known cause of pancreatitis and other gastrointestinal symptoms; however, most of these patients have medium vessel vasculitis like polyarteritis nodosa and often there are other associated conditions like hepatitis B or clinical manifestations that suggest the diagnosis. Wegener's granulomatosis is predominantly a reno-pulmonary disorder, rarely having gastrointestinal manifestations. CASE REPORT: We report a case of Wegener's granulomatosis initially presenting as acute pancreatitis and then rapidly progressing to severe multi-organ involvement over the next few months. DISCUSSION: Pancreatic association as an initial presentation of Wegener's granulomatosis is limited to only a few reports. This extremely rare initial presentation makes the diagnostic process challenging. Two different pancreatic manifestations have been reported: as a pancreatic mass mimicking a tumor or as acute pancreatitis. The patients who presented as pancreatic head masses underwent extensive surgical procedures before the diagnosis was established. Acute pancreatitis as the initial presentation is usually associated with an aggressive course of the vasculitis and often results in a fatal outcome. CONCLUSIONS: This case illustrates Wegener's granulomatosis as a rare cause of acute pancreatitis. It emphasizes the need for thorough continued systemic clinical evaluation of patients when the etiology is not readily evident. Also, since most patients with pancreatitis due to Wegener's granulomatosis rapidly progress to severe multiorgan involvement, knowledge of a broad differential of potential etiologies and a low index of suspicion is required for timely diagnosis and treatment.

Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells.

AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1) express p53 and one (KATO-III) with deleted p53. METHODS: Nuclear fragmentation was used to quanti-tate apoptotic cells; caspase activity was determined by photometric detection of cleaved substrates; formation of oxidized cytochrome C was used to measure cytochrome C activity, and Western blot analysis was used to determine protein expression. RESULTS: Gastric cancer cells, irrespective of their p53 status, responded to resveratrol with fragmentation of DNA and cleavage of nuclear lamins A and B and PARP. Resveratrol, however, has no effect on mitochondria-associated apoptotic proteins Bcl-2, Bcl-xl, Bax, Bid or Smac/Diablo, and did not promote sub-cellular redistribution of cytochrome C, indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated p53 protein in SNU-1 and AGS cells but there was a difference in response of intracellular apoptotic signals between these cell lines. SNU-1 cells responded to resveratrol treatment with down-regulation of survivin, whereas in AGS and KATO-III cells resveratrol stimulated caspase 3 and cytochrome C oxidase activities. CONCLUSION: These findings indicate that even within a specific cancer the intracellular apoptotic signals engaged by resveratrol are cell type dependent and suggest that such differences may be related to differentiation or lack of differentiation of these cells.

Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells.

Resveratrol, a dietary phytoalexin, has emerged as a promising chemopreventive agent due to its antiproliferative and pro-apoptotic action toward cancer cells and its ability to inhibit tumor growth in animals. Gastric adenocarcinoma cells respond to resveratrol treatment with suppression of DNA synthesis, activation of nitric oxide synthase, induction of apoptosis and inhibition of total PKC and PKC alpha activity. Here we demonstrate that treatment of gastric adenocarcinoma SNU-1 cells with resveratrol results in time and concentration dependent accumulation of tumor suppressors p21(cip1/WAF-1) and p53 and is preceded by loss of membrane-associated PKC delta protein and a concomitant increase in cytosolic PKC alpha. Arrest of the cell cycle at transition of S to G(2)/M phases correlates with the profile of (3)H-thymidine incorporation and accumulation of p21(cip1/WAF-1) and was temporally dependent on increase of p53. SNU-1 cells respond to resveratrol treatment with up-regulation of both Fas and Fas-L proteins, whereas in KATO-III cells, with deleted p53, only Fas-L is increased after resveratrol treatment. Although Fas and Fas-L proteins in SNU-1 cells and Fas-L in KATO-III cells were elevated within 24 h of cell treatment with low concentrations of resveratrol, significant apoptotic response at these concentrations was observed only after 48 h. Altogether, our findings indicate that resveratrol engages PKC alpha and delta signals in gastric adenocarcinoma SNU-1 cells prior to up-regulation of antiproliferative and pro-apoptotic signals. The specific cell death signals engaged by resveratrol appear to be cell type dependent and suggest that resveratrol has chemopreventive potential even after mutational changes have occurred.

Selenomethionine stimulates MAPK (ERK) phosphorylation, protein oxidation, and DNA synthesis in gastric cancer cells.

Selenium is an essential trace element and is required for the synthesis of cellular enzymes that protect against oxidative stress. Epidemiological findings indicate that low selenium intake is associated with increased cancer risk, and, although the majority of studies show that exposure of transformed cells to selenium results in apoptotic cell death, there are reports indicating that cells exposure to low selenium concentrations promotes cellular proliferation. Gastric adenocarcinoma SNU-1 cells responded to selenomethionine with a biphasic proliferative curve: enhanced incorporation of 3H-thymidine into DNA within a very narrow range of selenomethionine concentrations followed by decreased 3H-thymidine uptake at higher levels. Concentrations of selenomethionine that stimulate cellular proliferation also induce cellular oxidation and phosphorylation of MAPK (ERK), a component of cell signaling cascades. MAPK (ERK) phosphorylation is synonymous with MAPK activation and enhanced cell growth. Our findings support previous observations of enhanced proliferation in response to low levels of selenium and suggest that, at certain concentrations, selenomethionine induces mild oxidative stress that, in turn, stimulates DNA synthesis.

The survival of stage III gastric cancer patients is affected by the number of lymph nodes removed.

BACKGROUND: Lymph node (LN) removal has been an important component in surgical treatment of gastric cancer. However, it is not clear whether the number of lymph nodes resected affects patient survival. METHODS: We retrospectively reviewed the records of 147 patients with adenocarcinoma of the stomach who had undergone gastrectomy with curative intent between 1992 and 2001. Patients were divided into two groups: group I patients had < or =15 (n=124) and group II patients had >15 (n=23) LN reported. RESULTS: The two groups were similar in age, gender distribution, and tumor locations. Group II patients had more advanced tumor, node, and overall staging. The median survival was 23.0 and 31.8 months for groups I and II, respectively. In stage III patients, median survival was 14.4 months for group I and 33.8 months for group II (P=.006). Group II patients also had more proximal lesions (P<.001) and a decreased positive to removed LN ratio (P=.014). CONCLUSION: For stage III disease, removal of >15 LN appears to contribute to a considerable survival advantage. Because extended lymphadenectomy will most reliably allow >15 LN removed and add no operative morbidity and mortality, we strongly recommend it be considered in curative resections of gastric cancer.

Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide.

Resveratrol is a dietary phytochemical that has been shown to inhibit proliferation of a number of cell lines, and it behaves as a chemopreventive agent in assays that measure the three stages of carcinogenesis. We tested for its chemopreventive potential against gastric cancer by determining its interaction with signaling mechanisms that contribute to the proliferation of transformed cells. Low levels of exogenous reactive oxygen (H(2)O(2)) stimulated [(3)H]thymidine uptake in human gastric adenocarcinoma SNU-1 cells, whereas resveratrol suppressed both synthesis of DNA and generation of endogenous O(2)(-) but stimulated nitric oxide (NO) synthase (NOS) activity. To address the role of NO in the antioxidant action of resveratrol, we measured the effect of sodium nitroprusside (SNP), an NO donor, on O(2)(-) generation and on [(3)H]thymidine incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated O(2)(-) generation in a concentration-dependent manner. Our results revealed that the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells may reside in its ability to stimulate NOS to produce low levels of NO, which, in turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1 proliferation may be partly dependent on NO formation, and we hypothesize that resveratrol exerts its antiproliferative action by interfering with the action of endogenously produced reactive oxygen. These data are supportive of the action of NO against reactive oxygen and suggest that a resveratrol-rich diet may be chemopreventive against gastric cancer.

Extended lymphadenectomy for gastric cancer: results in a teaching hospital.

Lymphadenectomy including second-echelon lymph nodes (D2 resection) for gastric cancer has not been widely adopted partly as a result of a reported increase in operative morbidity and mortality. In the present study we examined the operative risk of D2 resection in a public teaching hospital. From 1995 to 1998, 57 patients underwent exploratory laparotomy for gastric neoplasm: nine with curative D2 resection (Group I), 17 with curative but less than D2 resection (Group II), 16 with palliative resection (Group III), and 15 with no resection (Group IV). Among the four groups, patients with curative D2 resection (Group I) were older and had increased operative time and estimated blood loss, but their need for blood transfusion, the operative morbidity and mortality, and the mean hospital stay were not increased. In contrast, those patients with palliative resection (Group III) had the highest morbidity among all groups, the only fatality, and prolonged hospital stay. Therefore, curative D2 resection can be performed safely even with significant resident involvement. The advanced patient age or the extensive dissection does not increase its surgical risk. Hence, D2 dissection should be considered whenever curative resection is feasible because it allows accurate staging with the added benefit of possible improvement in patient survival.