Effect of phenethyl isothiocyanate on Ca2+ movement and viability in MDCK canine renal tubular cells.

The effect of the natural compound phenethyl isothiocyanate (PEITC) on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in MDCK renal cells is unknown. This study explored whether PEITC changed [Ca(2+)](i) in MDCK cells using the Ca(2+)-sensitive fluorescent dye fura-2. PEITC at 200-700 µM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by removing extracellular Ca(2+). PEITC-induced Ca(2+) influx was inhibited by nifedipine, econazole, SK&F 96365 and protein kinase C modulators. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) or 2,5-di-tert-butylhydroquinone (BHQ) inhibited PEITC-induced rise in [Ca(2+)](i). Incubation with PEITC also inhibited TG or BHQ-induced rise in [Ca(2+)](i). Inhibition of phospholipase C with U73122 abolished PEITC-induced rise in [Ca(2+)](i). At 15-75 µM, PEITC decreased viability. The cytotoxic effect of PEITC was enhanced by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester. Annexin V-FITC data suggest that 20 and 50 µM PEITC induced apoptosis. At 10 and 15 µM, PEITC did not increase reactive oxygen species (ROS) production. Together, in renal tubular cells, PEITC-induced rise in [Ca(2+)](i) by inducing phospholipase C-dependent Ca(2+) release from endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. PEITC induced apoptosis in a concentration-dependent, ROS/Ca(2+)-independent manner.

External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice.

This study investigates the importance of intestinal bile flow in cellular immunity. Sprague-Dawley rats undergoing bile duct ligation (BDL) and sham ceiliotomy (Sham) for 14 and 21 days were investigated. Experimental animals following BDL were further divided into an external drainage (ED) group, an ED group with rat chow mixed with 2:2:1 cholic acid, chenodeoxycholic acid, and deoxycholic acid (ED + BF), and an internal drainage (ID) group. Fourteen days later, they were killed and analyzed for spleen lymphocytic [3H] thymidine uptake (LHU) under mitogen stimulation with phytohemagglutinin, blood biochemistry, hemogram, and liver pathology. In the 14-day BDL experiment, LHU and serum albumin level were decreased in the BDL group (P < 0.05). After drainage, they were not significantly different among sham, ED, ED + BF, and ID groups. In the 21-day BDL experiment, the red cell volume was decreased (P < 0.05). After drainage, the ED, ED + BF, and ID groups still had a significantly lower LHU than the sham group (P < 0.05). However, the ID group had higher LHU than the ED and ED + BF groups (P < 0.05). The ED + BF group had a slightly higher LHU than the ED group but not statistically significant. Liver pathology returned to normal after drainage in the 14-day BDL model. In contrast, the 21-day BDL group had prominent periportal necrosis and developed periportal fibrosis after drainage. The present study reveals the duration of BDL determines the severity of hepatic damage. In the 14-day BDL groups, all kinds of drainage completely reverse the impaired liver function and cellular immunity. In the 21-day BDL group, 14-day drainage is inadequate for recovery because irreversible pathological changes are found. The reversal of cellular immunity in ID is better and faster, because it provides a better hepatic functional, nutritional, and hematological recovery besides the presence of primarily secreted bile acids.

Cathepsin E and subtypes of intestinal metaplasia in carcinogenesis of the human stomach.

BACKGROUND: Cathepsin E is found mainly over the gastric surface and foveolar epithelial cells, and it also is found in the metaplastic pyloric glands and cancer cells. The exact function of cathepsin E in gastric mucosa remains unclear. The colonic type (type III) of intestinal metaplasia (IM) is strongly associated with intestinal-type gastric carcinoma. IM is considered to be a precancerous lesion. The aim of this study was to find out the role of cathepsin E in IM, dysplasia and cancer of stomach. METHODS: Sixty nine biopsy specimens with IM and dysplasia and 33 gastrectomy specimens with gastric carcinoma were fixed, sectioned and stained with PAS-alcian blue stain, high iron-diamine alcian blue stain to classify IM and immunohistochemical stain to localize cathepsin E. Those patients with dysplastic gastric lesions received regular endoscopic follow-up. RESULTS: Fifteen of 69 patients with gastric dysplasia developed cancer in a median 10.5 months follow-up. Severe dysplasia developed carcinoma significantly higher than mild dysplasia (12/20 vs. 1/25, p < 0.001), and type III intestinal metaplasia seemed to have significantly predilection for severe dysplasia and gastric cancer. Cathepsin E was stained in intestinal metaplasia with dysplastic change in 44/69 specimens (63.8%), and carcinoma in 28/48 (58.3%) specimens, there was no significant difference between intestinal type and diffuse type carcinoma in cathepsin E staining. The positive staining for cathepsin E decreased significantly in severe dysplastic gastric mucosa. CONCLUSIONS: Type III IM is commonly associated with severe dysplasia and cancer; it may be a precancerous lesion. The positive staining of cathepsin E decreased with the severity of gastric dysplasia, representing dedifferentiation of the cells.

Superior mesenteric arteriovenous fistula associated with portal obstruction.

Superior mesenteric arteriovenous fistula is rarely encountered. Unrecognized in early stage, it can cause hazardous sequelae of portal hypertension. Herein we report a rare case of portal obstruction associated with an aneurysmal dilatation of the superior mesenteric vein, which was caused by a superior mesenteric arteriovenous fistula. The patient was a 74-year-old woman admitted for continuous hemetemesis, presenting with a palpable abdominal mass. The computed tomogram revealed a 6.5 cm superior mesenteric venous aneurysm and thrombotic portal venous obstruction. On account of impending shock, an emergent portal venous thrombectomy and portocaval shunt was carried out. Superior mesenteric arterial angiography performed 4 months later confirmed the diagnosis. Being without symptoms, the patient was clinically followed and remained in stable condition for 3 and a half years. The clinical presentation of a mesenteric arteriovenous fistula varies, with occasional gastrointestinal tract hemorrhage. When complicated with portal obstruction, the condition can be disastrous. We believe that creation of a porto-systemic shunt with resection of the arterio-venous fistula is the proper treatment. This patient is now under close observation.

Risk factors of mortality in perforated peptic ulcer.

OBJECTIVE: To assess the risk factors that influence mortality from perforated peptic ulcer. DESIGN: Retrospective study. SETTING: General hospital, Taiwan. SUBJECTS: 179 patients who had their perforated peptic ulcers operated on and who had minimum follow-up of one year. MAIN OUTCOME MEASURES: Mortality. RESULTS: The overall mortality was 15% (26/179). Of the 26 patients who died, the cause of death was uncontrolled systemic infection in 21 (81%), hypovolaemic shock in 2, and fatal arrhythmia and heart failure in 1 each. 15 of the patients who died of sepsis did not have fulminant abdominal sepsis. Most deaths occurred early after operation, (range 1-96 days). Old age, preoperative shock, and type of operation seemed to be related to these deaths on univariate analysis, but multivariate analysis showed that coexisting medical illness, delayed treatment, and low albumin concentration were independent risk factors for mortality. CONCLUSIONS: To improve the result of treatment of perforated peptic ulcer, the diagnosis and treatment should not be delayed, the associated medical illnesses should be treated, and nutritional support should be given.

Analysis of prognostic factors in Chinese women with breast cancer in southern Taiwan.

BACKGROUND: We conducted a retrospective review of all early-stage breast cancer patients treated at the Veterans General Hospital-Kaohsiung to determine overall and disease-free survival rates, and to evaluate prognostic factors for these outcomes. METHODS: During the period of October, 1990, to December, 1997, 332 patients with early-stage breast cancer were treated at our institution. Cox's multivariate regression analysis was used to select prognostic factors significant for overall survival and disease-free survival. RESULTS: The survival rate for breast cancer patients was 88.35% at five years. Prognostic factors predicting breast cancer mortality included poorly differentiated histologic grade, four or more lymph nodes positive for metastasis and negative progesterone-receptor status. For disease recurrence, prognostic factors included positive nodes, aneuploidy and poorly differentiated histologic grading. CONCLUSIONS: We conclude that a combination of lymph node status, DNA ploidy, histologic grading and progesterone-receptor status help to evaluate the possible outcomes for patients with breast cancer and to plan for optimal therapy.

Primary non-Hodgkin's lymphoma of the breast: breast conservation therapy in two patients.

We report two patients with primary non-Hodgkin's lymphoma of the breast who were treated with breast conservation therapy. These two patients were diagnosed with primary breast lymphoma by fine-needle aspiration cytology and underwent tumorectomy followed by adjuvant chemoradiation therapy. Follow-up studies showed that the two patients were free of disease for two and three years, respectively. To date, there exists no therapeutic standard for this disease and there is no survival advantage for patients who undergo radical mastectomy. Despite the rarity of lymphoma in the breast, a preoperative accurate diagnosis is essential so that unnecessary, extended breast ablation or delayed treatment is avoided. Cytologic diagnosis of breast lymphoma is an easy procedure and provides guidance for appropriate preoperative management. Early diagnosis combined with breast conservation therapy and systemic adjuvant therapy results in a favorable outcome for patients with breast lymphoma.

Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.

A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.

Laparoscopic versus open preperitoneal prosthetic herniorrhaphy for recurrent inguinal hernia.

BACKGROUND: Laparoscopic herniorrhaphy (LH) shares the same repair principle as open preperitoneal prosthetic herniorrhaphy (PPH). Theoretically, the recurrence rate of LH for recurrent inguinal hernia will match the low recurrence rate of PPH (1.2-3%). METHODS: One-hundred forty-five cases of recurrent inguinal hernia were retrospectively studied between 1990 and 1994. Forty-two cases receiving LH were compared to 103 cases receiving PPH. RESULTS: There were no differences in operative time, hospital stay, morbidity rate, satisfaction scale and recurrence rate between the LH group and the PPH group. The LH group showed significantly less postoperative pain and 2 times shorter convalescence (p<0.01). Unsuspected asymptomatic contralateral hernia was found in 4.8% of patients receiving LH. 11.9% of patients had bilateral hernia repairing at the same time in the LH group. CONCLUSIONS: LH is suitable for recurrent inguinal hernia, but further investigation of this technique is required before its wide application.

APACHE II score: a useful tool for risk assessment and an aid to decision-making in emergency operation for bleeding gastric ulcer.

BACKGROUND: Operating for bleeding gastric ulcer remains controversial. Gastric resection bears a higher surgical risk while limited operation may result in more postoperative hemorrhage. There has been little discussion of effective risk assessment of patients. The aim of this study is to define surgical risk by using the APACHE II scoring system, and to determine optimal management. STUDY DESIGN: Records from October 1990 to December 1996 were retrospectively reviewed for patients (n=101) with bleeding gastric ulcer who had undergone emergency operation after failed endoscopic therapy. Mortality rates were examined according to different APACHE II scores, and the surgical risk was defined. From January 1997 to December 1997, 35 consecutive patients were enrolled for prospective study. Partial gastric resection (PGR) was performed for patients with huge ulcers (>2 cm) and for low-risk patients with ulcers at the antrum or angularis, while limited operation (oversewing or excision of bleeding ulcer) was reserved for others. The results were compared with the retrospective study. RESULTS: In the retrospective study, the mortality rates for the group with a score < 15 and > or = 15 were 5% (3 of 63) and 58% (22 of 38), respectively (p < 0.05). In the group with a score < 15, PGR was performed on 27 patients, and one died. For those patients with a score > or = 15, PGR carried a lower mortality than limited operation, although this was not statistically significant (47% vs 65%). Limited operation resulted in an overall rate of 22% postoperative hemorrhage and 12% reoperation rate, in which all patients with a score > or = 15 died. In the prospective study, the mortality rates in those scoring <15 and > or = 15 were 6% and 50%, respectively. This is not significantly different than the retrospective study. However, the rate of postoperative hemorrhage was diminished (5%). CONCLUSIONS: APACHE II score is a useful tool for assessing risk in patients with bleeding gastric ulcer. The mortality is minimal in those with a score <15, and PGR can be performed with low risk. Although high-risk patients have dreadful outcomes, limited operation cannot improve them if postoperative hemorrhage occurs. Decision making in emergency operation for such patients should be based on the ulcer conditions and the patient's hemodynamic status.

Ocular metastases from breast carcinoma: a report of two cases.

Breast carcinoma metastases to the eye occur more frequently than is clinically recognized. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs or because a number of eye lesions are small and asymptomatic. With the increasing length of survival, more breast cancer patients will require care for ocular metastases. A thorough ophthalmic evaluation, aided by computed tomography or magnetic resonance imaging, usually confirms the diagnosis. Rapid progression of a lesion demands emergency therapy since the dysfunction produced by progressive disease may not otherwise be corrected. Early diagnosis of ocular metastases in patients with breast cancer is important because timely treatment may improve vision and quality of life in the time remaining to patients. Experience with two cases of metastases to the eye from breast cancer are presented, with a review of the literature.

Correlation of hepatocyte growth factor-induced proliferation and calcium-activated potassium current in human gastric cancer cells.

Hepatocyte growth factor (HGF) has been found to stimulate proliferation and migration of human gastric carcinoma cells. Whether the HGF-induced responses are correlated with the expressed level of HGF receptors or the changes of ionic currents is not clear. The present study investigated the effects of HGF on the proliferation and ionic currents of two human gastric adenocarcinoma cell lines, which were found to express different amounts of HGF receptor. Results showed that HGF induced a dose-dependent growth stimulation and accelerated cell cycle progression in SC-M1 cells. In patch clamp study, HGF treatment induced an outward K+ current and increased the slope conductance at -80 mV from 110+/-15 pS/pF to 207+/-15 pS/pF. The HGF-induced K+ current was abolished when tetraethylammonium chloride was added in bathing solution or a low Ca2+ solution was included in the recording pipette. Furthermore, HGF (10 ng/ml) induced an oscillatory Ca2+-activated K+ current with a lag period of 5+/-3 min in SC-M1 cells. In contrast, HGF did not induce mitogenesis, cell cycle progression and changes in ionic currents in KATO-III cells, although this cell line expressed a higher level of HGF receptors than SC-M1 cells did. These findings provide evidence that the activity of Ca2+-activated K+ channel may be involved in the HGF-induced cell proliferation in human gastric cancer cells, but it did not correlate with the density of HGF receptors.

Effect of hepatocyte growth factor on cell cycle and c-met expression in human gastric cancer cells.

Hepatocyte growth factor (HGF) was found to stimulate the growth and progression of gastric cancer cells through hepatocyte growth factor receptor (HGFR). In the present study, the effects of HGF on the expression of HGFR in relation to cell cycle progression of human gastric cancer cells were investigated by two-parameter flow cytometric analysis. We found that the expression of HGFR in SC-M1 and KATO-III gastric cancer cells was cycle dependent, the level of HGFR increased from GO-G1 to S phase and the highest level of HGFR was found in G2-M phases. The level of HGFR was higher in KATO-III than SC-M1 cells. However, HGF treatment induced a dose-dependent stimulation of growth as well as down-regulation of HGFR in SC-M1 cells but not in KATO-III cells. These results suggest that functional HGFR rather than overexpressed HGFR may be more important for the growth of gastric cancer cells.

Induction intraarterial chemotherapy for T4 breast cancer through an implantable port-catheter system.

Eleven patients with T4 breast cancer received induction intraarterial chemotherapy (IACT) as the first step in multidisciplinary therapy. The IACT agents (epirubicin and mitomycin C), were delivered weekly in the outpatient department by bolus injection through an implantable port-catheter system. A modified technique of port-catheter system implantation was used. The precise localization of the catheter was dually confirmed by angiography and dye test. The effectiveness of the treatment was evaluated by clinical appearance, image study, and microscopic examination. A 91% response rate was obtained, and the lesions were resectable in < or = 8 weeks. No obvious systemic toxicity resulted from the IACT. Our results show that weekly IACT by bolus injection through a port-catheter system for treating locally advanced T4 breast cancer is feasible and efficacious.

Cytomegalovirus appendicitis in a patient with acquired immunodeficiency syndrome: a case report.

Cytomegalovirus (CMV) infection occurs predominantly in immunocompromised hosts. Involvement of the gastrointestinal tract in acquired immunodeficiency syndrome (AIDS) patients is frequent. Nevertheless, CMV appendicitis is exceeding rare. This report describes a patient with AIDS who presented with right lower quadrant abdominal pain, high fever, nausea and vomiting, but without leukocytosis. Diagnosis of CMV appendicitis was confirmed by appendectomy and histopathological examination. Problems related to the diagnosis and therapeutic management of CMV appendicitis in AIDS patients are discussed. The importance of early surgical intervention is emphasized, as is postoperative ganciclovir therapy for treatment of such patients.

Computed tomography in the diagnosis of organic bowel obstruction.

BACKGROUND: This study examined the usefulness of computed tomography (CT) scan for cases of organic intestinal obstruction, with two simple criteria. METHODS: One hundred and thirteen patients with clinical suspicion of bowel obstruction were referred for CT scans. A line was drawn between the dilated proximal, and the collapsed distal bowels. A careful search was conducted on this line for obstructive lesions. The results were reported to be organic obstruction if there was an abrupt change of caliber (Criterion I) or a soft tissue mass around the dilated bowel (Criterion II). The judgement based on the CT findings. RESULTS: Eighty-eight cases proved to have bowel obstruction. With Criterion I, the sensitivity was 59.1%, and specificity, 88% with Criterion II, the sensitivity was 56.3% and specificity 100%. If either of them was considered to be a positive sign of organic obstruction, the sensitivity was 100%, the specificity 88% and the accuracy 97.3%. The nature of the obstructions were precisely predicted in 76 patients (86%). CONCLUSIONS: With these two simple criteria, CT scan can achieve high accuracy and is a recommendation in virtually every instance when intestinal obstruction is suspected.

Obstructive jaundice caused by calcified portal venous thrombosis: a case report.

One case of bile duct obstruction because of calcified thrombosis of the portal vein is described. The patient had received splenectomy 20 years previously. He was admitted for fever, right upper abdominal pain and jaundice. The initial sonography and computed tomography showed dilatation of bilateral intrahepatic ducts and common bile duct with adjacent calcified portal vein mimicking common bile duct stones. Endoscopic retrograde cholangio-pancreatography showed external compression of the common bile duct by the calcified portal vein. Because of the patient's poor liver condition, biliary endoprosthesis was performed to relieve obstruction. This was an indication that the possibility of portal venous thrombosis should be included in the differential diagnosis of patients with obstructive jaundice who had previously received splenectomy.