Acid suppression and upper GI bleeding.
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Publications and source records attributed to P Netzer.
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PURPOSE: Studies have confirmed an association between idiopathic deep vein thrombosis (DVT) and malignant tumors. We assessed the usefulness of routine abdominal sonography in patients with idiopathic DVT to detect malignant tumors and other relevant findings. METHODS: We retrospectively analyzed abdominal sonograms and records from 135 consecutive patients with confirmed idiopathic DVT and interviewed patients and their physicians during the follow-up period (mean, 30 months). Malignancy and other clinically relevant findings determined by sonography were tabulated, and the cost of each malignancy detected by abdominal sonography in this study was calculated. RESULTS: Malignant tumors were found in 14 patients (10%), 7 by routine abdominal sonography, 3 by other means during hospitalization, and 4 during the follow-up period. Other clinically relevant findings detected by routine abdominal sonography were found in 33 patients (24%). The estimated cost of discovering malignancy by using screening abdominal sonography was approximately US$3,000/malignancy. CONCLUSIONS: Abdominal sonography was useful in detecting a variety of clinically relevant findings in addition to half of the malignant tumors found in our study.
PURPOSE: Screening endoscopy has the potential to reduce colorectal cancer mortality. However, the efficacy of screening flexible sigmoidoscopy compared with colonoscopy strongly depends on the frequency of advanced proximal neoplasms without an index polyp in the rectosigmoid. We have therefore determined this frequency in our endoscopy population. METHODS: Endoscopic and histologic data were analyzed from all patients on whom integral colonoscopy was performed between 1980 and 1995. Advanced neoplasia was defined as cancer or adenomas >10 mm in diameter, adenomas with a villous component, or severe dysplasia. Patients with polyposis syndrome or inflammatory bowel disease were excluded. RESULTS: Colonoscopy was performed on 11,760 patients. 2,272 (19.3 percent) had at least one colorectal neoplasm, of which 39 percent had the neoplasm above the rectosigmoid. Twenty-two percent of all patients with neoplasia had no index polyp in the rectosigmoid and 16 percent of these had no index polyp, but at least one advanced proximal neoplasm. CONCLUSIONS: Although 39 percent of patients had neoplasms above the rectosigmoid, only 16 percent had an advanced proximal neoplasm without an index polyp in the rectosigmoid. This gives a figure on which to base the evaluation of screening sigmoidoscopy programs against those of screening colonoscopy.
BACKGROUND: Over-the-counter status has recently been approved for low-dose H2-antagonists in several countries. Insufficient information is currently available on the effect of food in low-dose H2-antagonist therapy. AIM: Compare the antisecretory efficacy of low-dose ranitidine and famotidine in fasting and non-fasting volunteers. METHODS: Twenty volunteers were randomized into a double-blind, placebo-controlled, multiple-step crossover study comparing the antisecretory efficacy of 75 mg ranitidine, 10 mg famotidine and placebo over 12 h using intragastric pH-metry. Two standard meals were given after 4 h and 8 h of medication. Fifteen volunteers also participated in a second study comparing the antisecretory effect of both drugs, both with and without meals. RESULTS: In non-fasting subjects, the percentage of time with pH > 4 was similarly elevated for both drugs compared with placebo over the first 8 h: ranitidine 39.3%, famotidine 29.5%, placebo 9.5% (P < 0. 001); but not for the last 4 h after the second meal (P > 0.05). Comparing the first 4-h period with the second, the percentage of pH > 4 was significantly reduced for both drugs in the second period in the subjects given food at the end of the initial 4-h period (ranitidine 56.9% vs. 26.6%, P = 0.005; famotidine 46.6% vs. 13.3%, P < 0.001). It remained more or less constant, however, for the second 4-h period in fasting subjects (ranitidine 41% vs. 28.1%, P = 0.46; famotidine 52.7% vs. 52.2%, P = 0.12). CONCLUSION: In non-fasting volunteers both low-dose H2-antagonists had comparable antisecretory effects and were superior to placebo over the first 8 h of therapy. Both drugs achieved a slightly higher antisecretory effect without food intake compared to with food intake.
BACKGROUND: Esophageal function testing was developed to aid diagnosis in patients with negative endoscopy. Although combined 24-h esophageal pH-manometry is now commercially available, its routine clinical effectiveness has not yet been studied. METHODS: From 1992 to 1996 we evaluated 303 consecutive patients who were first-time referrals to our unit for 24-h esophageal pH-manometry. The referral indications were gastroesophageal reflux disease, 47.2%; dysphagia, 18.5%; non-cardiac chest pain, 14.9%; connective tissue disease, 13.2%; and symptomatic patients after antireflux surgery, 6.3%. RESULTS: Overall, esophageal function testing altered the diagnosis of 44% of the patients, confirmed it in 38%, and specifically changed the management of 66%. The final clinical 'diagnosis' was reflux disease, 54% (32% with non-specific esophageal motility disorder); connective tissue disease, 9.9%; achalasia, 9.6%; other specific esophageal motility disorders, 3.3%; non-specific esophageal motility disorders, 6.9%; and normal, 16.2%. The cost per testing was estimated to be US$305 and per change in management US$465. CONCLUSION: Combined 24-h pH-manometry has been shown to be a useful and cost-effective test for the management of selected patients in whom the primary investigation was insufficient.
OBJECTIVE: In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. METHODS: A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. RESULTS: Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. CONCLUSION: Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.
BACKGROUND: The expression of the KAI1 gene and its gene product were studied in metastatic and non-metastatic human colorectal cancer to evaluate its role in the metastatic process. METHODS: KAI1 mRNA and protein expression was examined in 36 primary colorectal carcinomas and 6 liver metastasis using Northern blot and Western blot analyses. Forty-six normal colonic tissue samples served as controls. The exact site of KAI1 expression was analyzed by in situ hybridization and by immunohistochemistry in primary tumors, in the corresponding normal tissues, in lymph node metastases and liver metastases. RESULTS: Densitometric analysis of Northern blots revealed overexpression of KAI1 mRNA in 87% of colonic cancer tissues in comparison with the corresponding normal colonic tissues. This increase was 9.1-fold in median (P < .001). KAI1 mRNA expression was strongly dependent on tumor stage. Colorectal cancer at stages II and III revealed significantly higher KAI1 mRNA levels than stage IV tumors (P < .03 and P < .015, respectively) or normal controls. In addition, liver metastases showed reduced KAI1 mRNA expression when compared with their corresponding primary tumor. In situ hybridization confirmed the stage-dependent expression results obtained by Northern blots, in which the KAI1 mRNA signal was exhibited almost exclusively in the epithelial cells. Lymph node and liver metastases were largely devoid of KAI1 mRNA. Western blot analysis showed a highly significant increase of KAI1 protein level in stage II cancers in comparison with the normal colon (P < .001) but also in comparison with the more advanced tumor stages III and IV (P < .03) and P < .02, respectively), when metastases were already present. In accordance, KAI1 immunostaining decreased successively with the advance of the tumor stage and was absent in lymph node and liver metastases. CONCLUSIONS: These data demonstrate that the KAI1 mRNA expression and the KAI1 protein level increase in an earlier tumor stage of colorectal cancer, decrease in advanced stages, and are lost in metastases. The loss of KAI1 might favor the ability of colorectal cancer cells to metastasize.
1. In the stomach, prostaglandins protect the gastric mucosa against injuries. One rate-limiting step in prostaglandin synthesis is mediated by prostaglandin endoperoxide synthase (PGHS), the target enzyme of non-steroidal anti-inflammatory drugs (NSAIDs). Two isoforms of PGHS exist: a constitutive (PGHS-1) and an inducible (PGHS-2) enzyme. PGHS-1 is the major source of gastric prostaglandins under physiological conditions. Inhibition of prostaglandin synthesis by traditional NSAIDs such as indomethacin and diclofenac which non-selectively inhibit both PGHS-1 and PGHS-2, causes gastric and intestinal ulceration and delays gastric ulcer healing in chronic models. It has been shown that selective PGHS-2 inhibitors such as L-745,337 (5-methanesulphonamide-6-(2,4-difluorothio-phenyl)-1-inda none) are not ulcerogenic and do not inhibit gastro-intestinal prostaglandin synthesis. However, minimal information is available on the long-term effects of PGHS-2 inhibitors on the healing of previously established gastric injuries. We assessed the cellular localization and expression of PGHS-1 and PGHS-2 during gastric ulcer healing and assessed the effects of L-745,337 on previously established cryoulcers in the rat gastric stomach. 2. PGHS-1 and PGHS-2 were located and quantified by immunohistochemistry during experimental gastric ulcer healing. PGHS-2 immunoreactivity was only negligible in the normal gastric wall, but after gastric ulcerations, it was strongly detected in monocytes, macrophages, fibroblasts and endothelial cells below and between the regenerative glands. PGHS-1 immunoreactivity detected in normal gastric mucosa, disappeared after gastric ulceration in the mucosa adjacent to the ulcer crater. However, it reappeared in the regenerative glands from day 5 onwards. Thus, PGHS-1 and PGHS-2 were located at different sites and their maximal expression followed a different time-sequence. 3. We assessed the effects of L-745,337, indomethacin and diclofenac on gastric ulcer healing and histological healing parameters in rats. L-745,337, indomethacin and diclofenac dose-dependently decreased the healing of gastric ulcers. L-745,337, indomethacin and diclofenac decreased epithelial cell proliferation in the ulcer margin and microvessel density in the ulcer bed on day 8 and increased the thickness of the granulation tissue below the ulcer crater and the gap between both edges of the muscularis mucosae on day 15. Indomethacin and diclofenac, but not L-745,337, decreased synthesis of 6-keto-PGF1alpha and PGE2 in tissue fragments from the stomach and terminal ileum and decreased platelet thromboxane B2 synthesis in clotting whole blood. 4. Dose-response curves for the inhibition of chronic gastric ulcer healing by L-745,337 (administered twice daily intragastrically) showed an ID50 value of 1.7 mg (4.3 micromol) kg(-1). Dose-response curves for the inhibition of PGE2 synthesis in inflammatory exudates in the acute carrageenin sponge rat model, showed ID50 values of 1.1 mg (3.1 micromol) kg(-1) and 1.3 (3.3 micromol) mg kg(-1) for indomethacin and L-745,337, respectively. Thus, inhibition of chronic gastric ulcer healing by L-745,337 occurs within a potentially therapeutic dose-range. 5. In summary, PGHS-2 is markedly accumulated after gastric ulceration in monocytes, macrophages, fibroblasts and endothelial cells in regions of maximal repair activity. Selective inhibition of PGHS-2 by L-745,337 delayed gastric ulcer healing though interference with epithelial cell proliferation, angiogenesis and maturation of granulation tissue in a potentially therapeutic dose range. PGHS-2-derived prostaglandins seem to have an important role in gastric ulcer healing.
BACKGROUND: Symptoms of functional dyspepsia are common and patients often self-medicate with antacids, or with low-dose H2-antagonists which are available as over-the-counter medications. To date, there has been limited information available comparing the effects on intragastric acidity of these two types of over-the-counter medication. Therefore we studied the effect of the antacid Rennie and two H2-antagonists on the intragastric pH of fasting volunteers. METHODS: Sixteen healthy, fasting volunteers were randomized into a double-blind, placebo-controlled, four-way crossover study comparing Rennie (calcium-magnesium carbonate) 1360 mg, ranitidine 75 mg, famotidine 10 mg and placebo. Their effect on gastric pH was monitored by a 4-h gastric pH-metry. The primary efficacy parameter was the time lag before an intragastric pH > 3.0 was reached after drug administration. RESULTS: The median time lag before pH > 3.0 was reached after drug administration was 5.8 min for Rennie, 64.9 min for ranitidine, 70.1 min for famotidine and 240.0 min for placebo. The percentage of time with values of pH > 3.0 was 10.4% for Rennie, 61.4% for ranitidine, 56.6% for famotidine and 1.4% for placebo. CONCLUSION: The onset of action in fasting volunteers was significantly faster with the antacid than with the two H2-antagonists. The duration of action was significantly longer with an H2-antagonist than with the antacid. This suggests that the two products should be used for different indications: antacids are superior for rapid pain relief, whereas H2-antagonists might be better for symptom prophylaxis--for example for nocturnal dyspepsia.
BACKGROUND: Malignant colorectal polyps are defined as endoscopically removed polyps with cancerous tissue which has invaded the submucosa. Various histological criteria exist for managing these patients. AIMS: To determine the significance of histological findings of patients with malignant polyps. METHODS: Five pathologists reviewed the specimens of 85 patients initially diagnosed with malignant polyps. High risk malignant polyps were defined as having one of the following: incomplete polypectomy, a margin not clearly cancer-free, lymphatic or venous invasion, or grade III carcinoma. Adverse outcome was defined as residual cancer in a resection specimen and local or metastatic recurrence in the follow up period (mean 67 months). RESULTS: Malignant polyps were confirmed in 70 cases. In the 32 low risk malignant polyps, no adverse outcomes occurred; 16 (42%) of the 38 patients with high risk polyps had adverse outcomes (p<0.001). Independent adverse risk factors were incomplete polypectomy and a resected margin not clearly cancer-free; all other risk factors were only associated with adverse outcome when in combination. CONCLUSION: As no patients with low risk malignant polyps had adverse outcomes, polypectomy alone seems sufficient for these cases. In the high risk group, surgery is recommended when either of the two independent risk factors, incomplete polypectomy or a resection margin not clearly cancer-free, is present or if there is a combination of other risk factors. As lymphatic or venous invasion or grade III cancer did not have an adverse outcome when the sole risk factor, operations in such cases should be individually assessed on the basis of surgical risk.
Retroperitoneal fibrosis is a rare chronic inflammatory disease usually involving the ureters, retroperitoneal vessels and nerves; however, any intestinal organ may also be involved. In recent years, a few successful immunosuppressive treatments of this disease have been described and surgery can, therefore, probably be avoided in most cases. We report here on a case of secondary retroperitoneal fibrosis with compression and midline deviation of the ureters and impaired renal function which was probably caused by ergotamine abuse because of migraine. The patient complained of diffuse abdominal pain, nausea and vomiting. After immunosuppressive treatment with azathioprine and prednisone for a year, we observed a complete resolution of the retroperitoneal mass on computed tomography, although renal function remained impaired. Eleven months after the cessation of treatment, the patient had not relapsed.
BACKGROUND: The management of invasive cancer in colorectal polyps (malignant polyps) is controversial, particularly with regard to the different sets of histologic criteria for deciding whether malignant colorectal polyps should be treated by polypectomy alone or be followed by surgical resection. We report on the outcome of patients in accordance with the histologic assessment of their malignant polyps. METHODS: Malignant polyps were defined as having favourable histology (free margin, grade I or II, and no angiolymphatic invasion) or unfavorable histology (no free margin, grade III, or angiolymphatic invasion). Malignant polyps with favourable histology were treated by endoscopic polypectomy alone, whereas further therapy was recommended for malignant polyps with unfavourable histology. Residual cancer in a resection specimen and local or metastatic recurrence during the follow-up period (mean, 60 months; range, 12 - 120) were defined as adverse outcome. RESULTS: Thirty-seven malignant polyps were detected in 35 (0.5%) of 6605 patients. Five of these 35 patients were treated by primary bowel resection and analysed separately. In the other 30 patients the following unfavourable histologic signs were detected in 20 (62.5%) of 32 malignant polyps; no free margin in 16, grade III in 1, and angiolymphatic invasion in 3 polyps. Twelve polyps with favourable histology had no adverse outcome; in contrast, 5 of 20 polyps with unfavourable histology had an average outcome (P < 0.05). CONCLUSIONS: Locally excised malignant polyps without unfavourable histologic signs may not need further surgical treatment; for all other malignant polyps an ensuing bowel resection is recommended.
Collagenous and lymphocytic colitis are two chronic inflammatory colonic diseases characterized by chronic watery diarrhea. They can only be diagnosed by histological examination of colonic biopsies. The pathogenesis is unknown, but may be of an inflammatory possibly autoimmune nature. Others hypothesize that a bacterial toxin or another noxious luminal factor is responsible for the development of the microscopic colitis syndrome. Some studies suggest that NSAIDs may be an etiologic factor in collagenous colitis in a subgroup of patients with this disease. These disorders may be different entities, although some data support the possibility that they are only different manifestations of the same disease. Therapy with 5-aminosalicylate and in severe cases corticosteroids, is successful in most patients. The course of these chronic diseases is commonly benign and is characterized by periods of spontaneous remissions and relapses, but clinical and histopathological resolutions are occasionally seen. On the basis of our own two cases and the literature, these two diseases will be discussed. These patients were admitted to our hospital within a month of each other due to therapy-refractive chronic watery diarrhea. A 70-year-old woman had been suffering from diarrhea for more than ten years. The histological examination produced a diagnosis of collagenous colitis. Lymphocytic colitis was diagnosed from a histological examination in a 30-year-old man who had been suffering from diarrhea for six months. Both received a therapy of mesalazine and the symptoms disappeared within three weeks.
HISTORY AND CLINICAL FINDINGS: A previously well 29-year-old man was referred to the emergency department because of acute left lower abdominal pain without intestinal symptoms. Physical examination was unremarkable except for moderate suprapubic pain on pressure. INVESTIGATIONS: There was evidence of a urinary infection. Erythrocyte sedimentation rate was increased (48 mm/h) and C-reactive protein elevated to 42 mg/l. There was mild leucocytosis (10000/microliter). Abdominal sonography revealed an enlarged left renal pelvis with hydroureter and possible prevesical stone, findings confirmed at excretion urography. TREATMENT AND COURSE: He was discharged with the suspected diagnosis of ureteric stone and given co-trimoxazole, diclofenac and hyoscine butylbromide. After discontinuing medication the same symptoms developed two weeks later. Cystoscopy and retrograde pyelography were unremarkable and it was assumed the stone had been passed. The patient was again discharged on the above medication. When it was discontinued the same symptoms recurred and he was again admitted. Computed tomography, selective small-intestine radiology, coloscopy and biopsy indicated Crohn's disease with hydronephrosis as complication. Treatment trial with prednisone and mesalazine brought about only transient improvement so that an ileocaecal resection and ureterolysis were performed. The patient has since been free of symptoms. CONCLUSION: If there are urological complications, chronic inflammatory intestinal disease should be included in the differential diagnosis even in the absence of any intestinal symptoms.
Gastroesophageal reflux disease accounts for approximately 75% of esophageal pathology. Accurate diagnosis can be complicated by the absence of endoscopic esophagitis in about 40% of patients with typical symptoms or atypical symptoms such as chest pain, chronic cough or wheezing. A number of tests have been developed to aid diagnosis, but 24-hour pH monitoring has emerged as the standard in reflux diagnostics. Although this method has been known for a long time, it has only become popular since small, portable digital recorders have been available. The aim of this retrospective study was to analyze our first experience with this method. Included in the study were the first 50 consecutive patients in our hospital who had undergone endoscopy of the upper GI tract followed by 24-hour pH monitoring. As a recorder we used the "GastrograpH-Fresenius Mark II". In agreement with the literature we considered the following findings as abnormal: esophageal acidity below pH 4 > 5% of total time or > 8% of upright time or > 3% of supine time, more than 4 reflux episodes of > 5 minutes, duration of the longest reflux episode more than 20 minutes. With this definition there were 24 patients (48%) with reflux disease. The reflux episodes chiefly occurred in daytime (68%), as known from the literature. The indications for this examination were chiefly given by pneumologists (50%), followed by gastroenterologists (22%) and cardiologists (14%). Acid block therapy was performed in 83%, with success in 42% and failure in 8%. In 50% of the patients the necessary data were lacking. Based on these results we conclude that 24-hour pH monitoring has shown itself reliable for the diagnosis of reflux disease and should always be performed in patients with negative endoscopic examination but typical or atypical symptoms of gastroesophageal reflux.
An association between venous thrombosis and cancer was first suggested by Armand Trousseau in 1865 and subsequently confirmed by a number of studies. It was therefore concluded that laboratory tests, chest radiograph and abdominal ultrasonography should be routinely performed on all patients with deep venous thrombosis. The aim of our retrospective study was to detect the clinical relevance of abdominal ultrasonography findings, especially tumors, in patients with deep venous thrombosis of the lower extremities. All patients with deep venous thrombosis hospitalized between 1990 and 1994 in the department of internal medicine of our hospital were registered. Only patients were included in the study who (1) underwent abdominal ultrasonography in our department; (2) had confirmed acute deep venous thrombosis; (3) had no known malignancy. Malignancies which appeared after hospital stay were detected by telephone inquiry among patients and general practitioners in February 1995. Of the 371 patients with deep venous thrombosis 104 were included in the study. We found abnormal ultrasound findings in 68 patients (65%), but only in 23 patients were the findings of clinical relevance, in 12 of whom (12%) there was a connection with deep venous thrombosis. Ultrasound detected 3 malignancies (3%). The overall rate of newly detected malignancies was 10 (10%), of which 6 were detected during hospitalization and 4 afterwards. Based on these results we can recommend routine performance of abdominal ultrasonography on patients with deep venous thrombosis. A literature overview is given.
Within the scope of the participation at the VI. European Crohn's Disease Study we observed under therapy with 4 g/day Mesalazine (Pentasa) a strong diffuse hair loss on two female patients which disappeared again after discontinuation of therapy. A repeated positive exposure in both patients confirmed the causality. One patient had thereafter a recurrence of Crohn's disease so she was given a reduced dose of Mesalazine (2 g/d). The hair loss began again but on an acceptable level for the patient. Thus, it looks like a dose-dependent side-effect as it is known in the medical literature. These are so far the first two cases of hair loss in connection with Pentasa recorded by the Swiss Drug Monitoring Center. In the medical literature there are reports about this side-effect from all producers known in Switzerland (Asacol, Pentasa, Salofalk), which suggests a Mesalazine specific side-effect. Since recently higher doses of Mesalazine (2-4 g/d) are used in Crohn's disease, a reversible and probably dose-dependent hair loss must be expected in 1-2% of these patients.