Randomized trial of adjuvant chemotherapy with mitomycin plus ftorafur versus mitomycin alone in resected locally advanced gastric cancer.

PURPOSE: We performed a clinical trial to determine whether postoperative adjuvant chemotherapy with two drugs versus one drug could prolong survival. PATIENTS AND METHODS: From 1985 to 1996, 85 patients with completely resected locally advanced gastric cancer were enrolled. The subjects were randomized into two treatment groups, as follows: mitomycin (MMC) 10 to 20 mg/m2 intravenously (i.v.) on day 1 every 6 weeks plus ftorafur (FT) 500 mg/m2/d for 36 consecutive days; or MMC alone, 10 to 20 mg/m2 i.v. every 6 weeks. All courses were repeated four times. RESULTS: After a median follow-up duration of 62 months, the overall 5-year survival rates were 67% for the MMC-FT group versus 44% for the MMC group (P = .04). Subgroup analysis to compare survival curves using the method of Mantel-Cox showed survival rates significantly in favor of the MMC-FT group in the subsets of patients with node-negative disease (P = .01) and those whose disease was stage IB or II (P = .008). CONCLUSION: Significantly better survival results were observed for MMC-FT versus MMC alone. Subset analysis suggest a strong benefit in patients with node-negative and early-stage resected gastric cancer.

Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients.

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.

Somatostatin compared with cimetidine in the treatment of bleeding peptic ulcer without visible vessel.

In a randomized double-blind trial 100 patients with severe bleeding peptic ulcers were treated with an intravenous (i.v.) infusion of cimetidine or somatostatin. Only those patients in whom endoscopy performed within 6 h of admission showed non-arterial bleeding or signs of recent haemorrhage without a visible vessel entered the trial. The two treatment groups were well matched for age, sex, presence of underlying disease, prior ingestion of ulcerogenic drugs, tobacco habits, type of bleeding, haematocrit at admission, presence of hypovolaemic shock, source of bleeding and endoscopic findings. Four patients in each group were excluded after randomization. Further haemorrhage occurred in eight (17.3%) patients in the somatostatin group and in 10 (21.7%) in the cimetidine group, but the difference was not statistically significant. The number of surgical procedures, blood transfusion requirement, duration of hospitalization and mortality rates were similar in the two treatment groups. These results suggest that somatostatin does not improve the results obtained with cimetidine in patients with bleeding peptic ulcer, in whom the endoscopy discloses non-arterial bleeding or signs of recent haemorrhage without a visible vessel.

Synthesis and degradation of collagen in pancreatic fibrogenesis.

The mechanism of fibrogenesis in the pancreas is not well known. We analyzed the role of prolylhydroxylase and collagenase activities in the development of fibrosis in chronic alcoholic pancreatitis (CAP). Nineteen patients with CAP and 11 controls (organ donors) with normal pancreatic histology were included in the study. Pancreatic tissue was obtained from all subjects to measure (a) area of fibrosis (histomorphometric method); (b) prolylhydroxylase activity (PHase), which reflects the intracellular synthesis of collagen (Hutton's method); and (c) collagenase activity, which reflects the degradation of collagen (collagenase assay system, 3H). The percentage of the fibrosis area in relation to the total area of pancreatic tissue was significantly higher in CAP than in the control group (70.6+/-20.2% vs. 4.6+/-1.8%; p<0.001). Mean pancreatic PHase activity was also significantly higher in CAP than in the control group (775+/-258 cpm/mg protein/h vs. 405+/-151 cpm/mg protein/h; p<0.001). The collagenase activity was significantly lower in CAP than in the control group (8.7+/-3.5 cpm/cpm added/mg protein vs. 18.0+/-3.9 cpm/cpm added/mg protein; p<0.001). A significant correlation was observed between percentage fibrosis evaluated histomorphometrically and PHase activity in all patients (r = 0.72; p<0.001), and between PHase and collagenase activities in controls (r = 0.70; p = 0.024), but not in CAP. Pancreatic tissue in CAP has an increased fibrogenic activity and an impaired collagen-degradation capacity. These findings might explain the excessive development of fibrosis in CAP.

Hepatic fibrogenic activity in chronic alcoholic pancreatitis.

The prevalence and the mechanisms of hepatic fibrosis in chronic alcoholic pancreatitis remain uncertain. The aim of this study was to investigate the fibrogenic activity of the liver in patients with chronic pancreatitis and its relation with either the alcohol or cholestasis. Liver biopsies were obtained from 16 patients with chronic pancreatitis at the time of surgery and from 10 organ donors. Samples were processed for histologic examination to assess the presence and extent of fibrosis, inflammatory reactions, and cholestasis- and alcohol-related lesions. In other samples, the collagen content was measured by morphometry, and prolylhydroxylase activity was determined. Liver-function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed before surgery in all the patients. Of patients with chronic pancreatitis, 75% had significantly greater hepatic fibrosis and prolylhydroxylase activity than the control group. Moreover, prolylhydroxylase activity in patients with chronic pancreatitis was higher in those with cholestasis or partial obstruction of the common bile duct than in those without cholestasis or partial obstruction of the common bile duct. Both the fibrogenic activity and the collagen content in the livers of patients with chronic alcoholic pancreatitis are significantly increased, even in those without histologic lesions, and these alterations may be secondary to a partial occlusion of the common bile duct.

Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism.

The aim of the study was to assess whether changes in gastric mucosal blood flow induced by acute normovolaemic anaemia influence the susceptibility of the gastric mucosa to ethanol-induced damage, and the relationship of these changes with nitric oxide biosynthesis. Acute normovolaemic anaemia, promoted by exchanging 3 ml of blood by a plasma expander, induced a significant increase in gastric mucosal blood flow measured by hydrogen gas clearance, without changes in arterial blood pressure. After intragastric 60% ethanol administration, gastric blood flow was still significantly higher in anaemic than in control rats, and this was associated with a lower macroscopic and microscopic gastric damage. Following ethanol administration, anaemic rats pretreated with an inhibitor of nitric oxide biosynthesis (L-NMMA, 50 mg/kg, i.v.) had a lower gastric blood flow and a higher macroscopic gastric damage than anaemic rats without pretreatment. Anaemic rats pretreated with vasopressin also had after ethanol administration a lower gastric blood flow and a higher macroscopic gastric damage. It is concluded that acute normovolaemic anaemia protects the gastric mucosa against damage induced by intragastric ethanol. The inhibition of nitric oxide biosynthesis reverts in part this protective effect, and this seems to be related with the capability of nitric oxide to increase gastric mucosal blood flow, since vasoconstriction by a nitric oxide-independent mechanism causes a similar effect.

Scintisplenoportography in assessing patency of distal splenorenal shunts.

Scintisplenoportography was performed on 33 occasions in 28 cirrhotic patients who had bled from esophagogastric varices. In 17 cases scintisplenoportography was carried out after a retroperitoneal distal splenorenal shunt procedure and in the remaining 16 instances in patients without any surgical shunt. In four patients scintisplenoportography was performed before and after a surgical shunt procedure, and in one case, before and after the shunt thrombosed. Gammagraphic patterns and spleen-heart times helped determine which patients did not have a surgical shunt, which had a patent shunt, and which patients had a thrombosed shunt. A patent shunt pattern and a thrombosed shunt pattern have been defined. It is concluded that scintisplenoportography is a useful, reproducible, and safe method to assess the patency of distal splenorenal shunts.

Sclerosing cholangitis after surgical treatment of hepatic echinococcal cysts. Report of three cases.

Three patients with sclerosing cholangitis after surgical treatment of echinococcosis of the liver are described. Before surgery, they had clinical symptoms that suggested a communication between the cyst and the biliary tract and, in two of them, the communication was later demonstrated by cholangiography. In each case, the cyst was injected with formalin solution. Soon after operation chronic cholestasis developed, with operative, cholangiographic, and histologic data suggesting sclerosing cholangitis. The role of formalin in the pathogenesis of this condition is discussed herein.

Hemosuccus pancreaticus from a pseudoaneurysm of the hepatic artery proper in a patient with a pancreatic pseudocyst.

Pseudoaneurysms of the visceral arteries due to pancreatitis, with subsequent rupture and hemorrhage into the pancreatic duct are unusual. To date, three cases of pseudoaneurysm of the hepatic artery with hemosuccus pancreaticus have been reported in the literature. We describe a case of a pseudoaneurysm of the hepatic artery proper, which ruptured into a pancreatic pseudocyst communicating with the pancreatic duct, and which was the cause of upper gastrointestinal bleeding. This case was successfully managed by resection of both the pseudoaneurysm and the pancreatic pseudocyst.

Endoscopic sclerotherapy to arrest uncontrolled variceal bleeding in cirrhotic patients with high surgical risk.

BACKGROUND/AIMS: In 20-50% of patients bleeding from esophageal varices, conservative procedures fail to obtain hemostasis and prevent early recurrence. METHODOLOGY: We retrospectively analyzed the efficacy and safety of endoscopic sclerotherapy in 66 cirrhotic patients with high surgical risk and persistence or recurrence of variceal bleeding in spite of adequate medical treatment (somatostatin and/or balloon tamponade). RESULTS: Emergency sclerosis controlled bleeding in 46 out of 66 patients (70%). The remaining 20 patients underwent additional procedures to arrest the hemorrhage, and 6 died because of massive bleeding. Early rebleeding occurred in 5 patients (10%). The mortality within 2 days, 1 week, and 6 weeks was 9%, 17% and 32%, respectively. Death was attributed to hemorrhage in 9 cases. Sclerotherapy was associated with complications in 9 patients (14%). CONCLUSION: These results suggest that emergency sclerotherapy is a safe and effective procedure in cirrhotic patients with high surgical risk and persistence or recurrence of bleeding after conservative hemostatic procedures.

Laparoscopic treatment of acute biliary pancreatitis.

UNLABELLED: Laparoscopic cholecystectomy (LC) has become the standard treatment of gallstones. Application of LC in certain complications of biliary stones such as acute biliary pancreatitis (ABP) is not well defined. 10-30% of patients with ABP present associated bile duct stones, and the realization of a preoperative ERCP has been routinely proposed. Nevertheless, this examination may be unnecessary in most patients. AIM: To investigate the applicability of laparoscopic surgery for treatment of ABP. MATERIALS AND METHODS: Between Jan-1992 and June-1995, 368 patients were prospectively evaluated for LC, 274 for indications other than ABP. (Group I, LC) and 91 as a consequence of ABP. (Group II, ABPxL). ERCP was indicated when ultrasonography showed a dilated bile duct (> 8 mm) or when the liver function test (LFT) presented high scores. Age, sex, operative time, incidence of bile duct stones, postoperative stay and morbimortality were evaluated. RESULTS: The two groups were well matched for age, sex and associated medical risk factors. There were no differences in the operative time, conversion rate or postoperative morbidity (10% vs 10%). ERCP was performed in 25 patients in Group II and bile duct stones were found in 12 cases. In all cases an intraoperative cholangiography was performed, and in 6 patients, bile duct stones were removed by laparoscopic means. Three patients were converted to open surgery on finding duct stones which could not be treated by laparoscopic means. Mean postoperative stay was significantly longer in Group II than in Group I. In two cases, pancreatic pseudocyst was attempted with a laparoscopic approach. CONCLUSIONS: Definitive treatment of ABP could be accomplished effectively by laparoscopy, with selective indication of ERCP.

[Chronic lymphatic leukemia and portal hypertension: a causal association?]. / Leucemia linfática crónica e hipertensión portal: una asociación causal?

The authors report two cases of chronic lymphocytic leukemia and portal hypertension without an apparent cause. In the first patient, the histopathological study disclosed severe lymphocytic infiltration of the liver with moderate fibrosis of portal spaces. In the second patient, regenerative nodular hyperplasia of the liver was shown to be associated with lymphocytic infiltration. On the basis of these two observations, the authors discuss the mechanisms of portal hypertension in chronic lymphocytic leukemia. It is concluded that there probably is a causal relationship between both disorders, although its pathogenesis may be diverse.

[Predictive factors of mortality in a series of 61 patients with severe acute pancreatitis]. / Factores predictivos de mortalidad en una serie de 61 pacientes con pancreatitis aguda grave.

The predictive value of eight clinical variables and 20 analytical variables on mortality was retrospectively analyzed in 61 patients with severe acute pancreatitis, fulfilling at least three Ranson criteria, admitted to the ICU between 1977 and 1987. The mean age of the series was 57 +/- 16.6 years. Twenty seven were males and 34 females. The mortality rate was 60%. Univariate analysis demonstrated that the variables with greater predictive value of mortality were: age, days of hospitalization, presence of associated diseases, plasma lactodehydrogenase, more than 10% hematocrit decrease during the first 48 hours, plasma ureic nitrogen on admission and a value greater than 1.8 mmol/l during the first 48 hours, calcemia, arterial oxygen pressure, plasma albumin, and prothrombin time. A logistic regression multivariate analysis disclosed that the variables with independent predictive value of mortality were: age, serum ureic nitrogen, calcemia, arterial oxygen pressure, plasma albumin, and hematocrit decrease after 48 hours. When the patients were grouped according to the presence of less than three, three, four or more than four of these risk factors (being, the average the cutting point) we obtained a good prognostic discriminative power since the mortality in those groups was 0, 30%, 60%, and 100%, respectively.

[Impact of sabbatical leave on hospital and university promotions]. / Influencia de los permisos sabáticos en la promoción hospitalaria y universitaria.

BACKGROUND: The aim of this study was the assessment of the scientific production and impact on academic and/or hospital promotion ob sabbatical leaves of medical staff from a University hospital. POPULATION AND METHODS: A matched case-control design was used. The Mantel-Haenszel odds ratio (ORMH) and its 95% confidence intervals were calculated. A total of 52 sabbaticals leaves were analyzed with successful matching for 43 pairs. RESULTS AND CONCLUSIONS: Taking a sabbatical leaves is associated with a significant higher chance of hospital promotion (ORMH = 7.5; CI 95%, 1.71-32.78; o = 0.004), but there is not a significantly higher chance of academic promotion (ORMH = 0.66; CI del 95%, 0.23-1.83; p = 0.60).

[Superficial gastric cancer in Barcelona. Importance of the detection of severe epithelial dysplasia in biopsies obtained under endoscopic control in the diagnosis of early gastric cancer]. / Cáncer gástrico superficial en Barcelona. Importancia de la detección de displasia epitelial acusada en las biopsias obtenidas bajo control endoscópico para el diagnóstico del cáncer gástrico incipiente.

BACKGROUND: Severe mucosal dysplasia (SMD) in endoscopic gastric biopsies is a controversial lesion because some authors consider it as an histologic lesion associated to superficial gastric cancer (SCG). This study is aimed to asses the prevalence of SCG in Barcelona; if the presence of SMD is associated to SCG and, the clinical and endoscopic manifestations which induced the diagnosis. METHODS: We studied a total of 4,800 patients who had been submitted to gastroscopy during 1.5 years. A total of 79 patients suffered gastric cancer, 56 of them were submitted to resection. Ten of these 56 patients (17%) had SCG. The most frequent first clinical manifestation of SCG was gastrointestinal haemorrhage. RESULTS: Endoscopic aspect suggested malignancy in five cases. Biopsies during endoscopy allow diagnosis of gastric cancer in five. In four histologic studies showed SMD. In the tenth patient, the first endoscopy with biopsies showed a gastric peptic ulcer. A later endoscopic control showed the persistence of the macroscopically benign lesion but one among seven biopsies showed adenocarcinoma. The four patients with SMD had gastric cancer in further endoscopic procedures, except in one which was operated after two endoscopies demonstrating SMD. CONCLUSIONS: This study suggests: 1) prevalence of SGC in Barcelona is similar than the other European countries. 2) haemorrhage is a frequent first manifestation of SCG, and 3) the finding of SMD in endoscopic biopsy strongly suggests the presence of SCG in the stomach.

[Massive pleural effusion secondary to pancreatic-pleural fistula as first manifestation of chronic pancreatitis. Report of three cases]. / Derrame pleural masivo secundario a una fístula pancreatopleural como primera manifestación de una pancreatitis crónica. Descripción de tres casos.

Patients with chronic pancreatitis develop massive pleural effusion in less than 1% and its frequency as the first clinical manifestation of the disease is unknown. Three patients with massive pleural effusion and dyspnea which led to the diagnosis of chronic pancreatitis are referred. The patients were 28, 37 and 41 years old, they were hard-drinking and they came to the hospital because of quick and progressive dyspnea, with hypoxemia and hypocapnia. Two patients had right and one left pleural effusion. The thoracothentesis gave 10, 9 and 3.5 l of serohematic liquid rich in pancreatic enzymes. All cases showed tomographic changes of chronic pancreatitis and pancreatic pseudocysts. Only in one of them the link between the pseudocyst and pleural effusion through a fistula in the right support of the diaphragm could be identified. The different therapeutic possibilities are discussed. Pancreatopleural fistula diagnosis should be considered in patients with massive fast pleural effusion and a history of high alcohol intake. High levels of pancreatic enzymes in the pleural liquid confirm the diagnosis.

[Nosocomial infections due to opportunistic fungi: analysis of a news outbreak in the Spanish press]. / Infecciones nosocomiales por hongos oportunistas: análisis de una serie de noticias publicadas en la prensa española.

BACKGROUND: To study an outbreak of media news related to nosocomial infections due to opportunistic fungi in Spanish hospitals. CASE DEFINITION: any news related to possible nosocomial infection due to opportunistic fungi in Spanish hospitals, published in national or local daily newspapers, over the pre-epidemic (July-December, 1998) and epidemic periods (January-June, 1999). All news were reviewed and identified using global press reports summaries, prepared by two independent sources, and were analyzed by three different observers. RESULTS: Over the pre-epidemic period there were not any news related to nosocomial infections due to opportunistic fungi. Over the epidemic period, a total of 218 news were identified, 154 (71%) published in national newspapers and 64 (29%) in local ones. We analyzed separately 18 editorials or opinion articles related to this subject. The epidemic curve (distribution of news by week) showed an incidence news peak at week 5 (102 news, 46.7% of all news published). The media mentioned up to 19 different hospitals as institutions with possible cases of nosocomial fungal infections. After week 8, news incidence drop, and remain thereafter at minimum levels. CONCLUSIONS: The example provided by the analysis of this outbreak of media news, related to nosocomial infections by Aspergillus an other opportunistic fungi, is useful to allow us understand how some medical news arise, develop and were transmitted. The public alert situation created in Spain was remarkable, and it is likely that there was a transient loss of confidence in the safety of public health institutions. Today's medicine requires a great and better openness to the media, and a better cooperation between both parts.

[Usefulness of ultrasonography and computerized tomography in predicting resectability of pancreatic carcinoma]. / Utilidad de la ultrasonografía y la tomografía computarizada en la predicción de la resecabilidad del carcinoma pancreático.

BACKGROUND: Surgical resection is the only curative treatment of pancreatic carcinoma (PC). An accurate assessment of the extension of PC is mandatory to select appropriate patients to this therapeutic option. This study was aimed at assessing the usefulness of abdominal ultrasonography (US) and computed tomography (CT) to establish tumoral staging and to predict tumor resectability. PATIENTS AND METHODS: Between January 1990 and December 1995, 84 PC patients were submitted to surgical procedures (potentially curative resection in 30%, biliodigestive anastomosis in 51% and exploratory laparotomy in 13%). Preoperative staging was carried out by means of abdominal US and/or CT. Definitive staging was established according to surgical findings, using the TNM classification. RESULTS: Accuracy of preoperative evaluation with regard to tumoral staging was 65%, being underestimated in 29 (35%) patients. This underestimation was mainly due to lesions in stage I. In addition, preoperative staging predicted tumor unresectability with a 50% sensitivity and a 83% specificity. CONCLUSIONS: US and CT have a good specificity in the staging and unresectability prediction of pancreatic cancer. However, their usefulness is limited by their low sensitivity.