Phase II study on weekly bolus topotecan in advanced or recurrent cervical cancer.

OBJECTIVE: It was the aim of our study to evaluate the efficacy and safety of weekly topotecan in patients with advanced or recurrent cervical disease. METHODS: Topotecan was administered intravenously as a weekly infusion at a dose of 3.5 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. After the second cycle, the dose was increased to 4 mg/m(2) if no grade >2 toxicity occurred. Treatment was continued until disease progression or unacceptable toxicity. RESULTS: Twenty-one patients were enrolled, but only 18 were evaluable for response and toxicity. Ten patients (56%) had received primary surgery + chemoradiation, 6 patients (33%) had previously received surgery + chemotherapy and 2 patients (11%) exclusive chemoradiation. Patients received a mean of 3.5 courses (range 1-6). No complete or partial responses were reported. Two patients (11%) presented disease stabilization as maximum response. Median progression-free survival was 11 weeks (95% CI 15-25), and median overall survival was 28 weeks (95% CI 24-72). The treatment was generally well tolerated. CONCLUSIONS: This trial did not report any activity of weekly bolus topotecan in the treatment of advanced or recurrent cervical cancer. Actually, there is no evidence to recommend this therapy in this patient population.

Retained gastric antrum syndrome diagnosed by [99mTc] pertechnetate scintiphotography in man: hormonal and radioisotopic study of two cases.

Retained-antrum syndrome is a rare condition, occurring in Billroth II gastrectomised patients, in which an ulcer recurs associated with high levels of circulating gastrin. Some gastrin tests are useful to differentiate a retained antrum from a gastrinoma, but a firm diagnosis is sometimes very difficult. We have studied two cases of retained-antrum syndrome both by gastrin tests and by [99mTc] pertechnetate scintiphotography. By this method a prominent area of activity was observed on the anatomic site of the duodenal stump bottom. It appeared after 20 or 30 min and lasted for the 2 hr of observation. After surgical resection, no area of activity was observed at the scintiphotographic followup. No false positive was observed out of the more than 30 subjects studied. Scintiphotography by pertechnetate seems able to demonstrate the presence and the size of retained gastric antrum in B II gastrectomised patients with recurrent ulcer.

Dynorphin B-like immunoreactivity in gastroduodenal biopsy specimens from gallstone patients.

Dynorphin B-like immunoreactivity (ir-dyn B) was measured by a validated radio-immunoassay in gastroduodenal biopsy specimens from control and gallstone patients. Levels were significantly lower in acetic acid extracts of specimens of the transverse portion of the duodenum from gallstone patients. Gel permeation chromatography showed that almost all ir-dyn B in duodenal samples corresponded to a molecular form co-eluting with authentic dyn B. Duodenal extracts from gallstone patients had less of this form. Reverse-phase high performance liquid chromatography of the pooled gel chromatography fractions showed up a molecular form with the same retention time as synthetic dyn B which was significantly less in fractions from duodenal extracts of gallstone patients. These results indicate the occurrence of dyn B in the human gastrointestinal tract; however, at this stage of our understanding, no causal relationship can be demonstrated with functional alterations of the biliary tree.

Different responses of serum cationic trypsinogen to secretin and bombesin in normal subjects and patients with chronic alcoholic pancreatitis.

We evaluated the behavior of serum cationic trypsinogen (SCT), an enzyme of solely pancreatic origin, in 30 patients with chronic pancreatitis and 25 healthy subjects as a control, after secretin and bombesin stimulation. After both the stimulations, serum cationic trypsinogen is unable to distinguish between the healthy control subjects and the patients with chronic pancreatitis. On the other hand, after secretin, the enzyme is able to separate chronic pancreatitis patients with different levels of exocrine function insufficiency. It does so with a greater statistical significance than that obtained by the rapid injection of bombesin and equal to that of trypsin into the duodenal juice during duodenal intubation. For these reasons, as well as the absence of any side-effects, secretin is preferred to bombesin stimulation in the evaluation of the exocrine pancreatic function in patients with chronic pancreatitis.

Serum elastase 1 in clinical practice.

Using radioimmunoassay, we tested serum elastase 1 (E1), an enzyme secreted only from the pancreas, in 200 subjects as follows: 39 healthy subjects as controls, 56 patients with diseases of the digestive tract, 66 patients with hepatobiliary diseases, and 39 patients with pancreatic diseases. The serum E1 showed high specificity and proved very useful in the diagnosis of acute pancreatitis. However it was not useful in diagnosis of clinically silent chronic pancreatitis, nor in its functional evaluation. On the other hand, it was found to be a valuable guide in revealing a concomitant pancreatic pathology during hepatobiliary diseases. Further investigation is needed of the behavior of E1 in patients who have undergone a total pancreatectomy, where the enzyme remains measurable, and in those with an ileocolic disease in an acute phase where E1 is increased in many patients.

Effect of secretin upon the levels of pancreatic enzymes in blood serum.

We have evaluated the serum changes of trypsin, pancreatic isoamylase and lipase, after rapid infusion of secretin, in 45 patients with chronic pancreatitis compared with 35 healthy control subjects. On the basis of duodenal intubation results, chronic pancreatitis patients were divided into two subgroups at different levels of functional impairment. Using the peak activities of the enzymes we have been able to separate the two chronic pancreatitis subgroups by statistical difference; only trypsin distinguishes healthy control subjects from mild to moderate chronic pancreatitis. Therefore, we propose to put into clinical practice this serum provocative test to evaluate the functional damage of an established chronic pancreatitis.

A new endoscopic balloon for sclerotherapy in active bleeding from esophageal varices.

A new balloon for flexible endoscopes has been developed and used in 25 patients with esophageal varices: sclerotherapy was carried out as prophylaxis against rebleeding in 17 cases, and during active hemorrhage in 8 cases. The balloon was shown to be effective in controlling hemorrhage and enabling sclerosing injections to be carried out, both in emergency and in cases of bleeding response to injections.

Absence of histopathological changes of ileum and colon in functional chronic diarrhea associated with bile acid malabsorption, assessed by SeHCAT test: a prospective study.

OBJECTIVES: Chronic diarrhea of unknown origin is often associated with bile acid malabsorption, the pathogenetic role of which is uncertain. The aim of this study was to identify morphological abnormalities in the ileal and colonic mucosa in patients with this disorder. METHODS: We performed a prospective and blinded histopathological study (between June 1991 and November 1992) of endoscopic biopsies of the distal ileum and colon of 23 patients suffering from chronic diarrhea of unknown origin. In 14, the SeHCAT (75-selena-homo-cholic acid taurine) test was abnormal owing to bile acid malabsorption; in the other nine, the diarrhea control group, the test results were normal. A detailed evaluation of surface epithelium, immune response and inflammatory changes was made. RESULTS: in two patients and two controls, mild villous atrophy was observed; there was also slight inflammation of the ileal and colonic mucosa occurring with the same frequency in both groups. A slight replacement of goblet cells was more evident in the diarrhea control group. CONCLUSIONS: Chronic diarrhea of unknown origin associated with bile acid malabsorption does not involve specific morphological changes of ileal or colonic mucosa, and its pathogenesis must be looked for in dysfunction of the ileum and/or colon.

Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test.

Although bile acid malabsorption (BAM) in post-cholecystectomy diarrhea (PCD) is a well-known clinical condition, its true etiopathogenetic role is not entirely clear. The SeHCAT (23-selena-25-homotaurocholic acid) test, a simple and reliable BAM test, was performed in 33 cholecystectomized patients, 26 with chronic diarrhea. The test revealed a marked degree of BAM in 25/26 cases. Cholestyramine in doses of 2-12 g/day was effective in 23/25, ineffective in two, and was not tolerated in one patient. When treatment was suspended, diarrhea recurred in nine, whereas bowel habit remained regular in 60%, with brief sporadic episodes of diarrhea in the other cases. The SeHCAT test was repeated in 11 cases after cholestyramine treatment interruption, and revealed the normalization of parameters in two patients and an improvement in three. We conclude that BAM is an important etiopathogenetic factor in PCD that responds favorably to cholestyramine. In 60% of the cases, it resolved diarrhea definitively, although without eliminating BAM in all cases: this suggests that existence of other factors associated with BAM. The SeHCAT test is essential for a differential diagnosis between PCD and the irritable bowel syndrome.

Lactulose hydrogen breath test in orocecal transit assessment. Critical evaluation by means of scintigraphic method.

Orocecal transit time can be studied easily using the hydrogen breath test with lactulose, but the method has some important limitations. The orocecal transit time of 10 patients suffering from irritable bowel syndrome was measured twice, at a one-week interval, by breath test and scintigraphy simultaneously using an aqueous solution of 20 g lactulose containing 74 MBq of [99mTc]DTPA. Abdominal radioactivity and alveolar hydrogen values obtained every 5 min were noted and used to obtain the following: orocecal transit time by the two methods; ileocecal lactulose flow; total and per gram of lactulose hydrogen production; mean hydrogen concentration during the right colon filling; and measurement error of the breath test with respect to the scintigraphy. In the case of the breath test, the orocecal transit time intrapatient reproducibility was better (coefficient of variation = 13.5%) when a hydrogen threshold increment of 5 ppm was used; the best correlation with the scintigraphic measurement was observed at this threshold (r = 0.90, P < 0.001). The breath test overestimated orocecal transit time with the error correlating negatively and significantly with the total hydrogen production and, particularly, the mean hydrogen concentration (r = 0.79, P < 0.01): for a mean hydrogen concentration of more than 15 ppm, the error was negligible, while within this value there was a noticeable overestimation. To conclude, the lactulose hydrogen breath test is capable of giving an accurate measurement of orocecal transit time if a hydrogen threshold increment of 5 ppm is chosen and if the mean hydrogen concentration in the first 30 min of the right colon filling is taken into account.

Scintigraphic evaluation of enterogastric reflux using 75Se-HCAT: methodology and first clinical observations.

The aim of this study was to assess the possibility of detecting enterogastric reflux (EGR) by 75Se-HCAT cholescintigraphy. The lowest detectable activity in the gastric area at different concentrations of the radiotracer in the gallbladder was preliminary measured both in a plastic phantom and in an in vivo model. Ten patients were studied after a single oral administration of 1480 KBq 75Se-HCAT. Gamma camera imaging was carried out for five consecutive days during both fasting and after meal ingestion. In our in vivo model an EGR corresponding to 1% of gallbladder content on day one and 8% on day five was detected. In three out of five patients in whom bile was present in the stomach at endoscopy, 75Se-HCAT cholescintigraphy demonstrated an EGR, while in three out of five patients in whom endoscopy was negative, 75Se-HCAT cholescintigraphy detected EGR either during fasting or after meal ingestion. As EGR is not constant, 75Se-HCAT may be a useful tracer of bile to detect EGR over a prolonged period of time and in different physiological conditions.