Laparoscopic liver resections for hepatocellular carcinoma. Is it a feasible option for patients with liver cirrhosis?

BACKGROUND: Laparoscopic surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver, above all for patients with hepatocellular carcinoma (HCC) and cirrhosis. This approach mainly includes diagnostic procedures and interstitial therapies. However, we believe there is room for laparoscopic liver resections in well-selected cases. The aim of this study is to assess: (a) the risk of intraoperative bleeding and postoperative complications, (b) the safety and the respect of oncological criteria, and (c) the potential benefit of laparoscopic ultrasound in guiding liver resection. METHODS: A prospective study of laparoscopic liver resections for hepatocellular carcinoma was undertaken in patients with compensated cirrhosis. Hepatic involvement had to be limited and located in the left or peripheral right segments (segments 2-6), and the tumor had to be 5 cm or smaller. Tumor location and its transection margins were defined by laparoscopic ultrasound. RESULTS: From January 1997, 22 out of 250 patients with HCC (9%) underwent laparoscopic liver resections. The mean patient age was 61.4 years (range, 50-79 years). In three patients, conversion to laparotomy was necessary. The laparoscopic resections included five bisegmentectoies (2 and 3), nine segmentectomies, two subsegmentectomies and three nonanatomical resections for extrahepatic growing lesions. The mean operative time, including laparoscopic ultrasonography, was 199 +/- 69 min (median, 220; range, 80-300). Perioperative blood loss was 183 +/- 72 ml (median, 160; range, 80-400 ml). There was no mortality. Postoperative complications occurred in two out of 19 patients: an abdominal wall hematoma occurred in one patient and a bleeding from a trocar access in the other patient requiring a laparoscopic re-exploration. Mean hospital stay of the whole series was 6.5 +/- 4.3 days (median, 5; range, 4-25), while the mean hospital stay of the 19 laparoscopic patients was 5.4 +/- 1 (median, 5; range, 4-8). CONCLUSION: Laparoscopic treatment should be considered in selected patients with HCC and liver cirrhosis in the left lobe or segments 5 and 6 of the liver. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by adequately skilled surgeons with appropriate instruments.

Trastuzumab in metastatic breast cancer.

Metastatic breast cancer is an incurable disease in a very high percentage of patients. Despite new progress in endocrine and other systemic therapies, this evidence remains challenging for patients and clinicians. HER2 protein is a member of the epidermal growth factor family of transmembrane receptors. HER2 is overexpressed in approximately 20% to 30% of breast cancers. Overexpression of HER2 has been shown to be associated with increased tumor proliferation and relative resistance to some types of chemotherapy and hormonal therapies. Trastuzumab, a humanized monoclonal antibody directed against HER2 protein, has been shown to be an efficacious and well tolerated treatment for HER2-overexpressing metastatic breast cancer, both as a single agent and when it is used in combination with chemotherapy.

In vitro characterization of tachykinin NK2-receptors modulating motor responses of human colonic muscle strips.

1. Human in vitro preparations of transverse or distal colonic circular smooth muscle were potently and dose-dependently contracted by neurokinin A (EC50, 4.9 nM), the tachykinin NK2-receptor selective agonist [beta-Ala8]neurokinin A (4-10) ([beta-Ala8]NKA (4-10)) (EC50, 5.0 nM), neurokinin B (EC50, 5.3 nM) and substance P (EC50, 160 nM), but not by the tachykinin NK1-receptor selective agonist [Sar9Met(O2)11] substance P, or the NK3-receptor selective agonists, senktide and [MePhe7] neurokinin B. No regional differences between transverse and distal colon were observed in response to [beta-Ala8]NKA (4-10). 2. Atropine (1 microM) and tetrodotoxin (1 microM) did not significantly inhibit responses to [beta-Ala8]NKA (4-10), neurokinin A, substance P or neurokinin B. 3. The newly developed non-peptide antagonists for tachykinin NK2-receptors SR 48968, SR 144190 and its N-demethyl (SR 144743) and N,N-demethyl (SR 144782) metabolites, were used to challenge agonist responses, as appropriate. SR 144190 and the metabolites all potently and competitively antagonized the response to [beta-Ala8]NKA (4-10), with similar potency (Schild plot pA2 values 9.4, 9.4 and 9.3, slope = 1). SR 48968 antagonism was not competitive: the Schild plot slope was biphasic with a high (X intercept approximately 9.3) and a low (X intercept 8.4, slope 1.6) affinity site. Co-incubation of SR 48968 (10, 100 nM) and SR 144782 (10 nM) produced additive effects; in this experimental condition, SR 48968 apparent affinity (pKB) was 8.2. In addition, SR 144782 (0.1 microM) antagonized responses to neurokinin A, substance P and neurokinin B, with pKB consistent with its affinity for tachykinin NK2-receptors. The potent and selective NK1 and NK3-receptor antagonists, SR 140333 and SR 142801 (both 0.1 microM), failed to inhibit contractions induced by SP or NKB. 4. In conclusion, the in vitro mechanical responses of circular smooth muscle preparations from human colon are strongly consistent with the presence of non-neuronal tachykinin NK2-receptors, but not tachykinin NK1- or NK3-receptors. Our findings with SR 48968 suggest the existence of two tachykinin NK2-receptor subtypes, that it seems to distinguish, unlike SR 144190 and its metabolites. However, the precise nature of SR 48968 allotopic antagonism remains to be elucidated, since allosteric effects at the tachykinin NK2-receptor might well account for the complexity of the observed interaction.

In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum.

We investigated the effect of the cannabinoid agonist (+)WIN-55212-2 on human ileum longitudinal smooth muscle preparations, either electrically stimulated or contracted by carbachol. Electrical field stimulation mostly activated cholinergic neurons, since atropine and tetrodotoxin (TTX), alone or coincubated, reduced twitch responses to a similar degree (85%). (+)WIN-55212-2 concentration-dependently inhibited twitch responses (IC50 73 nM), but had no additive effect with atropine or TTX. The cannabinoid CB1 receptor antagonist SR 141716 (pA2 8.2), but not the CB2 receptor antagonist, SR 144528, competitively antagonized twitch inhibition by (+)WIN-55212-2. Atropine but not (+)WIN-55212-2 or TTX prevented carbachol-induced tonic contraction. These results provide functional evidence of the existence of prejunctional cannabinoid CB1-receptors in the human ileum longitudinal smooth muscle. Agonist activation of these receptors prevents responses to electrical field stimulation, presumably by inhibiting acetylcholine release. SR 141716 is a potent and competitive antagonist of cannabinoid CB1 receptors naturally expressed in the human gut.

In vitro functional evidence of different neurotensin-receptors modulating the motor response of human colonic muscle strips.

1. The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT1 and NT2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT - PCR) analysis. 2. NT potently and dose-dependently contracted muscle strips, with significant regional differences in potency and efficacy between the transverse and distal colon: EC50, 3.6 and 7.5 nM; the maximal effect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM). 3. SR 142948 (10 nM - 1 microM) competitively antagonized NT responses in the transverse and distal colon with similar affinities: pA2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM - 10 microM) antagonized the NT response competitively in the distal colon (pA2 6.55, slope 0.79) and non-competitively in the transverse colon (pA2 8.0, slope 0.51). Neither compound had any agonist effect. 4. The fact that the specific antagonists prevented NT-evoked atropine- and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The finding of NT1 receptor transcript in both transverse and distal colon suggests its identity with the lower affinity site disclosed functionally by SR 48692 in these segments.

Thirty months experience with laparoscopic adjustable gastric banding.

INTRODUCTION: Since June 1996 we performed laparoscopic adjustable silicone gastric banding (LASGB), because of low invasivity, absence of malabsorption, reversibility, and postoperative regulation. MATERIALS AND METHODS: Criteria included body mass index (BMI) >40 or >35 with serious obesity-related conditions. 154 patients underwent LASGB. BMI ranged from 35 to 65.7 (mean 43.7+/-6.2). RESULTS: The laparoscopic procedure was successfully completed in 150 patients (97.4%). One patient was converted to the laparotomic procedure because of hepatomegaly; 4 patients had to be converted for gastric laceration during the laparoscopic approach. In one of these patients, the band was removed 7 days later for sepsis, followed by an uneventful postoperative course. The mean length of postoperative hospitalization was 2.3+/-0.9 days. Per cent of excess weight loss was 42.5+/-22.4 after 1 year. CONCLUSIONS: LASGB was feasible and effective.

Ultrasound measurement of visceral and subcutaneous fat in morbidly obese patients before and after laparoscopic adjustable gastric banding: comparison with computerized tomography and with anthropometric measurements.

BACKGROUND: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. METHODS: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. RESULTS: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. CONCLUSION: We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.

Nutritional survey of patients in a general surgical ward: is there an effective predictor of malnutrition?

A survey of patients in a general surgical ward was undertaken to establish biochemical and anthropometric standards which could be used to detect malnourished patients in hospital. Results of biochemical and anthropometric tests of nutritional status were compared with assessment by a clinician and the quick nutritional index of Seltzer. Triceps skinfold thickness and serum albumin concentrations indicated that 29% and 35% of patients, respectively, were undernourished compared with 16% by clinical assessment and 17% by the quick nutritional index. Significant correlations (p less than 0.001) between serum albumin and transferrin concentrations and arm muscle area were found for men but not for women. Poor nutritional specificity and sensitivity of some anthropometric and biochemical tests may account for the difference in the level of undernutrition found by these tests and clinical assessment. This shows the importance of the choice of test in influencing the level of undernutrition detected.

Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon.

BACKGROUND & AIMS: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut. METHODS: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro. RESULTS: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528. CONCLUSIONS: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.

Conservative management of cocaine-packet ingestion: experience in Milan, the main Italian smuggling center of South American cocaine.

OBJECTIVE: To assess retrospectively the effectiveness and the safety of the conservative medical management of asymptomatic cocaine body-packers. DESIGN: Case series collected during twelve years (1980-1992). SETTING: Milan Airports Health Center. Department of Surgery and Intensive Care Unit of San Raffaele Hospital-University of Milan. PARTICIPANTS: 189 suspected cocaine body packers (143 male, 53 female), aged between 18-53 years, were brought to our observation by customs after disembarking at the Milan International Airports of Malpensa and Linate. 61 subjects (32%) turned to be carriers of packets containing cocaine (ovules). INTERVENTIONS: Medical conservative treatment, based on close clinical observation and light solid diet, free assumption of liquids and oily laxatives. Plain abdominal X-ray and ultrasound were performed for the diagnosis of cocaine packet ingestion and then repeated up to the complete evacuation of all ovules. Two laparotomies with surgical removal of ovules in symptomatic patients (bowel obstruction and acute cocaine intoxication due to the intraluminal rupture). MEASURES: Physical examination with neurological assessment every 8 hours and vital signs (including blood pressure, heart frequency and temperature) every 4 hours to detect complications (acute cocaine intoxication, bowel obstruction or perforation) secondary to cocaine packet ingestion. Structural features of the containers, cocaine amount per ovule, and rate and indications for surgical treatment have been reviewed. RESULTS: Evacuation period lasted from 3 to 6 days. Ingested containers varied from 52 to 117 with a mean of 88 +/- 13 ovules for each body packer. Total amount of recovered 95% pure cocaine hydrochloride was 41 kilograms. Signs of cocaine toxicity and bowel obstruction requiring emergency laparotomy occurred in two cases (3.3%). Both patients recovered uneventfully. CONCLUSIONS: Conservative management during spontaneous evacuation of the containers is the first choice approach to the body-packet ingestion. Close clinical observation allows an early detection of the patients with complications requiring emergency surgical treatment.

Role of hepatic resection in the treatment of hepatolithiasis.

BACKGROUND: The aim of the present study was to evaluate the safety and the efficacy of hepatic resection in the treatment of hepatolithiasis with intrahepatic biliary strictures. EXPERIMENTAL DESIGN: retrospective study. SETTING: University hospital, Italy. PATIENTS: 6 consecutive patients with single lobe hepatolithiasis operated on during the 4-year period 1994-98 inclusive. INTERVENTIONS: major hepatic resections (3 left hepatectomies, 2 left lobectomies, 1 right hepatectomy). MAIN OUTCOME MEASURES: type and duration of the surgical procedure, intra/postoperative blood losses, intra/postoperative course and complications, pathology, and hepatolithiasis recurrence. RESULTS: Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was 233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood transfusions. No intraoperative complication was recorded. Mean postoperative hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was uneventful in 4 (66%) cases. No postoperative mortality was recorded. One pancreatitis and 1 biliary fistula occurred, for an overall postoperative morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had recurrent cholangitis due to right lobe lithiasis and 1 patient died for cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis and unreversible biliary strictures or possible presence of cholangiocarcinoma. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

Magnetic resonance (MR) imaging and MR spectroscopy of nerve regeneration and target muscle energy metabolism in a model of prosthesis-guided reinnervation in rats.

RATIONALE AND OBJECTIVES: We monitored the regeneration of the rat sciatic nerve after its transection and the concomitant alteration in the high-energy phosphates content in the target tibialis anterior muscle. METHODS: Rat sciatic nerve was resected and the gap connected with a prosthesis of polytetrafluoroethylene. Progress of reinnervation was monitored by 1H MR imaging, whereas muscular energy metabolism was evaluated by localized 31P MR spectroscopy. RESULTS: Reconstitution between the nerve stumps was resumed 8-12 weeks postoperatively. The ratio of phosphocreatine to inorganic phosphate reached a plateau at 46% of the initial level approximately 8 weeks after the operation and recovered thereafter. Immediately after the surgery, muscular pH became slightly alkaline and returned to normal with the progress of reinnervation. CONCLUSION: Recovery of the muscular energy metabolism began after the reconnection of the severed nerve stumps. The combination of MR imaging and MR spectroscopy followed noninvasively the progress of reinnervation and muscular energy metabolism of the prosthesis-guided nerve regeneration.

Morphological and functional evaluation of peripheral nerve regeneration in the rat using an expanded polytetrafluoroethylene (PTFE) microprosthesis.

The aim of our study was to evaluate in the rat the ability of a polytetrafluoroethylene microprosthesis (PTFE), to guide the peripheral nerve regeneration between the two extremities of a transected sciatic nerve. In 15 adult male Wistar rats, weighing 200 g, a segment of the right sciatic nerve was resected, leaving a gap of about 1 cm, bridged with microprosthesis, using our original microsurgical technique. Neurophysiological evaluations were performed at 6 and 9 months post-operatively to study the distal motor latency either in the right sciatic nerve or in the unoperated control side. In all the rats myoelectrical responses with an increased latency of the operated side were produced from the interosseous muscle of the foot. The animals were sacrificed 9 months post surgery. Histological sections at the level of the graft were done in all the rats, and in 10 animals biopsies of the tibialis anterior muscle (TA) of each side were performed. An active process of axonal regeneration was documented inside the graft, with no infiltration of nerve fibers through the wall of the prosthesis. A connective fibrous reaction was present around the external wall of the graft. Muscle biopsies showed definite signs of muscle reinnervation, with residual features of variable degree of denervation. These findings stress and confirm the ability of the PTFE graft to allow effective regeneration in a peripheral nerve gap in the rat.

Xenotransplantation rejection is antibody-mediated in both sensitized and nonsensitized recipients.

This study analyzes the mechanisms involved in xenotransplantation rejection between closely related species. Hamster hearts were transplanted heterotopically into both normal rats and rats previously sensitized by the transfusion of donor blood. Sequential ultrastructural and immunohistochemical analyses were performed on the grafts, spleens, and sera. The data obtained support the view that induced antibodies directed against the xenograft endothelium play a very important role in producing graft damage. Moreover, the demonstration of antibodies against myocyte determinants suggests that it is possible, in this particular model, that the antiendothelial antibodies are not the only ones involved in the injury process.

A modified technique of orthotopic transplant of the kidney in rabbits.

In this study kidneys were harvested from bred-for-research cats weighing 4 to 5 kg. General principles of donor bilateral nephrectomy en bloc with aorta, vena cava, renal vessels, and ureters were followed. After the harvest the grafts were placed in lactated Ringer slush. A cuff was prepared on the renal vein over a 10 French plastic tube. The aorta was divided and left in connection with the renal artery at each side. Twenty female checkered Flemish giant rabbits weighing 4.0-6.0 kg served as recipients. After premedication with 40 mg/kg of ketamine, anesthesia was maintained with repeated doses (every 10-15 min) of a 0.1-mL mixture of 5 parts ketamine and 1 part acepromazine diluted 50% in a normal saline. Arterial pressure, CVP, blood gases, and temperature were monitored. Through a limited midline incision a native left nephrectomy was performed. The venous anastomosis was performed with a cuff technique without clamping the vena cava (which causes severe hemodynamic instability); the anastomotic time was 2-3 min. The arterial anastomosis was performed with an end-to-side aorta-to-aorta anastomosis; the anastomotic time was 5 to 7 min. There were no episodes of venous or arterial thrombosis. The donor procedure took approximately 40 min, and the backtable preparation of the graft an additional 45 to 60 min. Preparation of the recipient for the anastomosis took 15 min and the anastomotic time (warm ischemia) was 13 +/- 5 min. In this model suitable for xenograft research the duration of the surgery in the recipient has been greatly reduced because of (1) the previous backtable preparation of the graft, and (2) the cuff technique used for venous anastomosis. The present anesthesia regimen and careful hemodynamic monitoring were also important in the success of this model.

Portal vein graft rectal evacuation after Whipple procedure. the Fabrizio's disease.

In selected cases, pancreatic resections may be performed "en bloc" with arterial and/or venous segments, which have to be replaced with autologous or synthetic grafts. Rectal evacuation of portal vein graft following a Whipple procedure is described, being a late graft infection supposed to underlie this event. Portal vein graft rectal evacuation has not previously been reported in the literature and it is worth keeping it in consideration when performing a regional pancreatectomy.

Right hepatic artery indwelling catheter for adjuvant chemotherapy after right hepatectomy.

Intraarterial hepatic adjuvant chemotherapy after radical hepatic resection for liver metastases from colorectal carcinoma lowers the rate of liver disease relapse. The technique for catheter implantation in the right hepatic artery for subsequent intraarterial hepatic adjuvant chemotherapy after right hepatectomy is herein described and recommended as an effective alternative approach to the standard catheter implantation in the gastroduodenal artery in cases of hepatectomies for liver metastases from colorectal cancer.

Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine (FUdR) for liver metastases from colorectal cancer.

Hepatic arterial infusion of floxuridine is an effective treatment for unresectable hepatic metastases from colorectal cancer. Despite its pharmacological advantage of higher tumor drug concentration with minimal systemic toxicity, hepatic arterial infusion of floxuridine is characterized by regional toxicity, including hepatobiliary damage resembling idiopathic sclerosing cholangitis (5-29% of treated cases). Unlike previous reports describing biliary damage of both intrahepatic and extrahepatic ducts, a case series of extrahepatic biliary stenosis after hepatic arterial infusion with floxuridine is herein described. Between September 1993 and February 1999, 54 patients received intraarterial hepatic chemotherapy based on continuous infusion of floxuridine (dose escalation 0.15-0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. Twenty-seven patients underwent laparotomy to implant the catheter into the hepatic artery, the other 27 patients receiving a percutaneous catheter into the hepatic artery through a transaxillary access. Five patients (9.2%) developed biliary toxicity with jaundice and cholangitis (3 cases), alterations of liver function tests and radiological features of biliary tract abnormalities. They received from 9 to 19 cycles (mean 14.5 +/- 6.3 cycles) of floxuridine infusion with a total drug delivered dose ranging from 20.3 to 41.02 mg/kg (mean: 31.4 +/- 13.5 mg/kg). Extrahepatic biliary sclerosis was discovered by computed tomography scan and ultrasound, followed by endoscopic retrograde cholangiopancreatography and/or percutaneous cholangiography in 3 cases. Radiological findings included common hepatic duct complete obstruction in 1 case, common hepatic duct stenosis in 2 cases, common bile duct obstruction in 1 case, and intrahepatic bile ducts dilation without a well-recognized obstruction in 1 case. Two patients were treated by sequentially percutaneous biliary drainage and balloon dilation while 1 patient had an endoscopic transpapillary biliary prosthesis placed. Percutaneous or endoscopic procedures obtained the improvement of hepatic function and cholestatic indexes without subsequent jaundice or cholangitis. In two patients suppression of floxuridine infusion allowed the improvement of hepatic function. The present series suggests that in some patients receiving hepatic arterial infusion of floxuridine extrahepatic biliary stenosis may represent the primary event leading to a secondary intrahepatic biliary damage that does not correlate with specific floxuridine toxicity but results from bile stasis and infection, recurrent cholangitis and eventually biliary sclerosis. Aggressive research for extrahepatic biliary sclerosis is advised, since an early nonsurgical treatment of extrahepatic biliary stenosis may prevent an irreversible intrahepatic biliary sclerosis worsening the prognosis of metastatic liver disease.

Evaluation of esaprazole activity on basal gastric secretion and on pentagastrin-stimulated secretion in healthy volunteers.

The antisecretory effects of esaprazole on basal gastric secretion and on pentagastrin-stimulated secretion (6 micrograms/kg subcutaneously) were evaluated in two trials carried out on 19 healthy volunteers. All trials were carried out according to a randomized double-blind crossover design versus a placebo. The oral administration of 900 mg of esaprazole 30 min before starting the secretion test, induced a certain reduction of all the gastric secretion parameters. The reduction of both basal and stimulated secretion was significantly (p less than 0.001) more evident after the oral administration (gastric instillation) of 1800 mg of the drug 60 min before starting the study. Esaprazole was shown to have a dose-dependent antisecretory activity which was particularly evident on secretion volume and acid output.

Prevention and early diagnosis of cancer in the rectal stump of ulcerative colitis patients after colectomy and topical treatment.

Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication.