Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

Role of fistulography in evaluating pancreatic fistula after pancreaticoduodenectomy.

OBJECTIVE: To evaluate the usefulness of fistulography as a diagnostic and management tool for clinically suspected pancreatic fistulas (PF) after pancreaticoduodenectomy (PD). METHODS: 84 consecutive fistulographies were performed for clinical suspicion of PF and retrospectively analysed. We radiologically defined two types of PF by means of fistulography, PF1 in the case of primary filling with contrast agent of the jejunal loop or stomach and PF2 in the case of secondary filling of the jejunal loop or stomach through a fistulous tract or a fluid collection. RESULTS: In 35/84 (41.7%) of the fistulograms, a PF1 was demonstrated owing to an instantaneous opacification of the intestinal lumen or the stomach, without evidence of a fistulous tract or fluid collection. In 49/84 (58.3%) fistulograms, a PF2 was demonstrated by the depiction of a fluid collection and/or a fistulous tract and a communication with the intestinal loop or the stomach anastomised with the pancreas. The mean healing time of a PF after PD was 2.7 days for PF1, and 9.8 days for PF2. CONCLUSION: Fistulography helps in the confirmation of clinically suspect PF, and can distinguish PF1 and PF2, thus decreasing post-operative morbidity significantly.

Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries.

BACKGROUND: Kinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs). PATIENTS AND METHODS: Thirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs. RESULTS: Somatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively. CONCLUSIONS: Only rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.

Renal function and volume of infants born with a very low birth-weight: a preliminary cross-sectional study.

AIM: The aim of our study was to compare the function and volumes of kidneys of very low birth-weight (VLBW) and of extremely low birth-weight (ELBW) infants at pre-school ages. PATIENTS AND METHODS: We did a revision of the neonatal records of infants born in our hospital that weighed < or =1500 g at birth. The children were divided into two groups according to their weight at birth: ELBW (<1000 g) and VLBW (1000-1500 g). At the age of 5.7 +/- 1.4 years, the children underwent clinical, laboratory and ultrasound renal assessments. RESULTS: Sixty-nine children fulfilled the requirements for the study. The rate of neonatal treatment with aminoglycosides was higher in ELBW preterms. Renal function parameters, i.e. estimated glomerular filtration rate and albuminuria, did not differ between the two groups of children. Urinary alpha1-microglobulin excretion was significantly higher and kidneys were significantly smaller in the ELBW group than in the VLBW group. CONCLUSION: No impairment or differences in renal parameters were found in pre-school children born ELBW compared with those born with VLBW, except for differences in kidney volume, renal cortical thickness and urinary alpha1-microglobulin excretion. Thus, patients born with ELBW would require a longer follow-up period.

Determination of vanadium(V) in the particulate matter of emissions and working areas by sequential dissolution and solid-phase extraction.

A method based on selective sequential dissolutions is proposed to determine total vanadium(V) in particulate matter of emissions and working areas at concentrations 1,000 times lower than the threshold limit of 0.05 mg m(-3). Separation and preconcentration of vanadium(V) has been achieved by solid-phase extraction on Chelex 100 resin. Possible influence of the matrix has been investigated for two standard reference materials (SRMs), NIST SRM 1648 and BCR-038, before and after spiking, with vanadium(V) recovery in the range 97-103%.

Cross-talk between inducible nitric oxide synthase and cyclooxygenase in Helicobacter-pylori-induced gastritis.

OBJECTIVES: The present study examined the cross-talk between prostanoids and nitric oxide (NO) in human gastric biopsies during Helicobacter pylori infection. SUBJECTS AND METHODS: A pool of 1 or 2 biopsies per patient (11 H. pylori positive and 9 H. pylori negative) were incubated in the medium with/without drugs, 1400W and NS-398, inhibitors of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Levels of NO and prostaglandin E(2) (PGE(2)), predominant products of activity of NOS and COX enzymes, were measured in the medium whereas the expressions of iNOS and COX protein, examined by Western blotting, were measured in the biopsies. RESULTS: The 11 patients with H. pylori infection showed a marked expression of COX-2 and iNOS proteins and high levels of PGE(2) and NO, as a consequence of iNOS and COX-2 activation, while proteins were absent and the level of nitrite and PGE(2) was low in the 9 noninfected patients. The COX-2 inhibitor decreased both NO and PGE(2). The iNOS-specific inhibitor decreased NO but did not have any effect on the increase in gastric mucosal PGE(2). Both inhibitors had no effect on the protein level of these two enzymes. CONCLUSIONS: The data showed that COX-2 inhibitor might modulate the iNOS pathway, suggesting that COX-2 activity and/or its products may be related to the functional activation of iNOS but not to the expression of iNOS protein.

Serum selenium concentrations in chronic pancreatitis and controls.

BACKGROUND: In the light of the recent hypothesis that one cause of pancreatic damage may be related to the toxic action of oxygen free radicals [Braganza JM. The pathogenesis of pancreatitis. Manchester: Manchester University Press; 1991; Braganza JM. A framework for the aetiogenesis of chronic pancreatitis. Digestion 1998;59(Suppl. 4):1-12], we were prompted to assess the role of selenium in pancreatic disease. OBJECTIVE: The objective of the study was to establish whether or not there is any correlation between selenium levels and the degree of impairment of exocrine pancreatic function in patients suffering from chronic pancreatitis. PATIENTS: Two groups of subjects were recruited, the first consisting of 38 patients with clinically quiescent chronic pancreatitis of alcoholic origin and the second of 48 control subjects selected from among healthy volunteers attending our Transfusion Centre. METHODS: Body mass index, smoking and drinking habits were evaluated and selenium serum levels were assayed in all subjects. The patients with pancreatic disease were subdivided into three groups on the basis of lipase output assayed with a duodenal probe. RESULTS.: Selenium serum levels in the chronic pancreatitis group as a whole were found to be significantly lower than in the control group, but when they were analysed in the three distinct subgroups, a significant difference was found against control group only in the groups with severe and moderate exocrine pancreatic insufficiency. CONCLUSIONS: The mean serum selenium levels were lower in chronic pancreatitis patients than control.

Survival rate and prognostic factors in patients with intestinal failure.

BACKGROUND: Intestinal failure impairs nutritional status and survival expectance. Though intestinal adaptation and enteral independence may be achieved, artificial nutrition is needed in about half of the patients. AIMS: This study is aimed at assessing the causes of death, survival rate, enteral independence in time, and factors affecting the clinical outcome in a group of patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with intestinal insufficiency, due to major intestinal resection in 60 cases (short bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23 cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8 cases, were enrolled and followed-up for (median) 36 months (25th and 75th percentile in 12 and 60 months, respectively). In 60 short bowel syndrome patients, the main conditions that led to intestinal failure were ischemic bowel (28), major surgery complications or severe adhesions (17), radiation enteritis (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma (others). METHODS: Seventeen variables age, underlying disorders, length of remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and home) and its variations in time, causes of death, survival rate and time were considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards regression model. RESULTS: At the time of admission to the hospital, none of the patients had nutritional independence, 54 (79.4%) were on parenteral nutrition and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%) patients showed enteral independence, 39 were on home parenteral nutrition, 3 on enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral supplementation with hydroelectrolyte solutions only. After a median value of 36 months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation with hydroelectrolyte solutions, and 26 cases reached enteral independence. A significant relationship was detected between the length of remnant bowel and types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r = 0.48; P = 0.001), parenteral nutrition being more frequent in patients with very short bowel. Twenty-two patients (32.4%) died (4 from newly occurring malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up. Eleven of 22 patients died from conditions related to intestinal failure (8 cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36, 48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%, respectively, but it was significantly lower for patients with <50 cm of remnant bowel than those with longer residual intestine (P < 0.05), and in patients who started home parenteral nutrition above the age of 45 years (P < 0.02). Survival rate was higher in patients with enteral independence than those with enteral dependence (P < 0.05). Better survival rates were registered in patients with chronic obstructive intestinal pseudo-obstruction and major surgery complications, whereas ischemic bowel and even more radiation enteritis were associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate of patients with intestinal failure quotes 88 and 78% at 3 and 5 years, respectively. It is influenced by the length of remnant intestine, age at the start of home parenteral nutrition, enteral independence and, to some extent at least, by the primary disorder. Enteral independence can be achieved in time by about 40% of the patients with intestinal insufficiency, but for home parenteral nutrition-dependent cases, intravenous feeding can be stopped in less than one out of five patients during a median 3-year period.

Hepatitis C virus infection: prevalence, predictor variables and prevention opportunities among drug users in Italy.

The study assessed rates and predictor variables of hepatitis C virus (HCV) infection among drug users receiving pharmacological treatment for opiates addiction. There was a large cohort study in 16 public centres for drug users in north-eastern Italy, with data collected by standardized face-to-face interviews between February 2001 and August 2001. Of 1095 participants, 74.2% were HCV seropositive. Anti-HCV status was independently associated with duration of drug use of over 10 years, injecting as a route of drug administration, and hepatitis B virus (HBV) and human immunodeficiency virus (HIV) seropositivity. Further statistical analysis was conducted by dividing the subjects on the basis of the duration of heroin use: more or <10 years. In the multivariate analyses, route of drug administration and HBV status were associated with HCV seropositivity among both groups. Less education was associated with HCV among the shorter term drug users. HIV status and having a sexual partner with a history of drug use were associated with HCV seropositivity among the longer term drug users. Half of the short-term heroin users were still HCV seronegative when starting treatment, suggesting opportunities for reducing new HCV infections. Remarkable was the relationship between vaccination for hepatitis B and HCV serostatus. Being HBV seropositive was strongly associated with being HCV seropositive. But heroin users who had been vaccinated for HBV were not significantly more likely to be HCV seropositive than heroin users who were HBV seronegative. HBV vaccination does not provide biological protection against HCV; however, vaccinating heroin users against HBV may help to create a stronger pro-health attitude among heroin users, leading to a reduction in HCV risk behaviour.

Carcinoma of pancreatic body and tail: are there improvements in diagnosis and treatment modalities over the past decade?

BACKGROUND AND AIM OF STUDY: The aim of the present study is to assess whether or not there has been improvement in the therapeutic strategy for body-tail pancreatic carcinoma over the past decade. PATIENTS AND METHODS: A total of 215 patients suffering from cytologically and histologically documented ductal carcinoma in the pancreatic body-tail, observed from 1990 to 1999, were analysed. Changes in tumour stage at diagnosis, in the percentage of patients treated surgically, in resectability rates and in the use of anticancer therapies over the years were sought. Survival curves were evaluated in relation to the treatments adopted. RESULTS: Over the 10-year period, no significant differences were observed with respect to the stage at diagnosis, resectability or type of surgery adopted. There was a significant increase in the percentage of unoperated patients (p < 0.0001) and, as expected, in the percentages of patients submitted to chemo- and/or radiotherapy (p < 0.0001). With the sole exception of tumour stage in the case of patients undergoing radiotherapy, a comparison between groups revealed no element of patient selection bias other than time. The survival of patients undergoing chemotherapy is significantly better, also at multivariate analysis, than that of patients not undergoing such therapy (13 vs. 5.8 months; p < 0.0001). CONCLUSIONS: There has been no change over the years in the direction of earlier diagnosis and the prognosis remains distinctly poor. More extensive use of anticancer therapies, however, has led to a significant increase in median survival. Radical resection, when possible, assures the longest survival.

Causas principales de muerte entre 2.708 heroinómanos del noreste italiano (1985-1998) / Main death causes among 2.708 heroin addicts of Italian northeast (1985-1998)

Objetivos. Establecer las causas de la muerte acaecidas entre 1985 y 1998 en un numeroso grupo de usuarios de droga por vía intravenosa (ADVP) acogidos en 36 Servicios Públicos para Toxicomanías (Ser T) del noroeste italiano. Métodos. Estudio realizado sobre datos recogidos en los archivos de los Ser. T y del Registro Municipal de cada una de las ULSS estudiadas. Individuos implicados. Todos los ADVP que hayan pasado por lo menos una vez por uno de los 36 Ser. T incluidos en el estudio. Resultados. El estudio analizó las causas de la muerte de 2708 individuos. La primera cauda de muerte es la sobredosis (37 por ciento), seguida del SIDA (32,5 por ciento) y de los accidentes de tráfico (9,4 por ciento). El porcentaje de muertes causadas por el SIDA aumentó progresivamente, pasando de un 2.7 por ciento en 1985 a un 42,2 por ciento en 1996, reduciéndose después al 16,9 por ciento en 1998. El porcentaje de fallecimientos por sobredosis se mantuvo prácticamente constante durante todo el tiempo. La edad media de muerte aumentó, pasando de 26 años a mediados de los años 80 a 34 años en 1998. La tasa de mortalidad entre ADVP es 13 veces mayor que en el conjunto de la población (95 por ciento, CI 11.3-14.6). En el conjunto de la población el porcentaje de fallecimientos en edades comprendidas entre los 15 y los 34 años atribuida al uso de opiáceos era en 1991 (año del últimocenso) del 16 por ciento. La prevalencia del VIH no resultó estadísticamente significativa en las causas de muerte por suicidio o sobredosis. Conclusiones. Se comprobó que la tasa de mortalidad era 13 veces superior a la de la población general. Se demostró la importancia del sexo femenino y el drop out de los tratamiento (al margen del tipo de tratamiento en cuestión) como factores de riesgo de sobredosis. La paulatina disminución de muertes por SIDA destaca la importancia de los tratamientos preventivos y terapéuticos adecuados contra la infección de VHC. Las medidas que se adopten en el campo de las drogodependencias, tanto en el ámbito de la política como en la investigación y la formación, deben tener presente el dramáticamente elevado porcentaje de individuos que mueren por consumo de heroína (AU)

Aims: To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy. Design: Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district. Setting: Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona. Participants: All IDUs who had sought medical care at least once in the PCDUs during the study period. Findings: Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose. Conclusions: The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use (AU)

Previous cholecystectomy, gastrectomy, and diabetes mellitus are not crucial risk factors for pancreatic cancer in patients with chronic pancreatitis.

INTRODUCTION: In the general population, cholecystectomy, diabetes, and chronic pancreatitis seem to be associated with an increased risk of developing pancreatic cancer. AIMS: We assessed whether previous cholecystectomy, gastrectomy, or diabetes mellitus may be risk factors for pancreatic cancer in patients with chronic pancreatitis. METHODOLOGY: We analyzed 853 patients with chronic pancreatitis (110 women, 743 men) with a median follow-up period of 14 years with particular reference to establishing which patients had previously undergone cholecystectomy or distal gastric resection (Billroth II anastomosis) or had diabetes or gallstone disease and the respective time scales involved. RESULTS: Pancreatic cancer developed in 17 patients with chronic pancreatitis after a median period of 8 years from onset of pancreatitis symptoms (range, 3-38 years). Excluding two cholecystectomies performed 1 year before diagnosis of cancer, cholecystectomy was performed in 7/17 (41%) patients with pancreatic cancer and in 381/836 (46%) of the other patients with chronic pancreatitis. Forty-nine (10%) patients with chronic pancreatitis and no pancreatic cancer had undergone cholecystectomy during the years before the onset of chronic pancreatitis, whereas none of the patients in whom a pancreatic malignancy developed had undergone cholecystectomy before the onset of chronic pancreatitis symptoms. Gastrectomies were performed in 116 patients (14%), 47 before the onset of chronic pancreatitis. Only 2/17 patients with pancreatic cancer had undergone previous gastrectomy, though in both cases only shortly before diagnosis of the cancer. Diabetes was diagnosed in 353 patients, but only in 30 (4%) before onset of chronic pancreatitis. Only 1/17 patients (6%) with pancreatic cancer had long-standing diabetes, whereas diabetes developed in 3/17 shortly before diagnosis of pancreatic cancer. CONCLUSIONS: Cholecystectomy, gastrectomy, and diabetes are not major risk factors for the development of pancreatic cancer in patients with chronic pancreatitis.

Study of 2708 heroin-related deaths in north-eastern Italy 1985-98 to establish the main causes of death.

AIMS: To ascertain the causes of deaths among a very large cohort of heroin injecting drug users (IDUs) who, from 1985 to 1998, attended 36 Public Health Authority Centres for Drug Users (PCDUs) in north-eastern Italy. DESIGN: Retrospective analysis of data, obtained from the Annual Register of each Centre and the Municipal Registry Office of each local health district. SETTING: Thirty-six PCDUs in north-eastern Italy and Medical Service for Addictive Disorders of the University of Verona. PARTICIPANTS: All IDUs who had sought medical care at least once in the PCDUs during the study period. FINDINGS: Of 2708 deaths, overdose was found to be the major cause (37%), followed by AIDS (32.5%) and road accidents (9.4%). The percentage of deaths due to AIDS increased steadily from 2.7% in 1985 to 42.2% in 1996, and then decreased to 16.9% in 1998. Deaths due to overdose remained almost constant. The average age of death per year rose from 26 in the mid eighties to 34 in 1998. The mortality rate among IDUs proved much higher compared to the general population of the same age (13-fold, 95% CI, 11.3-14.6). The proportion of all deaths attributable to regular use of illegal opiates in the 15-34 age group in the general population in 1991 was 16%. HIV prevalence was not a significant factor in suicides and deaths by overdose. CONCLUSIONS: The mortality rate was 13 times greater than in the general population. To be female and to have dropped out of any kind of treatment proved an important risk factor for overdose. The fall in deaths from AIDS enhances the problem to prevent and treat HCV infection. Decisions in drug projects, in research and in training should be influenced by the strikingly high percentage of deaths due to drug use.

[Does locoregional chemotherapy improve survival in patients with non-resectable pancreatic carcinoma? Results of an open controlled study]. / La chemioterapia locoregionale migliora la sopravvivenza dei pazienti affetti da carcinoma pancreatico non resecabile? Risultati di uno studio aperto, controllato.

About 90% of patients suffering from pancreatic carcinoma are diagnosed with disease that is not amenable to surgical intervention due to local infiltration or the presence of hepatic metastases. Palliative intra-arterial chemotherapy was developed to improve the response in these patients by increasing the antiblastic dose and minimizing the side effects. The aim of this study is to evaluate the efficacy of this treatment comparison to a control group. From December 1994 to February 1997, 135 patients with ductal carcinoma, in whom 68 were stage III and 67 stage IV, with a median age of 63.3 years (range 38.4-79), were enrolled in an open study. Sixty four patients were subjected to a median of 3.5 cycles, according to intra-arterial FLEC protocol. Four patients had a partial response (6.3%), 27 enjoyed a stabilization of their disease (42.2%) and 13 showed disease progression (20.3%). The toxicity was mild. The overall survival was 8.3 months, better in the treated group (9.6 months) in respect to the control one (7.1 months), although this was not statistically significant. The treatment reported here, therefore, does not seem to change the prognosis of patients affected by no resectable pancreatic carcinoma, but it may demonstrate good tolerability and minimal toxicity.

Antioxidant treatment in hereditary pancreatitis. A pilot study on three young patients.

BACKGROUND: Abdominal pain is the most challenging symptom of hereditary pancreatitis. No specific and proven therapy is yet available; analgesics, often in large doses, are required also in children and young patients. PATIENTS AND METHODS: We performed an open-label, pilot study on three young patients, coming from the same kindred, with hereditary pancreatitis. The study period lasted two years (July 1997-July 1999) and was divided into four sub-periods of six months each. In the first and third period the patients took only oral analgesics, if necessary; in the second and fourth period, an antioxidant regimen per os was added. This treatment consisted of sulphadenosyl-methionine (800 mg per day), Vitamin C (180 mg per day), Vitamin E (30 mg per day), Vitamin A (2,400 microg per day), and selenium (75 microg per day). RESULTS: Compliance of patients to the treatment schedule was satisfactory and no important side-effects were observed. Antioxidant treatment led to a significant reduction (p<0.05) in the number of days with abdominal pain experienced by the three patients and this was verified for both periods of treatment. Albeit, consumption of analgesics was lower in the antioxidant treatment periods. CONCLUSIONS: Oxidative stress may be one of the principle contributors to pain in hereditary pancreatitis and orally administered antioxidant treatment appears to be effective for control of the condition, in young patients, suffering from this rare disease.

Clinicopathological features and treatment of intraductal papillary mucinous tumour of the pancreas.

BACKGROUND: The surgical strategy in patients with a pancreatic intraductal papillary mucinous tumour (IPMT) is still controversial. In this study the pathological findings in a series of patients were used to rationalize surgical choice. METHODS: Fifty-one patients with IPMT were observed between 1988 and 1998 and treated by pancreatic resection. Factors evaluated included symptoms, tumour site, type of operation, histological findings and resection margins, tumour stage, follow-up and survival. RESULTS: Pancreaticoduodenectomy was the most frequent surgical treatment (33 patients; 65 per cent), followed by left pancreatectomy (ten), total pancreatectomy (five) and middle pancreatectomy (three). Histological assessment revealed the tumour to be an adenoma in 13 patients (25 per cent), a borderline tumour in ten (20 per cent) and a carcinoma in 28 (55 per cent), 19 of which were invasive. Mild to moderate dysplasia was present at the resection margin in 20 specimens (41 per cent), and carcinoma in one. Local recurrence was observed in four patients (8 per cent), all of whom underwent a second resection. The 3-year actuarial survival rate for benign and malignant disease was 94 and 69 per cent respectively (P = 0.03). CONCLUSION: These results suggest that resection should be the treatment for IPMT. Management of the resection margin could be crucial in avoiding tumour recurrence.

Clinical significance of mutator phenotype and chromosome 17p and 18q allelic loss in gastric cancer.

BACKGROUND: Tumour stage is the only reliable prognostic factor for gastric cancer. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. METHODS: Forty-four gastric cancers, treated by surgery alone, have been analysed for chromosome 17p and 18q allelic loss and for the presence of microsatellite instability (MSI), using microsatellite markers and DNA from paraffin-embedded tumours. RESULTS: Eight cancers showed a MSI-positive (MSI+) phenotype. Among the 36 MSI-negative cancers, chromosome 17p and 18q allelic losses were found in 22 of 34 and 19 of 33 informative cases respectively. Multivariate survival analysis indicated MSI status to be an independent prognostic factor along with the tumour stage. MSI+ cancers were associated with longer patient survival, whereas MSI-negative cancers had a significantly poorer prognosis (P = 0.007), with a median actuarial survival of 24 months. CONCLUSION: MSI status is an independent prognostic factor among gastric cancers at the same stage. Chromosome 17p and 18q status added no additional prognostic information to that of tumour stage. The combined use of tumour stage and MSI status may help in deciding whether patients with advanced gastric cancer require additional therapy other than surgery alone.

High resolution allelotype of nonfunctional pancreatic endocrine tumors: identification of two molecular subgroups with clinical implications.

A high resolution allelotype for nonfunctional pancreatic endocrine tumors (NF-PETs) has been generated by microsatellite analysis of DNA from 16 frozen cases, each probed with 394 markers. Two subgroups of NF-PETs were found. Seven cases showed frequent, large allelic deletions [loss of heterozygosity (LOH)] with an average fractional allelic loss (FAL) of 0.55, whereas nine cases showed a small number of random losses with a FAL of 0.15. Designated high or low FAL, respectively, these genetic phenotypes showed correlation with the ploidy status: high-FAL tumors were aneuploid, low-FAL were diploid. Chromosomes 6q and 11q showed LOH in >60% of cases. About 50% of cases had losses on 11p, 20q, and 21. Selected LOH analysis on an additional 16 paraffin-embedded NF-PETs confirmed the high frequency of 6q and 11q LOH. The allelotype of NF-PET is markedly different from that of either ductal or acinar tumors of the pancreas as well as from that of functional-PETs. Moreover, whereas deletions involving chromosome 11 also are a feature of functional-PETs, the involvement of chromosome 6q is characteristic of NF-PETs. Survival analysis showed that none of the single chromosomal alterations was associated with outcome, whereas ploidy status is an independent factor adding prognostic information to that furnished by the proliferative index measured by Ki-67 immunohistochemistry.

Autoimmune pancreatitis: possibilities of CT characterization.

BACKGROUND: Pancreatitis is defined as an inflammatory disease of the pancreas, leading to morphological and pathological changes. Recently, an autoimmune pathogenesis of this disease has been proposed. This type of pancreatitis should be differentiated from other pancreatic diseases, since appropriate therapy is effective and morphological changes and pancreatic function can recover to normal levels. AIM OF THE STUDY: To assess the possibility of distinguishing autoimmune pancreatitis from other pancreatic diseases with an analogous clinical presentation on the basis of CT findings alone. METHODS: The CT images of 7 patients with proven autoimmune pancreatitis, along with those of 20 patients with other pancreatic diseases, but with an analogous clinical presentation, were retrospectively evaluated in a blinded fashion by 2 radiologists. In particular, the radiologists had to search for the typical signs of autoimmune pancreatitis. Discordant cases were further analyzed in the presence of a 3rd radiologist. The final diagnosis was acquired by means of a majority or overall consensus. The sensitivity, specificity, positive and negative predictive values of CT were calculated against each of the diseases (autoimmune pancreatitis; other pancreatic diseases), in order to evaluate the diagnostic value of the scan. RESULTS: After the consensus evaluation, the correct diagnosis was reached in 25/27 (92.5%) cases, with only 2/27 wrong diagnoses (autoimmune pancreatitis diagnosed as another pancreatic disease and vice versa). The sensitivity and specificity of CT against autoimmune pancreatitis were 86 and 95%, respectively. The positive and negative predictive values were 89 and 93%, respectively. CONCLUSION: Patients with autoimmune pancreatitis demonstrate imaging findings that enable the correct diagnosis by dynamic CT, even in the presence of nonspecific clinical symptoms. The precise classification of the disease is extremely important, since simple steroid therapy then represents the correct treatment, and leads to complete recovery.