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C Bassi

Publications and source records attributed to C Bassi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4.

The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. We analyzed 22 cell lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. Alterations in p16INK4a were found in all cases and included nine homozygous deletions, seven mutations and promoter methylation in six cases. Eight cell lines (36%) had an alteration of DPC4, including one mutation and seven homozygous deletions. The most typical mutational profile involved K-ras, p53, and p16INK4a, concurrently aberrated in 20 cases (91%). Eight cell lines had alterations in all four genes. Inactivation of DPC4 was always accompanied by alteration of all of the other three genes. This comprehensive data regarding the cumulative genetic alterations in pancreatic carcinoma cell lines will be of great value for studies involving drug sensitivity or resistance that may be associated with inactivation of a particular gene or molecular pathway.

Carcinoma, Pancreatic Ductal↗
PubMed2001

The structure of duplications on human acrocentric chromosome short arms derived by the analysis of 15p.

We report the molecular analysis of a 130-kb DNA region containing a junction between beta and non-beta satellite DNA from chromosome 15p. The genomic region is characterized by beta satellite blocks intermingled with variants of the D4Z4 repeat, and duplicons from 4q24 and 4q35. Besides the p-arm of acrocentric chromosomes, the duplicons showed a wide genomespread involving pericentromeric, sub-telomeric, and interstitial regions. In this regard, the paralogous sequences were characterized by a high similarity index (96%), thus indicating a recent transposition during the evolution. The acrocentrics differedwith regard to the location of the 4q24 paralogous region, since it mapped on the p-arm of chromosomes 13-15 and 21, but only on 22q11.2. Conversely, the 4q35 duplication marked the p-arm of all the acrocentrics. In different individuals, the short arm of acrocentric chromosomes revealed a great variability of sequence representation and location at p11 and/or p13 for both the 4q24 and 4q35 duplications. The studied genomic region from chromosome 15p, of which a contig of approximately 200 kb has been derived, could lead to more detailed investigations into the sequence organization and possible biological function of chromosome regions that are located close to the rDNA array.

Alu Elements↗
PubMed2001

Prophylaxis for septic complications in acute necrotizing pancreatitis.

Because the mortality of severe pancreatitis is higher when infected necrosis supervenes, prevention of infections has become a relevant endpoint for management. The "ideal" drug should be characterized by specific activity against the bacteria known to be responsible for infection and should be able to penetrate the gland in a sufficient concentration. To date there have been eight prospective trials with antibiotics, one on selective digestive decontamination, and others with enteral nutrition. A meta-analysis regarding experiences with antimicrobial drugs reports a significant reduction in the incidence of infected necrosis and pancreatic abscesses during severe pancreatitis. In conclusion, among the several options aimed at reducing infections during necrotizing pancreatitis, the prophylactic use of antibacterial drugs is the only one to have been tested to date in several randomized studies. Strong consideration should be given to treating patients with severe pancreatitis with broadspectrum antibiotics, selective digestive decontamination, and enteral nutrition.

Animals↗
PubMed2001

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.

Adenocarcinoma, Mucinous↗
PubMed2001

Infection prevention in necrotizing pancreatitis: an old challenge with new perspectives.

Necrotizing pancreatitis still remains a life-threatening disease despite several improvements in diagnosis, prevention and treatment. In recent years, some important questions have been answered such as the need for early intensive medical treatment rather than early surgery, but others are still strongly debated. The aim of this paper is to present an up-to-date assessment of current challenges in the management of necrotizing pancreatitis in order to prevent infection.

Antibiotic Prophylaxis↗
PubMed2001

Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis.

Alterations of K- ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPMT), 6 acinar carcinomas (PAC), 5 solid-pseudopapillary tumours (SPT), 16 ampulla of Vater cancers (AVC) and 41 PET. All tumours were also presently or previously analysed for K- ras and p53 mutations and allelic loss at 9p, 17p and 18q. Alterations in K- ras, p53, p16 and DPC4 were found in 82%, 53%, 38% and 9% of PDC, respectively and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were virtually absent in PET, PAC or SPT, while in IPMT only K- ras mutations were present (30%). Positive immunostaining confirmed the absence of DPC4 alterations in all IPMT, SPT, PAC and PET, while 47% of PDC and 38% of AVC were immunonegative. These data suggest that pancreatic exocrine and endocrine tumourigenesis involves different genetic targets and that among exocrine pancreatic neoplasms, only ductal and ampullary cancers share common molecular events.

Adenocarcinoma, Mucinous↗
PubMed2001

Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial.

OBJECTIVE: To assess the influence of resection margins on survival for patients with resected pancreatic cancer treated within the context of the adjuvant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study. SUMMARY BACKGROUND DATA: Pancreatic cancer is associated with a poor long-term survival rate of only 10% to 15% after resection. Patients with positive microscopic resection margins (R1) have a worse survival, but it is not known how they fare in adjuvant studies. METHODS: ESPAC-1, the largest randomized adjuvant study of resectable pancreatic cancer ever performed, set out to look at the roles of chemoradiation and chemotherapy. Randomization was stratified prospectively by resection margin status. RESULTS: Of 541 patients with a median follow-up of 10 months, 101 (19%) had R1 resections. Resection margin status was confirmed as an influential prognostic factor, with a median survival of 10.9 months for R1 versus 16.9 months months for patients with R0 margins. Resection margin status remained an independent factor in a Cox proportional hazards model only in the absence of tumor grade and nodal status. There was a survival benefit for chemotherapy but not chemoradiation, irrespective of R0/R1 status. The median survival was 19.7 months with chemotherapy versus 14.0 months without. For patients with R0 margins, chemotherapy produced longer survival compared with to no chemotherapy. This difference was less apparent for the smaller subgroup of R1 patients, but there was no significant heterogeneity between the R0 and R1 groups. CONCLUSIONS: Resection margin-positive pancreatic tumors represent a biologically more aggressive cancer; these patients benefit from resection and adjuvant chemotherapy but not chemoradiation. The magnitude of benefit for chemotherapy treatment is reduced for patients with R1 margins versus those with R0 margins. Patients with R1 tumors should be included in future trials of adjuvant treatments and randomization and analysis should be stratified by this significant prognostic factor.

Adenocarcinoma↗
PubMed2001

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.

Cholecystectomy↗
PubMed2001

Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis.

BACKGROUND: Infection is the commonest cause of death in acute pancreatitis. Early reduction of commensal flora (particularly Lactobacillus species) and, at the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli, have recently been described during acute pancreatitis. Lactobacillus plantarum has been shown to be effective in reducing the egress of endotoxin and microbial translocation in several experimental models such as chemically induced hepatitis and ulcerative colitis. AIM: The aim of the study was to determine whether L. plantarum 299v (Lp 299v) is capable of effectively reducing microbial translocation in experimental pancreatitis. METHODS: Acute pancreatitis was induced by isolation and ligation of the biliopancreatic duct in Lewis rats weighing 250-350 g. The animals were divided into 3 groups: group A, sham operation; group B, induction of pancreatitis and no further treatment, and group C, induction of pancreatitis + daily administration by gavage of a 5-ml/day suspension of Lp 299v at 0.5-1.0 x 10(9) bacteria/ml for 8 days, 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 h. Histological studies and microbiological analyses were performed. RESULTS: At sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute pancreatitis was the specific disease investigated, only these animals were subjected to further study. In group B, we found pathogenic micro-organisms in the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in 10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus faecalis, Pseudomonas and Proteus species. In contrast, when the animals were kept under an 'umbrella' of Lp 299v, growth of E. faecalis or E. coli were detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic tissue cultures. CONCLUSIONS: Lp 299v is effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative to antibiotic therapy.

Acute Disease↗
PubMed2001

Management of complications after pancreaticoduodenectomy in a high volume centre: results on 150 consecutive patients.

Pancreaticoduodenectomy (PD) is still a difficult procedure with significant morbidity. We report 150 consecutive PDs performed during a 3-year period. All the cases have been prospectively evaluated with regard to the surgical outcome. Mortality in this series was 3/150 (2%) with a re-operation rate of 5/150 (3.3%); surgical complications were experienced in 57/150 (38%). The most frequent complications were collections in 25/150 (16.6%) and pancreatic fistulas in 16/150 (10.7%). The majority of these complications were conservatively managed: only one abscess and one fistula due to an anastomotic dehiscence required re-operation. The complication most responsible for mortality was haemorrhage secondary to arterial pseudoaneurysms in patients with severe post-operative pancreatitis. The continued high morbidity of PDs is compensated by the ability to treat complications non-operatively, resulting in a surgical risk that should now be considered medium to low in high volume centres.

Acute Disease↗
PubMed2001

In vivo octreotide administration acutely reduces exocrine granule size in the human pancreas.

BACKGROUND: Octreotide has been found to be effective in the prevention of postoperative complications of pancreatic surgery, but the benefit of preoperative octreotide administration has not been assessed. AIMS: To evaluate the ability of octreotide in reducing the amount of digestive enzymes in the pancreas before surgery, a morphometric ultrastructural study of the gland was undertaken in patients undergoing demolitive pancreatic surgery. METHODS: Twenty-three inpatients received saline (n = 8) or octreotide (100 micrograms s.c.) before surgery either once (n = 5), or three (n = 5) or six (n = 5) times at 8-hour intervals. At surgery, biopsies of the pancreas were taken and processed for electron microscopy. Several parameters were assessed in exocrine cells by means of ultrastructural morphometry. RESULTS: A single administration of octreotide significantly reduced the exocrine granule number and the mean and total granular surface sectional area, and the ratio between granule area and cytoplasmic area. Repeated octreotide administrations were associated with partial (3 administrations) and complete (6 administrations) recovery of all parameters to control values. CONCLUSION: Preoperative administration of octreotide, the synthetic analogue of somatostatin, acutely reduces exocrine granule number and size in the pancreatic cell. This finding can partially explain the prophylactic effect of the drug on early complications of pancreatic surgery. Such an effect is not maintained over multiple administrations of the somatostatin analogue. Possible explanations for this latter finding are discussed.

Adult↗
PubMed2001

Infections in pancreatic inflammatory disease: clinical trials for antibiotic prophylaxis.

The clinical significance and incidence of the specific pancreatic infections during severe pancreatitis, such as infected pancreatic necrosis and pancreatic abscesses, is very well known in the literature. The up-to-date knowledge in both the microbiological and pharmacological field related to pancreatitis suggests a series of antibiotics which are potentially useful in the prophylaxis of pancreatic infections. Here we review the most important controlled clinical experiences reported up to now.

Antibiotic Prophylaxis↗
PubMed2001

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.

Adult↗
PubMed2001

IS-741 (Ishihara Sangyo).

IS-741 is a phospholipase A2 (PLA2) inhibitor under development by Ishihara Sangyo Kaisha and Sumitomo as a potential treatment for pancreatitis 1187575]. Sumitomo is developing the drug in phase II trials for acute pancreatitis 13990261. In an animal model, IS-741 has been shown to prevent pancreatitis-associated lung injury following endotoxemia [337503].

Animals↗
PubMed2000

Molecular structure and evolution of DNA sequences located at the alpha satellite boundary of chromosome 20.

We have isolated and characterised one PAC clone (dJ233C1) containing a linkage between alphoid and non-alphoid DNA. The non-alphoid DNA was found to map at the pericentromeric region of chromosome 20, both on p and q sides, and to contain homologies with one contig (ctg176, Sanger Centre), also located in the same chromosome region. At variance with the chromosome specificity shown by the majority of non-alphoid DNA, a subset of alphoid repeats derived from the PAC yielded FISH hybridisation signals located at the centromeric region of several human chromosomes, belonging to three different suprachromosomal families. The evolutionary conservation of this boundary region was investigated by comparative FISH experiments on chromosomes from great apes. The non-alphoid DNA was found to have undergone events of expansion and transposition to different pericentromeric regions of great apes chromosomes. Alphoid sequences revealed a very wide distribution of FISH signals in the great apes. The pattern was substantially discordant with the data available in the literature, which is essentially derived from the central alphoid subset. These results add further support to the emerging opinion that the pericentromeric regions are high plastics, and that the alpha satellite junctions do not share the evolutionary history with the main subsets.

Animals↗