Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS: We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS: Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION: We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.

Practical guidelines for acute pancreatitis.

INTRODUCTION: The following is a summary of the official guidelines of the Italian Association for the Study of the Pancreas regarding the medical, endoscopic and surgical management of acute pancreatitis. STATEMENTS: Clinical features together with elevation of the plasma concentrations of pancreatic enzymes are the cornerstones of diagnosis (recommendation A). Contrast-enhanced computed tomography (CT) provides good evidence for the presence of pancreatitis (recommendation C) and it should be carried out 48-72 h after the onset of symptoms in patients with predicted severe pancreatitis. Severity assessment is essential for the selection of the proper initial treatment in the management of acute pancreatitis (recommendation A) and should be done using the APACHE II score, serum C-reactive protein and CT assessment (recommendation C). The etiology of acute pancreatitis should be able to be determined in at least 80% of cases (recommendation B). An adequate volume of intravenous fluid should be administered promptly to correct the volume deficit and maintain basal fluid requirements (recommendation A); analgesia is crucial for the correct treatment of the disease (recommendation A). Enteral feeding is indicated in severe necrotizing pancreatitis and it is better than total parenteral nutrition (recommendation A). The use of prophylactic broad-spectrum antibiotics reduces infection rates in CT-proven necrotizing pancreatitis (recommendation A). Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for intervention, including surgery and radiological drainage (recommendation B). CONCLUSIONS: The participants agreed to revise the guidelines every 3 years in order to re-evaluate each question on the management of acute pancreatitis patients according to the most recent literature.

Pancreatic and extrapancreatic lesions in patients with intraductal papillary mucinous neoplasms of the pancreas: a single-centre experience.

PURPOSE: This study was performed to describe the possible presence of extrapancreatic neoplasms in patients with intraductal papillary mucinous neoplasm (IPMN) and to evaluate whether the extrapancreatic tumours were synchronous or metachronous to IPMNs. MATERIALS AND METHODS: One hundred and forty-two patients (56 men and 86 women; mean age 69.5 years, range 37-98) with IPMN diagnosed using the Sendai criteria were enrolled. Six patients (4.2%) had type I, 103 (72.5%) type II and 33 (23.2%) type III IPMN. All patients were studied using the following imaging techniques: ultrasonography (US), multidetector computed tomography (MDCT) and magnetic resonance cholangiopancreatography (MRCP). RESULTS: Pancreatic IPMN was localised in the head in 43 patients (30.3%), in the body in 13 (9.2%), in the tail in ten (7.0%), in the head-body in 17 (12.0%), in the body-tail in 15 (10.6%) diffuse throughout the gland in 44 (31.0%). The mean size of the cystic lesions was [(mean+/-standard deviation (SD)] 1.9+/-1.9 cm (range 0.5-8.0 cm). Twenty patients (14.1%) had associated pancreatic or extrapancreatic diseases. In evaluating the distribution of pancreatic or extrapancreatic diseases according to IPMN type, we found that this was not significantly different among types I, II and III (p=0.776). CONCLUSIONS: The majority of pancreatic and extrapancreatic cancers occur before the diagnosis of IPMNs is made and is not related to the type of IPMN.

Severe acute pancreatitis: eight fundamental steps revised according to the 'PANCREAS' acronym.

Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ dysfunction. By means of a mnemonic 'PANCREAS', eight important steps in the management of severe acute pancreatitis are highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during clinical treatment. The first step is perfusion: the goal is to reach a central venous pressure of 12-15mmHg, urinary output 0.5-1ml/kg/hour and inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position. Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis, unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and 'walled-off necrosis'. Antibiotics come next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is documented pancreatic infection. The last step is surgery: the dogma is represented by the 'three Ds' (delay, drain, debride). The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the previous treatment fails.

Evaluation of patient-reported outcome in subjects treated medically for acute pancreatitis: a follow-up study.

AIMS: To explore the quality of life in patients treated medically during the acute phase of pancreatitis as well as at 2 and 12 months after discharge from the hospital. PATIENTS: 40 patients were studied. The etiology of the pancreatitis was biliary causes in 31 patients and non-biliary causes in 9; mild disease was present in 29 patients and severe disease in 11. 30 patients completed the two surveys at 2 and 12 months after hospital discharge. METHODS: The SF-12 and EORTC QLQ-C30 questionnaires were used for the purpose of the study. RESULTS: The two physical and mental component summaries of SF-12, all the domains of EORTC QLQ-C30 (except for physical functioning and cognitive functioning) and some symptom scales of EORTC QLQ-C30 (fatigue, nausea/vomiting, pain, and constipation) were significantly impaired during the acute phase of pancreatitis. There was a significant improvement in the SF-12 physical component summary, and global health, role functioning, social functioning, nausea/vomiting, pain, dyspnea, and financial difficulties (EORTC QLQ-C30) at 2 months after discharge as compared to the basal evaluation. Similar results were found after 12 months except for the mental component score at 12-month evaluation, which was significantly impaired in acute pancreatitis patients in comparison to the norms. The physical functioning of the EORTC QLQ-C30 at basal evaluation was significantly impaired in patients with severe pancreatitis in comparison to patients with mild pancreatitis. CONCLUSIONS: Two different patterns can be recognized in the quality of life of patients with acute pancreatitis: physical impairment is immediately present followed by mental impairment which appears progressively in the follow-up period.

Effect of early antibiotic prophylaxis with ertapenem and meropenem in experimental acute pancreatitis in rats.

BACKGROUND: The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat. METHODS: Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection. RESULTS: Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05). CONCLUSIONS: In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.

Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs.

Gastric endocrine tumors associated with autoimmune chronic atrophic gastritis (gastric carcinoid type I) are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. For this reason, the role of octreotide in the treatment of these neoplastic lesions is controversial. Nine patients with more than five type I gastric endocrine tumors each <1 cm in size, without invasion of the muscularis propria and with Ki-67 index lower than 3%, were treated with long-acting somatostatin analogs for 12 months. After 6 months and again after 12 months, all the patients underwent upper gastrointestinal (GI) endoscopy with multiple biopsies. The plasma chromogranin A (CgA) levels and the gastrin levels in the serum were also determined. In all patients, the gastric neoplastic lesions disappeared after 12 months of somatostatin analog therapy. We also observed a significant reduction of CgA and gastrin levels at 6 and at 12 months of therapy as compared with the baseline values. We demonstrate that somatostatin analog treatment provokes the pathological regression of type I gastric carcinoids. This therapeutic approach should be considered as a valid option in selected patients with multiple type I gastric endocrine tumors.

Steroid responsiveness and treatment regimen of steroids in acute autoimmune pancreatitis.

Autoimmune pancreatitis is the pancreatic manifestation of a systemic inflammatory disease in which affected organs are characterized by intense lymphoplasmacytic infiltration. The diagnosis of autoimmune pancreatitis sometimes is puzzling and its differentiation from pancreatic cancer is a clinical challenge. The features of autoimmune pancreatitis are its typical histological pattern, imaging, serology (increase of immunoglobulins and the presence of autoantibodies), associated non-pancreatic organ involvement and response to steroid therapy. Recent advances in identifying these features have resulted in enhanced recognition, diagnosis of this benign disease and the avoidance of unnecessary surgical procedures for suspected malignancy. In this article, the authors will review recent updates in the steroid treatment of autoimmune pancreatitis.

Assessment of the quality of life in chronic pancreatitis using Sf-12 and EORTC Qlq-C30 questionnaires.

BACKGROUND: SF-12 Health Survey, and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 are the two main questionnaires proposed and validated for assessing the quality of life in chronic pancreatitis. AIMS: To evaluate the role of the information furnished by both the SF-12 Health Survey and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 questionnaires, and to determine which of these two questionnaires may be considered more efficacious, in clinical practice, in describing the quality of life of patients with chronic pancreatitis. PATIENTS: We studied 163 consecutive patients with proven chronic pancreatitis. METHODS: The Italian version of the SF-12 Health Survey and the Italian neutral version of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 Version 3.0 questionnaires were administered. RESULTS: Pancreatic pain was the only clinical variable able to significantly impair the SF-12 Health Survey component summaries as well as all domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30, while body mass index was positively related to the physical component summary-12 and to the domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30. A high level of reliability of the domains/scores of the two questionnaires in evaluating the quality of life in patients with chronic pancreatitis was found and two main factors were identified. These two factors were mainly related to the two SF-12 Health Survey summary components. CONCLUSIONS: From a practical point of view, the SF-12 Health Survey is more reliable and easier to use in routine clinical practice than the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30.

Diagnostic assessment and outcome of acute pancreatitis in Italy: results of a prospective multicentre study. ProInf-AISP: Progetto informatizzato pancreatite acuta, Associazione Italiana Studio Pancreas, phase II.

BACKGROUND AND AIM: Up till now, only one study providing practically complete information on acute pancreatitis in Italy has been published. The aim of this prospective study was to evaluate the clinical characteristics, in terms of diagnostic assessment and outcome, of a large series of patients affected by acute pancreatitis in Italy. MATERIALS AND METHODS: The study involved 56 Italian centres, homogeneously distributed throughout the entire national territory. Each participating centre was furnished with an ad hoc software including 530 items along with subsequent collection, tabulation and quality control of the data. RESULTS: One thousand five hundred and forty case report forms of patients affected by acute pancreatitis were collected but 367 of them (24%) were subsequently eliminated from the final analysis. Therefore, 1173 patients (581 females and 592 males) were recruited. Mean age of patients was 62.0+/-18.2 years (95% confidence interval, 60.9-63.0). On the basis of Atlanta classification, 1006 patients (85.8%) were defined as mild and 167 (14.2%) as severe pancreatitis. Biliary forms represented the most frequent aetiological category (813 cases, 69.3%) while alcoholic forms only 6.6% (77 cases); the remaining aetiologies accounted for 7.1% (83 cases) while 200 cases (17.1%) remained without a definite aetiological factor. Complete recovery was achieved in 1016 patients (86.6%) whereas morphological sequelae were found in 121 patients (10.3%) and mortality in 36 patients (3.1%; 0.4% in mild and 19.2% in severe acute pancreatitis). Ultrasonography was largely utilised as a first line diagnostic tool in all patients, with valuable visualisation of the pancreas in 85% of patients. Computer tomography scan was also widely used, with 66.7% of exams in mild and 33.3% in severe pancreatitis. Patients affected by biliary pancreatitis presented more severe (p=0.004) and necrotizing forms (p=0.021). Mortality was significantly related (p<0.001) with the extension of pancreatic necrosis and with an age of over 70 years. Body mass index presented significantly greater values in severe than in mild forms (p<0.001). CONCLUSIONS: Association of creatinine serum level over 2mg/dl with an abnormal chest X-ray showed a high significant correlation with a more severe outcome in terms of morphological sequelae and mortality (p=0.0001). Acute pancreatitis in Italy more commonly presents biliary aetiology and favourable outcome with low rate of complications and mortality. From a cost-effectiveness standpoint, diagnostic approach to this disease needs to be better standardised.

A prospective multicentre survey on the treatment of acute pancreatitis in Italy.

BACKGROUND: The Italian Association for the Study of the Pancreas released a diagnostic and therapeutic algorithm for acute pancreatitis in 1999. AIM: This study focused on the analysis of the therapeutic approach for the treatment of acute pancreatitis in Italy. PATIENTS: One thousand, one hundred and seventy-three patients were recruited: 1006 patients (85.8%) had mild acute pancreatitis (MAP) and 167 (14.2%) had the severe acute pancreatitis (SAP); 161 patients showed pancreatic necrosis at computed tomography; 121 patients (10.3%) had sequelae and 36 (3.1%) died. RESULTS: Non-steroidal anti-inflammatory drugs and tramadol were used more frequently in patients with the MAP whereas opioids and the association schedules were used more frequently in patients with the SAP (P<0.001). Gabexate mesilate was utilised in 831 out of 1173 patients (70.8%); in particular, gabexate mesilate was used in 70.6% patients with MAP and in 73.1% of those with SAP (P=0.521). The duration of the drug administration was significantly shorter in those having MAP than in those having the SAP (P<0.001). The antibiotics most frequently used for the prophylaxis against infection from pancreatic necrosis (43.1%) were carbapenems. Only a small number of patients received enteral nutrition (4.7%). Endoscopic retrograde cholangiopancreatography was carried out in 344 of the 1173 patients (29.3%). Surgery was performed in 48 with SAP (19 had elective biliary surgery and 29 had pancreatic surgery). CONCLUSIONS: The results of this survey indicate a lack of compliance with the guidelines which regard the indications mainly for interventional endoscopy and surgery.

Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology.

Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l-Arg and of l-Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l-Arg and l-Cit concentrations were measured by a cation-exchange chromatography system. l-Arg and l-Cit levels of men with A-ED were compared with those of male with BL-ED and NA-ED. Median level of l-Arg and l-Cit in 122 erectile dysfunction patients (41 A-ED, 23 ED-BL, 58 NA-ED) was 82.7 and 35.4 µmol/L, respectively. l-Arg and l-Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l-Arg and l-Cit levels in control patients were significantly higher (p < 0.001 and p < 0.018, respectively) than in A-ED patients, but no difference (p > 0.50) was observed in controls and in both BL-ED and NA-ED patients. Patients with severe/complete-erectile dysfunction (IIEF-5 < 10) had l-Arg or l-Cit level significantly lower (-17%, p < 0.03; -13%, p < 0.04) and were more frequent (p < 0.01 and p < 0.04) under the respective median level (82.7 and 35.4 µmol/L) than those with mild-erectile dysfunction (IIEF-5 = 16-20). l-Arg and l-Cit levels in A-ED were significantly lower (p < 0.007 and p < 0.001, respectively) than in NA-ED patients. Penile echo-color-Doppler revealed that A-ED (peak systolic velocity ≤ 25 cm/sec) was more frequent in men with l-Arg under 82.7 µmol/L or l-Cit under 35.4 µmol/L and in the same population, the median peak systolic velocity values were lower in l-Arg deficient (29 vs. 35; p < 0.04) and also in l-Cit deficient (31 vs. 33, p > 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic etiology. Low levels of these nitric oxide synthase substrates might increase the erectile dysfunction risk by reducing the concentration of nitric oxide.

The quality of life in patients with chronic pancreatitis evaluated using the SF-12 questionnaire: a comparative study with the SF-36 questionnaire.

BACKGROUND: In clinical practice there is the need to utilise a time saving questionnaire to assess the quality of life. AIMS: To establish the validity of the SF-12 questionnaire in chronic pancreatitis patients and to identify the predictors capable of modifying the physical and mental summaries in these patients. QUESTIONNAIRES: SF-12 and SF-36 questionnaires were used. SUBJECTS: One hundred and forty-one outpatients with proven chronic pancreatitis. The data of 141 sex- and age-matched Italian subjects of two normative groups (61,434 Italian subjects for SF-12 and 2031 Italian subjects for SF-36) were used as controls. RESULTS: Chronic pancreatitis patients had the SF-12 physical and mental component summaries significantly related to the SF-36 physical and mental component summaries (P<0.001). The presence of pancreatic pain and non-pancreatic surgery accounted for 41.3% in the formation of the PCS-36 score and 37.2% in that of the PCS-12 score, respectively. Gender, BMI and pancreatic pain accounted for 15.3% of the information in the formation of the MCS-36 and for 14.7% in that of the MCS-12; using these clinical variables, the loss of information in applying the SF-12 instead of the SF-36 was very low (4.1 and 0.6% for the PCS and the MCS, respectively). CONCLUSIONS: The SF-12 is a good alternative to the SF-36 in assessing the quality of life in chronic pancreatitis.

Quality of life in patients with chronic pancreatitis.

INTRODUCTION: Health-related quality of life is becoming a major issue in the evaluation of any therapeutic intervention in patients with chronic or hard to cure diseases. AIMS: To assess the quality of life in patients with chronic pancreatitis, the majority of whom have had the disease for a long time, and to evaluate which factors linked to the disease are able to influence the quality of life. SUBJECTS AND METHODS: A total of 190 consecutive patients (157 males, 33 females; mean age 58.6+/-12.7 years, range 18-92 years) with proven chronic pancreatitis were enrolled. The SF-36 questionnaire was used for assessing the health-related quality of life. RESULTS: The z-scores of the eight domains of the patients with chronic pancreatitis were significantly negative indicating an overall impairment of the quality of life when compared to the Italian normative sample. Pancreatic pain was the unique clinical variable able to significantly impair all eight domains of the SF-36, while Wirsung dilation and diabetes were negatively related to some physical and mental domains. The body mass index was the unique variable positively related with some SF-36 domains. CONCLUSIONS: Pain may be considered the most important factor affecting the quality of life of chronic pancreatitis patients; moreover, alimentary and metabolic factors deserve more attention in improving the quality of life of these subjects.

CCK-1 receptor blockade for treatment of biliary colic: a pilot study.

BACKGROUND: Loxiglumide is a potent and selective cholecystokinin-1 (CCK-1) receptor antagonist able to inhibit gall-bladder contraction. AIM: To assess the effect of CCK-1 receptor blockade on the pain of patients with biliary colic. PATIENTS AND METHODS: Fourteen patients with biliary colic but no suspicion for acute cholecystitis, were randomly and blindly assigned to loxiglumide (50 mg i.v.) or hyoscine-N-butyl bromide (20 mg i.v.) treatment. Pain intensity was monitored by a Visual Analogue Scale. Patients with less than 80% response at 30 min, were retreated with a second injection of the same compound. RESULTS: Reduction in pain score (mean +/- S.E.M.) was faster and significantly greater in patients treated with loxiglumide (n = 7) than in controls (n = 7): 88 +/- 7% vs. 47 +/- 12% after 20 min, P < 0.05; 92 +/- 6% vs. 49 +/- 13%, after 30 min, P < 0.05. Only one of seven patients treated with loxiglumide needed a second injection at 30 min (vs. six of seven controls, P < 0.05). No adverse effect was observed after either treatment. CONCLUSIONS: Loxiglumide is highly effective in obtaining pain relief in patients with biliary colic. The analgesic effect of CCK-1 receptor blockade is superior to that of a conventional anticholinergic treatment.

Aging and exocrine pancreatic function.

In view of the limited information concerning the influence of aging on exocrine pancreatic function, the authors undertook the present study. To examine a large number of elderly persons, including people of very advanced age (80 years and over), pancreatic function was studied by using the fluorescein dilaurate test (pancreolauryl test), one of the most recent tubeless, noninvasive pancreatic function tests. Sixty healthy noninstitutionalized elderly individuals (35 women and 25 men, aged 66 to 88 years, mean 78) participated in the study. Thirty-six healthy younger subjects (16 women and 20 men, aged 21 to 57 years, mean 36) were also studied as controls. All elderly subjects showed a strictly normal fluorescein dilaurate test. No significant differences in the pancreatic function test results were observed between the elderly under 80 years old and those over 80 years old. The authors conclude that the aging process per se does not significantly affect exocrine pancreatic function and, more particularly, does not impair the digestive capacity of the elderly person.

Diagnostic value of the amino acid consumption test in pancreatic diseases.

The amino acid consumption test (AACT) has been proposed as a simple tubeless test of pancreatic function, but studies of its diagnostic accuracy have produced conflicting results. Eighty-three consecutive patients with clinical suspicion of pancreatic disease underwent pancreatic stimulation for 1 h with an intravenous infusion of cerulein (50 ng/kg/h); the total plasma amino acid concentration was measured at -15, 0, 30, 45, and 60 min of infusion. The maximal percentage decrease in plasma amino acid concentration during cerulein infusion was taken as an index of pancreatic function. In addition, patients had pancreatic function assessed with the pancreolauryl test (PLT). Of the 83 patients studied, 24 were found to have chronic pancreatitis and four pancreatic cancer; the remaining 55 had various nonpancreatic digestive disorders. Pancreatic function, as assessed by the PLT, was impaired in 22 of the 28 patients with pancreatic diseases, and it was normal in all but four patients with nonpancreatic disorders. Cerulein infusion caused a decrease in total plasma amino acid concentration that was generally more pronounced in patients with nonpancreatic diseases (maximal percentage decrease: median, 14%; range, 4-28%) than in those with pancreatic diseases (maximal percentage decrease: median, 9%; range, 0-21%) (p < 0.001). Using a cutoff of a 14% amino acid decrease, the sensitivity of the AACT was 89% and the specificity 53% (diagnostic accuracy, 65%); with a cutoff of 12%, the sensitivity was 75% and the specificity 69% (diagnostic accuracy, 71%). The sensitivity of the PLT was 79% and the specificity 93% (diagnostic accuracy, 88%). The results indicate that the sensitivity of the AACT is relatively high, but they show that the specificity is low, making the test unsuitable for clinical use, at least in its present form.

Coffee and cancer of the pancreas: an Italian multicenter study.

While cigarette smoking is a well-established risk factor for pancreatic cancer, the role of alcohol, coffee and tea consumption remains controversial. In view of this, and because of the limited information on possible environmental risk factors of pancreatic cancer in Italy, we carried out this study. Five hundred seventy patients with newly diagnosed pancreatic cancer and 570 controls from 14 Italian centers were studied. Using a standardized questionnaire, all were interviewed personally about their smoking habits, as well as habitual alcohol, coffee, and tea consumption throughout their lives prior to clinical onset of the disease. Details were also obtained on exposure to potential occupational carcinogens. A moderate association, statistically significant only in women (odds ratio, 2.18; 95% confidence interval, 1.30-3.68), was found between pancreatic cancer and cigarette smoking, but none was observed with alcohol or tea consumption or with any particular occupational exposure. Consumption of 1 or 2 cups of coffee per day was not associated with increased risk; 3 coffees per day increased the risk, but not significantly (odds ratio, 1.49; 95% confidence interval, 0.97-2.30); with consumption of more than 3 coffees per day the increase in risk was highly significant (odds ratio, 2.53; 95% confidence interval, 1.53-4.18). A statistically significant dose-response relationship (p < 0.001) was observed in each sex. The association between coffee use and pancreatic cancer still held after controlling for potential confounding factors such as cigarette smoking or alcohol use, and when the analysis was restricted to nonsmoking coffee drinkers. The results of this study, one of the largest of its type so far published, suggest that a causal relationship may exist between coffee consumption and pancreatic cancer.

Behavior of serum interleukin 12 in human acute pancreatitis.

We evaluated the behavior of sera interleukin p70 (IL-12p70) and IL-12p40 in patients with acute pancreatitis. Twenty-three acute pancreatitis patients were studied (12 had severe pancreatitis and 11 had mild pancreatitis). Twenty healthy subjects were studied as controls. Serum concentrations of total IL-12, IL-12p70, IL-12p40, and IL-6 were determined in all subjects on admission to the hospital; in patients with acute pancreatitis, the serum levels of these molecules also were determined for the 5 days after admission. Acute pancreatitis patients had serum concentrations of total IL-12, IL-12p40, and IL-6 significantly higher (p < 0.05) than those of the healthy subjects from the first to the sixth day of the study; serum concentrations of IL-12p70 were significantly higher in acute pancreatitis patients (p < 0.02) than in the healthy subjects on the first of the disease and significantly lower (p < 0.05) on the second, third, and fourth days of illness. Reduction of IL-12p70 in acute pancreatitis patients was not due to a failure of the monocytes because the production of IL-6 was increased. Increased amounts of IL-12p40 in acute pancreatitis patients may be responsible for their increased susceptibility to infection.