Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.

Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4).

BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Cigar and pipe smoking, smokeless tobacco use and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4).

BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

Adenocarcinomas of the esophagus and gastric cardia: medical conditions, tobacco, alcohol, and socioeconomic factors.

Adenocarcinomas of the esophagus and gastric cardia have increased in incidence over the past 10-15 years in Western countries. The cause for this increase in incidence is still unknown. Our study was designed to investigate potential risk factors for adenocarcinomas of the esophagus and gastric cardia and to compare the risk profiles of a group of patients with this cancer with those having distal stomach cancer. We studied 95 incident cases with the pathological diagnosis of adenocarcinomas of the esophagus and gastric cardia, 67 patients with adenocarcinomas of the distal stomach, and 132 cancerfree controls. Patients were seen at Memorial Sloan-Kettering Cancer Center from November 1, 1992 to November 1, 1994. Epidemiological data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Risk factors were analyzed using Mantel-Haenszel methods and a logistic regression model. Hypertension was associated with a 2-fold increased risk of adenocarcinomas of esophagus and gastric cardia after controlling for age, sex, race, education, pack-years of smoking, alcohol use, body mass index, and total dietary intake of calories. Increased risk of adenocarcinomas of esophagus and gastric cardia was associated with age, male gender, and Caucasian race. Tobacco smoking was related to a modest risk of adenocarcinomas of esophagus and gastric cardia. In contrast, the risk of distal stomach cancer was associated with stomach ulcers and pack-years of cigarette smoking. Iron deficiency was significantly associated with increased risk of both adenocarcinomas of the esophagus and gastric cardia and adenocarcinomas of the distal stomach. No obvious associations were identified for occupational exposures, family history of cancer, and physical activities. This study suggests that medical conditions such as hypertension and iron deficiency may be related to the risk of adenocarcinomas of esophagus and gastric cardia and confirms the moderate risk associated with tobacco smoking. Our results indicated an etiological heterogeneity with respect to risk factors identified between adenocarcinomas of esophagus and gastric cardia and those of the distal stomach.

GSTT1 and GSTM1 null genotypes and the risk of gastric cancer: a case-control study in a Chinese population.

Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. The homozygous deletions or null genotypes of GSTT1 (theta class) and GSTM1 (mu class) genes may be associated with an increased risk of cancer. Few studies have evaluated the relationship between GSTT1, GSTM1 and the risk of gastric cancer, as well as the potential interactions between these genetic markers and other risk factors of gastric cancer in the Chinese population. We conducted a case-control study with 143 cases with gastric cancer, 166 chronic gastritis (CG) cases and 433 cancer-free population controls from Yangzhong County, China. The epidemiological data were collected by a standard questionnaire for all of the subjects, and blood samples were obtained from 91 gastric cancer cases, 146 CG cases, and 429 controls. GSTT1 and GSTM1 genotypes were assayed by the PCR method, and Helicobacter pylori infection was measured by the ELISA method. Using logistic regression model in SAS, we assessed the independent effects of GSTT1 and GSTM1 null genotypes on the risk of gastric cancer and their potential interactions with other factors. The prevalence of GSTM1 null genotype was 48% in gastric cancer cases, 60% in CG patients, and 51% in controls. The prevalence of GSTT1 null genotype was 54% in gastric cancer cases, 48% in CG patients, and 46% in controls. After controlling for age, gender, education, pack-years of smoking, alcohol drinking, body mass index, H. pylori infection, and fruit and salt intake, the adjusted odds ratio (OR) for GSTT1 and gastric cancer was 2.50 (95% confidence interval (CI), 1.01-6.22). When gastric cancer cases were compared with CG patients, the adjusted OR for GSTT1 was 2.33 (95% CI, 0.75-7.25). However, GSTT1 null genotype was not associated with the risk of CG when using population controls. No obvious association was found between GSTM1 and the risk of both gastric cancer and CG. Our results suggest that GSTT1 null genotype may be associated with an increased risk of gastric cancer in a Chinese population.

Gastrointestinal emergencies in the critically ill cancer patient.

Gastrointestinal (GI) problems are a common occurrence in the critically ill cancer patient. These GI complications are often not related to the underlying cancer, but mimic the GI problems seen in noncancer patients. Common GI disorders such as peptic ulcer disease, gastritis, diverticulitis, and alcohol-related liver disease are often the underlying issue. This review summarizes the most common GI emergencies, which may arise in a patient with a current or past history of cancer.

Cryptosporidiosis. Case report in a health team worker.

Cryptosporidium is a coccidial protozoan of the intestinal tract; cryptosporidiosis in veterinarians has been reported as a cause of diarrhea. It has also been reported as a cause of diarrhea in marrow transplant recipients. Cryptosporidiosis has gained attention recently because of its occurrence in patients with the acquired immune deficiency syndrome (AIDS). A healthy intensive care unit nurse who acquired cryptosporidiosis from a bone marrow transplant recipient with diarrhea caused by cryptosporidiosis is described. Results of laboratory examination, including T lymphocyte subsets, were normal. She was treated with bed rest and a liquid diet and her symptoms completely resolved after 15 days. Health care workers should be aware that cryptosporidiosis can be transmitted to them from patients and should follow precautions to avoid acquiring the disease.

Comparison of magnetic resonance and endoscopic retrograde cholangiopancreatography in malignant pancreaticobiliary obstruction.

HYPOTHESIS: We hypothesize that magnetic resonance cholangiopancreatography (MRCP) is comparable to endoscopic retrograde cholangiopancreatographic (ERCP) as a diagnostic tool in patients with malignant biliary obstruction. DESIGN: Eighteen patients with suspected pancreaticobiliary malignancy were evaluated by ERCP and MRCP in 8 months (March 1, 1996, to October 31, 1996). Magnetic resonance cholangiopancreatography was performed with a 1.5-T scanner using 4-mm slices. Images were obtained in a 14- to 28-second breath-hold. Images from MRCP were retrospectively evaluated by a radiologist for image quality, ductal dilation, level of obstruction, and overall diagnostic impression. Images from ERCP were retrospectively evaluated by a biliary endoscopist (L.H.S.) and served as the standard for calculating sensitivity, specificity, and positive predictive values. In addition, intraoperative findings were compared with MRCP results in all patients explored. RESULTS: Diagnostic-quality MR images were obtained in 18 patients (100%). Diagnostic-quality endoscopic images were obtained in 16 (89%) of 18 attempted biliary cannulations and 11 (78%) of 14 attempted pancreatic cannulations. Magnetic resonance CP accurately delineated the level of extrahepatic biliary ductal obstruction in 13 (87%) of 15 patients. More important, MRCP provided valuable staging information in most patients. Findings from MRCP correlated with operative findings (size and location of tumor and mesenteric vascular involvement) in 8 (80%) of 10 patients who underwent surgery, while failing in 2 patients (20%) with carcinomatosis. CONCLUSIONS: Magnetic resonance CP is a sensitive study for detecting the presence and level of biliary ductal obstruction in patients with cancer. The results are comparable to those of ERCP; however, MRCP provides additional data regarding extent of disease that is not available from ERCP alone.

Does spontaneous bacterial peritonitis occur in malignant ascites?

Spontaneous bacterial peritonitis is a well-described entity estimated to occur in 8% of patients with cirrhotic ascites. Characteristic clinical findings may often be absent and the only manifestation may be decompensation of liver function. Ascites at Memorial Hospital is most commonly related to malignancy. We reviewed the records of 101 patients with ascitic fluid cytology positive for malignancy during the calendar year 1979. The most common malignant cytological diagnosis was adenocarcinoma, seen in 76 patients. Of the 101 patients with positive ascitic fluid cytology, 65 fluid specimens had microbiological studies performed which included aerobic, anerobic, fungal, and acid fast bacterial cultures. Only three patients had positive ascitic fluid cultures. We believe that these three patients had other reasons for peritonitis and do not represent true spontaneous bacterial peritonitis. Ascites alone, without liver disease, seem to predispose to spontaneous bacterial peritonitis. Perhaps, the presence of liver disease with less than normally effective hepatic reticuloendothelial function and portasystemic shunting is needed for the development of spontaneous bacterial peritonitis.

Gastrointestinal cancer in the elderly.

The older patient population, aged 70 years and greater, represent a large proportion of patients diagnosed with gastrointestinal malignancies. Surgery remains the mainstay of treatment for these malignancy sites. Chronologic age alone should not determine the extent of surgical or medical management. The authors describe those aspects of gastrointestinal cancer detection and therapy that are unique to the aging population.

A randomized trial using videotape to present consent information for colonoscopy.

A randomized controlled trial was conducted to determine if a videotaped presentation by a physician conveys information more effectively than an in-person discussion by the same physician using the identical script. Two hundred one patients undergoing colonoscopy were enrolled in the study. Patients were randomly assigned to one of three groups: video plus discussion, video alone, and discussion alone. A validated, 13-item knowledge test and the State-Trait Anxiety Inventory were administered to all patients. Mean number of correct test answers for video plus discussion was 11.04; for video alone, 10.70; and for discussion alone, 9.61. ANOVA with planned orthogonal comparisons showed that the patients in the two video groups had significantly better scores (p < 0.001) than those in the discussion-only group. No difference was noted between the two video groups (p = 0.32). Anxiety did not increase with increased understanding of the risks and benefits of colonoscopy. This approach may work as well for other invasive medical procedures and could save physician time while laying a foundation for a more personalized discussion.

Patient satisfaction with an informed consent process.

PURPOSE: This study evaluates patient and family member level of satisfaction with alternative approaches in obtaining informed consent before colonoscopy or upper gastrointestinal endoscopy. DESCRIPTION: A convenience sample of 204 endoscopy patients at Memorial Sloan-Kettering cancer Center in new York and 102 of their family members were approached to participate in the study. All patients were 19 years of age or older, able to speak and read English, and mentally competent. After proceeding through the informed consent process using both videotape and physician discussion, participants completed a ten-question survey on their previous informed consent experience and their preferences regarding receiving consent information. RESULTS: Overall, participants reported that a combination of videotape and physician explanation was preferred for receiving consent information over either method alone. The participants found that the videotape helped to make the information easier to understand and provided the appropriate amount of information about risks, benefits, and alternatives to the prospective endoscopic procedure. CLINICAL IMPLICATIONS: Patient satisfaction should be a factor in determining the best method of providing informed consent information. Because this study indicates that participants are most satisfied with the method of videotape followed by physician discussion, the addition of the videotape to the informed consent process may be beneficial in preparing the participant for a meaningful dialogue with the physician. The use of the videotape also may eliminate the problem of readability of the written document and ensure that all patients receive the same information. With a concerted effort on the part of oncology healthcare providers, including oncologists, nurses, and patient education professionals, this method may hold promise for ensuring the achievement of informed consent in oncology patients.