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Henry A Pitt

Publications and source records attributed to Henry A Pitt.

At least 19 recordsLinked to original sources
PubMed2006

Pioglitazone increases gallbladder volume in insulin-resistant obese mice.

BACKGROUND: Both obesity and diabetes are associated with an increased incidence of gallstones. Recent animal and human data from our laboratory suggest that insulin resistance is associated with increased gallbladder volume and/or impaired gallbladder emptying. Pioglitazone is a thiazolidinedione that has been shown to improve insulin resistance. Therefore, we tested the hypothesis that pioglitazone would improve insulin resistance, decrease resting gallbladder volume and improve gallbladder response to neurotransmitters in insulin-resistant obese mice fed a 25% carbohydrate diet. MATERIALS AND METHODS: Twenty eight-week-old insulin-resistant obese (Lep(ob)) mice fed a 25% carbohydrate diet for 4 weeks. Half of the animals had 0.3 g/kg pioglitazone added to their diet. At 12 weeks all animals were fasted and underwent cholecystectomy. Gallbladder volume and weight were measured, and fresh gallbladders were placed in a muscle bath to assess response to acetylcholine (ACh 10(-5)M), neuropeptide Y (NPY 10(-8,-7,-6)M) and cholecystokinin (CCK 10(-10,-9,-8,-7)M). Serum glucose and insulin were measured, and HOMA Index, a measure of insulin resistance, was calculated. RESULTS: Fasting serum insulin and HOMA Index were significantly decreased (P < 0.03), but gallbladder volume was significantly increased (P < 0.03) in the pioglitazone treated group. Pioglitazone did not alter gallbladder weight or response to ACh, NPY, or CCK. CONCLUSION: These data suggest that in insulin-resistant obese mice pioglitazone 1) lowers insulin-resistance, 2) increases resting gallbladder volume, and 3) does not alter gallbladder response to neurotransmitters. Therefore, we conclude that pioglitazone, while improving insulin resistance, paradoxically increases gallbladder volume and, thereby, may increase the propensity for gallstone formation by enhancing gallbladder stasis.

Acetylcholine↗
PubMed2006

Operative approach to gallbladder cancer.

In most Western countries gallbladder cancer is a rare tumor with a poor prognosis. The majority of patients present with advanced-stage tumors (stage IV) that are not amenable to surgical resection. At the other end of the spectrum a small percentage of patients present with stage I disease that may be cured by cholecystectomy. The role for surgery in patients with stage II and III disease remains controversial, but most hepatobiliary surgeons believe that an aggressive surgical approach improves survival for these patients. However, the extent of hepatic and lymph node resection, the need for resection of the extrahepatic ducts in nonjaundiced patients, the role of vascular resection, and the advisability of hepatopancreatoduodenectomy remain a matter of debate. Although no data from prospective, randomized studies are available, resection of the gallbladder and adjacent liver with or without the extrahepatic bile ducts and with a regional lymph node dissection is the operative approach recommended for selected patients with gallbladder cancer.

Bile Ducts, Extrahepatic↗
PubMed2006

Nonalcoholic Fatty gallbladder disease: the influence of diet in lean and obese mice.

The obesity epidemic has contributed to an increased prevalence of gallstones and a higher percentage of chronic acalculous cholecystitis. Obesity is associated with Type II diabetes and hyperlipidemia in murine models. In addition, we have previously demonstrated that serum glucose, insulin, cholesterol, and triglycerides correlated with gallbladder contractility in murine models. However, the relative role of insulin resistance and gallbladder fat infiltration in this phenomenon remain unclear. Therefore, we tested the hypothesis that gallbladder wall lipids are related to obesity and diet and are inversely correlated with gallbladder contractility. One hundred lean control (C7BL/6J) and 36 obese leptin-deficient (Lep(ob)) 8-week-old female mice were fed either a chow diet or a 1.0% cholesterol, 15% butterfat (high-lipid) diet for four weeks. Pooled gallbladders were then analyzed for free fatty acids (FFA), phospholipids (PL), total cholesterol (TC), and triglycerides (TG). Cholesterol/phospholipid ratios were then calculated. The Lep(ob) mice fed a chow diet had significantly higher (P < 0.01) gallbladder lipids than the three other groups. The lean mice that were fed a high-lipid diet had increased (P < 0.05) gallbladder TC compared to the lean mice on a chow diet. In addition, the cholesterol/phospholipid ratio was significantly increased (P < 0.01) in the lean mice fed a high-lipid diet compared to the other three groups. Finally, the high-lipid diet decreased gallbladder FFA (P < 0.01), PL (P = 0.08), and TC (P < 0.05) in Lep(ob) mice. These data suggest that (1) obese mice have increased gallbladder lipids; (2) a high-cholesterol, high-fat diet increases gallbladder lipids and the cholesterol/phospholipid ratio in lean mice; but (3) decreases gallbladder fatty acids, phospholipids, and cholesterol in obese mice. Prior studies have documented similarly decreased gallbladder response to neurotransmitters in obese mice on a chow diet, as well as lean and obese mice on a high-lipid diet. Therefore, we conclude that leptin-deficient obesity and/or a high-fat diet causes nonalcoholic fatty gallbladder disease, which is manifested by diminished gallbladder contractility.

Adipose Tissue↗
PubMed2006

Altered small intestinal absorptive enzyme activities in leptin-deficient obese mice: influence of bowel resection.

BACKGROUND: Residual bowel increases absorption after massive small bowel resection. Leptin affects intestinal adaptation, carbohydrate, peptide, and lipid handling. Sucrase, peptidase, and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) are involved in carbohydrate, protein, and lipid absorption. We hypothesized that leptin-deficient obese mice would have altered absorptive enzymes compared with controls before and after small bowel resection. METHODS: Sucrase, peptidase (aminopeptidase N [ApN], dipeptidyl peptidase IV [DPPIV]), and MGAT activities were determined from lean control (C57BL/6J, n = 16) and leptin-deficient (Lep(ob), n = 16) mice small bowel before and after 50% resection. RESULTS: Ileal sucrase activity was greater in obese mice before and after resection. Jejunal ApN and DPPIV activities were lower for obese mice before resection; ileal ApN activity was unaltered after resection for both strains. Resection increased DPPIV activity in both strains. Jejunal MGAT in obese mice decreased postresection. In both strains, ileal MGAT activity decreased after resection, and obese mice had greater activity in remnant ileum. CONCLUSIONS: After small bowel resection, leptin-deficient mice have increased sucrase activity and diminished ileal ApN, DPPIV, and MGAT activity compared with controls. Therefore, we conclude that leptin deficiency alters intestinal enzyme activity in unresected animals and after small bowel resection. Altered handling of carbohydrate, protein, and lipid may contribute to obesity and diabetes in leptin-deficient mice.

Acyltransferases↗
PubMed2006

Ciliary neurotrophic factor restores gallbladder contractility in leptin-resistant obese diabetic mice.

BACKGROUND: Obesity and diabetes are major risk factors for cholesterol gallstones, and the majority of obese people are leptin-resistant. Our previous work has shown that both leptin-deficient (Lepob) and leptin-resistant (Lepdb) obese diabetic mice have decreased in vitro gallbladder motility. Leptin administration to leptin-deficient (Lepob) animals restores gallbladder motility and reverses obesity and hyperinsulinemia. However, additional leptin in leptin-resistant obesity would not be expected to improve obesity-related parameters. Recent studies demonstrate that ciliary neurotrophic factor (CNTF) reduces weight and hyperinsulinemia in leptin-resistant obesity. Our hypothesis is that CNFT would cause weight loss, lower blood sugars, and restore gallbladder contractility in leptin-resistant (Lepdb) mice. MATERIALS AND METHODS: 20 C57b/6J and 20 Lepdb 8-week-old female mice were injected daily with either intraperitoneal saline or 0.3 microg/g CNTFAx15 for 17 days. Gallbladders were mounted in muscle baths and stimulated with acetylcholine, neuropeptide Y, and cholecystokinin. Gallbladder volume, serum glucose, insulin, liver weight, liver fat, and gallbladder responses were measured. Data were analyzed by ANOVA. RESULTS: Saline treated obese mice had greater body weight and obesity parameters, but decreased gallbladder contractility to neurotransmitters compared to saline treated lean mice. CNTF administration to obese mice decreased body weight and obesity parameters, and restored gallbladder contractility. CNTF treated lean animals had weight loss and decreased gallbladder contraction to acetylcholine and cholecystokinin compared to saline treated lean animals. CONCLUSIONS: Ciliary neurotrophic factor (CNTF) causes 1) weight loss, 2) improvement of diabetes, and 3) alterations in gallbladder motility that is improved in obese mice but decreased in lean mice. We conclude that CNTF may improve gallbladder contractility in leptin-resistant obesity with diabetes.

Animals↗
PubMed2006

Chemoembolization in patients at high risk: results and complications.

PURPOSE: Transarterial chemoembolization (TACE) has become a standard treatment option for unresectable hepatocellular carcinoma (HCC) and is often used to palliate hepatic metastases. Many patients who are candidates for TACE present with poor hepatic reserve, advanced tumor stage with major portal vein (PV) invasion or thrombosis, and/or biliary dilation. These factors have been associated with a poor prognosis and increased complications after chemoembolization. Accordingly, these patients are classified as being at high risk and may not be considered for therapy. The aim of this study is to evaluate the results of TACE in these patients. MATERIALS AND METHODS: Over a period of 5 years, 141 patients underwent 355 TACE procedures. Thirty-six patients (26%) were in the high-risk group as a result of major PV thrombosis, increased serum bilirubin level (>2 mg/dL), and/or intrahepatic biliary dilation. HCC was the underlying tumor in 60% of patients. Thirty-seven percent of patients had Child-Pugh class B/C disease. Patients in the high-risk group received more selective embolization with fewer particles and fewer procedures (2.0 vs 2.7; P < .04). RESULTS: Patients in the high-risk group were more likely to have HCC (83% vs 51%; P < .01) and were also more likely to have advanced disease according to Child-Pugh classification versus patients in the low-risk group (49% vs 20%; P < .01). The overall complication rate was 4.3%, with no significant difference in complication rate between groups (3.2% vs 8.2%; P = .12). The overall 30-day mortality rate was 2.3%, and no significant difference in 30-day mortality rate was observed between the high- and low-risk groups (5.5% vs 1.4%; P = .11). A trend toward increased survival in the low-risk group did not reach statistical significance. CONCLUSIONS: These data suggest that patients with advanced disease and decreased hepatic reserve who are treated with TACE exhibit no significant increase in morbidity or mortality and no significant decrease in survival. With variations in technique, TACE can be performed safely in patients with the relative risk factors that may classify them in high-risk groups.

Adult↗
PubMed2005

Altered intestinal motility in leptin-deficient obese mice.

INTRODUCTION: Leptin is produced by adipocytes and causes satiety by regulating hypothalamic neurotransmission and energy expenditure. Leptin functions through the active long form of its receptor, which is expressed throughout the gastrointestinal tract, including the vagal neurons concerned with small intestinal motility. However, the role of leptin in small intestinal motility is poorly understood. Therefore, we hypothesized that leptin-deficient (Lepob) obese mice would have altered small intestinal response to neurotransmitters and transit time. MATERIALS AND METHODS: Responses of jejunal and ileal segments from lean control and leptin-deficient obese animals to acetylcholine (ACh) and cholecystokinin (CCK) were determined in an organ bath. In addition, gastric emptying was determined as the amount of gavaged liquid diet remaining in the stomach after 1 h, and intestinal transit time was determined by calculating the geometric center (GC) of passage of a fluorescent-labeled marker. RESULTS: Leptin deficiency resulted in increased jejunal responses to CCK (P <0.05) and a similar response to ACh compared to lean controls. Also, gastric emptying (97% versus 91%, P <0.001) in obese mice was greater. Overall small intestinal transit (GC) in obese mice was decreased (7.3 versus 8.4, P <0.05) even though proximal transit was increased (5.3 versus 1.5, P <0.06). CONCLUSIONS: These studies indicate that leptin-deficient (Lepob) obese mice have an increased jejunal response to CCK as well as an increased proximal intestinal transit, but an overall decrease in small intestinal transit.

Acetylcholine↗
PubMed2005

Leptin increases small intestinal response to cholecystokinin in leptin-deficient obese mice.

INTRODUCTION: Leptin receptors are present in the jejunum, ileum, and vagal neurons. Leptin increases duodenal secretion of cholecystokinin (CCK) and acts with CCK on vagal mechanoreceptors in the regulation of small intestinal motility. We have demonstrated that leptin-deficient (Lepob) obese mice have increased jejunal and normal ileal responses to CCK. Therefore, we hypothesized that leptin administration alters small intestinal motility observed in leptin-deficient obese mice. MATERIALS AND METHODS: Twelve-week-old female leptin-deficient (Lepob) obese mice received either saline (n=12) or 5 microg/g leptin ip (n=12) injections daily. After 4 weeks, jejunal and ileal segments were harvested, mounted in an organ bath, and reacted with acetylcholine (ACh, 10(-5)M) and CCK (10(-8,-7,-6)M). Data were expressed as N/cm2 and compared by ANOVA and Student's t test. RESULTS: The average body weights in the leptin-treated group were significantly decreased compared to those of the saline-treated group (34 versus 49 g, P <0.01). Jejunal responses to ACh within each group were significantly decreased (P <0.05) when compared to ileal responses. No significant differences in responses to ACh were observed between groups. Jejunal responses to 10(-7,-6)M CCK in the leptin-treated group were significantly greater than those in the saline-treated group. Ileal responses in the leptin group were similarly increased at all CCK concentrations. CONCLUSIONS: These data suggest that daily leptin administration for 4 weeks in leptin-deficient (Lepob) obese mice increases jejunal and ileal responses to CCK and does not alter responses to ACh. Therefore, we conclude that regulation of small intestinal motility may be influenced by synergistic action of cholecystokinin and leptin.

Acetylcholine↗
PubMed2005

Surgical management of bile duct injuries sustained during laparoscopic cholecystectomy: perioperative results in 200 patients.

OBJECTIVE: A single institution retrospective analysis of 200 patients with major bile duct injuries was completed. Three patients died without surgery due to uncontrolled sepsis. One hundred seventy-five patients underwent surgical repair, with a 1.7% postoperative mortality and a complication rate of 42.9%. SUMMARY BACKGROUND DATA: The widespread application of laparoscopic cholecystectomy (LC) has led to a rise in the incidence of major bile duct injuries (BDI). Despite the frequency of these injuries and their complex management, the published literature contains few substantial reports regarding the perioperative management of BDI. METHODS: From January 1990 to April 2003, a prospective database of all patients with a BDI following LC was maintained. Patients' charts were retrospectively reviewed to analyze perioperative surgical management. RESULTS: Over 13 years, 200 patients were treated for a major BDI following LC. Patient demographics were notable for 150 women (75%) with a mean age of 45.5 years (median 44 years). One hundred eighty-eight sustained their BDI at an outside hospital. The mean interval from the time of BDI to referral was 29.1 weeks (median 3 weeks). One hundred nine patients (58%) were referred within 1 month of their injury for acute complications including bile leak, biloma, or jaundice. Twenty-five patients did not undergo a surgical repair at our institution. Three patients (1.5%) died after delayed referral before an attempt at repair due to uncontrolled sepsis. Twenty-two patients, having intact biliary-enteric continuity, underwent successful balloon dilatation of an anastomotic stricture. A total of 175 patients underwent definitive biliary reconstruction, including 172 hepaticojejunostomies (98%) and 3 end-to-end repairs. There were 3 deaths in the postoperative period (1.7%). Seventy-five patients (42.9%) sustained at least 1 postoperative complication. The most common complications were wound infection (8%), cholangitis (5.7%), and intraabdominal abscess/biloma (2.9%). Minor biliary stent complications occurred in 5.7% of patients. Early postoperative cholangiography revealed an anastomotic leak in 4.6% of patients and extravasation at the liver dome-stent exit site in 10.3% of patients. Postoperative interventions included percutaneous abscess drainage in 9 patients (5.1%) and new percutaneous transhepatic cholangiography and stent placement in 4 patients (2.3%). No patient required reoperation in the postoperative period. The mean postoperative length of stay was 9.5 days (median 9 days). The timing of operation (early, intermediate, delayed), presenting symptoms, and history of prior repair did not affect the incidence of the most common perioperative complications or length of postoperative hospital stay. CONCLUSIONS: This series represents the largest single institution experience reporting the perioperative management of BDI following LC. Although perioperative complications are frequent, nearly all can be managed nonoperatively. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results.

Adult↗
PubMed2005

Neuroendocrine hepatic metastases: does aggressive management improve survival?

OBJECTIVE: The aim of this study was to determine whether aggressive management of neuroendocrine hepatic metastases improves survival. SUMMARY BACKGROUND DATA: Survival in patients with carcinoid and pancreatic neuroendocrine tumors is significantly better than adenocarcinomas arising from the same organs. However, survival and quality of life are diminished in patients with neuroendocrine hepatic metastases. In recent years, aggressive treatment of hepatic neuroendocrine tumors has been shown to relieve symptoms. Minimal data are available, however, to document improved survival with this approach. METHODS: The records of patients with carcinoid (n = 84) and pancreatic neuroendocrine tumors (n = 69) managed at our institution from January 1990 through July 2004 were reviewed. Eighty-four patients had malignant tumors, and hepatic metastases were present in 60 of these patients. Of these 60 patients, 23 received no aggressive treatment of their liver metastases, 19 were treated with hepatic resection and/or ablation, and 18 were managed with transarterial chemoembolization (TACE) frequently (n = 11) in addition to resection and/or ablation. These groups did not differ with respect to age, gender, tumor type, or extent of liver involvement. RESULTS: Median and 5-year survival were 20 months and 25% for the Nonaggressive group, >96 months and 72% for the Resection/Ablation group, and 50 months and 50% for the TACE group. The survival for the Resection/Ablation and the TACE groups was significantly better (P < 0.05) when compared with the Nonaggressive group. Patients with more than 50% liver involvement had a poor outcome (P < 0.001). CONCLUSIONS: These data suggest that aggressive management of neuroendocrine hepatic metastases does improve survival, that chemoembolization increases the patient population eligible for this strategy, and that patients with more than 50% liver involvement may not benefit from an aggressive approach.

Carcinoid Tumor↗
PubMed2004

Nonobese diabetic mice have diminished gallbladder motility and shortened crystal observation time.

Diabetes and obesity are strongly associated and are risk factors for cholesterol gallstone disease. Leptin-deficient and leptin-resistant diabetic obese mice have enlarged, hypomotile gallbladders. In addition, bile from gallbladders of leptin-deficient mice has enhanced cholesterol crystal formation, whereas bile from gallbladders of leptin-resistant mice has delayed crystal observation time. To determine the effect of diabetes alone, we hypothesized that leptin-normal, nonobese diabetic (NOD) mice would have reduced biliary motility and rapid crystal formation. Twenty control and 9 prediabetic and 11 diabetic NOD, 12- to 26-week-old mice underwent glucose measurement and cholecystectomy for muscle bath stimulation with neurotransmitters. An additional group of 200 control and 78 NOD 12-week-old mice underwent microscopic bile examination for cholesterol crystal formation. Compared with control mice, prediabetic NOD mice had similar glucose levels and gallbladder volumes. Diabetic NOD mice had higher sugar levels and larger gallbladder volumes (P < 0.001) than control mice. Prediabetic NOD gallbladders had less contractility (P < 0.01) than control gallbladders, and contractility worsened (P < 0.01) in diabetic NOD mice. NOD mice formed cholesterol crystals earlier than did control mice (P < 0.05). Nonobese diabetic NOD mice have (1) decreased gallbladder contraction to neurotransmitters, which worsens with development of diabetes, and (2) rapid crystal formation. We conclude that diabetes alone alters gallbladder motility and cholesterol crystal formation.

Animals↗
PubMed2004

Leptin-resistant obese mice do not form biliary crystals on a high cholesterol diet.

INTRODUCTION: Human obesity is associated with leptin resistance and cholesterol gallstone formation. Previously, we demonstrated that leptin-resistant (Lep(db)) obese mice fed a low cholesterol diet have enlarged gallbladders, but a decreased cholesterol saturation index, despite elevated serum cholesterol. Obese humans, however, consume a high cholesterol diet. Therefore, we hypothesized that on a high cholesterol diet, leptin-resistant mice would have cholesterol saturated bile and would form biliary crystals. METHODS: Eight-week old female lean control (n = 70) and leptin-resistant (n = 72) mice were fed a 1% cholesterol diet for 4 weeks. All animals then had cholecystectomies. Bile was collected, grouped into pools to determine cholesterol saturation index (CSI), and examined for cholesterol crystals. Serum cholesterol and leptin were also measured. RESULTS: Gallbladder volumes for Lep(db) mice were enlarged compared with the lean mice (35.8 microl versus 19.1 microl, P < 0.001), but the CSI for the Lep(db) mice was lower than for the lean animals (0.91 versus 1.15, P < 0.03). The obese animals did not form cholesterol crystals, whereas the lean animals averaged 2.2 crystals per high-powered field (hpf) (P < 0.001). Serum cholesterol and leptin were also elevated (P < 0.001) in the obese animals. CONCLUSIONS: These data suggest that Lep(db) obese mice fed a high cholesterol diet have increased gallbladder volume and decreased biliary cholesterol saturation and crystal formation despite elevated serum cholesterol compared with lean control mice. We conclude that the link among obesity, diet, and gallstone formation may not require hypersecretion of biliary cholesterol and may be related to the effects of diabetes, hyperlipidemia, or both on gallbladder motility.

Animals↗
PubMed2004

Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice.

BACKGROUND: Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lepob) and leptin-resistant (Lepdb) mice are hyperglycemic and have enlarged gallbladders with diminished response in vitro to cholecystokinin (CCK) and acetylcholine (ACh). Whether this phenomenon is secondary to hyperosmolar myocytes and/or decreased neuromuscular transmission remains unclear. We hypothesize that myocytes from Lepob and Lepdb obese mice would not respond normally to neurotransmitters. METHODS: Cholecystectomy was performed on 39 lean, 19 Lepob, and 20 Lepdb 12-week-old female mice. The gallbladder was divided and enzymatically digested. Half of each gallbladder's myocytes had contraction induced by CCK (10(-8) mol/L, n = 38) or ACh (10(-5) mol/L, n = 40). RESULTS: Body weights, gallbladder volumes, and serum glucoses were greater for Lep(ob) and Lepdb mice compared to controls (P < .001). Resting myocyte lengths from Lepob and Lepdb mice were 93% and 91% of the length of controls (P < .001). In response to CCK, lean myocytes shortened 6% (P < .01), while myocytes from obese mice demonstrated no shortening. None of the myocytes demonstrated significant shortening with ACh. CONCLUSIONS: These data suggest that gallbladder myocytes from obese mice are (1) foreshortened and (2) have a diminished response to cholecystokinin. We conclude that altered leptin and/or increased glucose may foreshorten myocytes and decrease response to cholecystokinin.

Acetylcholine↗
PubMed2004

Cystic pancreatic neoplasms: observe or operate.

OBJECTIVE: The objectives of this analysis were to define the incidence, natural history, and predictors of neoplasia in pancreatic cysts to determine which patients can safely be observed and which should undergo an operation. SUMMARY BACKGROUND DATA: With advancements in imaging technology, cystic lesions of the pancreas are being detected with increased frequency. Many of these lesions are small and asymptomatic, but they may be associated with pancreatitis or have malignant potential. Therefore, the management of these patients is complex, and knowledge of pancreatic cyst natural history and predictors of neoplasia are important. METHODS: From January 1995 through December 2002, all radiologic, surgical, and pathology records were reviewed for the presence of pancreatic cysts. In determining natural history, only patients with 2 scans more than 1 month apart at our institution were included. Patients with a clinical history and laboratory evidence of pancreatitis and/or pathologic confirmation of a pseudocyst were excluded. Factors analyzed as potential predictors of neoplasia included age, gender, cyst size, and symptoms. Serous cystadenomas, solid and cystic papillary (Hamoudi) tumors, lymphoepithelial cysts and simple cysts were all benign, whereas mucinous cystic neoplasms, intraductal papillary mucinous neoplasm, cystic neuroendocrine tumors, and cystadenocarcinomas were considered to be premalignant or malignant. RESULTS: Among 24,039 CT or MR scans, 290 patients (1.2%) had pancreatic cysts, and 168 of these patients (0.7%) had no documentation of pancreatitis. Seventy-nine of these patients with 103 cysts had more than 1 scan with an average interval of 16 months. These cysts increased in size in 19%, did not change in 59% and decreased in 22% of patients. Forty-nine patients underwent surgery for 14 benign (serous cystadenomas = 10, Hamoudi = 2, lymphoepithelial = 1, simple = 1) 25 premalignant (mucinous cystic neoplasm =16, intraductal papillary mucinous neoplasm = 5, neuroendocrine tumors = 4), or 10 malignant (intraductal papillary mucinous neoplasm = 7, cystadenocarcinomas = 3) lesions. Gender and cyst size did not predict neoplasia. However, presence of symptoms predicted premalignant or malignant pathology (60% vs. 23%, P < 0.05), and age over 70 years was associated with malignancy (60% vs. 21%, P < 0.02). CONCLUSIONS: These data suggest that cystic pancreatic neoplasms 1) occur in 0.7% of patients, 2) increase in 19% over 16 months, and 3) are likely (60%) to be malignant in patients older than 70 years. Therefore, we recommend surgical excision for pancreatic cysts that are increasing under observation, symptomatic, or detected radiologically in fit older patients.

Aged↗
PubMed2003

Thymidylate synthase expression predicts the response to 5-fluorouracil-based adjuvant therapy in pancreatic cancer.

PURPOSE: Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU), and TS expression may determine clinical response and survival after therapy with 5-FU in colorectal cancer. 5-FU is also widely used in the adjuvant therapy of pancreatic cancer. Therefore, we explored the hypothesis that TS expression was associated with patient prognosis and the response to adjuvant therapy in pancreatic cancer. EXPERIMENTAL DESIGN: Cylindrical tissue cores from a large retrospective, nonrandomized series covering 132 resected patients were used to build a pancreatic cancer tissue microarray. TS expression was determined using immunohistochemistry. RESULTS: High intratumoral TS expression and low intratumoral TS expression were present in 83 of 132 (63%) and 49 of 132 (37%) tumors, respectively. Median survival among patients with low intratumoral TS expression (18 months) was longer than that among patients with high TS expression (12 months). In multivariate analysis, more advanced pathological stage [risk ratio (RR) = 1.70; P = 0.015], poorly differentiated histology (RR = 1.71; P = 0.015), management with adjuvant therapy (RR = 0.49; P = 0.011), and high TS expression [RR = 1.66; 95% confidence interval (CI) = 1.05-2.63; P = 0.029] were independent predictors of mortality. The risk of death was significantly reduced by any adjuvant therapy (RR = 0.40; 95% CI = 0.18-0.90; P = 0.001) among patients with high TS expression. This difference in survival among patients with low- and high-TS-expressing tumors became more significant when the analysis was restricted to the 73 patients receiving 5-FU-based adjuvant therapy (RR = 0.37; 95% CI = 0.16-0.86; P = 0.0006). In contrast, 5-FU-based adjuvant therapy did not influence survival among patients with low-TS-expressing pancreatic cancer. CONCLUSIONS: High TS expression is a marker of poor prognosis in resected pancreatic cancer. Patients with high intratumoral TS expression benefit from adjuvant therapy.

Adenocarcinoma↗
PubMed2003

Acute cholangitis.

Acute cholangitis is an infectious disease of the biliary tract with a wide spectrum of presentation ranging in severity from a mild form with fever and jaundice, to a severe form with septic shock. Supportive care with hydration, antibiotics, and biliary decompression remain the cornerstones of care. Broad-spectrum antibiotics should include coverage of E.coli, Klebsiella sp., Enterococcus sp., and in severely critically ill patients, coverage of additional pathogens such as Bacteriodes sp., Pseudomonas, and yeast should be considered. Biliary decompression should be performed early in the course of the illness when the patient has not improved or if they worsen with hydration and antibiotics. Stable patients should have biliary decompression usually within 72 hours when the fever has resolved. Urgent decompression with a percutaneous or endoscopic stent is preferred over an operative decompression in most institutions. Outcome is dependent on the etiology of the obstruction (benign versus malignant) and the ability to achieve biliary decompression.

Acute Disease↗
PubMed2003

Vitamin A deficiency inhibits intestinal adaptation by modulating apoptosis, proliferation, and enterocyte migration.

In a prior study, vitamin A-deficient rats subjected to submassive small bowel resections did not mount a normal intestinal adaptive response by 10 days postoperatively, although adaptive increases in crypt cell proliferation were not attenuated and there were no differences in apoptotic indexes. The present study was designed to address the mechanisms by which vitamin A status effects adaptation by analyzing proliferation, apoptosis, and enterocyte migration in the early postoperative period (16 and 48 h) in vitamin A-sufficient, -deficient, and partially replenished sham-resected and resected rats. At 16 h postresection, apoptosis was significantly greater in the remnant ileum of resected vitamin A-deficient rats compared with the sufficient controls. Crypt cell proliferation was increased by resection in all dietary groups at both timepoints. However, at 48 h postresection, proliferation was significantly decreased in the vitamin A-deficient and partially replenished rats. By 48 h after resection, vitamin A deficiency also reduced enterocyte migration rates by 44%. This occurred in conjunction with decreased immunoreactive collagen IV at 48 h and 10 days postoperation. Laminin expression was also reduced by deficiency at 10 days postresection, whereas fibronectin and pancadherin were unchanged at 48 h and 10 days. These studies indicate that vitamin A deficiency inhibits intestinal adaptation following partial small bowel resection by reducing crypt cell proliferation, by enhancing early crypt cell apoptosis, and by markedly reducing enterocyte migration rates, which may be related to changes in the expression of collagen IV and other extracellular matrix components.

Adaptation, Physiological↗