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Biomedical subjects

Henry A Pitt

Publications and source records attributed to Henry A Pitt.

34 records · Page 2Linked to original sources
PubMed2003

Surgical treatment of choledochal cysts.

Biliary cystic disease is uncommon in Asia and very rare in Europe and the Americas. Patients with biliary cysts may present as infants, children, or adults. When patients present as adults, they are more likely to have stones in the gallbladder, common duct, or intrahepatic ducts and to present with biliary colic, acute cholecystitis, cholangitis, or gallstone pancreatitis. With increasing age at presentation, the risks of intrahepatic strictures and stones, segmented hepatic atrophy/hypertrophy, secondary biliary cirrhosis, portal hypertension, and biliary malignancy all increase significantly. Factors to be considered when performing surgery on patients with biliary cystic disease include: (1) age, (2) presenting symptoms, (3) cyst type, (4) associated biliary stones, (5) prior biliary surgery, (6) intrahepatic strictures, (7) hepatic atrophy/hypertrophy, (8) biliary cirrhosis, (9) portal hypertension, and (10) associated biliary malignancy. In general, regardless of age, presenting symptoms, biliary stones, prior surgery or other secondary problems, surgery should include cholecystectomy and excision of extrahepatic cyst(s). With respect to the distal bile duct, the surgical principle should be excision of a portion of the intrapancreatic bile duct with care to not injure the pancreatic duct or a long common channel. Resection of the pancreatic head should be reserved for patients with an established malignancy. With respect to the intrahepatic ducts, surgery should be individualized depending on whether (1) both lobes are involved, (2) strictures and stones are present, (3) cirrhosis has developed, or (4) an associated malignancy is localized or metastatic. When the liver is not cirrhotic, hepatic parenchyma should be preserved even when strictures and stones are present. If cirrhosis is advanced, hepatic transplantation may be indicated, but this sequence of events is unusual. If a malignancy has developed, oncologic principles should be followed. Whenever possible, resection of a localized tumor including adjacent hepatic parenchyma and regional lymph nodes should be performed.

Adult↗
PubMed2003

Diabetes and hyperlipidemia correlate with gallbladder contractility in leptin-related murine obesity.

Obesity is associated with many comorbid conditions including diabetes, hyperlipidemia, and gallstones. However, the interaction among these modalities remains unclear. We recently demonstrated that both leptin-deficient and leptin-resistant obese mice have impaired biliary motility. These obese mice also are diabetic and hyperlipidemic. Therefore, we tested the hypothesis that serum glucose, insulin, cholesterol, and triglyceride levels would correlate with gallbladder contractility. Thirty-four lean control, 10 lean heterozygous leptin-deficient, 18 obese homozygous leptin-deficient, and 12 obese homozygous leptin-resistant mice were fed a nonlithogenic chow diet while nine lean control and nine obese homozygous leptin-deficient mice were fed a high-cholesterol diet for 4 weeks. In vitro gallbladder responses to cholecystokinin (CCK; 10(-8) mol/L), acetylcholine (ACh; 10(-5) mol/L), and neuropeptide Y (NPY; 10(-6) mol/L) were measured. Serum glucose, insulin, cholesterol, and triglyceride levels were measured from pooled serum from an additional 704 animals. Gallbladder responses were greatest for CCK, intermediate for ACh, and least for NPY. Serum glucose, insulin, cholesterol, and triglyceride levels and body weight all correlated similarly, negatively, and significantly (P<0.001) with gallbladder contractility. Hyperglycemia, insulin-resistance, hyperlipidemia, and body weight in obese mice with leptin dysfunction are associated with poor gallbladder contractility, which in turn may contribute to the association between obesity and gallstone formation.

Animals↗
PubMed2003

Cystic pancreatic neoplasms: enucleate or resect?

Asymptomatic cystic pancreatic neoplasms are being detected by abdominal imaging with increasing frequency. Enucleation of small cystic neoplasms can be performed without recurrence but has been associated with a higher incidence of pancreatic fistula. Thus the procedure has been modified to include intraoperative ultrasound imaging and closure of the pancreatic defect. This analysis was performed to determine whether these modifications have improved operative outcome. Thirty patients with mucinous cystic neoplasms (n=16), serous cystadenomas (n=10), and cystic islet cell tumors (n=4) were studied. Enucleation was performed in 11 patients (7 with mucinous cystic neoplasms, 2 with serous cystadenomas and 2 with islet cell tumors), whereas 19 underwent resection of cystic tumors (pancreatoduodenectomy in 8 and distal pancreatectomy in 11). The mean groups did not differ with regard to age (57 years), gender (73% female), presentation (63% incidental), or site (43% head, neck, or uncinate). Patients undergoing enucleation had smaller tumors (2.2 vs. 4.7 cm, P<0.01) that were less likely to be in the tail (9% vs. 42%). Operative time was significantly shorter in the enucleation group (199 vs. 298 minutes, P<0.01). Blood loss also was significantly reduced in the enucleation group (114 vs. 450 ml, P<0.001). Pancreatic fistula rates (27% vs. 26%) and length of hospital stay (12.6 vs. 15.7 days) were similar in the two groups. Enucleation of benign cystic pancreatic neoplasms reduces operative time and blood loss without increasing postoperative complications or length of stay. Therefore enucleation should be the standard operation for small benign cystic neoplasms in the uncinate, head, neck, and body of the pancreas.

Adenoma, Islet Cell↗
PubMed2003

Gallbladder motility in agouti-yellow and leptin-resistant obese mice.

BACKGROUND: Obesity is a polygenic disorder that is associated with gallstone disease. We have previously shown that leptin deficiency in obese mice correlates with decreased gallbladder motility, suggesting that leptin plays a role in the link between gallstone disease and obesity. However, most obese humans are leptin-resistant, and relatively few are leptin-deficient. To confirm that leptin dysfunction is responsible for impaired gallbladder motility in obese mice, we hypothesized that leptin-resistant obese mice (Lep(db)) would have abnormal gallbladder motility while obese mice with intact leptin function (Agouti Yellow, A(y)) would have normal gallbladder motility. MATERIALS AND METHODS: Eighteen lean control (C57BL/6J), 10 A(y) and 12 Lep(db) female mice were fasted overnight, weighed, and livers and gallbladders were harvested. Liver weights and gallbladder volumes were measured. Gallbladder contractile responses (N/cm(2)) to acetylcholine (10(-5)M), neuropeptide Y (10(-8,-7,-6) M) and cholecystokinin (10(-10,-9,-8,-7)M) were determined in muscle bath chambers. Results were analyzed by analysis of various (ANOVA) and with the Mann-Whitney Rank Sum Test. RESULTS: Both Agouti yellow (A(y)) and leptin-resistant (Lep(db)) obese mice had body weights, liver weights and gallbladder volumes that were significantly greater (P < 0.01) than lean control mice. Leptin-resistant obese mice had gallbladder responses to acetylcholine, neuropeptide Y and cholecystokinin that were significantly less (P < 0.01) than both lean control and Agouti yellow obese mice. CONCLUSIONS: These data suggest that (1). leptin-resistant obese mice (Lep(db)) have abnormal gallbladder motility and (2). obese mice with normal leptin metabolism (A(y)) have normal gallbladder response to neurotransmitters. We conclude that leptin represents a link between obesity, gallbladder motility and gallstone formation.

Acetylcholine↗
PubMed2003

Leptin-resistant obese mice have paradoxically low biliary cholesterol saturation.

BACKGROUND: Human obesity is associated with leptin resistance, elevated serum glucose and lipids, hepatic steatosis, and cholesterol gallstone formation. These gallstones are thought to result from hypersecretion of biliary cholesterol as well as biliary stasis. Leptin-resistant Lep(db) obese mice, which are known to have elevated serum leptin, glucose, and lipids, as well as hepatic steatosis, should be an appropriate model for human gallstone formation. Therefore, we tested the hypothesis that leptin-resistant mice would have increased gallbladder volume, biliary cholesterol saturation, and cholesterol crystal formation. METHODS: Sixty lean control mice and 60 Lep(db) obese mice on a low cholesterol chow diet were studied. Gallbladder volumes were measured and bile was pooled to calculate cholesterol saturation index. Serum cholesterol, glucose, and leptin levels were determined from pooled serum. Hepatic fat vacuoles were counted. Bile from a second group of 90 lean control and 59 obese mice was observed microscopically for cholesterol crystal formation. RESULTS: Leptin-resistant obese mice have significantly higher serum cholesterol, glucose, and leptin levels, hepatic fat vacuoles, and gallbladder volume than lean control mice. However, biliary cholesterol saturation index and cholesterol crystal formation were significantly diminished in the obese mice. CONCLUSIONS: These data suggest that leptin-resistant Lep(db) obese mice have (1) increased gallbladder volume, (2) decreased biliary cholesterol saturation despite elevated serum cholesterol and hepatic steatosis, and (3) decreased in vitro cholesterol crystal formation. We conclude that the link between obesity and gallstone formation does not require hypersecretion of biliary cholesterol.

Animals↗
PubMed2002

Improved survival in resected biliary malignancies.

BACKGROUND: For many years the prognosis for patients with biliary malignancies has been poor. However, recent advances in radiology and laparoscopy have improved staging, and active biliary stent management may improve outcome in these patients. In the past the goal with surgery was to excise all gross tumor. Now, the surgical goal is to achieve negative microscopic margins even if a major hepatic resection is required. Similarly, chemotherapy or radiation was frequently given in isolation, but chemoradiation has become the standard. Therefore, the aim of this analysis was to determine whether survival has improved with better staging, active stent management, more aggressive surgery, and chemoradiation. METHODS: From 1990 through 2001, 140 patients with biliary malignancies were treated at the Medical College of Wisconsin. One hundred eleven malignancies were cholangiocarcinomas (intrahepatic, 22%; perihilar, 65%; and distal, 13%), and 29 were gallbladder (GB) cancers. Eighty-six of the 140 patients (61%) underwent exploration (intrahepatic, 58%; perihilar, 57%; distal, 67%, and GB, 72%). Forty-four of these 86 patients (51%) underwent resection (intrahepatic, 64%; perihilar, 41%; distal, 70%; and GB, 52%). Chemoradiation with confocal radiation, 5-fluorouracil, and gemcitabine was used more frequently in the patients resected since 1998. RESULTS: Thirty-day operative mortality was 4%. In the resected patients (n = 44) the 5-year actuarial survival was 31% and the median survival was 27.8 months. Patients resected between 1998 and 2001 (n = 25) had a median survival longer than 44 months with a 3-year actuarial survival of 70% as compared to patients resected between 1990 and 1997 (n = 19), who had a median survival of 13 months and a 3-year actuarial survival of 21% (P <.01). CONCLUSIONS: These data suggest that (1) approximately one third of patients with biliary malignancies have resectable disease and (2) surgery in carefully selected patients with adjuvant chemoradiation has improved survival in resected patients. We suspect that a combination of improved staging, active biliary stenting, safe but extensive surgery to obtain negative margins, and newer techniques for chemoradiation have resulted in improved outcomes for patients with biliary malignancies.

Aged↗
PubMed2002

Gallstones: genetics versus environment.

OBJECTIVE: The aim of this study was to determine if a significant genetic component contributes to the pathogenesis of symptomatic gallstones. SUMMARY BACKGROUND DATA: Gallstones represent a polygenic disorder that affects more than 30,000,000 Americans and results in more than 750,000 cholecystectomies in the United States annually. Risk factors include age, gender, race, parity, obesity, and diabetes. A family history of gallstones also has been identified as a risk factor suggesting that genetics play a role in gallstone formation. However, the role of genetics in the pathogenesis of gallstone formation has not been determined. METHODS: A gallbladder disease-specific questionnaire was administered to 904 healthy unrelated adult volunteers (association study). The questionnaire ascertained a history of cholecystectomy and gallstone disease in first-degree relatives, as well as medical history, demographic, and anthropometric data. A logistic regression model was used to identify risk factors for symptomatic gallstone disease in a multivariate analysis. A maximum likelihood based variance decomposition approach was then used in 1,038 individuals from 358 families (family study) to estimate the additive genetic heritability of symptomatic gallstone disease. RESULTS: In the association study significant risk factors for symptomatic gallstone disease were female gender (relative risk 8.8, P <.003), obesity (BMI > 30, relative risk 3.7, P <.001), age > 50 (relative risk 2.5, P <.001), and a positive family history of previous cholecystectomy in a first-degree family member (relative risk 2.2, P <.01). In the family study the additive genetic heritability of symptomatic gallstones was 29% (P <.02), age and gender were significant covariates and explained 9.3% of the phenotypic variation in gallbladder disease. CONCLUSIONS: These data suggest that genetic factors are responsible for at least 30% of symptomatic gallstone disease. However, the true role of heredity in gallstone pathogenesis is probably higher because data based on symptomatic gallbladder disease underestimates the true prevalence in the population.

Adolescent↗
PubMed2002

Surgical management of pancreatic cancer.

Pancreatic cancer is the fifth leading cause of cancer death in the United States, with an overall survival rate of 3%. Unfortunately, only a minority of patients present with localized disease amenable to surgical resection. Over the past 20 years, improvements in operative and perioperative management have led to a decrease in operative mortality, shorter hospital stay, and overall 5-year survival of approximately 20% in patients undergoing pancreaticoduodenectomy. Despite advances in nonoperative palliation, surgery continues to play an important role in the management of patients with locally advanced, unresectable pancreatic cancer.

Humans↗
PubMedDate not supplied

Choledochal cysts in western adults: complexities compared to children.

Choledochal cysts occur most frequently in East Asian children and rarely in Western adults. Over the past two decades, pediatric treatment has been standardized, but relatively little information is available on the management of Western adults with choledochal cysts. Therefore the aims of this analysis were to compare the presentation, management, and late results of Western adults and children with choledochal cysts. Records were reviewed of patients with choledochal cysts at three academic institutions in Wisconsin. Fifty-seven patients were identified, and 51 of these patients (89%) were managed surgically. Thirty-one patients (54%) were adults, and the adults were more likely to be male (29% vs. 4%, P<0.02). Pain (81% vs. 42%, P<0.01) and cholangitis (35% vs. 15%) were more common in adults. Forty-one patients (71%) had type I cysts, but type IVa or V cysts with dilated intrahepatic ducts were more common in adults (39% vs. 15%, P=0.05). Seventeen adults had undergone biliary surgery prior to referral compared to only four children (59% vs. 15%, P<0.01). Preoperative endoscopic or percutaneous stents were employed more commonly in adults (42% vs. 15%, P<0.01). Hospital mortality was 0%, and morbidity was low in both adults and children (25% vs. 8%). An associated biliary malignancy correlated with age (P<0.05): 0 to 30 years (0%), 31 to 50 years (19%), and 51 to 70 years (50%). In addition, adults were more likely to have late problems with cholangitis (19% vs. 4%, P<0.07) and secondary biliary cirrhosis (13% vs. 4%). This analysis suggests that compared to children, Western adults with choledochal cysts are more likely to have (1) type IVA or V cysts, (2) undergone prior surgery, (3) preoperative biliary stents, (4) an associated biliary malignancy, and (5) late hepatobiliary problems. We conclude that surgery in Western adults with choledochal cysts is frequently complicated and should be performed by specialists in complex biliary surgery.

Adult↗
PubMedDate not supplied

Insulin resistance causes human gallbladder dysmotility.

Obesity, diabetes, and hyperlipidemia are known risk factors for the development of gallstones. A growing body of animal and human data has correlated insulin resistance with organ dysfunction. The relationship among obesity, diabetes, hyperlipidemia, and abnormal gallbladder motility remains unclear. Therefore, we designed a study to investigate the association among obesity, insulin resistance, hyperlipidemia, and gallbladder dysmotility. One hundred ninety-two healthy adult nondiabetic volunteers were studied. Gallbladder ultrasounds were performed before and after a standardized fatty meal. A gallbladder ejection fraction (EF) was calculated, and an EF of < 25% was considered abnormal. Serum was analyzed for cholesterol, triglycerides, cholecystokinin, leptin, glucose, and insulin. The homeostasis assessment model (HOMA) was used to determine insulin resistance. The volunteers had a mean age of 38 years (range, 18-77), and 55% were female. Thirty subjects (15%) had gallstones and were excluded from the study. Thirty subjects (19%) had abnormal gallbladder motility (EF < 25%). In lean subjects (n = 96) fasting glucose was significantly increased in the 16 subjects with gallbladder EF < 25% versus the 80 subjects with gallbladder EF > 25% (109 +/- 20 mg/dl versus 78 +/- 2 mg/dl, P < 0.05). Similarly, the HOMA index was significantly greater in subjects with gallbladder EF < 25% versus gallbladder EF >25% (3.3 +/- 1.2 versus 2.0 +/- 0.2, P < 0.05). In obese subjects (n = 66), fasting glucose, insulin, and insulin resistance were not associated with a gallbladder EF < 25%. These data suggest that in lean, nondiabetic volunteers without gallstones, gallbladder dysmotility is associated with an elevated fasting glucose as well as a high index of insulin resistance. We conclude that insulin resistance alone may be responsible for gallbladder dysmotility that may result in acalculous cholecystitis or gallstone formation.

Adolescent↗
PubMedDate not supplied

American Hepato-Pancreato-Biliary Association: who are we and where are we going?

The American Hepato-Pancreato-Biliary Association (AHPBA) was initiated in 1994 following the first World Congress of the International Hepato-Pancreato-Biliary Association (IHPBA), which was held in Boston. Presently, the AHPBA has more than 500 dues-paying members whose median age is in the mid-40s. More than 90% of members reside in North America. Approximately 80% of members have completed a fellowship in transplantation, hepato-pancreato-biliary surgery and/or research, surgical oncology, gastroenterology, or laparoscopy. Approximately 90% have a faculty appointment with 80% of these being full-time faculty. More than half of the average AHPBA member's time is spent in patient care, but approximately 45% of time is divided equally among research, teaching, and administration. Approximately 85% of members perform biliary, 75% hepatic, and 45% pancreatic surgery, whereas 25% perform liver and pancreatic transplantation. Nearly 90% are members of the American College of Surgeons, two thirds The Society for Surgery of the Alimentary Tract, 60% the Association for Academic Surgery, and 40% the IHPBA. The AHPBA's vision is to be the leading American association devoted to hepato-pancreato-biliary education, research, surgical training, and patient care and to serve as the American chapter of the IHPBA. The AHPBA mission is as follows: (1) to disseminate knowledge of hepato-pancreato-biliary disease, techniques, and research; ( 2) to facilitate clinical trials in hepato-pancreato-biliary disease; (3) to coordinate advanced training in hepato-pancreato-biliary surgery; and (4) to foster excellence in the care of patients with hepato-pancreato-biliary disease. The AHPBA has strategic initiatives to increase membership, bring value to a journal affiliation, and enhance its education, research, and training missions through multiple collaborations and better communication.

Adult↗
PubMedDate not supplied

Cystic pancreatic neuroendocrine tumors: is preoperative diagnosis possible?

Pancreatic neuroendocrine tumors rarely undergo cystic degeneration leading to a radiologic appearance, which is often interpreted as a pancreatic mucinous cystadenoma or pseudocyst. We reviewed our experience with 38 neuroendocrine tumors, four of which were cystic, and 24 other cystic pancreatic tumors (mucinous cystadenoma [n = 5], cystadenocarcinoma [n = 6], serous cystadenoma [n = 3], solid/cystic papillary neoplasm [n = 3], intraductal papillary mucinous tumor [n = 6], and mucinous adenocarcinoma [n = 1]) managed operatively between 1990 and 2000. This review was undertaken to identify clinical and pathologic features useful for preoperative diagnosis of cystic neuroendocrine tumors. Two of the four patients with cystic neuroendocrine tumors presented with abdominal pain, one patient was asymptomatic, and one patient had hypoglycemia. Three of the four cystic neuroendocrine tumors were identified by CT scan, and none were biopsied preoperatively. Preoperative diagnoses included mucinous cystadenoma in two patients (n = 2), pancreatic cystic neoplasm in one patient, (n = 1) and insulinoma in one patient (n = 1). All four cystic neuroendocrine tumors were benign and were completely resected (distal pancreatectomy [n = 2], enucleation [n = 2]). Cystic neuroendocrine tumors are difficult to diagnose preoperatively because the majority of these tumors are nonfunctional, and CT does not differentiate these tumors from other cystic neoplasms. Cystic neuroendocrine tumors represent a subgroup of pancreatic cystic and neuroendocrine tumors with malignant potential. Their high resectability rate further supports the role of surgical exploration and resection in the treatment of pancreatic cystic neoplasms.

Adult↗
PubMedDate not supplied

Decreased gallbladder response in leptin-deficient obese mice.

Obesity is a major risk factor for gallstone formation, but the pathogenesis of this phenomenon remains unclear. Human data on gallbladder emptying are conflicting, and no animal data exist on the effect of obesity on gallbladder motility. Leptin, a hormone produced by adipocytes, is known to have central effects on neuropeptide Y and cholecystokinin, but the influence of leptin on the biliary effects of these hormones is unknown. Therefore we tested the hypothesis that leptin-deficient C57BL/6J-lep(ob) obese mice would have decreased gallbladder responses to excitatory stimuli. Twelve-week-old lean control (C57BL/6J) (n = 22) and C57BL/6J-lep(ob) obese (n = 20) female mice were fed a nonlithogenic diet. The mice were fasted overnight and underwent cholecystectomy. Whole gallbladders were placed in 3 ml muscle baths. After optimal length was determined with acetylcholine (10(-5) mol/L, responses to increasing doses of neuropeptide Y (10(-8) to 10(-6) mol/L) and cholecystokinin-8 (10(-10) to 10(-7) mol/L) were measured. Student's t test and two-way analysis of variance were used where appropriate. Results were expressed as Newtons per cross-sectional area. The lean control mice had significantly greater excitatory responses to acetylcholine than the obese mice (0.37 +/- 0.05 vs. 0.16 +/- 0.02, P < 0.01). The gallbladder responses were also greater when mice were treated with neuropeptide Y (10(-8) mol/L: 0.00 +/- 0.00 vs. 0.00 +/- 0.00, NS; 10(-7) mol/L: 0.12 +/- 0.02 vs. 0.05 +/- 0.01, P < 0.01; 10(-6) mol/L: 0.26 +/- 0.08 vs. 0.06 +/- 0.01, P < 0.01) and cholecystokinin (10(-10) mol/L: 0.27 +/- 0.04 vs. 0.13 +/- 0.02, P < 0.01; 10(-9) mol/L: 0.59 +/- 0.08 vs. 0.27 +/- 0.04, P < 0.01; 10(-8) mol/L: 0.80 +/- 0.11 vs. 0.37 +/- 0.05, P < 0.01; 10(-7) mol/L: 0.86 +/- 0.11 vs. 0.44 +/- 0.06, P < 0.01). These data suggest that genetically obese, leptin-deficient mice have decreased responses to acetylcholine, neuropeptide Y, and cholecystokinin. We conclude that decreased gallbladder motility contributes to the increased incidence of gallstones associated with obesity.

Animals↗
PubMedDate not supplied

Impaired intestinal cell proliferation and cell death in leptin-deficient obese mice.

BACKGROUND: After massive small-bowel resection and loss of absorptive capacity, residual intestine has compensatory ability to adapt by cellular hyperplasia and increased absorptive function. Growth factors have been shown to enhance intestinal adaptation, but the mechanisms involved are not well defined. Leptin has been shown to function as a trophic factor in the intestine and enhances carbohydrate absorption after small-bowel resection. Therefore, we hypothesized that leptin deficiency may impair the adaptive response by modulating cellular proliferation or cell death after small-bowel resection. METHODS: Twelve-week-old male lean control (C57BL/6J, n = 28) and leptin-deficient (Lep(ob), n = 24) obese mice underwent sham laparotomy, intestinal transection, or 50% proximal small-bowel resection. Mice were killed at 48 hours postresection, and remnant intestine was harvested. Phenotypic analysis to assess adaptation included characterization of cell proliferation (percentage BrdU incorporation), apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling assay), and morphometric response (villus height, crypt depth). RESULTS: The percentage S-bromodeoxyuridine (BrdU) incorporation and apoptotic indices of obese transected mice were significantly lower than lean transected mice (7.3 vs 21.9% and 0.70 vs 1.53% respectively, p < .05). In resected animals, the percentage BrdU incorporation and apoptotic indices of obese resected mice were significantly lower than for lean resected (6.1 vs 22.0% and 0.93 vs 1.80% respectively, p < .05). No differences between groups, regardless of surgery, were identified in villus height or crypt depth. CONCLUSIONS: Therefore, we conclude that leptin deficiency impairs both cell proliferation and cell death in the early adaptive period after either small-bowel transection or resection.

Adaptation, Physiological↗