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Biomedical subjects

J L Cameron

Publications and source records attributed to J L Cameron.

At least 109 records · Page 6Linked to original sources

A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy.

OBJECTIVE: The authors hypothesized that pancreaticogastrostomy is safer than pancreaticojejunostomy after pancreaticoduodenectomy and less likely to be associated with a postoperative pancreatic fistula. SUMMARY BACKGROUND DATA: Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy, occurring in 10% to 20% of patients. Nonrandomized reports have suggested that pancreaticogastrostomy is less likely than pancreaticojejunostomy to be associated with postoperative complications. METHODS: Between May 1993 and January 1995, the findings for 145 patients were analyzed in this prospective trial at The Johns Hopkins Hospital. After giving their appropriate preoperative informed consent, patients were randomly assigned to pancreaticogastrostomy or pancreaticojejunostomy after completion of the pancreaticoduodenal resection. All pancreatic anastomoses were performed in two layers without pancreatic duct stents and with closed suction drainage. Pancreatic fistula was defined as drainage of greater than 50 mL of amylase-rich fluid on or after postoperative day 10. RESULTS: The pancreaticogastrostomy (n = 73) and pancreaticojejunostomy (n = 72) groups were comparable with regard to multiple parameters, including demographics, medical history, preoperative laboratory values, and intraoperative factors, such as operative time, blood transfusions, pancreatic texture, length of pancreatic remnant mobilized, and pancreatic duct diameter. The overall incidence of pancreatic fistula after pancreaticoduodenectomy was 11.7% (17/145). The incidence of pancreatic fistula was similar for the pancreaticogastrostomy (12.3%) and pancreaticojejunostomy (11.1%) groups. Pancreatic fistula was associated with a significant prolongation of postoperative hospital stay (36 +/- 5 vs. 15 +/- 1 days) (p < 0.001). Factors significantly increasing the risk of pancreatic fistula by univariate logistic regression analysis included ampullary or duodenal disease, soft pancreatic texture, longer operative time, greater intraoperative red blood cell transfusions, and lower surgical volume (p < 0.05). A multivariate logistic regression analysis revealed the factors most highly associated with pancreatic fistula to be lower surgical volume and ampullary or duodenal disease in the resected specimen. CONCLUSIONS: Pancreatic fistula is a common complication after pancreaticoduodenectomy, with an incidence most strongly associated with surgical volume and underlying disease. These data do not support the hypothesis that pancreaticogastrostomy is safer than pancreaticojejunostomy or is associated with a lower incidence of pancreatic fistula.

Anastomosis, Surgical↗

The current management of carcinoma of the head of the pancreas.

Carcinoma of the head of the pancreas can be diagnosed and staged effectively by computed tomography (CT) scan and by visceral angiography. If the tumor appears to be resectable, no further studies such as percutaneous biopsy are required. Pancreaticoduodenectomy is the only potentially curable treatment. This operation can be performed with a hospital mortality rate of approximately 2%. If the resection is curative, five-year survival in excess of 20% can be anticipated. Utilizing multivariate analysis, negative lymph node status, the absence of microscopic evidence of blood vessel involvement, and two or fewer blood transfusions during surgery are all independent predictors of long-term survival. Adjuvant therapy is effective and should be used routinely.

Chemotherapy, Adjuvant↗

Pancreaticogastrostomy and the Whipple procedure: radiographic appearance and complications.

PURPOSE: To evaluate the radiographic appearance of a pancreaticogastrostomy (PG) and its complications. MATERIALS AND METHODS: Seventy-two patients underwent pancreaticoduodenectomy and PG or pancreaticojejunostomy. Those who underwent PG and were evaluated postoperatively with T-tube cholangiography and upper gastrointestinal (UGI) series constitute the study group (n = 22; 10 men, 12 women; age range, 33-88 years). RESULTS: Twenty-one of the patients had a gastric filling defect radiographically detected. Four patients had clinically apparent delayed gastric emptying and one patient had a clinically apparent pancreatic fistula not detected radiographically. Two patients outside the study group had complications: One had a pancreatic fistula seen only with sinography, and one had a PG leak seen only with repeat UGI series and computed tomography (CT). CONCLUSION: PG caused a gastric filling defect in most patients. Suspected pancreatic fistulas are best confirmed with sinography, and suspected PG leaks may require repeat evaluation and CT. Clinical findings of delayed gastric emptying do not correlate with findings of UGI.

Adult↗

Potentially resectable pancreatic adenocarcinoma: spiral CT assessment with surgical and pathologic correlation.

PURPOSE: To evaluate the accuracy of spiral computed tomography (CT) in assessing the resectability of small pancreatic ductal adenocarcinoma and to correlate the CT findings with histopathologic and surgical findings. MATERIALS AND METHODS: Spiral CT scans obtained in 64 patients who underwent surgery for potentially resectable pancreatic adenocarcinoma were prospectively assessed for tumor resectability. CT findings were correlated with surgically assessed extent of tumor and pathologic findings. RESULTS: Fifty-seven (89%) of 64 carcinomas were detected with spiral CT. Twenty-four carcinomas were resectable at surgery and 40 were not. The average size of resectable tumors was 3.1 cm (range, 1.0-7.5 cm). The overall accuracy of spiral CT for assessing resectability was 70%. Of resected tumors, 14 were hypoattenuating compared with the remaining pancreas and 10 were isoattenuating. Eleven tumors showed neointimal proliferation in arterioles at histologic examination. CONCLUSION: Further progress in preoperative staging of pancreatic ductal adenocarcinoma with spiral CT should be directed toward improving detection of small pancreatic tumors and assessment of early metastatic disease.

Adenocarcinoma↗

The role of pancreaticoduodenectomy for locally recurrent or metastatic carcinoma to the periampullary region.

BACKGROUND: The efficacy of operative resection of metastatic lesions to the liver, lung, and brain is well established. However, the appropriate management of metastatic or locally recurrent malignancies to the periampullary region is less well established. STUDY DESIGN: A retrospective review of The Johns Hopkins Hospital experience with pancreaticoduodenectomy for metastatic or locally recurrent periampullary lesions was performed. RESULTS: From 1988 to 1993, 27 patients with a past history of malignancy underwent pancreaticoduodenectomy. In six patients (22 percent), the lesion was determined to be from a metastasis or a local recurrence, and in 21 patients (78 percent), the lesion was a new primary. Patients with metastatic or locally recurrent lesions were younger (51.3 compared to 67.1 years of age) and presented with a shorter interval from their initial neoplasm (33 compared to 120 months). Of the six patients undergoing pancreaticoduodenectomy for a metastatic or locally recurrent lesion, three patients are alive an average of 38 months and three patients died an average of 11 months postoperatively. This compares favorably with the survival rate of the new primary group in which 12 patients are alive a mean of 22 months and nine patients died a mean of 14 months postoperatively. CONCLUSIONS: These results suggest that patients with metastatic or locally recurrent lesions in the periampullary region from a previously treated neoplasm should be considered candidates for pancreaticoduodenectomy.

Actuarial Analysis↗

Overexpression of p53 protein in adenocarcinoma of the pancreas.

Mutations in the p53 tumor suppressor gene are frequently identified in human neoplasms. These mutations may be associated with stabilization and, therefore, with overexpression of the p53 protein product as determined by immunohistochemical staining. Using a new antigen retrieval method and a polyclonal antibody to p53 (CM-1), the authors examined 48 formalin-fixed paraffin-embedded adenocarcinomas of the pancreas for overexpression of the p53 gene product. These 48 carcinomas were obtained from a series of patients with well-documented clinical histories and extensive follow-up. The carcinomas had been analyzed previously for K-ras gene mutations, tumor ploidy, and tumor proliferating index. Specific diffuse nuclear staining for the p53 protein was identified in 19 of the 48 (40%) infiltrating carcinomas examined. Focal or negative staining was seen in the remaining 29 cases (60%). In addition, 17 of the neoplasms contained synchronous in situ carcinomas; two (12%) of these displayed diffuse nuclear staining for the p53 protein. Overexpression of p53 was associated with aneuploidy (P = .05), which had been a poor prognosticator in this series of adenocarcinomas of the pancreas. Although overexpression of p53 appeared to be associated with poor prognosis (hazard ratio, 1.8; P = .07), this was not statistically significant. Overexpression of p53 was not significantly associated with K-ras oncogene mutations or tumor proliferating index. The authors conclude that overexpression of the p53 protein occurs frequently in invasive adenocarcinomas of the pancreas and in some in situ carcinomas, as well.

Adenocarcinoma↗

Induction of anaerobic glucose metabolism during the development of acute pancreatitis.

OBJECTIVE: Studies were performed with the ex vivo perfused canine pancreas preparation to characterize acinar cell metabolism during the development of acute pancreatitis. SUMMARY BACKGROUND DATA: Acute pancreatitis can be initiated in the ex vivo perfused canine pancreas preparation by five different stimuli as follows: (1) the infusion of oleic acid (FFA), (2) partial obstruction of the pancreatic duct and secretin stimulation (POSS), (3) a 2-hour ischemic period before perfusion (ISCH 2), (4) a 1-hour ischemic period followed by acetaldehyde infusion (ISCH 1 + AA), and (5) supramaximal stimulation by cerulein (CER-HIGH). In each model, weight gain, edema formation, and hyperamylasemia occur, signifying the development of pancreatitis. Previously, the authors demonstrated that intracellular adenosine triphosphate (ATP) levels decline during the development of pancreatitis in the FFA model but not in the other four models. METHODS: The ex vivo perfused canine pancreas preparation was used to study five different stimuli that result in the initiation of acute pancreatitis, as manifested by weight gain, edema formation, and hyperamylasemia during a 4-hour perfusion period. Glucose metabolism (using 13C-labeled glucose) and intracellular pH and ATP levels were monitored by magnetic resonance spectroscopy. Oxygen consumption and pancreatic secretion were measured directly. RESULTS: In control preparations, a glucose signal appeared in the 13C-labeled spectra within 15 minutes, and a signal from glycogen appeared at the end of the 4-hour perfusion. In the preparations with an ischemic period (ISCH 2 and ISCH 1 + AA), a lactate signal appeared during the ischemia, disappeared during the early perfusion, and appeared again later during the perfusion as the physiologic injury response of pancreatitis developed. Similarly, in the POSS and CER-HIGH pancreatitis preparations, lactate accumulated in the pancreas during the perfusion period. In these four preparations, the intracellular pH did not differ significantly during the perfusion from that of the control preparations. Oxygen consumption was unchanged during the perfusion in the ISCH 2 and ISCH 1 + AA preparations and increased in the POSS and CER-HIGH preparations. In the FFA pancreatitis preparations, only a trace of glycogen was observed, and the metabolites of glucose were not detected. Intracellular pH and oxygen consumption both dropped significantly during the perfusion. CONCLUSIONS: In four of the five acute experimental pancreatitis models, anaerobic glucose metabolism was induced, despite continuous oxygen extraction by the pancreas. This induction of anaerobic glucose metabolism may be important in maintaining normal levels of intracellular ATP early after the induction of pancreatitis because the absence of anaerobic glucose metabolism in the FFA model was associated with a remarkable decrease in intracellular ATP levels and pH. The FFA model of pancreatitis is the most severe of the five models.

Acute Disease↗

Altered angiotensin-II receptors in human hepatocellular and hepatic metastatic colon cancers.

OBJECTIVE: To characterize angiotensin-II receptor density and affinity in normal and cirrhotic livers and in hepatocellular and metastatic colorectal cancer. SUMMARY BACKGROUND DATA: Several studies have indicated a possible beneficial effect of angiotensin-II as a biologic response modifier in the treatment of hepatic or metastatic colon cancer. This is based on evidence that angiotensin-II will cause a selective increase in arterial vasoconstriction in normal liver compared with tumor. METHODS: Human hepatoma (5), metastatic colon (10), or cirrhotic (3) liver was obtained. Non-tumor-bearing regions served as normal liver. Angiotensin-II receptor binding was determined on membranes with 125I-angiotensin-II and in situ studies were performed using the biotin-avidin detection system. RESULTS: Angiotensin-II receptor density was markedly down-regulated in tumor compared with normal or cirrhotic liver. CONCLUSIONS: A loss of angiotensin-II receptors occurs on the neovasculature of hepatic tumors.

Adult↗

Intrahepatic stones. The transhepatic team approach.

OBJECTIVE: The authors reviewed the combined interventional radiologic and surgical management of 54 patients with intrahepatic stones at the Johns Hopkins Hospital. The team approach used large-bore transhepatic stents to access the intrahepatic ducts until they were stone free. SUMMARY BACKGROUND DATA: Intrahepatic stones are uncommon in western countries. As a result, few American institutions have had much experience, and multiple management algorithms have been suggested. Nonoperative, operative, and combination surgical and nonoperative approaches have been advocated. At Johns Hopkins, combined surgical and percutaneous management has been used for 18 years. METHODS: This team approach includes (1) percutaneous placement of transhepatic access catheters, (2) surgery for underlying biliary disease and stone removal, and, when necessary (3) postoperative percutaneous choledochoscopy and stone removal through the transhepatic stents. RESULTS: The median age of the 54 patients was 50 years, and 32 were men. Biliary disease included 27 benign strictures, 7 sclerosing cholangitis, 5 choledochal cysts, 5 parasitic infections, 5 choledocholithiasis, and 5 biliary tumors. Fourteen patients (26%) were treated exclusively with percutaneous techniques. Forty patients (74%) had surgery, including 36 Roux-en-Y hepatico- or choledochojejunostomies with large-bore transhepatic stents. Eighteen of these 40 patients (45%) with multiple intrahepatic stones, strictures, or both required additional procedures after operation. No hospital deaths occurred after any of the percutaneous or surgical procedures. With a mean follow-up of 60 months, 94% of patients were stone free, 87% of patients were symptom free, and 73% have had their transhepatic stents removed. CONCLUSIONS: A combined radiologic and surgical approach with transhepatic stents is a safe and effective method for managing intrahepatic stones.

Adult↗

Choledochal cyst disease. A changing pattern of presentation.

OBJECTIVE: The authors compared the presentation, treatment, and long-term outcome of children and adults with choledochal cysts. SUMMARY BACKGROUND DATA: The typical patient with choledochal cyst disease has been the female infant with the triad of jaundice, an abdominal mass, and pain. However, the recent experience of the authors suggested that the disease currently is recognized more commonly in adults. METHODS: Forty-two patients (11 children, 32 adults) with choledochal cyst disease were treated primarily at this institution between 1976 and 1993. Patients presentation, clinical evaluation, and operative treatment were obtained from existing records. Long-term follow-up was obtained by records, physician, or direct patient contact. RESULTS: One child--but no adults--had the classic triad of jaundice, abdominal mass, and pain. Children were more likely to have two of the three signs or symptoms (82% vs. 25%; p = < 0.05). Adult patients most commonly had abdominal pain and were thought to have pancreatitis (23%) or acute biliary tract symptoms, prompting cholecystectomy (50%). The type of choledochal cyst seen in children and adults was similar; the fusiform extrahepatic (Type I) was most common (50%), and the combined intrahepatic and extrahepatic (Type IVA) was the next most prominent (33%). For both children and adults, treatment consisted of excision of the cyst and biliary reconstruction with a hepaticojejunostomy. There was no surgical mortality. Gallbladder or cholangiocarcinoma was identified in three adults (9.7%), two of which were manifest on presentation. Long-term follow-up revealed one patient with a biliary stricture and three patients with Type IVA cysts who had intrahepatic stones. CONCLUSIONS: Children and adults differ in presentation of choledochal cysts, with adults commonly having acute biliary tract or pancreatic symptoms. Surgical treatment with cysts excision and biliary bypass is safe and effective in children and adults with excellent long-term results that minimize the development of malignancy.

Adolescent↗

Effect of cysteamine injection on vasopressin and oxytocin biosynthesis in rat hypothalamus.

Cysteamine (CSH), a sulfhydryl agent that promotes disulfide-exchange reactions, was studied for its effects on the immunoreactive (IR) levels and synthesis of oxytocin and vasopressin in the hypothalamus. CSH injection (300 mg/kg s.c.) caused a rapid (1 h) suppression of 35S-cysteine incorporation into hypothalamic arginine vasopressin (VP) and oxytocin (OT). The reduction in labeling persisted for about 8 h; label incorporation was normal within 10 h of CSH administration. The drug did not influence 35S-cysteine incorporation into acid-precipitable protein, nor did it influence 35S-cysteine specific activity in the hypothalamus. In addition, 35S-VP and 35S-OT molecules could not be recovered from hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing and then reoxidizing conditions. Despite the reduction in peptide labeling, CSH treatment produced no alterations in the IR VP and OT contents of hypothalamus or posterior pituitary. These results indicate that CSH causes a true suppression of both VP and OT formation in hypothalamus, and suggest that the effect is either too transient to promote a reduction in endogenous stores of either peptide, or that the drug equally inhibits peptide production and removal (i.e., axonal transport, secretion).

Animals↗

Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation.

BACKGROUND: Several nonoperative and operative options are available for palliation of patients with unresectable hilar cholangiocarcinoma. This retrospective analysis compares the results of nonoperative percutaneous stenting and operative palliation in 65 patients. METHODS: Twenty-one patients were managed with percutaneous biliary stents (group A), and 44 patients underwent laparotomy (group B) with placement of large-bore silicone rubber transhepatic stents in 33. The two groups were similar with respect to age, gender, mean laboratory data, and cholangiographic extent of tumor. RESULTS: Group A and group B patients were comparable in hospital morbidity (67% vs 61%), hospital mortality (14% vs 7%), and mean initial hospital stay (27 vs 31 days). Survival was greater in group B laparotomy patients at 1, 3, and 6 months (p < 0.01), and median survival was 5 months for group A compared with 8 months for group B patients (p = 0.06). Group A patients who were managed with percutaneous stents required more stent changes per month of survival (0.5 vs 0.3, p = 0.06). However, group B patients who underwent operative palliation were more likely to undergo a second operation (0% vs 21%, p = 0.05), most often for duodenal or small-bowel obstruction. CONCLUSIONS: Operative placement of large-bore transhepatic stents may reduce cholangitis, delay hepatic failure, and prolong survival. We conclude that patients with unresectable hilar cholangiocarcinoma who are fit for surgery may benefit from operative palliation.

Adult↗

Surgery--still an "old boys' club"?

BACKGROUND: Currently more than 40% of first-year medical students are female, yet less than 20% of those entering surgical residencies are women. It has been suggested that the surgical environment experienced during medical school clinical clerkships may be perceived as being unfavorable to female students, thus accounting for this disparity. METHODS: One hundred and five medical students at The Johns Hopkins University School of Medicine responded to a questionnaire administered before graduation to assess career choice, the influence of a number of conditions on choice of specialty, the perception of a specialty's attitudes toward their gender, and the students' experiences during clinical rotations. RESULTS: Thirty-four percent of men and 13% of women chose surgery or one of its subspecialties as their career (p < 0.01). Eighty-seven percent of women responding perceived a specialty as unfavorable toward their gender versus 21% of men (p < 0.0001). None of the men believed that surgery was unfavorable toward their gender, whereas 96% of these women believed that surgery was unfavorable (p < 0.00001). Fifty percent of women felt out of place on a clinical service, with 92% of these having this perception on a surgical service. Only 9% of men ever felt out of place on a clinical service (p < 0.0001), and none of the men felt out of place in surgery (p < 0.0001). CONCLUSIONS: Female medical students perceive a gender bias on surgical services, suggesting that an "old boys' club" attitude may still exist in surgery.

Female↗

Detection of K-ras mutations in mucinous pancreatic duct hyperplasia from a patient with a family history of pancreatic carcinoma.

Mutations in the K-ras oncogene and in the p53 tumor suppressor gene are commonly identified in sporadic cases of pancreatic adenocarcinoma. Although these genes might serve as useful markers for early diagnosis of pancreatic carcinoma in patients at risk for the development of this disease, familial pancreatic carcinomas have not been studied for these mutations. We recently had the opportunity to examine a pancreas prophylactically removed from a patient with a strong family history of pancreatic carcinoma. This gave us the unique opportunity to study the early events in the development of familial adenocarcinoma of the pancreas. Histopathological examination of the pancreas revealed multifocal papillary and nonpapillary mucinous duct hyperplasia. Seven of these foci were microdissected and analyzed for K-ras and p53 mutations. The K-ras mutations were detected by combined mutant-enriched polymerase chain reaction-restriction fragment length polymorphism analysis and characterized further by allele-specific oligonucleotide hybridization. Five of the seven duct lesions harbored activating point mutations in codon 12 of K-ras; a G to A transition was found in four and a G to C transversion in one. In contrast, these lesions did not harbor detectable p53 mutations as determined by denaturing gradient gel electrophoresis of exons 5 to 8, nor was there overexpression of the p53 protein as determined by immunohistochemistry. These findings suggest that mutations in K-ras represent an early event in the pathogenesis of pancreatic carcinoma. In addition, monitoring of patients with a strong family history of pancreatic carcinoma for K-ras mutations may identify patients at risk for the development of invasive carcinoma.

Base Sequence↗