Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia.

Pancreatic cancer (PC) is thought to develop through a series of duct lesions termed pancreatic intraepithelial neoplasia (PanIN). Characterization of the molecular pathology of these lesions may lead to additional understanding of pancreatic ductal carcinogenesis. We examined the protein expression of four functionally related genes, p21(WAF1/CIP1) (CDKN1A), p53, cyclin D1 (CCND1), and DPC4/Smad4 (MADH4), aberrations of which are associated with PC, within 451 PanIN lesions present in the pancreata of 60 patients. p21(WAF1/CIP1) overexpression was present in the normal ducts of 9% of patients and increased progressively to 16% of patients with PanIN-1A lesions, to 32% of patients with PanIN-1B lesions, 56% of patients with PanIN-2 lesions, 80% of patients with PanIN-3 lesions, and 85% of patients with invasive carcinomas (P < 0.01). p53 and cyclin D1 overexpression occurred predominantly in PanIN-3 lesions (P < 0.01), and loss of DPC4/Smad4 expression occurred predominantly in PanIN-3 lesions and invasive carcinoma (P < 0.01). In addition, p21(WAF1/CIP1) overexpression occurred independently of p53 and DPC4/Smad4 expression within invasive carcinoma and PanIN-3 lesions. Cyclin D1 overexpression or loss of DPC4/Smad4 expression was apparent in 85% of invasive carcinomas but in only 14% of PanIN-2 lesions. These data demonstrate that overexpression of p21(WAF1/CIP1) occurs early in the development of PanIN, before aberrations in p53, cyclin D1, and DPC4/Smad4 expression. p21(WAF1/CIP1) overexpression, independent of p53 and/or DPC4/Smad4 expression, may reflect increased Ras activity, either directly through activating K-ras mutations or as a consequence of HER-2/neu (ERBB2) overexpression, both of which are common in PC and in early events in the development of PanIN. These data support further the current progression model for PC and demonstrate that aberrant expression of key cell cycle regulatory genes may be important in the early development and progression of PanIN.

Incidence of deep vein thrombosis after laparoscopic vs minilaparotomy cholecystectomy.

OBJECTIVES: To determine the frequency of deep vein thrombosis (DVT) associated with minimally invasive cholecystectomy and to determine, using minilaparotomy cholecystectomy as a control operation, the influence of the laparoscopic pneumoperitoneum on DVT formation. DESIGN: Prospective nonrandomized control trial. SETTING: Tertiary care university hospital. PATIENTS: One hundred consecutive patients intended to undergo either laparoscopic cholecystectomy (59 patients) or minilaparotomy cholecystectomy (41 patients) with either of 2 surgeons were prospectively enrolled between April 1996 and April 1997. The minilaparotomy cholecystectomy group served as controls to isolate the effect of the pneumoperitoneum. Patient details, operative details, and any thromboembolic or bleeding complications were recorded. The same thromboprophylaxis regimen was prescribed for each group; namely, preoperative and postoperative subcutaneous low-molecular-weight heparin (LMWH), graduated compression stockings, and intraoperative intermittent calf compression. INTERVENTION: Minimally invasive cholecystectomy. MAIN OUTCOME MEASURE: Frequency of DVT. Bilateral lower limb venous color duplex scanning was used to detect DVT. Scans were performed on 3 occasions: (1) preoperatively on admission to hospital, (2) on the first postoperative day, and (3) between 2 and 4 weeks postoperatively. RESULTS: Three patients in the laparoscopic group and 2 patients in the minilaparotomy group underwent conversion to conventional open cholecystectomy. There were no significant differences between patients in the 2 groups for age, sex, body mass index, preoperative white blood cell count, platelet count, prothrombin time, or activated partial thromboplastin time. There were no significant differences between the 2 groups for elective vs emergency operations, public hospital vs private hospital admissions, or consultant vs resident surgeon. Macroscopic gallbladder pathology grades for both groups were not significantly different, and there was no significant difference in the duration of postoperative hospital stay. Operative cholangiography was performed in a significantly larger proportion of laparoscopic cases (86% vs 66% in the minilaparotomy group; chi(2) test, P=.002), and the duration of anesthesia was significantly longer for the laparoscopic operation (118 minutes vs 98 minutes; t test, P=.05). Ninety-seven patients received preoperative LMWH and all patients received graduated compression stockings, intraoperative intermittent calf compression, and postoperative LMWH. Two of the 100 patients had postoperative DVT, 1 after laparoscopic cholecystectomy and 1 after minilaparotomy cholecystectomy. Both DVTs were detected by duplex examination on the first postoperative day. The DVT found after laparoscopic cholecystectomy was in 1 of the 3 patients who did not receive preoperative LMWH. There were no DVTs in any of the 40 patients who had an additional duplex scan between 2 and 4 weeks after operation. CONCLUSIONS: Despite the theoretical risk of thromboembolic disease due to use of the laparoscopic pneumoperitoneum, the frequency of DVT after either laparoscopic cholecystectomy or minilaparotomy cholecystectomy is low if adequate thromboprophylaxis is provided.

Simplified EEA stapled anastomosis by the end-insertion technique.

A simplified technique for stapled esophagojejunal anastomosis after total gastrectomy using the GIA and EEA stapling instruments is described. The technique is also suitable for esophagogastric and ileorectal anastomosis.

Contact cholangiography.

A technic of intraoperative contact cholangiography is described in which a sterile wrapped film is placed behind the mobilized duodenum and common bile duct. In series of 120 cholecystectomies this technic, in conjunction with conventional cholangiography, allowed a low rate of exploration of the common bile duct (15 per cent) and has detected otherwise unsuspected stones in two patients.

Laparoscopic anatomy of the cystic artery.

Uncontrolled arterial bleeding during laparoscopic cholecystectomy is a serious problem and may increase the risk of bile duct damage. Therefore, accurate identification of the anatomy of the cystic artery is important. We reviewed the anatomy of the cystic artery and its variations as seen through the video laparoscope. A "normal" cystic artery was found in only 72% of patients. The most important laparoscopically noted variations were doubling of the cystic artery (22%) and an artery that ran inferior to the cystic duct (6%). Small branches of the cystic artery, which we suggest be named Calot's arteries, supply the cystic duct and may cause troublesome bleeding during laparoscopic dissection in the hepatobiliary triangle. A scissor dissection technique was found most useful for identifying the arterial anatomy. Careful identification of arterial anomalies should help to reduce the incidence of bile duct injuries during laparoscopic cholecystectomy.

Antral patch esophagoplasty. A new procedure for acid-peptic esophageal stricture.

Antral patch esophagoplasty is a new procedure for intractable fibrous stricture of the esophagus secondary to acid-peptic reflux. A full-thickness patch of gastric antrum, supplied by a pedicle based on the left gastroepiploic vessels, is inserted, mucosal surface to lumen, into the opened stricture. A fundoplication is done below the esophagoplasty to prevent reflux. The functional results were excellent in five of six patients. The procedure may have application also in other types of benign esophageal stricture.

Gastric patch esophagoplasty: an experimental study.

To determine whether the use of pedicled full-thickness gastric patches would be feasible and safe in esophageal reconstruction, studies were undertaken in eleven dogs. The results demonstrate that patches containing parietal cell mucosa are likely to produce localized adjacent esophagitis. Patches containing antral mucosa do not produce esophagitis and are not associated with a subsequent increase in circulating serum gastrin levels.

Suggested new rules for exploration of the common bile duct at cholecystectomy.

Traditional indications for exploration of the common bile duct have been made anachronistic by developments in operative cholangiography. A new technique of contact cholangiography, described in this paper, improves the precision of operative cholangiography and allows the traditional indications for exploration to be modified. A new set of guidelines for exploration of the common duct, based on high-quality operative cholangiography, is outlined, and the place of the supraduodenal and transduodenal routes for exploration is discussed. The results of the application of these policies in a series of 120 cholecystectomies are presented.

The gastrectomy cripple: results of jejunal loop interposition.

The use of an interposed antiperistaltic jejunal loop between the stomach and the duodenum in the treatment of severe postgastrectomy nutritional disorder is described in two patients. Both patients had a gratifying return of digestive comfort and a striking increase in weight after the interposition operation. Several aspects of operative technique are described. This procedure should be considered in any patient suffering from this disorder.

Laparoscopic intraperitoneal foreign body from adhesive drapes.

The present paper reports three cases where portions of adhesive drape were drawn into the peritoneal cavity during cannula insertion. If adhesive drapes are used it is recommended that generous skin incisions be made to avoid this complication.

Cherry stalk in the common bile duct.

Ingested biliary foreign bodies occur most frequently in patients who have had previous biliary operations, which predisposes them to enterobiliary reflux. This report describes an unusual ingested foreign body of the common bile duct in a patient with no history of previous gastrointestinal surgery.

Scissor dissection technique for laparoscopic cholecystectomy: an alternative to laser and electrocautery.

A sharp dissection technique, using specially designed curved insulated scissors, is described for use in laparoscopic cholecystectomy. This technique is a suitable alternative to laser and electrocautery, and produced a significant shortening of operating time.

Pregnancy complicated by an insulinoma.

The case of a 33-year-old patient suffering from severe hypoglycaemia due to an insulinoma during the first trimester of pregnancy is reported. The diagnosis was established on clinical grounds and by the demonstration of hypoglycaemia, inappropriate hyperinsulinism and an increase in the percentage of circulating proinsulin. Dietary therapy maintained blood glucose at a satisfactory level from the 9th to the 17th gestational week. Localization of the tumour was achieved at that time by limited CT scanning with a narrow field. A 2 cm tumour was removed from the head of the pancreas and the blood sugar levels and insulin secretion returned to normal. Pregnancy proceeded normally and a healthy male infant weighing 3,880g was delivered at term. Ten months after delivery both mother and child were well.