Transgenic mice containing a human heavy chain immunoglobulin gene fragment cloned in a yeast artificial chromosome.

We have developed a method for the introduction of yeast artificial chromosomes (YACs) into transgenic mice. An 85 kilobase (kb) fragment of the human heavy chain immunoglobulin gene was cloned as a YAC, and embryonic stem cell lines carrying intact, integrated YACs were derived by co-lipofection of the YAC with an unlinked selectable marker. Chimaeric founder animals were produced by blastocyst injection, and offspring transgenic for the YAC were obtained. Analysis of serum from these offspring for human heavy chain antibody subunits demonstrated expression of the YAC-borne immunoglobulin gene fragment. Co-lipofection may prove to be a highly-successful means of producing transgenic mice containing large gene fragments in YACs.

Intraoperative flexible choledochoscopy for intrahepatic and extrahepatic biliary calculi.

This prospective study evaluates the use of intraoperative flexible choledochoscopy in the detection and removal of additional stones after conventional bile duct exploration. The biliary system of 109 patients was examined with an Olympus CHF-B4 choledochoscope after conventional methods of exploration. Sixty-five patients had only common duct stones and 44 patients had intrahepatic stones with or without stones in the common duct. Additional stones were detected in 11 patients (16.9%) in the group with common duct stones; eight of these patients had their stones completely removed. Unsuspected residual stones were discovered by means of postoperative cholangiography in three more patients (4.6%); thus the total number of patients with residual stones was six (9.2%). Additional stones were detected in 39 patients (88.6%) in the group with intrahepatic stones. Of these, only 13 patients managed to be freed of stones with the use of the choledochoscope. A further 10 patients underwent liver resection to achieve stone clearance. Unsuspected retained stones were found postoperatively in seven of the 28 patients (25%) whose biliary systems were considered clear of stones. The overall number of patients with retained stones in the group with intrahepatic stones was 23 (52.3%). We concluded that intraoperative flexible choledochoscopy is useful in detecting intrahepatic stones left behind after conventional exploration. However, complete removal of the stones is difficult to achieve.

Malignant hilar biliary obstruction treated by segmental bilioenteric anastomosis.

Segmental bilioenteric anastomosis procedures were performed on 22 patients with malignant hilar biliary obstructions. The majority of the bypasses were done to the segment 3 duct and a single anastomosis was performed in each patient. The operative mortality rate was 13.6% and morbidity, 27.3%. The biliary obstruction was completely relieved in 5 patients, partially but satisfactorily relieved in 11 patients, and not relieved in 3 patients. The mean survival was 8 months, and the median survival was 6 months. Late complications were seen in 42% of the patients, and these complications included cholangitis, liver failure, and duodenal obstruction. An analysis of the operative results with respect to the presence of right and left ductal system communication showed that when communication was absent, there was a greater incidence of unsuccessful relief of the biliary obstruction. When communication was present, the incidence of late cholangitis that involved the undrained side was greater.

Treatment of hepatolithiasis: improvement of result by a systematic approach.

In previous decades the result of treatment of hepatolithiasis has been unsatisfactory. The incidence of residual stones after surgery might reach 77%. In the past 6 years we adopted a systematic approach comprised of accurate delineation of disease in the liver and biliary tract by direct cholangiography, ultrasonography, and computed tomography; tailored surgical treatment according to the extent of involvement of the liver and biliary tract; access to the intrahepatic ducts through the left duct or round ligament approach when there was difficulty with common bile duct exposure; routine use of flexible choledochoscopy; and application of electrohydraulic lithotripsy for large and impacted stones. Complete stone clearance was achieved in 114 of 127 patients (89.8%). Of those patients who had incomplete stone clearance, only six cases (4.7%) were related to technical failure of postoperative choledochoscopy. The incidence of stone recurrence was 15.8%, the lowest rate so far reported. It was the same regardless of whether a biliary drainage procedure had been performed, but the treatment for recurrent stones was facilitated by previous hepaticocutaneous jejunostomy. Overall the surgical treatment required for stone recurrence was of a lesser magnitude than that in the past.

Severe acute cholangitis: the role of emergency nasobiliary drainage.

The role of emergency endoscopic nasobiliary drainage (NBD) in the management of severe acute cholangitis was evaluated by comparing the outcome of 15 patients who underwent the procedure as an initial treatment with that of 20 patients who underwent emergency surgery. Biliary sepsis was successfully controlled without complication in all 15 patients by the insertion of a 7F nasobiliary catheter through a limited papillotomy. Subsequent definitive elective treatment included endoscopic stone clearance (n = 6), common duct exploration (n = 8), and bili-enteric reconstruction (n = 1). Among the 20 patients who had surgical treatment, cholecystectomy (n = 11), cholecystostomy (n = 1), and transhepatic intubation (n = 1) were done in addition to common duct exploration. Although patients undergoing endoscopic NBD were significantly older (75.3 years vs 60.1 years; p less than 0.05) and more jaundiced (total bilirubin, 120.3 mmol/L vs 70.4 mmol/L; p less than 0.05), comparable morbidity (40% vs 65%) and mortality (6.7% vs 20%) was observed. Initial endoscopic NBD provides a safe and effective therapeutic option for the management of fulminant biliary sepsis. Among patients with complicated ductal anatomy, endoscopic NBD should first be attempted because, when successful, definitive reconstruction may be performed on an elective basis. The value of its routine application for all patients, however, remains to be validated by further clinical studies.

Acute cholangitis secondary to hepatolithiasis.

In a series of 88 patients with acute cholangitis secondary to hepatolithiasis, 26 (30%) required emergency therapeutic intervention because of septicemic shock (n = 15), persistent fever (n = 8), or spreading peritonitis (n = 3). Analysis was made to define factors that predisposed to failure of conservative treatment and characteristics that could predict the need for emergency biliary decompression. The age, incidence of concomitant medical diseases, previous biliary surgery, positive blood culture, bacterial strains resistant to antibiotics used, and multiplicity of bacterial strains in bile cultures in patients who required emergency intervention were similar to these factors in patients who had elective operations after successful conservative management. The incidence of intrahepatic segmental obstruction by stones or strictures was similar, but many more patients who required emergency intervention had concomitant extrahepatic obstruction due to impacted common ductal stones or strictures. Logistic regression analysis of clinical, hematological, and biochemical data showed that maximum pulse rate within 24 hours of presentation (greater than 100 beats per minute, relative risk, 2.8) and platelet count at the time of admission (less than 150 x 10(9)/L, relative risk, 5.2) were the factors with independent significance in predicting the need for emergency therapeutic procedures. This finding may serve as a guideline for identifying high-risk patients for early intervention.

Late result of sphincteroplasty in the treatment of primary cholangitis.

Sphincteroplasty is one of the surgical procedures used in the treatment of primary cholangitis. We performed this operation on 342 patients over a 13-year period, with an operative mortality of 4.7%. Postoperative examination of 271 patients (average follow-up, seven years four months) showed that a good result was achieved in 226 patients, a fair result in 23 patients, and a poor result in 22 patients. Analysis of the reoperations in 17 patients showed that stone reformation is the most common finding, followed by sphincteroplasty stricture, liver abscess, and empyema of the gallbladder. When performed with proper indications in the management of primary cholangitis, sphincteroplasty is a safe procedure, and the majority of patients can expect good results.

Surgery during acute pancreatitis. Observations in 50 patients.

Surgery was performed during the acute phase of illness in 50 of 348 patients with acute pancreatitis. The operative mortality was 40 percent. Analysis of the indications for operation, the operative findings, and the mortality rate revealed that the suspected complications for which operation was planned were not always borne out by the operative findings. In addition, the deterioration of patients while being treated conservatively, or the presence of severe acute pancreatitis preoperatively, were not predictive of the finding of hemorrhagic or necrotizing pancreatitis at operation. In a significant proportion of patients with severe pancreatitis, the diagnosis of pancreatitis was first made at laparotomy. More use should be made of the newer investigative methods to better identify any complications which may have occurred and the necessity for operative intervention.

Bronchoscopy and carcinoma of the esophagus I. Findings of bronchoscopy in carcinoma of the esophagus.

Tracheobronchial involvement frequently occurs in patients with carcinoma of the esophagus. A study of the results of 525 bronchoscopies performed on patients with carcinoma of the esophagus who were evaluated for surgery revealed that abnormalities were found in 33.9 percent. The incidence was highest for those with cervical and upper-third thoracic tumors; however, a significant number of lower-third thoracic and abdominal tumors also showed abnormalities (12.5 and 5 percent, respectively). The incidence was also higher with large tumors, but again, a significant number of apparently small tumors also showed abnormalities. The abnormalities could be broadly classified into two groups: those showing only impingement and those showing actual invasion. Further studies are needed to determine whether the tumors with impingement are resectable.

Bronchoscopy and carcinoma of the esophagus II. Carcinoma of the esophagus with tracheobronchial involvement.

Involvement of the tracheobronchial tree, as observed through the bronchoscope, was in the form of impingement or invasion. Bronchoscopy was performed on 525 patients with carcinoma of the esophagus. Impingement was found in 91 patients and invasion in 87 patients. Forty-eight of the 63 patients with impingement and 7 of the 51 patients with invasion were found to have resectable tumors. Bypass operations were performed on the rest of the patients. The operative mortality was high for both bypass and resection procedures. The median survival for bypassed patients and resected patients were 4 months and 9 months, respectively. Four resected patients survived 3 years or more, 2 of whom had no evidence of recurrence. Most patients with impingement have resectable tumors and long-term survival is possible if the tumor can be resected.

Survival after surgery for advanced carcinoma of the stomach other than the cardia.

The survival of 103 patients operated on for advanced carcinoma of the stomach other than the cardia was assessed. The median duration of survival for patients subjected to palliative partial gastrectomy, total gastrectomy, gastrojejunostomy, and biopsy only was 24, 22, 11, and 10 weeks, respectively. All of these patients had definite residual tumor. In the 27 patients with preoperative signs of incurable tumor, the high operative mortality rate (19 percent), the low rate of resectability (26 percent), and the short duration of survival in the patients who had resection (median 11 weeks) combined lead to the conclusion that exploration for the possibility of resection is not worthwhile.

Pancreatic phlegmon: what is it?

In a retrospective study of 264 patients with acute pancreatitis, 22 were identified as having phlegmon by combined radiologic and clinical criteria. The radiologic criteria consisted of demonstration of abnormal lesion on computed tomography scan which was composed of masses of mixed density, free of extraluminal gas and lacking a well-defined wall. The clinical criteria was that the clinical course was free of sepsis. Half of the group thus identified had severe pancreatitis as defined as having three or more poor prognostic signs. Fever, leukocytosis, and serum amylase elevation persisted for a longer period than usual. Complication was infrequent but the lesion could persist for 3 to 4 months without producing symptoms. This is a relatively benign condition and surgery should be avoided.

Urgent biliary decompression after endoscopic retrograde cholangiopancreatography.

Acute cholangitis complicating diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is potentially fatal. Among 323 consecutive patients with proved biliary obstruction, 21 (7 percent) developed acute cholangitis after examination. Four patients underwent emergency surgery for the control of sepsis with two deaths. Of the 21 parameters chosen for evaluation, malignant obstruction, fever (higher than 37.5 degrees C) within 72 hours before the procedure or when afebrile, and an increased aspartate transaminase level of 70 IU or more were the independent predictive factors identified by multivariate analysis. An increased temperature should be regarded as an absolute contraindication to examination unless followed by immediate ductal drainage. Since the risk of septic complications is minimal when none of the risk factors are present, routine urgent biliary decompression after ERCP is probably unnecessary for these selected patients. For patients with malignant obstruction or other risk factors, early elective surgical drainage is advisable. When surgery is not feasible, nonoperative drainage of the obstructed biliary system as a preventive measure might be considered.

Regional chemotherapy for recurrent squamous head and neck cancers through a saphenous vein interposition graft.

Regional chemotherapy for head and neck cancers is effective, but the intra-arterial catheter is not without problems. We interposed a segment of saphenous vein within the carotid system to administer chemotherapeutic agents percutaneously via the arterialized venous segment. From 1983 to 1990, saphenous vein interposition graft was performed after radiotherapy in 24 patients with persistent or recurrent squamous head and neck cancers, which were also considered unresectable. There was no operative mortality. Two patients developed thrombosed vein graft; another two had wound infection; and one patient had a neck hematoma. Cisplatin was administered percutaneously every week via the saphenous vein graft. The response rate was 64% (complete response, 23%; partial response, 41%), and the 5-year actuarial survival rate was 31%. The 1-year survival rates for patients with complete, partial, and no response were 80%, 33%, and 13%, respectively. Saphenous vein interposition graft is a safe and convenient way of delivering intra-arterial chemotherapy, and it provides significant palliation for patients with recurrent nonresectable squamous head and neck cancers after radiotherapy.

Cholangiographic appearance in clonorchiasis.

Clonorchiasis may lead to cholangitis. Clonorchis sinensis infiltration of the biliary system produces an easily recognisable cholangiographic picture. The findings consist of characteristic filling defects and changes in the intrahepatic and extrahepatic ducts. The filling defects are usually small and irregular and the size is uniform. The change in the intrahepatic ducts consists of ductal dilatation involving especially the smaller ducts, apparent elongation, tortuosity and duct wall irregularities. The changes in the extrahepatic ducts consist mainly of duct wall irregularities and a mild degree of dilatation. The recognition is important as the management may have to be modified if cholangitis is the result of clonorchiasis alone.

Childhood recurrent pyogenic cholangitis.

Recurrent pyogenic cholangitis (RPC) is characterized by repeated attacks of bacterial infection of the biliary tract by enteric organisms resulting in formation of strictures and stones in the intrahepatic as well as the extrahepatic bile ducts. Between 1973 and 1984, we managed ten children with RPC. Presentation was acute, septicemia being invariably present. Four children responded to vigorous intravenous (IV) fluid and antibiotic therapy; of these, three subsequently required elective transduodenal sphincteroplasty. Six children required emergency biliary tract decompression surgically and three of them also had concomitant definitive drainage procedures (transduodenal sphincteroplasty, two; supraduodenal choledochoduodenostomy, one). The other three had T-tube drainage initially followed by elective drainage procedures (transduodenal sphincteroplasty, one; supraduodenal choledochoduodenostomy, two). At exploration, pigment stones and/or mud were invariably present in the bile ducts. One child required reexploration for hemostasis following sphincteroplasty, and one child died from septicemia and respiratory failure following operation. The rest are well, having been followed for 3 to 12 years. Major advances in recent years include (1) endoscopic retrograde cholangiopancreatography (ERCP) for accurate definition of the biliary tract and confirmation of the presence and location of stones during the quiescent phase, (2) the intraoperative choledochoscopic extraction of intrahepatic and extrahepatic stones, and (3) postoperative stone removal via the T-tube tract.

Results of surgical resection for hepatocellular carcinoma.

The results of surgical resection in 174 patients with hepatocellular carcinoma was studied. The patients included 147 male and 27 female with a mean age of 54 years. Serum alfa-fetoprotein was elevated in 74% and 67% had liver cirrhosis. The operative morbidity was 46.6% and 30 day mortality was 13.2%. The most common complications were hemorrhage and liver failure. The five and eight year survival rates were 15% and 12% respectively. Long survival of more than ten years was possible after resection of large tumours, even in patients with liver cirrhosis.

Surgical resection for hepatocellular carcinoma.

The result of liver resection for symptomatic hepatocellular carcinoma (HCC) is poor. For Oriental patients, the operative mortality is between 6.7% and 36%. The one-year and five-year survival are 40% and 15% respectively. Coexisting liver cirrhosis is a problem and is responsible for the high operative mortality as well as a significant proportion of late deaths. Technical innovations are being applied to liver resection but further evaluation is necessary to prove their claimed efficacy. Screening of the whole population or high risk individuals enable HCC to be detected early. Most tumours discovered by screening is resectable and the prognosis is better. More efforts should be directed toward improving the accuracy and yield of screening procedures.