Preservation of the pylorus and resection of the head of the pancreas

The historical evolution of the pylorus-preservation resection of the head of the pancreas is traced from the first resections early in this century to relative standardization of the operation, to a lowering of the operative mortality, and to an interest in improving nutritional status after resection. There are many theoretical advantages for the function of the upper gastrointestinal tract after pylorus and gastric preservation, such as maintenance of gastric capacitance and equilibration of osmotic pressure in gastric digestants, foodstuff digestion and absorption, and bowel motility. After the pylorus-preserving resection, gastric emptying is normal, pyloric function to prevent duodenal reflux is often normal, and gastric acids and serum levels of duodenal hormones are at normal levels, whereas after standard pancreatoduodenectomy, all of these are often abnormal. No prospective blinded studies have been published comparing nutritional values after the two operative procedures, but evidence is presented of a satisfactory result with regard to gastric capacitance, body weight gain, and lack of postgastrectomy symptoms. An undoubted advantage of the pylorus-preserving feature is a simplification of the operation. These gains are achieved without increase in operative mortality, without increase in the incidence of jejunal ulcer, and without theoretical or actual decrease in value of the procedure as a cancer operation, except in patients with duodenal carcinoma proximal to the ampulla of Vater.     

Preservation of the pylorus during pancreaticoduodenectomy —Evolution and current indications

The Whipple procedure has been improved by preservation of afunctioning pylorus. A functioning pylorus is important because marginal ulceration is avoided and, compared to the standard Whipple procedure with hemigastrectomy, more patients can gain weight postoperatively. The most common indications for this procedure are severe complication of chronic pancreatitis and periampullary tumors. In patients with pancreatic adenocarcinoma, the pylorus-preserving variety results in equal or better survival rates than those of the standard Whipple procedure with hemigastrectomy. Surgery alone is not sufficient to improve survival rates in patients with adenocarcinoma of the pancreas. Improved imaging modalities are required to diagnose the disease earlier. The most likely combination of treatment to prolong survival time is a combination of resection for cure in a patient with an early diagnosis plus an aggressive adjuvant chemoradiotherapy protocol. This protocol is most likely to be completed if a patient has preserved endocrine, exocrine, and digestive ability. A radical (R1) pylorus-preserving Whipple procedure would have the following advantages to result in the best survival rates — the patients can gain weight and thereby withstand the chemoradiotherapy protocol while, at the same time, the weakest aspect of the radical resection is addressed, i.e., the retroperitoneal margin of the pancreatic head.     

The anatomy of the parapancreaticoduodenal vessels and the introduction of a new pylorus-preserving pancreatoduodenectomy with increased vessel preservation

Classical pancreaticoduodenectomy for malignant tumors of the pancreatoduodenal region or chronic pancreatitis has recently been discussed in terms of the quality of life, associated with long-term postoperative morbidity. Pylorus-preserving pancreatoduodenectomy (PPPD) for the patient with chronic pancreatitis was first reported by Traverso and Longmire. Since that time, PPPD has become an accepted surgical procedure that is being increasingly indicated for certain malignancies. Herein, we report a PPPD that also preserves the parapancreatoduodenal vessels. The reasons why PPPD with the preservation of these vessels is significant are related to the length of the preserved duodenum and the reactions of gastrointestinal hormones. However, it may appear that this new PPPD poses a little greater risk of cancer recurrence, since the surgery is less radical than the usual PD. If the indications listed below are strictly observed, this operation should enable. The indications are: (1) chronic pancreatitis with tumor formation in the pancreatic head, (2) ampullary carcinoma, (3) inferion biliary duct carcinoma, (4) early duodenal carcinoma (all without pancreatic invasion), and (5) certain benign cystic tumors. Whether this operation should also be recommended for patients with small carcinomas or islet cell tumors arising in the head of the pancreas is now being investigated.     

Pylorus-preserving pancreaticoduodenectomy with combined resection of the portal vein and gastrointestinal reconstruction by imanaga procedure for ductal cancer of the head of the pancreas

Twenty-six patients who underwent pyloruspreserving pancreaticoduodenectomy (PPPD) for ductal cancer of the head of the pancreas between 1983 and 1993 were reviewed. Gastrointestinal continuity was restored by the methods of Imanaga (n=21) and Traverso (n=5). Combined resection of the portal vein and/or superior mesenteric vein was performed in 13 patients. Surgical complications occurred in 5 patients, but there were no postoperative deaths. Delayed gastric emptying was observed in 42% of patients. The median survival time for all 26 patients was 13 months. Three patients survived for more than 3 years, and one of them is currently alive without recurrence at 10 years. Differences in survival rates were not apparent between patients who underwent PPPD with and without portal vein resection. Survival rate after PPPD was compared with that after pancreaticoduodenectomy (PD) performed between 1974 and 1992; the difference was not significant. Patients who underwent noncurative PPPD had a significantly better survival rate than those who underwent noncurative PD (P<0.05). PPPD has improved the quality of life of the resected patients, without reducing survival rate. At present, PPPD by the Imanaga procedure could be the best choice for management of cancer of the pancreatic head.     

Bile duct carcinoma following abdominal radiation for urologic neoplasms

This report concerns three cases of bile duct carcinoma which occurred 15–40 years after patients received treatment for urogenital neoplasia. All three patients had initially received radiation therapy in addition to urological surgery. Jaundice was the major clinical symptom of the second tumor. Two of the three patients were able to be surgically treated when presenting with their second carcinoma (partial pancreaticoduodenectomy, bile duct resection; central liver resection), whereas the third patient was in such a poor state of health that he was biopsied only and treated with a pigtail drain. All three patients died within 3 months to 3 years following the diagnosis of the second tumor. The more than coincidential occurrence of the rare bile duct carcinoma in our three patients with previous urogenital neoplasia warrants a new discussion concerning the connection between primary carcinoma, radiation therapy, and the occurrence of a second tumor.     

A retrospective study of the preventive effect of transarterial chemotherapy for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

A major problem in treating hepatocellular carcinoma (HCC) is intrahepatic recurrence after partial hepatectomy, despite the relatively early detection now possible due to recent developments in non-invasive diagnostic modalities. The present study evaluated the usefulness of preventive therapy for intrahepatic recurrence of HCC. In order to suppress intrahepatic recurrence in HCC patients at high risk of recurrence after tumor removal, we performed preventive transarterial chemotherapy in 23 such patients. Doxorubicin, at a dose of 0.5 mg/kg body weight, was administered, via a catheter inserted at the junction of the common hepatic artery and the gastroduodenal artery, every 2 weeks for the first 2 months, and every month thereafter for at least 1 year. The control group consisted of 30 patients with similar risk of recurrence who underwent partial hepatectomy during the same period without receiving transarterial preventive therapy. The 1-, 2-, 3-, and 5-year cumulative cancer-free survival rates in patients who received transarterial preventive chemotherapy after partial hepatectomy were 87.0%, 47.1%, 21.2%, and 21.2%, respectively, compared to 53.3%, 30.0%, 20.0%, and 13.3%, respectively, in the control group (P<0.05). The 1-, 2-, 3-, and 5-year cumulative overall survival rates were 95.7%, 81.2%, 58.4%, and 48.7%, respectively, in the preventive chemotherapy group, compared to 70.0%, 49.4%, 41.7%, and 19.5%, respectively, in the control group (P<0.05). Thus, the present study demonstrates the limited but significant effect of preventive transarterial chemotherapy for the intrahepatic recurrence of HCC after partial hepatectomy.     

Cell kinetic study of the gallbladder epithelium,with special reference to the pancreaticobiliary maljunction

The bromodeoxyuridine labelling index (BrdU-LI), ornithine decarboxylase (ODC) activity, and bile elements in the gallbladder were examined in 23 patients to investigate cell kinetics and oncogenesis in gallbladder epithelium with pancreaticobiliary maljunction (PBMJ). The patients were classified into five groups: group I (4 patients without biliary disorder), group II (8 patients with cholecystolithiasis), group III (4 patients with PBMJ), group IV (3 patients with gallbladder cancer and PBMJ), and group V (4 patients with gallbladder cancer). In non-cancerous epithelium, the BrdU-LI in groups III (2.88±3.07%), IV (4.92±2.73), and V (5.93±2.08) was significantly higher than in group I (0.06±0.12), and the ODC activity in groups III (7.83±6.82 pmole CO₂/h per mg protein), IV (17.21±9.44), and V (11.27±12.33) was also significantly higher than that in group I (1.39±1.78). Both BrdU-LI and ODC activity were high in epithelium showing metaplasia in 3 patients from groups III and IV. In groups I and II, the lithocholic acid (LCA) fraction showed a positive correlation with BrdU-LI (correlation coefficient, 0.90) and ODC activity (correlation coefficient, 0.91). From these results, it can be concluded that the gallbladder epithelium in patients with PBMJ, and its metaplastic changes, show an increase in cell proliferation, which is important in the progression of cancer.     

Histogenesis of hyperplastic polyps of the stomach in terms of cellular proliferation

We investigated the histogenesis of hyperplastic polyps of the stomach, in terms of cellular proliferation, by studying endoscopically removed and gastrectomized human gastric polyps either labeled with bromodeoxyuridine (BrdU) by in vitro flash labeling techniques or labeled in an isolated organ circulation system, in both of which, perfluorochemical artificial blood was employed. Immunohistochemistry with antibodies against BrdU and proliferating cell nuclear antigen (PCNA) was simultaneously employed. The generative cell zone of pedunculated and semipedunculated polyps was markedly expanded compared with that of the background mucosa, and this change also appeared in sessile polyps, although to a lesser degree. Enhanced proliferative activity was observed in both epithelial and stromal cells in areas of erosion. Our results demonstrate that the initial change in the histogenesis of hyperplastic polyps is an expansion of the generative cell zone, followed by interstitial edema and stromal cell proliferation, and that erosion can facilitate these changes. No correlation was found between the size of the polyps and the labeling indices. This finding explains, in part, the diversity of chronological changes in the size and shape of hyperplastic polyps.     

Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women,evaluated by dual-energy X-ray absorptiometry

To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P<0.001) and in those with cirrhosis of the liver (P<0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone.     

Long-Term survivor of ruptured hepatocellular carcinoma after two hepatic resections

We report here a long-term survivor of ruptured hepatocellular carcinoma (HCC). A 37-year-old Japanese man complained of sudden abdominal pain after taking an alcoholic drink. Ultrasonographic examination showed a large amount of fluid in the abdominal cavity. Emergency laparotomy was performed. A solid mass showing extrahepatic growth was present in the right lobe of the liver. No active bleeding site was detected, but the tumor was covered with old blood coagula. The tumor was covered with the greater omentum to prevent further hemorrhage. Following assessment of the extent of the tumor and of liver function, delayed hepatectomy was performed. Histological examination indicated the tumor to be HCC. Twenty-six months after initial hepatic resection, partial resection of the liver was performed again for recurrent tumor. The patient has survived without recurrence for more than 5 years. The long survival was due, we believe to the liver being non-cirrhotic, the delayed hepatic resection, and the early detection of the recurrent tumor.     

Biosynthesis and secretion of mucin-related products in Hs746T gastric cancer cells

We have previously studied the biosynthesis and secretion of mucin in the normal human stomach and reported that the tetramer of the 60-kDa subunit of mucin core protein was synthesized and highly glycosylated, and that only high molecular weight mucin was secreted. In this study, we investigated the mucin-related products of a gastric cancer cell line (Hs746T). Analysis of intracellular and extracellular products immunoprecipitated with an anti-apomucin monoclonal antibody revealed that a 110-kDa protein, the dimer of the 55-kDa subunit, was synthesized and secreted. Tunicamycin treatment inhibited the secretion of the 110-kDa protein. These findings suggest thatN-glycosylation may be involved in the secretory mechanism of the mucin-related product.     

Treatment of cholelithiasis with acetylcysteine,a new gallstone solvent

An improved technique for making thin sections of gallstones has enabled us to examine their morphology microscopically. Using this technique in various types of gallstones, we found a network of mucin, which was considered to play an important role in gallstone formation. The effectiveness of a mucolytic agent, acetylcysteine, for the direct dissolution of gallstones was evaluated in this study. Immersion in acetycysteine led to the prompt disintegration of various types of gallstones into small fragments. As acetylcysteine is commercially available as a mucolytic agent, a clinical trial was undertaken for the treatment of cholelithiasis (hepatolithiasis,n=5; choledocholithiasis,n=1). Because of the disintegrating effect of acetylcysteine, after the injection of this agent, many fragments flowed out through the percutaneous transhepatic biliary drainage tube. Acetylcysteine gallstone dissolution combined with percutaneous transhepatic cholangioscopic lithotripsy significantly aided the lithotriptic action, due to the disappearance of mucin from the bile duct. No side effects were observed either during or after the treatment. We concluded that acetylcysteine can be used as a new agent for the direct dissolution of most types of gallstones in patients with cholelithiasis.     

Management of pancreatic pseudocyst

The natural course, complications, and management of 37 patients with pancreatic pseudocyst treated at our institution were reviewed. The lesions were classified into three groups, cysts secondary to acute pancreatitis, to chronic pancreatitis, and to trauma. Spontaneous resolution or cyst diminution was observed in 75% of the patients with acute pancreatitis and trauma, but in only 33% of those with chronic pancreatitis. The interval until resolution or diminution in chronic pancreatitis was shorter than that in pseudocyst of other etiologies, but the incidence of complications in patients with chronic pancreatitis was not significantly higher than that among patients with other etiologies. Multiple complications were found only among the patients with chronic pancreatitis. Surgical management was performed in 25% of the patients with acute pancreatitis and trauma and 66% of the patients with chronic pancreatitis. The postoperative mortality rate was 10%. Reoperation was necessary in 6 of 7 patients who had undergone external drainage, including 3 patients treated with ultrasonography-guided percutaneous catheter drainage (US-PCD). These results suggest that it is necessary to closely monitor patients with chronic pancreatitis and/or external drainage, and in these patients it may become necessary to reoperate. US-PCD was useful as an emergency procedure in pseudocyst patients whose general condition was poor, despite the disadvantages of the piercing of adjacent organs by the catheter, infection, and pseudocyst recurrence.     

Mechanism,management, and prevention of bile duct injury in laparoscopic cholecystectomy

Injury to the bile duct is one of the most serious complications of laparoscopic cholecystectomy. The incidence of bile duct injury during laparoscopic cholecystectomy may be higher than during open cholecystectomy. Most of these injuries occur early in a surgeon’s experience with the new technique. The classical laparoscopic bile duct injury occurs when the common duct is mistaken for the cystic duct; the common bile duct is transected and a part of the extrahepatic biliary system is resected. The bile duct may also be injured by excessive diathermy, resulting in a bile leak or a stricture. Insecure clipping of the cystic duct may also result in bile leakage. If these injuries are not recognized at the time of surgery, they present as bile collections or jaundice postoperatively. ERCP will delineate the exact injury accurately. These injuries are preventable by careful attention to technique and a willingness to convert to open surgery when difficulties are encountered. To minimize the risk to patients, programs of training, proctoring, and accreditation in laparoscopic surgery should be established.     

Biochemical and metabolic assessments of liver graft preserved with oncotic oxygen carrier

The effect of an oxygen-carrying agent, as a component of the preservation solution, on the biochemical viability and energy metabolism of the graft in liver preservation was evaluated. Two preservation methods, simple hypothermic storage and continuous machine perfusion, both performed at 4°C for 48 h, were studied in male Lewis rats. Pyridoxylated hemoglobin-polyoxyethylene conjugate (PHP) was used as the oncotic oxygen carrier. University of Wisconsin (UW) solution served as a control solution. The test solution (PHP+UW) was a 1∶1 mixture of PHP and UW solutions with 4.0g% of hemoglobin. We observed that oxygen consumption during perfusion was significantly higher in the PHP+UW than in the UW group. Hepatic mitochondrial function and tissue adenosine-5′-triphosphate (ATP) levels were better preserved in the PHP+UW than in the UW group, and were also better preserved in continuous machine perfusion than in simple hypothermic storage. No significant differences were observed in perfusate biochemical parameters. These results indicate that the incorporation of an oxygen-carrying agent into preservation solution provides significantly better oxygen delivery to liver grafts, and may improve hepatic viability.     

Lymphatic drainage of the gallbladder

Based upon detailed dissections of the lymphatic system in adult cadavers, the lymphatic drainage of the gallbladder was divided into three pathways: (1) The cholecystoretropancreatic pathway, which had two routes, one running spirally from the anterior surface of the common bile duct to the right rear, and the other running almost straight down from the posterior surface of the common bile duct. These routes converged at the principal retroportal node at the posterior surface of the head of the pancreas. (2) The cholecysto-celiac pathway; this was the route running to the left through the hepatoduodenal ligament to reach the celiac nodes. (3) The cholecysto-mesenteric pathway; this was the route running to the left in front of the portal vein to connect with the nodes at the superior mesenteric root. The cholecysto-retropancreatic pathway can be regarded as the main pathway, and the principal retroportal node appeared to be critical as the main terminal node in the visceral lymphatic system of the gallbladder. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein, and the nodes in the interaortico-caval space were considered to be of particular importance.     

Gross dissection and radiological studies of abnormal pancreatico-choledocho-ductal junction

The reliability of radiological diagnosis of abnormal pancreatico-choledocho-ductal junction (APCDJ) in comparison with findings of gross dissection of the pancreatic choledocho-ductal junction was studied in 8 patients, based on comparison between radiologic and macroscopic findings of the junction in 99 patients who had received pancreatoduodenectomy. APCDJ, that is the joining of the common bile duct and the pancreatic duct in the pancreatic parenchyma extraduodenally, was identified in 5 patients both radiologically and macroscopically. Macroscopically, the length of their common channel ranged from 20 to 32 mm. with a mean of 29 mm. In the other three patients, APCDJ was misdiagnosed radiologically, for the following reasons. In a patient with pancreatic carcinoma, a rather long common channel, 15 mm in length, while ran in the submucosal layer of the duodenum, was though to be APCDJ on radiologic examinations. In a patient with bile duct carcinoma, an abnormal closing between the common bile duct and the pancreatic duct due to carcinomatous infiltration of the pancreas led to a radiologication misinterpretation for APCDJ. In the last patient, APCDJ was identified only macroscopically, not radiologically, because of a relatively short common channel and the location of common bile duct carcinoma. Thus, APCDJ was clearly identified in patients with a long common channel, whereas it was difficult to identify in patients with a short common channel.     

Laparoscopic cholecystectomy — key technical points to prevent bile duct injury

During the period May, 1990 to the end of December, 1992, 434 patients (203 males and 231 females; aged 16–87 years; mean 49.4 years) underwent laparoscopic cholecystectomy at our Department, Teikyo University Hospital, Mizonokuchi. Eleven out of these 434 patients were converted to open cholecystectomy, due to uncontrollable bleeding from the cystic artery (n=1), venous bleeding due to portal hypertension (n=1), extensive adhesions of the omentum and the duodenum to the gallbladder (n=2), extensive adhesions around the gallbladder (n=4), and extensive adhesion between the gallbladder and the common duct (n=3). The time taken to complete the procedure ranged from 25 to 235 min, the mean being 74 min. Seventeen complications manifested intra- or postoperatively. Three cases of bile duct injury which manifested after operation required laparotomy. In 1 patient, injury to the right hemidiaphragm resulted in a right pneumothorax. One patient had periumbilical subcutaneous emphysema, 2 patients had mild bile leaks that cleared up within a few days, and 1 patient had considerable bile leaks which stopped 6 days later. Indications for laparoscopic cholecystectomy widened as our experience grew. Common bile duct stones and previous gastrectomy are no longer contraindications for this procedure. Based on our experience with laparoscopic cholecystectomy, we describe here our technique and the rules we consider important for the successful accomplishment of this procedure.     

Clinicopathological studies of anomalous arrangement of the pancreaticobiliary ductal system with pancreas divisum

We examined the morphological aspects of the pancreaticobiliary ductal system in 13 patients with both anomalous arrangement of the pancreaticobiliary ductal system (AAPB) and associated pancreas divisum (PD), and compared their clinicopathological findings with those of patients with either AAPB or PD alone. PD is classified into three types, i.e., separate pancreas, nonfusion of the ventral and dorsal pancreatic ducts, and partial fusion of the ventral and dorsal pancreatic ducts. Of the 13 patients with AAPB and associated PD, 5 were male and 8 female; their mean age was 57 years. Nine of the 13 had clinical symptoms. Five of the 13 had gallbladder cancer, 3 had cholecystolithiasis, and 2 choledochal cyst. One patient showed nonfusion of both pancreatic ducts and the others showed partial fusion of the ducts. The length of the common duct from the orifice of the papilla of Vater to the junction of the common bile duct with the ventral pancreatic duct and the location of the union varied. The presence of both AAPB and PD made the arrangement of the pancreaticobiliary ducts very complicated. Clinical aspects were similar to those of AAPB and the patients were likely to be treated for a condition other than PD. However, since relapsing acute pancreatitis and intermittent epigastric pain are typical symptoms in patients with AAPB as well as in those with PD, we should carefully follow up those patients with both AAPB and PD.