Susumu Kawate

Amplification of c-myc in Hepatocellular Carcinoma: Correlation with Clinicopathologic Features, Proliferative Activity and p53 Overexpression

Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with α-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.

Low-Dose Erythromycin Reduces Delayed Gastric Emptying and Improves Gastric Motility After Billroth I Pylorus-Preserving Pancreaticoduodenectomy

ObjectiveTo test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). Summary Background DataDelayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. MethodsThirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. ResultsPreoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. ConclusionsLow doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.

Perioperative real‐time monitoring of indocyanine green clearance by pulse spectrophotometry predicts remnant liver functional reserve in resection of hepatocellular carcinoma

There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time.

Results of duct-to-mucosa pancreaticojejunostomy for pancreaticoduodenectomy Billroth I type reconstruction in 100 consecutive patients.

BACKGROUND This study retrospectively analyzed 100 consecutive patients who underwent pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) with a Billroth I type reconstruction and pancreaticojejunostomy by duct-to-mucosal anastomosis using a continuous running suture. STUDY DESIGN Seventy patients underwent PD and 30 patients PPPD for pancreatic cancer in 33, bile duct cancer in 28, ampullary or duodenal tumor in 22, chronic pancreatitis in 8, and other gastrointestinal cancer in 9. Postoperative pancreatic anastomotic leakage was diagnosed from skin excoriation around the drain site, and was defined as a high concentration of amylase in drainage fluid or leakage demonstrated on x-ray. RESULTS The mortality rate was 2% overall (2.8% in PD, 0% in PPPD). The morbidity rate was 23% overall (12.8% in PD, 46.7% in PPPD). Pancreatic anastomotic leakage was 4.0% overall (2.8% in PD, 6.7% in PPPD).. The incidence in the ampullary or duodenal tumors was 9.1% overall (0% in PD, 14.3% in PPPD). Biliary leakage occurred in four patients, 4.0% overall (4.3% in PD, 3.3% in PPPD), intraabdominal hemorrhage in 2% (2.8% in PD, 0% in PPPD), and lethal anastomotic leakage in one patient, overall rate 1% (1.4% in PD, 0% in PPPD). Delayed gastric emptying had the highest morbidity and was seen exclusively in PPPD (39.3%). CONCLUSIONS A simple continuous running suture and parachuting for duct-to-mucosal pancreaticojejunostomy makes pancreaticoduodenectomy a safe procedure, even in a Billroth I type reconstruction.

Amplification of c-myc and cyclin D1 genes in primary and metastatic carcinomas of the liver.

The c‐myc and cyclin D1 genes are included among the oncogenes the amplifications of which have been detected in cancers of various organs. However, there have been few reports on the amplification of both these genes in primary and metastatic liver carcinomas. In the present study, c‐myc and cyclin D1 gene amplification was examined in 76 primary and metastatic liver carcinomas using formalin‐fixed paraffin‐embedded tissue sections and a differential polymerase chain reaction procedure. c‐myc and cyclin D1 gene amplification was detected in 15 (33%) and two (4%) of 46 hepatocellular carcinomas (HCC), one (10%) and 0 (0%) of 10 intrahepatic cholangiocarcinomas (ICC), one (33%) and 0 (0%) of three combined hepatocellular and cholangiocarcinomas (HCC + ICC), and nine (56%) and three (19%) of 16 metastatic lesions to the liver from colorectal adenocarcinoma (MCA), respectively. The incidence of c‐myc amplification was significantly higher in MCA than in ICC (P = 0.023), and it tended to be higher in HCC than in ICC. These results indicate that the amplification of the c‐myc proto‐oncogene is not unusual in HCC and MCA, and its detection may have a useful diagnostic significance in differentiating ICC from MCA or HCC from ICC.

Left renal vein graft for vascular reconstruction in abdominal malignancy.

BackgroundAdvanced abdominal malignancies are occasionally invasive for the major blood vessels, such as the portal vein (PV), inferior vena cava (IVC), and major hepatic veins (HVs), and complete removal of the tumors is required for patients undergoing vascular resection and reconstruction. We used left renal vein (LRV) grafts for vascular reconstruction in patients with these malignancies and evaluated their clinical relevance.MethodsA total of 113 patients underwent vascular resection including the PV (42 patients), IVC (68 patients), and HV (3 patients) for hepatobiliary-pancreatic or abdominal tumor resection. Of these, 11 patients underwent vascular reconstruction with a LRV graft of the PV, superior mesenteric vein (SMV), and HVs in 3 patients each, and the IVC in 2 patients. The HVs were resected with segmentectomy involving Couinaud’s segments VII, VIII, and IV; VII, VIII, and II; or III, IV, VIII in each patient. The PV and SMV were resected in 5 patients undergoing pancreaticoduodenectomy for pancreatic carcinoma, and in 1 patient being treated with extended right hepatectomy and pancreaticoduodenectomy for hepatic hilar carcinoma. The IVC was partially resected in 1 patient with advanced colon cancer and 1 with malignant schwannoma.ResultsThe mean graft length of LRV obtained was 3.6 (3.5–4.0) cm. The graft was used as a tube in 9 patients, and as a patch in 2 patients. The mean duration of clamping time was 41.9 (35–60) min. Portal vein thrombosis was encountered in 2 patients, and anastomotic stenosis in 1 patient. Other morbidity was not related to vascular reconstruction. One patient who underwent extended right hepatectomy and pancreaticoduodenectomy died of liver failure in the hospital. The serum creatinine level after surgery did not deteriorate except in the one patient who died in the hospital. Graft patency was maintained during the follow-up period in all patients.ConclusionsA LRV graft may enhance the possibility of vascular reconstruction without deteriorating serum creatinine level, and it provides sound graft patency.

Combined Liver and Inferior Vena Cava Resection for Adrenocortical Carcinoma

PurposeAdrenocortical carcinoma (ACC) is a rare malignancy, usually diagnosed at an advanced stage when it has invaded or adhered to adjacent organs. We report our experience of performing combined liver and inferior vena cava (IVC) resection for ACC.MethodsSix patients with clinical stage III (n = 4) or IV (n = 2) ACC underwent combined resection of the liver and IVC. Two patients underwent extended right hepatectomy, and four underwent segmentectomy. In four patients, the IVC was resected segmentally: it was replaced with expanded polytetrafluoroethylene (ePTFE) in three of these patients, and not reconstructed in one. In two patients, the IVC was partially resected and closed directly.ResultsPerioperative mortality was zero, and morbidity was 33.3%, with temporary liver failure in two patients and renal failure in one patient. Recurrence was found within 8.1 months in three (50%) of the six patients. The mean recurrence-free survival period was 20.1 ± 7.7 months (95% confidence interval [CI]: 5.1–35.4), and the median survival time was 6.1 ± 9.8 months (95% CI: 00–25.3). The 5-year disease-free survival rate was 16.7%.ConclusionsPatients with ACC involving both the liver and IVC are candidates for partial hepatectomy and segmental IVC resection. Resection affords the possibility of negative margins, acceptable perioperative morbidity and mortality, and prolonged survival in some patients.

Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial.

AbstractPURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10–3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/ leucovorin.

Ileal Perforation Caused by Cytomegalovirus Infection in a Patient with Recurrent Gastric Cancer: Report of a Case

Abstract.We report a case of ileal perforation caused by cytomegalovirus (CMV) infection in a patient with peritoneal recurrence of gastric cancer. Emergency laparotomy revealed a pinhole-sized perforation in a reddish segment of the small bowel, 100 cm proximal to the terminal ileum, and peritoneal carcinosis of recurrent gastric cancer invading the transverse colon and the gastrojejunal anastomosis of a Billroth-II procedure. The affected ileum was resected, a primary anastomosis was performed, and a colostomy was made in the ascending colon. The histology of the ileum revealed acute inflammation with vasculitis and CMV inclusions in the macrophages and endothelial cells and evidence of CMV on immunostaining. There was no evidence of cancer cell invasion or any other pathogens. Although the prognosis associated with bowel perforation due to CMV infection is poor, emergency surgery saved our patients life.

Sudden Hemorrhage of the Breast Caused by Breast Cancer Without Skin Invasion: Report of a Case

A rare case of sudden hemorrhage caused by breast cancer is herein presented. A 65-year-old woman was admitted to our hospital because of bleeding from her left breast. On physical examination, a continuous hemorrhage accompanied by an open cavity formation was observed in her left breast. She had no history of breast trauma. Her bleeding profile studies and liver function were both normal. In addition, no anticoagulation medication had been administered. The histological findings of the cavity wall indicated invasive ductal carcinoma without skin invasion. After carrying out chemotherapy, a standard radical mastectomy was performed.