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

BACKGROUND: There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time. METHODS: Indocyanine green (ICG) clearance (K) was measured non-invasively and instantaneously using pulse spectrophotometry before surgery, during inflow occlusion and after hepatectomy in 75 patients who underwent anatomical liver resection for hepatocellular carcinoma (HCC). RESULTS: Eight patients (11 per cent) suffered liver failure and one (1 per cent) died in hospital. An estimated remnant K value of 0.090 per min was the cut-off value for liver failure. In a logistic regression model, the estimated remnant K (0.090 per min; P = 0.022) and age (65 years; P = 0.025) were significant predictors of postoperative liver failure. There was a correlation between the estimated and measured post-hepatectomy K, and between the inflow occlusion K and measured post-hepatectomy K (P < 0.001). The cut-off value of less than 0.090 per min for the estimated remnant K resulted in 88 per cent sensitivity and 82 per cent specificity for predicting liver failure. CONCLUSION: Perioperative real-time monitoring of ICG-K is useful for evaluating the remnant liver functional reserve before, during and after liver resection for HCC. The estimated remnant K is a significant predictor of liver failure.

Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study.

Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n=123) or III (n=82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6-80.4%) with PSK (n=137) and 58.8% (95% CI 47.1-70.5%) in the controls (n=68) (P=0.016). Polysaccharide K reduced the recurrence by 43.6% (95% CI 4.5-66.7%) and mortality by 40.2% (95% CI -12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3-88.2%) in the PSK group and 72.1% (95% CI 61.4-82.7%) in the control group (P=0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1-72.9%) and 74.6% (95% CI 63.0-86.1%) in the PSK group as compared with 32.1% (95% CI 14.8-49.4%) and 46.4% (95% CI 28.0-64.9%) in the controls (P=0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P=0.02; odds ratio 0.27; 95% CI 0.09-0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712-5.165; P<0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221-3.633; P=0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017-19.014; P=0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.

Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy.

OBJECTIVE: To 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 DATA: Delayed 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. METHODS: Thirty-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. RESULTS: Preoperative, 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. CONCLUSIONS: Low 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.

Effects of endothelin receptor antagonist TAK-044 on small bowel autograft from a controlled non-heart-beating donor model.

BACKGROUND: This study investigated the possibility of pharmacologic protection using an endothelin (ET) receptor antagonist, TAK-044 (TAK), for small bowel autograft in a canine controlled non-heart-beating donor (NHBD) model. METHODS: Sixteen adult mongrel dogs were allocated into 2 groups. TAK (3 mg/kg) (n = 8) was administered intravenously 30 minutes before ischemia and 30 minutes before graft reperfusion. Vehicle was administered in the control (n = 8). The superior mesenteric artery and vein were clamped for 90 minutes to induce warm ischemia as a controlled NHBD model. The entire small bowel then was harvested and stored in 4 degrees C University of Wisconsin solution for 4 hours. The autograft was transplanted orthotopically. Mucosal tissue blood flow, intramucosal pH (pHi), and serum ET-1 levels were measured. Specimens were evaluated histopathologically and ET-1 immunohistochemically. RESULTS: TAK provided significantly higher tissue blood flow and pHi at 3 and 6 hours after graft reperfusion and significantly higher serum ET-1 levels at 1 hour after graft reperfusion as compared with the control group. TAK had histopathologic tissue damage graded as superficial, did not reach to grade 5 on Park's grading as in controls, and provided less intense immunoreactivity for ET-1 immunohistochemical staining. CONCLUSIONS: TAK may have clinical application in small bowel transplantation from controlled NHBD or conditions related to ischemia-reperfusion (I/R) injury.

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.

Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma.

Resistance to the transforming growth factor-beta (TGF-beta) is a frequently found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a possibility that constitutive activation of the anti-Smads by a somatic mutation may impair the TGF-beta signaling pathway. We tested this hypothesis by screening the entire coding sequences of these anti-Smads for mutations in 52 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand conformation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 and Smad7 genes are not the main cause of the TGF-beta resistance in human HCC.

Ventral pancreas-preserving pancreatic head and body resection.

A new procedure that included ventral pancreas-preserving pancreatic head and body resection for a huge mucinous cystic neoplasm was performed to preserve pancreatic function. A 45-year-old man was diagnosed as having a huge mucin-producing pancreatic neoplasm. The ventral pancreas-preserving pancreatic head and body resection was performed. The stumps of the caudal pancreas and the uncinate process were negative for cancer by frozen-section histology. The remaining pancreas was anastomosed by a method of double pancreatojejunostomy with a Roux-en-Y loop. The resected specimen was 15 x 10 cm in size and contained mucin. The papillary tumor was 5.0 x 4.5 x 3.0 cm in size, which was an intraductal papillary adenocarcinoma without pancreatic invasion microscopically. The postoperative course was uneventful and the patient was discharged 14 days after surgery. Glucose tolerance test was normal 24 months after surgery and both sides of the pancreatic duct were patent confirmed by magnetic resonance. The patient is well now two years after surgery. A new limited pancreatic resection, ventral pancreas-preserving pancreatic head and body resection, was safely applied to a huge mucinous cystic neoplasm of the pancreas.

Omentoplasty for cervical esophagogastrostomy following radical esophagectomy with three-field dissection.

BACKGROUND/AIMS: Anastomotic leakage is the main cause of postoperative mortality and incidence of which, following three-field lymph node dissection, is around 30%. The study was undertaken to investigate the role of omentoplasty to reinforce cervical esophagogastrostomy with the expectation of lowering the rate of anastomotic leakage after radical esophagectomy with three-field lymph node dissection. METHODOLOGY: Between July 1995 and Dec 1997, a total of 32 patients underwent total thoracic esophagectomy with three-field lymph node dissection and cervical esophagogastrostomy. Eleven patients were stage IIA, 3 stage IIB, 5 stage III and 13 stage IV. After radical esophagectomy and lymph node dissection, several omental branches of the gastroepiploic vessels remained to supply a gastric tube. An end-to-side cervical esophagogastrostomy was performed on the posterior wall of the gastric tube using a circular stapler. The omentoplasty--wrapping the esophagogastrostomy--was performed. A retrosternal route for reconstruction was used in 23 patients and a posterior mediastinal route in 9 patients. RESULTS: Esophageal anastomotic leakage occurred in only 1 patient, 3.1% overall. There was neither pyothorax nor mediastinitis. There was no lethal anastomotic leakage. Later, 2 patients (6.2%) developed an anastomotic stricture that required balloon dilatation. CONCLUSIONS: Omentoplasty to reinforce cervical esophagogastrostomy decreases anastomotic failure following radical esophagectomy with three-field lymph node dissection.

The resection of non-hepatic intraabdominal recurrence of gastric cancer.

BACKGROUND/AIMS: Surgical resection of hepatic or pulmonary metastases from gastrointestinal cancer has been recognized as a curative modality in some patients. However, the role and outcome of the surgical management of a non-hepatic intraabdominal recurrence of gastrointestinal cancer have not been clearly delineated. METHODOLOGY: We treated 5 patients for non-hepatic intraabdominal recurrence of gastric carcinoma surgically. All the resected specimens were microscopically identified as recurrent gastric cancer. Three of 5 patients received postoperative chemotherapy. The clinicopathological findings were analyzed according to the general rules for gastric cancer study. RESULTS: The lymph nodes were dissected for lymph node metastases. Surgical resection of the tumors combined with total gastrectomy, esophagectomy, or colectomy was performed for the local and peritoneal recurrences. All of the recurrent tumors were macroscopically resected with curative states. One patient died of sepsis 54 days after surgery. Three patients died of recurrent gastric cancer: 2 within 1 year of surgery and 1 after 3 years. One patient still survives disease free 3 years and 6 months after the 2nd operation. CONCLUSIONS: Surgical resection for non-hepatic intraabdominal recurrence of gastric cancer is the treatment of choice for selected patients. Surgical resection followed by adjuvant chemotherapy may improve the outcome of these patients.

Esophageal anastomosis following gastrectomy for gastric cancer: comparison of hand-sewn and stapling technique.

BACKGROUND/AIMS: During the past 4 years, we have experienced a marked reduction in the incidence of esophageal anastomotic leakage and/or stricture coinciding with the use of a mechanical circular stapler for gastric cancer patients. METHODOLOGY: We reviewed medical records of gastric cancer patients who underwent a total or proximal gastrectomy, and compared the leakage or stricture of stapled anastomosis with the hand-sewn anastomosis technique. A total of 390 esophageal anastomosis were performed between January 1978 and August 1997. Two types of mechanical circular staplers were used (EEA and CDH). RESULTS: Anastomotic leakage occurred in 13 (3.3%) of 390 cases; three (4.5%) of 66 cases with hand-sewn anastomosis, and 10 (3.1%) of 324 cases with stapled anastomosis (EEA: 4.5%, CDH: 0%). The anastomotic leakage rate was significantly lower in the CDH stapler group than in the EEA stapler group. Anastomotic stricture occurred in one (1.5%) of 66 cases of hand-sewn anastomosis, and 16 (4.9%) of 324 cases of stapled anastomosis (EEA: 5.9%, CDH: 2.9%). There were no significant differences in the stricture rate between the hand-sewn group and the stapler group. CONCLUSIONS: Stapling anastomosis using a CDH stapler led to a reduction in the incidence of anastomotic leakage. Surgeons must, however, continue to be aware of anastomotic stricture.

Absence of p51 mutation in human hepatocellular carcinoma.

The p51 gene encodes a protein with significant homology to p53. To investigate the involvement of the p51 gene in human hepatocarcinogenesis, mutation analysis of the p51 gene was performed in 54 cases of hepatocellular carcinoma (HCC). No mutations causing amino acid substitutions or frameshifts were found by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of the entire coding region. The result indicated that mutation of the p51 gene does not play a major role in the development of HCC in Japanese patients. Further studies on p51 expression and its functions, including the interaction with p53, are necessary to elucidate the role of the p51 gene in human hepatocarcinogenesis.

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 alpha-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.

Mutation analysis of transforming growth factor beta type II receptor, Smad2, and Smad4 in hepatocellular carcinoma.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII), Smad2, and Smad4 genes have been detected in several human cancers. However, there are no reports of mutation analysis of the entire coding regions in these genes in hepatocellular carcinoma, and the roles of these genes in hepatocarcinogenesis remain unknown. We screened 30 hepatocellular carcinomas for mutations of these genes using polymerase chain reaction single-strand conformation polymorphism. We detected no mutations, but did find 3 cases of loss of heterozygosity of chromosome 17p13.1. These results suggest that mutations of the TGFbetaRII, Smad2, and Smad4 genes are rare, and that genetic instability is uncommon in human hepatocellular carcinoma.

Low MIB-1 labeling index in anti-HCV positive hepatocellular carcinoma.

It has been reported that hepatitis C virus-related hepatocellular carcinoma (HCC) patients survive longer than hepatitis B virus-related patients. In this study, since HCC patients positive for anti-HCV antibody had significantly longer disease-free survival (p<0.05), we evaluated the proliferative activity of 58 resected HCCs and the status of their viral infections. Ki-67 (MIB-1) immunostaining, argyrophilic nucleolar organizer regions and c-myc gene amplification were examined as parameters of proliferation, and p53 overexpression was examined in relation to clinicopathologic features and prognosis. Thirty-nine patients with HCC (67%) were positive for anti-HCV antibody alone, five (9%) were negative for both anti-HCV and HBV antibodies, two (3%) were positive for both anti-HCV and HBV antibodies, and 12 (21%) had HBsAg alone. HCC patients with anti-HCV antibody had a lower MIB-1 labeling index (LI) than HCC patients negative for the antibody (p<0.05), irrespective of the serum HBsAg status. However, there was no significant correlation between anti-HCV antibody and other proliferative parameters. MIB-1 could simply be related to cellular proliferation. On the other hand, the other parameters may be related to tumor progression as well as proliferation. HCV-related HCC does have lower proliferative activity and a better prognosis.

[Moderately differentiated adenocarcinoma of the rectum: a case report of remarkable response to preoperative administration of FT suppository].

A 50-year-old man with moderately differentiated adenocarcinoma of the rectum was operated upon following preoperative administration of FT suppository. Digital examination, colonoscopy, and barium enema showed an elevated lesion with central ulcer of the rectum. Microscopically, the biopsy specimen demonstrated moderately differentiated adenocarcinoma. FT suppository (1,500 mg/day for 52 days, total 78 g) was administered on an outpatient basis. Rectal amputation including lymph node dissection was performed. The tumor markedly reduced in size and changed into a small ulcer in the resected specimen. Microscopically, the tumor degenerated and changed into xanthogranulomatous tissue with foamy histiocytes. Only two tubules of degenerated adenocarcinoma remained. FT suppository for rectal cancer is considered to be safe and effective.

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.