Katsuyoshi Hatakeyama

Appraisal of 1 cm Hepatectomy Margins for Intrahepatic Micrometastases in Patients with Colorectal Carcinoma Liver Metastasis

BackgroundThis study sought to clarify the distribution of intrahepatic micrometastases and elucidate an adequate hepatectomy margin for colorectal carcinoma liver metastases.MethodsIntrahepatic micrometastases in resected specimens from 90 patients who underwent hepatectomy for colorectal carcinoma liver metastases were examined retrospectively. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. Distances from these lesions to the hepatic tumor borders were measured histologically, and the density of intrahepatic micrometastases (number of lesions/mm2) calculated relative to the advancing tumor border in a zone <1xa0cm from the border (close) orxa0≥1xa0cm away (distant). Median follow-up time was 127xa0months.ResultsA total of 294 intrahepatic micrometastases were detected in 52 (58%) patients; 95% of these occurred in the close zone. The density of intrahepatic micrometastases was significantly higher in the close zone (mean 74.8xa0×xa010−4xa0xa0lesions/mm2) than in the distant zone (mean 7.4xa0×xa010−4xa0xa0lesions/mm2; Pxa0<xa00.001). Hepatectomy margin status was positive by 0xa0cm in 10 patients or negative by <1xa0cm in 51, and byxa0≥1xa0cm in 29 patients. The median survival times were 18, 33, and 89xa0months in patients with hepatectomy margins 0xa0cm, <1xa0cm, andxa0≥1xa0cm, respectively. Hepatectomy margin status independently influenced survival (Pxa0<xa00.001) and disease-free survival (Pxa0<xa00.001).ConclusionThe currently recommendedxa0≥1xa0cm hepatectomy margin should remain the goal for resections of colorectal carcinoma liver metastases, based on the distribution of intrahepatic micrometastases and survival risk.

Preoperative predictors of vascular invasion in hepatocellular carcinoma

AIMSnVascular invasion is an established adverse prognostic factor in hepatocellular carcinoma (HCC). The aim of the current study was to identify the preoperative predictors of vascular invasion in patients undergoing partial hepatectomy for HCC.nnnMETHODSnA retrospective analysis of 227 consecutive patients who underwent partial hepatectomy for HCC was conducted. Vascular invasion was defined as gross or microscopic involvement of the vessels (portal vein or hepatic vein) within the peritumoral liver tissue.nnnRESULTSnSeventy-six (33%) patients had vascular invasion. Among the preoperative factors, only the tumour size (relative risk, 16.78; p<0.01) and the serum alpha-fetoprotein (AFP) level (relative risk, 3.57; p<0.01) independently predicted vascular invasion. As the tumour size increased, the incidence of vascular invasion increased: < or =2 cm, 3%; 2.1-3 cm, 20%; 3.1-5 cm, 38%; and > 5 cm, 65%. The incidence of vascular invasion was 32% in patients with serum AFP levels < or =1000 ng/mL, compared to 61% in patients with higher serum AFP levels (p<0.01). Patients with both tumours >5 cm and serum AFP levels >1000 ng/mL had an 82% incidence of vascular invasion.nnnCONCLUSIONSnThe tumour size and serum AFP level, alone or in combination, are useful in predicting the presence or absence of vascular invasion before hepatectomy for HCC.

Combined Major Hepatectomy and Pancreaticoduodenectomy for Locally Advanced Biliary Carcinoma: Long-Term Results

BackgroundThis study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure.MethodsA retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (nxa0=xa017) or gallbladder carcinoma (nxa0=xa011). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pylorus-preserving pancreaticoduodenectomy. The median follow-up time was 169xa0months.ResultsMorbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9xa0months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (Pxa0=xa00.0012). Residual tumor status was the only independent prognostic factor of significance (relative risk 4.65; Pxa0=xa00.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor.ConclusionsCombined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.

Overexpression of osteopontin independently correlates with vascular invasion and poor prognosis in patients with hepatocellular carcinoma.

This study retrospectively evaluated the immunohistochemical expression of 3 cell adhesion molecules (CAMs), E-cadherin, beta-catenin, and osteopontin, according to tumor grade in 125 surgically resected specimens of hepatocellular carcinoma (HCC). The aims of this study were to identify factors associated with vascular invasion and to elucidate the prognostic value of CAMs. The median follow-up time was 110 months. The levels of E-cadherin, beta-catenin, and osteopontin immunoreactivity were significantly associated with Edmondson-Steiner grade but not with tumor size. There was increased loss of E-cadherin, nonnuclear overexpression of beta-catenin, and overexpression of osteopontin in tumors of higher histologic grade. Vascular invasion was found in 44 (35%) of 125 resected specimens. Logistic regression analysis identified 3 tumor-related factors that were independently associated with vascular invasion-tumor size more than 3 cm, Edmondson-Steiner grades III to IV, and overexpression of osteopontin. Among the tested CAMs, osteopontin (P = .0110) and E-cadherin (P = .0287) were significant prognostic factors by univariate analysis. The Cox proportional hazard regression analysis revealed that Edmondson-Steiner grades III to IV (relative risk [RR], 3.028; P < .001), the presence of vascular invasion (RR, 1.964; P = .011), overexpression of osteopontin (RR, 1.755; P = .034), serum alpha-fetoprotein level more than 20 ng/mL (RR, 1.834; P = .037), and Child-Pugh classification B to C (RR, 1.880; P = .040) were found to be independently significant factors associated with survival after hepatectomy. These results suggest that overexpression of osteopontin independently correlates with vascular invasion and thus predicts poor survival for patients with HCC, whereas aberrant expression of E-cadherin or beta-catenin does not.

Risk Factors of Reflux Esophagitis in the Cervical Remnant Following Esophagectomy with Gastric Tube Reconstruction

BackgroundThe risk factors and suitable treatment of reflux esophagitis (RE) of the cervical remnant in patients undergoing radical esophagectomy remain unclear. The aim of this study was to evaluate the risk factors in patients with RE in the cervical remnant.MethodsWe retrospectively examined 141 consecutive patients who underwent esophagectomy and reconstruction with gastric tubing. RE was diagnosed by upper gastrointestinal endoscopy and graded according to the Los Angeles Classification. Statistically, 11 potential risk factors of RE were evaluated. The postoperative follow-up time ranged from 18 to 204xa0months (median 60xa0months).ResultsAmong a total of 141 patients, 48 (34%) had RE in the cervical remnant, with 14 (29%) cases categorized as grade B, nine (19%) as grade C, and 25 (52%) as grade D. The cumulative incidence of RE in the cervical remnant was 24% at 5xa0years after surgery and 60% at 10xa0years, respectively. Pyloroplasty and bile reflux were identified as independent risk factors of RE in the cervical remnant by univariate and multivariate analyses.ConclusionsThe results of this study show a high incidence and high grade of RE in the cervical remnant after esophagectomy. Routine endoscopic examination and suitable medication is required for the control of RE in the cervical remnant together with surgical procedures to avoid bile reflux.

Short-and long-term outcomes of surgery for diffuse peritonitis in patients 80 years of age and older

PurposeWe evaluated the impact of advanced age on the morbidity, mortality, and long-term outcome after emergency surgery for diffuse peritonitis.MethodsWe retrospectively evaluated the mortality and morbidity rates in 36 patients who were 80 years of age or older and who had undergone emergency surgery for diffuse peritonitis, and calculated 5-year survival by the Kaplan-Meier method. Factors compromising prognosis were identified by univariate and multivariate analyses.ResultsThe median patient age was 84 years (range, 80–97 years); 16 patients were men and 20 were women. Preoperative concomitant disease was present in 81% of patients; cardiac disease was most common. Sites of visceral perforation were in the upper gastrointestinal tract in five patients, colon or rectum in 30, and gallbladder in 1. The postoperative morbidity rate was 72%, the surgical mortality rate was 11%, and the in-hospital mortality rate was 28%. The median hospital stay was 56 days. The median survival was 41 months, with a 5-year survival rate of 23%. A multivariate analysis identified number of failing organs as the only independent adverse prognostic factor (P < 0.001; relative risk 5.51, 95% confidence interval 1.97–15.4).ConclusionsElderly patients with diffuse peritonitis had an unsatisfactory rate of short-term morbidity and mortality compared with those undergoing elective surgery. Postoperative organ failure was most likely to compromise survival.

Establishment and Characterization of Monoclonal and Polyclonal Antibodies Against Human Intestinal Fatty Acid‐Binding Protein (I‐FABP) using Synthetic Regional Peptides and Recombinant I‐FABP

Abstract We have succeeded in raising highly specific anti‐human intestinal fatty acid‐binding protein (I‐FABP) monoclonal antibodies by immunizing animals with three synthetic regional peptides, i.e., the amino terminal (RP‐1: N‐acetylated 1‐19‐cysteine), middle portion (RP‐2: cysteinyl‐91‐107) and carboxylic terminal (RP‐3: cysteinyl‐121‐131) regions of human I‐FABP, and the whole I‐FABP molecule as antigens. We also raised a polyclonal antibody by immunizing with a recombinant (r) I‐FABP. To ascertain the specificity of these antibodies for human I‐FABP, the immunological reactivity of each was examined by a binding assay using rI‐FABP, partially purified native I‐FABP and related proteins such as liver‐type (L)‐FABP, heart‐type (H)‐FABP, as well as the regional peptides as reactants, and by Western blot analysis. In addition, the expression and distribution of I‐FABP in the human gastrointestinal tract were investigated by an immunohistochemical technique using a carboxylic terminal region‐specific monoclonal antibody, 8F9, and a polyclonal antibody, DN‐R2. Our results indicated that both the monoclonal and polyclonal antibodies established in this study were highly specific for I‐FABP, but not for L‐FABP and H‐FABP. Especially, the monoclonal antibodies raised against the regional peptides, showed regional specificity for the I‐FABP molecule. Immunoreactivity of I‐FABP was demonstrated in the mucosal epithelium of the jejunum and ileum by immunohistochemical staining, and the immunoreactivity was based on the presence of the whole I‐FABP molecule but not the presence of any precursors or degradation products containing a carboxylic terminal fragment. It is concluded that some of these monoclonal and polyclonal antibodies, such as 8F9, 4205, and DN‐R2, will be suitable for use in research on the immunochemistry and clinical chemistry of I‐FABP because those antibodies can recognize both types of native and denatured I‐FABP. In order to detect I‐FABP in blood samples, it is essential to use this type of antibody, reactive to native type of I‐FABP. It is anticipated that, in the near future, such a method for measuring I‐FABP will be developed as a useful tool for diagnosing intestinal ischemia by using some of these antibodies.

Thrombotic Microangiopathy After ABO-Incompatible Living Donor Liver Transplantation: A Case Report

Thrombotic microangiopathy (TMA) has rarely been reported in the setting of liver transplantation. Herein we have reported a successful case of TMA after ABO-incompatible living donor liver transplantation (LDLT) treated with plasma exchange and high-dose intravenous gamma-globulin infusion. A 50-year-old woman was diagnosed with hepatitis C virus-related cirrhosis. We performed an ABO-incompatible LDLT (group B to O) with preoperative plasma exchange to reduce the anti-B hemagglutinin titers to 1:8. The immunosuppressants consisted of tacrolimus, mycophenolate mofetil, and steroid. On postoperative day (POD) 8, her anti-B hemagglutinin titer suddenly increased to 1:64. The serum lactate dehydrogenase (LDH) level was grossly elevated (1518 IU/L). On POD 13, we suspected infection of an intra-abdominal hematoma (Serratia marcescens) which was drained surgically. On day 5 after the reoperation, thrombocytopenia developed with a platelet count of 3 x 10(4)/mm3. A peripheral blood film showed severe red blood cell (RBC) fragmentation. Thus, we made a clinical diagnosis of TMA and reduced the tacrolimus dose. We started intensive daily plasma exchange (4 L/d) with fresh frozen plasma and high-dose intravenous gamma-globulin infusions. One week thereafter, thrombocytopenia improved with reduced transfusion requirements. The peripheral blood film showed normal RBC morphology. The serum LDH returned to baseline levels. Four factors were considered to have caused TMA in this case: the prescription of tacrolimus, ABO-incompatible liver transplantation, bacterial infection, and surgical stress. These factors may have all contributed by causing significant endothelial injury and TMA.

Temporary Cardiac Pacing for Fatal Arrhythmia in Living-Donor Liver Transplantation: Three Case Reports

Cardiac pacing often turns out to be the only effective treatment of severe, life-threatening arrhythmias. We performed 77 living-donor liver transplantations (LDLT) from 1999 to 2007. In these cases, three recipients experienced fatal arrhythmia and required temporary cardiac pacing during the perioperative period. The first case was a 68-year-old woman diagnosed with liver cirrhosis and hepatocellular carcinoma (HCC). Her Model for End-Stage Liver Disease (MELD) score was 34. We performed LDLT using a right lobe graft. She showed complete atrioventricular block with cardiac arrest at postoperative day (POD) 42 after a bacterial infection. We performed a resuscitation and instituted temporary cardiac pacing. However, she was dead at POD 43. Pathologic findings at autopsy showed a diffuse myocardial abscess, which caused the fatal arrhythmia. The second case was a 58-year-old man diagnosed with HCC and liver cirrhosis; his MELD score was 9. We performed LDLT using a right lobe graft. He showed atrial fibrillation after septic shock. He also showed sinus bradycardia with a cardiac arrest at POD 10. We performed resuscitation and emergent temporary pacing. He recovered and was alive without recurrence of arrhythmia or infection. The third case was a 58-year-old woman diagnosed with multiple HCC. During preoperative regular check-up, she was diagnosed to have cardiac hypertrophy and was started on beta-blockers as treatment for cardiac hypertrophy. However, severe bradycardia necessitated temporary cardiac pacing. LDLT was performed safely after implantation of a pacemaker. Early use of temporary cardiac pacing for severe arrhythmias may be effective to maintain the hemodynamic state in LDLT.

Successful treatment for a benign esophagorespiratory fistula with perioperative nutritional management and multistep esophageal bypass operation: a case report

A 49-year-old man was referred to our hospital for treatment of an esophagorespiratory fistula following 5-year airway stenting for stenosis of tracheal anastomosis. In consideration of the prior polysurgery and the patient’s poor general status and malnutrition, we selected multistep esophageal bypass combined with feeding enterostomy for nutritional support. Respiratory symptoms and pneumonia were rapidly improved by esophageal transection and decompression via a catheter esophagostomy. Nutritional status was also improved by enteral nutrition via a catheter gastrostomy. Four months after the esophageal transection, we conducted an esophageal bypass using an ileocolonic conduit because the right gastroepiploic artery had been used for omental reinforcement of tracheal anastomosis. The patient had no postoperative complications and was discharged 53 days after the bypass surgery. Multistep esophageal bypass including feeding enterostomy for perioperative nutritional management is a safe and useful alternative to direct closure for a critically ill patient with an esophagorespiratory fistula who is at high risk for operative mortality.