Prognostic grade for resecting hepatocellular carcinoma: multicentre retrospective study.

BACKGROUND: Surgical treatment for hepatocellular carcinoma (HCC) is advancing, but a robust prediction model for survival after resection is not available. The aim of this study was to propose a prognostic grading system for resection of HCC. METHODS: This was a retrospective, multicentre study of patients who underwent first resection of HCC with curative intent between 2000 and 2007. Patients were divided randomly by a cross-validation method into training and validation sets. Prognostic factors were identified using a Cox proportional hazards model. The predictive model was built by decision-tree analysis to define the resection grades, and subsequently validated. RESULTS: A total of 16 931 patients from 795 hospitals were included. In the training set (8465 patients), four surgical grades were classified based on prognosis: grade A1 (1236 patients, 14.6 per cent; single tumour 3 cm or smaller and anatomical R0 resection); grade A2 (3614, 42.7 per cent; single tumour larger than 3 cm, or non-anatomical R0 resection); grade B (2277, 26.9 per cent; multiple tumours, or vascular invasion, and R0 resection); and grade C (1338, 15.8 per cent; multiple tumours with vascular invasion and R0 resection, or R1 resection). Five-year survival rates were 73.9 per cent (hazard ratio (HR) 1.00), 64.7 per cent (HR 1.51, 95 per cent c.i. 1.29 to 1.78), 50.6 per cent (HR 2.53, 2.15 to 2.98), and 34.8 per cent (HR 4.60, 3.90 to 5.42) for grades A1, A2, B, and C respectively. In the validation set (8466 patients), the grades had equivalent reproducibility for both overall and recurrence-free survival (all P < 0.001). CONCLUSION: This grade is used to predict prognosis of patients undergoing resection of HCC.

Significance of the surgical hepatic resection margin in patients with a single hepatocellular carcinoma.

BACKGROUND: The impact of a wide surgical margin on the outcome of patients with hepatocellular carcinoma (HCC) has not been evaluated in relation to the type of liver resection performed, anatomical or non-anatomical. The aim of this study was to evaluate the impact of surgical margin status on outcomes in patients undergoing anatomical or non-anatomical resection for solitary HCC. METHODS: Data from patients with solitary HCC who had undergone non-anatomical partial resection (Hr0 group) or anatomical resection of one Couinaud segment (HrS group) between 2000 and 2007 were extracted from a nationwide survey database in Japan. Overall and recurrence-free survival associated with the surgical margin status and width were evaluated in the two groups. RESULTS: A total of 4457 patients were included in the Hr0 group and 3507 in the HrS group. A microscopically positive surgical margin was associated with poor overall survival in both groups. A negative but 0-mm surgical margin was associated with poorer overall and recurrence-free survival than a wider margin only in the Hr0 group. In the HrS group, the width of the surgical margin was not associated with patient outcome. CONCLUSION: Anatomical resection with a negative 0-mm surgical margin may be acceptable. Non-anatomical resection with a negative 0-mm margin was associated with a less favourable survival outcome.

ANTECEDENTES: El impacto de un margen quirúrgico (surgical margin, SM) amplio en el resultado de pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) no ha sido evaluado en relación con el tipo de resección hepática realizada: anatómica o no anatómica. El objetivo del presente estudio fue evaluar el impacto del estado del SM en los resultados en pacientes sometidos a resección anatómica o no anatómica por un HCC solitario. MÉTODOS: Los datos de pacientes con un HCC solitario sometidos a resección parcial no anatómica (grupo Hr0) o resección anatómica de un segmento de Couinaud (grupo HrS) entre 2000 y 2007 se obtuvieron a partir de una base de datos nacional de Japón. En los grupos Hr0 y HrS se evaluaron la supervivencia global y la supervivencia libre de recidiva asociadas al estado microscópico del SM y a la amplitud del SM. RESULTADOS: Se incluyeron un total de 4.457 pacientes en el grupo Hr0 y 3.507 en el grupo HrS. Un SM microscópico positivo se asoció con una pobre supervivencia global en ambos grupos. Un SM negativo, pero a una distancia de 0 mm se asoció con una peor supervivencia global y libre de recidiva en comparación con aquellos asociados a un SM más amplio, solo en el grupo Hr0. En el grupo HrS, la amplitud del SM no se asoció con los resultados del paciente. CONCLUSIÓN: La resección anatómica con un SM negativo a una distancia de 0 mm puede ser aceptable. La resección no anatómica con un SM negativo a una distancia de 0 mm se asoció con resultados de supervivencia menos favorables.

Influence of anti-HBc seropositivity on the risk of hepatocellular carcinoma in HCV-infected patients after adjusting for confounding factors.

It is controversial whether past hepatitis B virus infection constitutes an additional risk of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV). The incidence of HCC between 1994 and 2004 was analysed among 1262 patients who were only positive for HCV. The cumulative incidence of HCC was assessed by Kaplan-Meier analysis and the difference between two groups was assessed by the log-rank test. The effect of anti-HBc positivity on the risk of HCC was assessed with multivariate Cox proportional analysis. Anti-HBc was positive in 522 (41.4%) patients. The proportion of male patients (56.7 vs 46.8%, P < 0.001) and mean age (60.8 vs 56.9 years, P < 0.001) were significantly higher in the anti-HBc positive group. HCC developed in 339 patients (mean follow-up 7.0 years), with cumulative incidence rates at 3, 5 and 10 years of 12.7, 24.5 and 41.9% in the anti-HBc positive group and 10.6, 17.7 and 33.4% in the negative group, respectively (P = 0.005). However, anti-HBc seropositivity did not reach statistical significance in multivariate analysis including age and gender (hazard ratio, 1.06; 95% CI, 0.85-1.31; P = 0.63). Anti-HBc positivity and HCC incidence were confounded by male gender and older age.

Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH.

BACKGROUND AND AIMS: Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study. METHODS: 62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors. RESULTS: The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence. CONCLUSIONS: Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.

Percutaneous radiofrequency ablation of liver cancer in the hepatic dome using the intrapleural fluid infusion technique.

BACKGROUND: Intrapleural fluid infusion improves ultrasonographic visualization of tumours in the hepatic dome. The aim of this study was to assess the safety and long-term efficacy of ultrasonographically guided percutaneous radiofrequency ablation for tumours in the hepatic dome with intrapleural infusion. METHODS: Of 2575 patients with hepatocellular carcinoma or hepatic metastases treated with radiofrequency ablation, intrapleural fluid infusion was performed in 587 patients for tumours in the hepatic dome. After the tip of a 14-G metallic needle was positioned in the pleural cavity under ultrasonographic guidance, 500-1000 ml of 5 per cent glucose solution was infused in 5-15 min. Radiofrequency ablation was performed using an internally cooled electrode. Long-term results were evaluated in 347 patients with a single hepatocellular carcinoma who were naive to any treatment. RESULTS: Intrapleural fluid infusion was successfully performed in all 587 patients. The major complication rate on a per tumour basis was similar for patients treated with and without intrapleural infusion (1.6 versus 1.6 per cent; P = 0.924). The overall and recurrence-free survival were both similar for naive patients with a single hepatocellular carcinoma treated with and without intrapleural infusion (P = 0.429 and P = 0.109 respectively). Intrapleural infusion was not associated with lower overall survival in multivariable analysis. CONCLUSION: With intrapleural fluid infusion, radiofrequency ablation for tumours in the hepatic dome was safe and effective, resulting in satisfactory overall and recurrence-free survival.

Mixed colony formation composed of erythroblasts and myeloblasts by leukemic blast progenitors in patients with erythroleukemia.

To determine the clonal origin and growth requirement of leukemic blast progenitors in erythroleukemia, acute myelogenous leukemia (AML) M6, T cell-depleted mononuclear cells obtained from 5 erythroleukemia patients were cultured in methylcellulose media. Although plating efficiency did not significantly differ from those in the other AML subtypes, the morphology of colonies in erythroleukemia was distinct. Two types of colonies were formed; one was composed of myeloblasts, and the other consisted of erythroblasts and myeloblasts. The "mixed" colony formation was not stimulated by interleukin-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor or erythropoietin. Both types of colonies were formed spontaneously in the absence of supplemented growth-stimulatory factor when cultured at high density. The results suggest that leukemic blast progenitors in erythroleukemia originated at the stage of bipotent hematopoietic precursor capable of differentiating into erythroid and myeloid lineages. The formation of mixed colonies composed of erythroblasts and myeloblasts in the absence of erythropoietin or colony-stimulating factor may indicate the deranged hematopoiesis in erythroleukemia.

The in vitro growth patterns and drug sensitivities of leukemic blast progenitors among the subtypes of acute myelocytic leukemia.

The in vitro growth activities and drug sensitivities of leukemic blast progenitors were compared among the subgroups of acute myelocytic leukemia (AML) classified according to the French-American-British (FAB) cooperative group. Leukemic cells separated from the peripheral bloods of AML patients were cultured in methylcellulose media, and the plating efficiencies of primary colonies (PE1) and secondary colonies after replating (PE2) were determined. PE1 and PE2 have been considered to reflect the capacities of terminal divisions and self-renewal of leukemic blast progenitors, respectively. PE1 and PE2 were variable among AML patients; these findings suggest that AML is a heterogeneous disease in terms of the proliferative activities of leukemic cells. No significant correlation was noted between PE1 or PE2 and the AML subtype. The sensitivities to cytosine arabinoside (Ara-C) of leukemic blast progenitors were studied in methylcellulose and suspension cultures. Ara-C sensitivity was not significantly correlated with the AML subtype, either. In contrast, there was statistically significant correlation between PE2 and the remission outcome of the patients, whereas PE1 was not significantly associated with the clinical outcome. The results in the present study indicate that the proliferative activity, especially self-renewal capacity, of leukemic blast progenitors is highly predictive of the prognosis of AML patients but is not significantly correlated with the AML subtype classified by the blast morphology.

Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses.

The epidermal growth factor receptor variant III (EGFRvIII) is exclusively expressed on the cell surface in ~50% of glioblastoma multiforme (GBM). This variant strongly and persistently activates the phosphatidylinositol 3-kinase-Akt signaling pathway in a ligand-independent manner resulting in enhanced tumorigenicity, cellular motility and resistance to chemoradiotherapy. Our group generated a recombinant single-chain variable fragment (scFv) antibody specific to the EGFRvIII, referred to as 3C10-scFv. In the current study, we constructed a lentiviral vector transducing the chimeric antigen receptor (CAR) that consisted of 3C10-scFv, CD3ζ, CD28 and 4-1BB (3C10-CAR). The 3C10-CAR-transduced peripheral blood mononuclear cells (PBMCs) and CD3(+) T cells specifically lysed the glioma cells that express EGFRvIII. Moreover, we demonstrated that CAR CD3(+) T cells migrated to the intracranial xenograft of GBM in the mice treated with 3C10-CAR PBMCs. An important and novel finding of our study was that a thalidomide derivative lenalidomide induced 3C10-CAR PBMC proliferation and enhanced the persistent antitumor effect of the cells in vivo. Lenalidomide also exhibited enhanced immunological synapses between the effector cells and the target cells as determined by CD11a and F-actin polymerization. Collectively, lentiviral-mediated transduction of CAR effectors targeting the EGFRvIII showed specific efficacy, and lenalidomide even intensified CAR cell therapy by enhanced formation of immunological synapses.

Serum lipoproteins in Japanese rural community with low cardiovascular mortality.

The lipid profiles of sera obtained from the adult inhabitants of a rural community with low cardiovascular mortality named Kin-cho in Okinawa were studied by the lipoprotein profiling system. The results were compared with those of the control sera obtained from healthy adults in Tokyo. Serum lipid profiles of the inhabitants in Kin-cho revealed significantly higher HDL cholesterol and significantly lower atherogenic indices than those of the control group in both sexes. The favorable lipid profiles as well as the open-minded temperament of Kin-cho inhabitants and favorable weather conditions are supposed to contribute to their long life expectancy and low cardiovascular mortality.

Percutaneous ethanol injection therapy for hepatocellular-carcinoma (review).

Recently, ultrasound-guided percutaneous ethanol injection therapy (PEIT) has been widely performed in the treatment of hepatocellular carcinoma. Histopathologic examinations after the therapy have revealed that PEIT can destroy the tumor completely in most cases. Findings in imaging modalities and serum tumor marker levels have also shown a remarkable anticancer effect of this procedure. In addition, PEIT has achieved considerably high long-term survival rates. PEIT is a generally safe procedure and serious complications are rare. PEIT seems to be a valuable therapy and could even be an alternative to surgery in the treatment of hepatocellular carcinoma. This paper reviews the pertinent literature on this new therapy.

New approach to transport improvement in a helical magnetic axis system by introduction of effective toroidal curvature

A new approach to transport improvement in a helical magnetic axis stellarator is proposed. First of all, the proposal is presented for the L = 1 system. The effective toroidal curvature term epsilon(T), defined as the sum of the usual toroidal curvature and one of the nearest satellite harmonics of the helical field, determines confinement conditions of localized trapped particles. There exists a certain correlation between the smallness of epsilon(T) and the omnigeneity. This approach would give rise to the possibility of a stellarator design study in a wider parameter domain than quasisymmetry approaches.

Churg-Strauss syndrome (allergic granulomatous angiitis) with multiple perforating ulcers of the small intestine, multiple ulcers of the colon, and mononeuritis multiplex.

A case of Churg-Strauss syndrome with multiple perforations of the small intestine is described. A 31-year-old woman was admitted with a complaint of epigastric pain. She had a history of bronchial asthma. One week before admission, white blood cell count was 20,800/mm3 with 59% eosinophils. Neurological examination on admission disclosed mononeuritis multiplex with paresthesia in both the lower and upper extremities. At colonoscopy, there were scattered aphthous ulcers in the colon. Ophthalmological examination revealed allergic conjunctivitis. After admission, hypereosinophilia increased to as high as 36,000/mm3. Oral administration of prednisolone (60 mg/day) was begun. On the 3rd day of the treatment, the eosinophil count decreased dramatically, to 400/mm3, while severe abdominal pain developed. Since abdominal X-ray film revealed free air in the abdominal cavity, emergency laparotomy was performed and multiple intestinal ulcers with perforations were found. Partial ileectomy was performed. Pathological findings of the resected specimen were interpreted as a necrotizing angiitis with extravascular granuloma. Since the operation, the patient has been asymptomatic, except for neurological symptoms. Hypereosinophilia has decreased without treatment to counts averaging 270/mm3, within 3 months. On the basis of the clinical features and histopathological findings, a diagnosis of Churg-Strauss syndrome was established.

A case of primary gastric choriocarcinoma and a review of the Japanese literature.

A 63-year old woman who had experienced melena for 2 weeks was admitted to Tokyo University Hospital. Gastric adenocarcinoma was diagnosed endoscopically and histologically, and a total gastrectomy was performed soon thereafter. Pathological examination of the resected stomach revealed choriocarcinoma of the stomach. Although chemotherapy was administered after surgery, she died 3 months after admission. Autopsy confirmed the diagnosis of primary gastric choriocarcinoma, a rare, but highly malignant tumor. It is characteristic; macroscopically it forms a necrotic mass with bleeding, and microscopically it often consists of adenocarcinoma and choriocarcinoma. Since its prognosis is extremely poor, we must take into account the possibility of primary gastric choriocarcinoma when a hemorrhagic gastric tumor with necrosis is found.

Pseudomyxoma peritonei due to adenocarcinoma of the lung: case report.

A rare case of pseudomyxoma peritonei whose primary site was presumed to be the lung is reported. A 76-year-old woman was admitted to Hospital presenting with progressive abdominal distention. She had been admitted twice, 2 and 1 year previously for the evaluation of high plasma carcinoembryonic antigen (CEA) level, of 11.6 ng/ml. Chest computed tomography (CT) scan and chest X-ray film on the third admission revealed a nodular lesion in the left lower lung field, and transbronchial lung biopsy (TBLB) revealed mucus-producing tall columnar epithelial carcinoma. Paracentesis revealed gelatinous ascitic fluid. At laparotomy, appendix and ovary were normal, and there were many small cystic tumors on the peritoneal surface and omentum. The patient died 2 years later, after repeated episodes of dynamic ileus. The lung and abdominal tumors gradually increased in size during the 2-year period, but she developed no respiratory symptoms. Based on both the clinical and pathophysiological findings, the final diagnosis made was pseudomyxoma peritonei whose origin was a lung adenocarcinoma.

Hepatocellular carcinoma depicted as hypoattenuation on CT hepatic arteriography (CTA) and hyperattenuation on CT during arterial portography (CTAP).

We report a 68-year-old man with three nodules of hepatocellular carcinoma (HCC) in a cirrhotic liver; the largest nodule was 3.0cm in diameter. The nodules showed hypoattenuation on computed tomography (CT) hepatic arteriography (CTA) and hyperattenuation on CT during arterial portography (CTAP), indicating that the dominant vascularity of the HCC nodules may have been the portal vein. A biopsy specimen obtained from the nodules showed well differentiated HCC (Edmondson-Steiner grade I). The imaging findings of the nodules on both CTA and CTAP are unusual, in spite of the rather large size, so this seemed suggestive of the hemodynamic properties of relatively large nodules of well differentiated HCC.

Early detection of haemobilia associated with percutaneous ethanol injection for hepatocellular carcinoma.

OBJECTIVE: Haemobilia often results from iatrogenic injury caused by therapeutic procedures. The objective of this study was to evaluate the efficacy of early diagnosis of haemobilia based on ultrasonography in patients with hepatocellular carcinoma undergoing percutaneous ethanol injection. PATIENTS AND METHODS: A combination retrospective and prospective study on the early detection of haemobilia caused by percutaneous ethanol injection was conducted on 365 patients in 1995-1996. The retrospective study reviewed the clinical, laboratory and imaging data of 172 patients who had undergone ethanol injection therapy in 1995. The results showed that ultrasonographic changes in the gallbladder, namely the rapid appearance of echogenic material in the gallbladder lumen, are a useful early sign of haemobilia. Based on the results of the retrospective study, a prospective study on the early detection of haemobilia was carried out in 1996. In the prospective study, percutaneous ethanol injection was halted as soon as haemobilia was detected. RESULTS: The incidence of haemobilia in the prospective group (3.6%) was not different from that in the retrospective group (4.7%). However, the mean duration between percutaneous ethanol injection and diagnosis of haemobilia was only 0.3 +/- 0.2 days in the prospective group, compared with 2.8 +/- 2.1 days in the retrospective group (P < 0.001), and the mean duration of jaundice in the prospective group (4.3 days) was significantly shorter than in the retrospective group (40.0 days) (P< 0.05). CONCLUSION: Early diagnosis of haemobilia based on ultrasonographic findings of the gallbladder lumen effectively reduces the severity of haemobilia-related complications due to immediate interruption of the interventional procedure.

[Past, present and future of optical cards for medical use].

In the hospital, the chart is an important medical information record. However, it is not easy to refer to chart records. Although a computer is useful in referring to the chart, the most critical defect is the lack of exchangeability between hospitals. An optical card is a new medium for medical use. It has a large capacity for electronic storage, low price and high security. Therefore, the author considers this card a second medical chart. As another card, there is the IC card, which has some limitations in medical use. Although both systems are being examined experimentally, there is no actual practice in the medical field. The reason for this lack of wide use, it is thought that these systems are not yet supported by national health insurance.

[Future of administration and management in clinical laboratory].

Some problems in administering and managing clinical laboratories relate to technology, safety and health. Total systematization will help resolve these problems, and includes several new ideas, such as total investigation, total automation, total safety, total flexibility, total standardization, total estimation and a totally open-door. Patient-orientation is also important. In our physiological department, this aim was obtained to some extent by the introduction of computerization, optical data filing system and personnel arrangement.

[Development of a user-friendly laboratory information system].

We developed user-friendly laboratory information system based on the responses of users who were shown many versions of prototypes. This method was applied to the development of on-line computer systems used by laboratory staff, and resulted in a decrease of difficulty using the systems, an improvement in the productivity of laboratory staff, and a decrease in the time needed for developing the systems.

[Personal laboratory data management system using optical card].

This paper describes the development and state of the medical optical card system. Recently, computerized medical information systems have been developed in many hospitals and they allow quick access and automatic processing of the patient's data in medical practice and research. However, the use of the information stored by such a system has been limited to each hospital while it is not rare for a patient to change hospitals. It is desirable to develop a personal medical data management system which allows the patient to carry his own medical records for a long period of time, and hospitals to share the information about the patient. The optical card is a transportable information medium with a large capacity. Since data are recorded optically with a laser beam, the card is tolerant to environmental factors such as static electricity, magnetism and impact which injure other transportable media such as IC card, magnetic stripe card and floppy disk. Therefore, the optical card suits our purpose. We developed a prototype of the medical optical card system. In our system, the card can contain character data, numerical data, two-valued image data and electrocardiographical data. In order to share laboratory data among different database systems, we defined a data descriptive language which enables complete and compact data description without any external code tables. The recorded patient data are presented in the original multi-window system, which allows the doctor to see any combination of any part of the patient's information simultaneously.