BACKGROUND/PURPOSE: To prevent or reduce hepatic complications after hepatectomy, it is important to employ preoperative predictive parameters and to determine the indications for hepatectomy. In the present study, we evaluated risk parameters in patients who underwent hepatectomy between 1994 and 2003, and selected three parameters to modify the surgical indications. Using these indications before surgery in patients who underwent hepatectomy between 2004 and 2008, we compared the prevalences of postoperative complications in the the two groups of patients. METHODS: We examined 250 consecutive patients who underwent hepatectomy for liver disease [149 in 1994-2003 (termed the early period) and 101 in 2004 to 2008 (termed the later period)]. RESULTS: In the early period, uncontrolled ascites was observed in 55 patients and hepatic failure was observed in 15 of the 149 patients. Multivariate analysis identified volume of the resected liver (>/=50%), intraoperative blood loss (>/=1500 ml), prothrombin activity (<70%), hyaluronic acid level (>/=200 ng/ml), and LHL15 (hepatic uptake ratio of technetium-99m galactosyl human serum albumin ((99m)Tc-GSA) (<0.85) as risk factors; the latter three parameters were evaluated as predictors of outcome. From 2004, we used these three parameters, in addition to the indocyanine green retention rate at 15 min (ICGR15), as criteria for indications for hepatectomy. Despite the lower prevalence of normal liver in the later period, comparisons showed decreases in the rates of uncontrolled ascites (23 vs. 37%, P = 0.03), hepatic failure (4 vs. 10%, P = 0.12), and hepatic complications (25 vs. 44%, P = 0.003) in patients in the later period compared with these rates in the previous period. CONCLUSIONS: The use of prothrombin activity, and levels of hyaluronic acid and LHL15, as parameters of functional liver reserve in the selection of candidates for surgery reduced the incidence of hepatic complications after hepatectomy.

The aim of this study was to evaluate the clinical outcomes of chest wall reconstruction using a new, expanded polytetrafluoroethylene prosthesis, 'DualMesh'. Between December 2005 and March 2010, chest wall reconstruction using 2-mm DualMesh was performed in 11 patients. The indication for resection was primary lung cancer in six patients, malignant mesothelioma in one patient, recurrent lung cancer in one patient, recurrent invasive thymoma in one patient, postirradiated osteomyelitis in one patient, and chondro-hamartoma in one patient. The mean observation period was 23 months, and four cases were observed for more than three years. There were no operative deaths and no wound infections. There were two postoperative complications: prolonged air leakage occurred in a patient with pulmonary emphysema who underwent right lower lobectomy, and slight paradoxical respiration occurred in the patient who underwent resection of the entire sternal body for osteomyelitis. Follow-up chest computed tomography was performed routinely. No dehiscence occurred in any cases. Chest wall reconstruction using DualMesh demonstrated acceptable durability and biocompatibility, even after long-term follow-up. DualMesh has the potential to become an ideal prosthesis for the bony chest wall as an alternative to conventional polytetrafluoroethylene or polypropylene grafts. Keywords: DualMesh; Expanded polytetrafluoroethylene; Chest wall reconstruction.

BACKGROUND/AIMS: Cancer death in the early period after hepatectomy remains problematic in patients with hepatocellular carcinoma (HCC). We examined the relationship between clinicopathological parameters' and survival periods in 234 HCC patients who underwent hepatectomy. METHODOLOGY: Patients were divided into four groups: Group 1, survival > 5 years; Group 2, survival for 2-5 years; Group 3, cancer death at 2-5 years; and Group 4, cancer death in < 2 years. RESULTS: Numbers of patients in each subgroup were: Group 1, n = 87 (37%); Group 2, n = 44 (19%); Group 3, n = 46 (20%); and Group 4, n = 57 (24%). Child-Pugh B status, blood loss > 1500 ml, multiple tumors, tumor size > 5 cm, not meeting Milan criteria, irregular macroscopic findings, invasion of Glissonian pedicle, invasion of hepatic vein, higher modified Japan Integrated Staging score (3-5), long-term ascites after hepatectomy and postoperative tumor recurrence within 12 months were frequent in Group 4 ( p < 0.05). Multivariate analysis revealed AFP level > or = 1000 ng/ml (hazard ratio (HR), 2.6) and early tumor relapse (HR, 8.1) as independently related parameters ( p < 0.05). CONCLUSIONS: Careful follow-up for early tumor relapse may be important for improving postoperative outcomes in HCC patients with high preoperative AFP levels.

There is strong evidence that the angiopoietin family is involved in the regulation of tumour progression, cellular growth and differentiation. Recently, it has been reported that angiopoietin-like 4 (ANGPTL4) in cancer cell promotes the metastatic process by increasing vascular permeability. To elucidate ANGPTL4 expression and its association with clinicopathological factors and prognosis in human gastric adenocarcinomas, we examined 103 cases of surgically-resected human gastric adenocarcinoma by immunohistochemistry. Among 103 cases of adenocarcinoma, 38 cases (36.9%) showed positive staining in the cytoplasm of the carcinoma cells for ANGPTL4. Histologically, papillary and mucinous adenocarcinomas showed relatively high expression of ANGPTL4 (60 and 60%, respectively). The expression of ANGPTL4 was correlated with the depth of tumour invasion (p<0.005), lymph node metastasis (p<0.001), venous invasion (p<0.00005) and TNM stage (p<0.001) in the total carcinoma. In univariate survival analysis, ANGPTL4 expression was not associated with the overall survival. RT-PCR or Western blot analysis showed the expression of mRNA or protein of ANGPTL4 in all four surgically-resected samples and all four cell lines of human gastric adenocarcinoma. ANGPTL4 expression was correlated with several clinicopathological factors, especially venous invasion. These findings suggest that the ANGPTL4 is one of the factors involved in the progression of human gastric cancer.

BACKGROUND: Photodynamic therapy (PDT) is a relatively new approach for the treatment of biliary tract carcinoma, and its effects have not been investigated in detail to date. This study investigated the mechanisms of human biliary cancer cell death by PDT by focusing on apoptosis induction in vitro and in vivo. MATERIALS AND METHODS: In vitro, NOZ cells were incubated with porfimer sodium (Photofrin(R)) for up to 24 hours before exposure to laser light. Cell viability was assessed using a methyltetrazolium assay after PDT. DNA fragmentation, cell cycle analysis and caspase-3 activity assay were performed to evaluate apoptotic cells induced by PDT. In vivo, DNA fragmentation was detected by TUNEL assay. RESULTS: DNA ladder formation and activation of caspase-3 were observed within 24 hours. The proportion of cells with DNA fragmentation on flow cytometric analysis was increased significantly to 22.2% at 24 hours after PDT. In the in vivo model, TUNEL-positive cells began to increase in the implanted tumour from 6 hours after PDT, and peaked 12 hours later. CONCLUSION: PDT with Photofrin in this human biliary cancer cell line has antitumor effects and induces apoptotic cell death after PDT.

OBJECTIVE: The purpose of this study was to evaluate the clinical significance of multiple focal pure ground-glass opacities (GGOs) on high-resolution CT images of patients with lung cancer. MATERIALS AND METHODS: The cases of 23 patients with proven lung cancer and associated multiple focal pure GGOs on high-resolution CT images were retrospectively reviewed. The number, size, distribution, and morphologic characteristics of focal pure GGOs were evaluated. Serial changes in focal pure GGOs that were not surgically resected were analyzed at follow-up high-resolution CT. RESULTS: The number of focal pure GGOs was 196 in total. The size of the opacities ranged from 2 to 30 mm in largest diameter. Lung cancer and focal pure GGOs were seen in the same lobe and/or in the other lobes. One hundred seventy-one of the lesions (87%) had a well-defined border or round shape. Histologic findings were obtained for 15 lesions representing 74 focal pure GGOs that were surgically resected: 11 atypical adenomatous hyperplasia lesions, three bronchioloalveolar carcinomas, and one lesion of focal fibrosis. In 110 of the cases of focal pure GGOs, all of which were followed up with HRCT for a median duration of 1,351 days, the size of 105 lesions (95%) did not change, the size of one decreased, and four lesions disappeared. CONCLUSION: The size of most focal pure GGOs associated with lung cancer did not change during the follow-up period. Most of the small number of lesions histologically diagnosed were atypical adenomatous hyperplasia or bronchioloalveolar carcinoma. These data justify the therapeutic strategy of resecting the primary tumor without therapeutic intervention in the remaining focal pure GGOs.

BACKGROUND: Minimization of blood loss during resection of the hepatic parenchyma in hepatectomy remains a major problem. The usefulness of the LigaSure sealing system has been reported. OBJECTIVES: To evaluate the efficacy of combination procedure of LigaSure and forceps clamping for control blood loss and transection time in hepatectomy. METHODS: Here, we report our experience with the combination technique of LigaSure Precise, a clamp forceps type, and crush clamping method for hepatic transection in 33 patients who underwent hepatectomy. RESULTS: The combination technique allows fast and bloodless transection even along the major intrahepatic vessels. Blood loss and transection time were significantly reduced in the group of LigaSure use (P < 0.05). Efficient hemostasis could be achieved also in patients with extensive liver injury such as cirrhosis. The rates of postoperative intraabdominal abscess formation in the combination technique of LigaSure and crush clamping were lower compared with the conventional crush clamping method (P < 0.05). CONCLUSIONS: The combined use of LigaSure Precise and crush clamping technique is safe and allows rapid completion of hepatic resection. J. Surg. Oncol. 2010;102:179-183. (c) 2010 Wiley-Liss, Inc.

Keratinocyte growth factor (KGF) is involved in the development and regeneration of a variety of tissues. To clarify the role of KGF in cartilage wound healing, we examined the expression of KGF and its receptor (KGFR) immunohistochemically in the wound healing area of rat tracheal cartilage, and the direct effect of recombinant KGF on the proliferation and differentiation of primary cultures of rat chondrocytes. KGF was found in the cytoplasm of both chondrocytes and perichondrial cells. On the other hand, KGFR was detected only in the plasma membrane of chondrocytes. Although the expression of KGF was similar in the cartilage and perichondrial area before and after injury, KGFR expression was induced after injury and limited to proliferating chondrocytes. The staining pattern of KGF and KGFR was same in the mature and the immature rat tracheal cartilage. Moreover, in vitro experiments using primary cultured chondrocytes revealed that KGF at 200 ng/ml significantly increased the number of chondrocytes (~1.5-fold), and significantly reduced acid mucopolysaccharide production. These results indicate that KGF stimulates chondrocyte proliferation, suggesting that KGF could therapeutically modulate the wound healing process in the tracheal cartilage.

Familial arteriovenous malformations (AVM) in the brain is a very rare disease. It is defined as its occurrence in two or more relatives (up to third-degree relatives) in a family without any associated disorders, such as hereditary hemorrhagic telangiectasia. We encountered a Japanese family with brain AVM in which four affected members in four successive generations were observed. One DNA sample extracted from leukocytes of the proband and ten DNA samples from clipped finger nails of other members were available. A genome-wide linkage analysis was performed on this pedigree using Affymetrix GeneCip 10K 2.0 Xba Array and MERLIN software. We obtained sufficient performance of SNP genotyping in the fingernail samples with the mean SNP call rate of 92.49%, and identified 18 regions with positive LOD scores.Haplotype and linkage analyses with microsatellite markers at these regions confirmed three possible disease-responsible regions, i.e., 5p13.2-q14.1, 15q11.2-q13.1 and 18p11.32-p11.22. Sequence analysis was conducted for ten selected candidate genes at 5p13.2-q14.1, such as MAP3K1, DAB2, OCLN, FGF10, ESM1, ITGA1, ITGA2, EGFLAM, ERBB2IP, and PIK3R1, but no causative genetic alteration was detected. This is the first experience of adoption of fingernail DNA to genome-wide, high-density SNP microarray analysis, showing candidate brain AVM susceptible regions.

BACKGROUND/AIMS: Thoraco-abdominal approach is a suitable choice for hepatectomy to secure good view for mobilization. The aim of this study was to assess efficacy of thoraco-abdominal approach (TAA) for hepatectomy. METHODOLOGY: There were compared clinicopathological data, surgical results and postoperative complications of 425 consecutive patients who underwent hepatectomy via abdominal (AA) (n = 147) or TAA (n = 278). RESULTS: Blood loss and operating time were significantly higher in TAA than AA group (970 vs. 830 ml and 408 vs. 372 min.) (p < 0.05). Prevalence of pleural effusion was significantly higher in TAA than AA group (24 vs. 9%) (p < 0.01). However, proportions of patients who developed hepatic complications such as biloma (14 vs. 23%), and wound infection (8 vs.25%) were significantly less in TAA than AA group (p < 0.05). Hospital stay after hepatectomy and mortality were similar between both groups. Presence of chronic viral hepatitis, lower platelet count, higher level of serum hyaluronic acid, larger blood loss and TAA correlated significantly with thoracic complications (p < 0.05). Multivariate analysis showed that increased blood loss (p = 0.011), but not TAA, was a significant determinant of thoracic complications (p = 0.08). CONCLUSIONS: TAA can be considered a relatively safe approach for hepatectomy with minimal abdominal complications nevertheless of frequent pleural effusion.

Intrahepatic clear cell cholangiocarcinoma is very rare - only 8 cases have been reported. A 56-year-old Japanese man with chronic hepatitis B infection was diagnosed with a 2.2 cm hepatocellular carcinoma on imaging, and hepatic segmentectomy was performed. Histopathologically, the tumor cells had copious clear cytoplasm and formed glandular structures or solid nests. These pathological findings suggested the tumor was a clear cell variant of intrahepatic cholangiocarcinoma. Particular stains and radiological images suggested that the cause of the clear cell change had been glycogen, not mucin nor lipid. On immunohistochemical staining, cytokeratin (CK) 7 and CK19 were positive, whereas CK20 was negative. Vimentin was detected on the cell membranes, and CD56 was focally positive. The patient was given adjuvant chemotherapy and is currently free from the tumor 7 mo postoperatively. Careful follow-up with adequate postoperative supplementary chemotherapy is necessary because the characteristics of this type of tumor are unknown.

We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer. The immunohistochemical analyses revealed substantially aberrant IRF3 expression specific to the cancer lesions (2 and 6 tumors with nuclear staining, and 4 and 5 tumors with negative staining, in adenocarcinoma and squamous cell carcinoma, respectively), while the morphologically normal region around the tumors exhibited only cytoplasmic staining. In addition, we determined the sequence of the entire IRF3 coding region, and found two novel variants with the amino acid changes (S(175)(AGC)-->R(175)(CGC) and A(208)(GCC)-->D(208) (GAC)). The R(175) variant was also detected in a morphologically normal region around the nuclear staining squamous cell carcinoma, and exhibited almost the same functions as the wild type IRF3. On the other hand, the D(208) variant, found in the negative staining squamous cell carcinoma cases, reduced the nuclear translocation in response to IkappaB kinase epsilon stimulation, as compared to the wild type IRF3, but the same variant was detected in the surrounding morphologically normal region. The aberrant expression of IRF3 and the novel D(208) variant may provide clues to elucidate the etiology of primary lung cancer.

BACKGROUND: It is difficult to diagnose lymph node metastasis in biliary and pancreas carcinomas before surgery. AIM: The aim of this study was to assess the utility of the combination of multi-detector computed tomographic (MDCT) findings and serum carbohydrate antigen (CA)19-9 level in the diagnosis of lymph node metastasis in biliary and pancreas carcinomas. METHODS: The subjects were 139 patients with biliary and pancreas carcinomas who underwent surgical resection. We calculated the positive predictive values (PPV), sensitivities, specificities, positive likelihood ratios (PLR) and accuracies of diagnosis by MDCT alone, serum CA19-9 level alone, and their combination. RESULTS: The PPV and sensitivity were higher for node metastasis in hepatoduodenal ligament than in common hepatic artery (CHA) or para-aortic region (PAR). Specificity, accuracy and PLR were highest for CHA in biliary carcinoma. With pancreatic carcinoma, PLR was slightly higher in PAR compared to other regions. The sensitivity of CA19-9 for node metastasis was higher than that of MDCT, while the PPV, specificity, accuracy and PLR were low for both biliary and pancreas carcinoma. The combination of positive CT findings and high CA19-9 level had the highest positive rate for node metastasis for both types of carcinomas. Nodes around the supra-mesenteric vein could not be fully observed on CT. CONCLUSION: The combination of high-resolution MDCT and CA19-9 is useful for the diagnosis of lymph node metastasis in biliary and pancreas carcinomas.

BACKGROUND AND OBJECTIVES: Vascular infiltration (VI) is an important prognostic factor for hepatocellular carcinoma (HCC) and predictive parameters are necessary to preoperatively decide treatment strategies in patients with HCC. METHODS: Relationships between presence and degree of VI in the portal and hepatic veins and bile duct, and post-hepatectomy survival were examined in 271 HCC patients who underwent hepatectomy. RESULTS: VI was observed in 81 patients (30%). Disease-free and overall survival rates was significantly lower in patients with VI than in patients without VI, and became poorer according to the degree of infiltration (P < 0.01). Multiple, increased size, non-meeting of Milan criteria, irregular macroscopic findings and increased PIVKA-II levels were associated with degree of VI in portal vein (P < 0.01). Increased size and increased PIVKA-II level were associated with degree of VI in hepatic vein (P < 0.05). Non-meeting of Milan criteria was associated with degree of infiltration in bile duct (P = 0.034). Survival was significantly better following anatomical resection than with non-anatomical resection and, furthermore, survival was better with surgical margins >5 mm than with shorter margins in patients who underwent non-anatomical resection. CONCLUSION: Adequate extent of operative procedures, but not limited resection with short margins, is useful when predictive parameters associated with VI are observed. J. Surg. Oncol. (c) 2010 Wiley-Liss, Inc.

BACKGROUND: First-line treatment for </=3 hepatocellular carcinomas (HCCs) </=3 cm in size remains controversial. The superiority of survival benefit needs to be clarified between these modalities for such lesions. METHODS: We examined post-treatment survival of 144 consecutive HCC patients who underwent hepatectomy and of 56 consecutive HCC patients who underwent thermal ablation therapy limited to the HCC (</=3 cm, </=3 lesions). RESULTS: Pretreatment liver function was significantly worse and prevalence of Child-Pugh classification B/C was significantly higher in the ablation group compared to the hepatectomy group. Prevalence of tumor recurrence after treatment did not differ significantly between groups, irrespective of solitary or multiple HCC. In solitary HCC, overall survival rates in both groups did not differ significantly. Even in Child-Pugh B patients, survival was not significantly different between hepatectomy and ablation. In HCC with 2-3 lesions </=3 cm, overall survival was significantly longer with hepatectomy than with ablation and mean survival periods in the hepatectomy and ablation groups were 4.5 and 1.2 years, respectively. CONCLUSION: In cases of multiple small HCCs, hepatic resection is recommended over local ablation therapy as the first-line treatment in cases where liver function has been preserved. J. Surg. Oncol. (c) 2010 Wiley-Liss, Inc.

Diffuse alveolar hemorrhage (DAH) syndrome is potentially fatal. We encountered a nearly fatal case of DAH possibly due to intravenous itraconazole (ITCZ). A 53-year-old man with chronic pulmonary aspergillosis underwent pneumonectomy of the left lung 15 days prior to the onset of DAH, which was confirmed by bronchoalveloar lavage. The battery of diagnostic evaluations performed revealed no other positive etiological factor, leading to the diagnosis of DAH possibly induced by intravenous ITCZ with a positive drug lymphocyte stimulation test. The patient did not respond to pulse methylprednisolone therapy, but responded dramatically to direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX) therapy.

BACKGROUND: The histopathologic pattern is currently the most important prognostic marker for idiopathic interstitial pneumonia (IIP). However, more highly sensitive markers are now required. Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and it has been demonstrated that HSP47 expression is significantly higher in the lung specimens of idiopathic UIP than in UIP associated with collagen vascular diseases (CVD). However, its expression in nonspecific interstitial pneumonia (NSIP), the other common pathological pattern of IIP, has not been well investigated. Therefore, the association between lung fibroblast HSP47 expression and prognosis in fibrotic NSIP was evaluated. METHODS: Surgical lung biopsy specimens of 63 patients [idiopathic fibrotic NSIP=19, fibrotic NSIP associated with CVD=9, idiopathic UIP=26, and UIP associated with CVD=9] were reviewed, and a score for lung fibroblast HSP47 expression was assigned. These patients' clinical features and survival were also analyzed. RESULTS: There was no significant difference in HSP47 expression between idiopathic fibrotic NSIP and fibrotic NSIP associated with CVD. The idiopathic fibrotic NSIP patients with higher HSP47 expression levels in their lung specimens had a poorer prognosis than patients with lower HSP47 expression levels. CONCLUSIONS: The present results suggest that lung fibroblast HSP47 expression may be a useful new prognostic marker for idiopathic fibrotic nonspecific interstitial pneumonia.

A case of traumatic pancreatitis with subsequent joint pain and osteolytic lesions is presented. A 10-year-old girl was admitted to our hospital with abdominal pain caused by blunt epigastric injury. She was diagnosed with traumatic pancreatitis, and multiple pancreatic pseudocysts subsequently developed. Two weeks after admission, she complained of joint pain, and MR revealed osteolytic lesions of both knee joints. On the 58th day, endoscopic transgastric pseudocyst drainage was performed. Joint pain and osteolytic lesions resolved rapidly, in parallel with the decrease in serum amylase level and pseudocyst size.