Kuniaki Kojima

Hepatic resection using the harmonic scalpel.

We describe herein our technique of performing extensive resection of the liver by blunt dissection in combination with excision using a harmonic scalpel. A ball coagulator was inserted at 3-cm intervals along the proposed cutting line in the liver, and the liver parenchyma between these holes was then cut using coagulation shears. Regardless of the condition of the liver, good coagulation and cutting were achieved using the harmonic scalpel without vascular occlusion when dividing the shallow layer of the liver, and no complications in association with the harmonic scalpel, such as postoperative bleeding, bile leakage, or abscess formation at the cut margins, occurred. In the deep layer below the main trunk of the hepatic vein, blunt dissection was used, since it was difficult to achieve sufficient control of bleeding from large vessels using the harmonic scalpel alone. Therefore, when used in combination with other techniques, the harmonic scalpel appears to be an effective device for liver surgery that minimizes bleeding and decreases the vascular clamping time.

The Significance of p53 Mutations as an Indicator of the Biological Behavior of Recurrent Hepatocellular Carcinomas

The significance of p53 mutations in the primary lesion for recurrent hepatocellular carcinoma (HCC) was evaluated. Mutations of p53 were examined using non-radioisotopic (nonRI)-polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) in 98 resected HCCs. Of the 98 cases, 25 (26%) had a p53 mutation. In 83 patients who survived surgery, the presence of a p53 mutation was associated with a shortened overall survival (P<0.001) and a shortened cancer-free survival (P<0.05). In 43 patients who developed recurrence, there was no statistically significant correlation between the status of p53 in the primary lesion and the clinical features of recurrent HCCs examined, i.e., extrahepatic metastasis, the number of recurrent tumors, extent of recurrent tumors, and treatment for recurrent tumors. However, postrecurrence survival was significantly lower in patients in whom a p53 mutation had been detected in the primary lesion (P<0.01). A multivariate analysis for prognostic value after recurrence revealed that the p53 mutation was a useful independent prognostic factor affecting survival after recurrence (P<0.01). In conclusion, our findings suggest that HCCs with p53 mutations have a high malignant potential based on their poor prognosis. Therefore, a p53 mutation in the primary lesion is useful as an indicator of the biological behavior of recurrent HCCs.

Role of Preoperative Transcatheter Arterial Chemoembolization for Resectable Hepatocellular Carcinoma: Relation between Postoperative Course and the Pattern of Tumor Recurrence

The effects of preoperative transcatheter arterial chemoembolization (TACE) were retrospectively evaluated in patients with resectable hepatocellular carcinoma (HCC). A total of 227 patients who underwent hepatectomy for HCC were studied (146 underwent preoperative TACE and 81 did not). We compared operative outcome, mortality, and disease-free survival between TACE and non-TACE groups. We also compared the pattern of recurrence and postrecurrence survival between subgroups according to staging. Of the 227 patients, 105 with tumor stage I-II were assigned to group A (group A/TACE, n = 69; group A/non-TACE, n = 36), and the remaining 122 with tumor stage III-IV were assigned to group B (group B/TACE, n =77; group B/non-TACE, n =45). Complete necrosis was found to be more frequent in the TACE group (p < 0.01). Operating time, blood loss, and mortality did not differ between those who did and did not undergo preoperative TACE. TACE did not significantly improve disease-free survival within either the entire TACE group or group A/TACE. In contrast, in group B/TACE the disease-free survival rates were significantly higher than in group B/non-TACE. Furthermore, both extrahepatic metastasis and diffuse intrahepatic metastasis were significantly more frequent in group B/non-TACE than in group B/TACE. The preoperative TACE also improved the postrecurrence survival in group B. We speculate that preoperative TACE reduced tumor recurrence and that it might confer a survival advantage after surgery, particularly in patients with advanced HCC. In addition, it is expected that this procedure may improve the pattern of tumor recurrence when it does occur.

Relationship between the histological degrees of hepatitis and the postoperative recurrence of hepatocellular carcinoma in patients with hepatitis C

The relationship between the recurrence of hepatocellular carcinoma (HCC) and the degree of inflammation was evaluated in resected livers with the hepatitis C virus (HCV) -associated HCC. Seventy-three patients with HCV-associated HCC who were followed up for more than 2 years were selected for this study. In these cases, the degree of chronic hepatitis in noncancerous regions at the time of surgery was classified according to the New Inuyama Classification as follows, the degree of necroinflammatory activity (Grading) was graded from A0 to A3, and the degree of fibrosis (Staging) was staged on F0-F4. In addition, among these patients, 41 patients who were followed by blood tests every 3 months were divided into two groups (high or low group) according to annual average levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), the platelet counts (Plt), and alpha-fetoprotein (AFP). As a result, cancer-free survival rate was significantly lower in the high-grade group (A3) than in the low-grade group (A1 or 2) (P=0.01). The high ALT (>80 IU) group and the high AFP (>20 mg/ml) group also had significantly worse cancer-free survival rate than the low ALT group and the low AFP group (P=0.04 for ALT, P=0.03 for AFP). A multivariate analysis for the prognostic values revealed the AFP level (P=0.02) and the Grading (P=0.04) were useful as independent prognostic factors concerning recurrence. In conclusion, the degree of inflammatory activity (Grading) is considered to be a useful factor regarding recurrence after liver resection in patients with HCC. Furthermore, the inhibition of inflammation in remnant liver may also contribute to the prevention of recurrence.

IgG4‐related tumour‐forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour‐forming mastitis

Ogura K, Matsumoto T, Aoki Y, Kitabatake T, Fujisawa M & Kojima K
(2010) Histopathology 57, 39–45
IgG4‐related tumour‐forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour‐forming mastitis

Detecting KRAS mutations in peripheral blood of colorectal cancer patients by peptide nucleic acid clamp PCR

We investigated the effectiveness of peptide nucleic acid (PNA) clamp PCR for detecting KRAS mutations in peripheral blood samples of colorectal cancer (CRC) patients. We compared KRAS point mutations between tumour tissue and blood samples. Forty-two patients were included in this study. We observed KRAS mutations in formalin-fixed, paraffin-embedded tissues by PCR direct sequencing and in blood samples by PNA clamp PCR. KRAS point mutations were detected in primary tumour tissue samples of 13 patients (31.0%) and in peripheral blood samples of 10 patients (23.8%). KRAS point mutations were detected in both samples for 8 patients (19.0%). The sensitivity, specificity and accuracy for detecting KRAS mutations in peripheral blood and tumour tissue samples were 61.5, 93.1 and 83.3%, respectively. The positive and negative predictive values were 80.0 and 84.4%, respectively. Five patients with mutant KRAS in their plasma preoperatively, did not exhibit KRAS mutations postoperatively. Our method detected KRAS point mutations in peripheral blood samples of CRC patients, which contained extremely small amounts of mutant cells. This method is helpful for identifying metastatic CRC patients in whom metastases will respond to EGFR-targeted monoclonal antibody therapy.

Correlation of Thymidine Phosphorylase Staining and the Ki-67 Labeling Index to Clinicopathologic Factors and Hepatic Metastasis in Patients with Colorectal Cancer

AbstractPurpose. Our aim was to investigate the thymidine phosphorylase (TdRPase) expression and Ki-67 labeling index (LI) of primary tumors of colorectal cancer and hepatic metastases immunochemically and to evaluate the relationship of these parameters to various clinicopathologic factors and hepatic metastasis. Methods. We performed immunochemical studies in 74 patients with colorectal cancer, using anti-TdRPase antibody and MIB-1 antibody. Results. TdRPase expression and a Ki-67 LI ≧30% in primary lesions were significantly more common in patients with lymphatic invasion (ly), venous invasion (v), lymph node involvement (n), and hepatic metastasis. A Ki-67 LI ≧ 30% of the primary tumor was associated with a significantly higher frequency of metachronous liver metastasis. In the same patients, the mean Ki-67 LI was 24.3 ± 17.9 for primary lesions and 5.0 ± 4.2 for hepatic metastases, this difference being significant. Conclusions. These results indicate that TdRPase expression and the Ki-67 LI are related to various clinicopathologic factors, suggesting their usefulness as indices of tumor malignancy. We suggest that the Ki-67 LI of primary colorectal cancer could be an important predictor of the future development of metachronous liver metastasis.

Long-Term prognosis of non-shunt operation for idiopathic portal hypertension

Abstract: This report presents 46 Japanese patients with idiopathic portal hypertension (IPH) in whom non-shunt operation was performed for the management of esophageal varices. Non-shunt operation included transthoracic esophageal transection (Sugiuras procedure) in 37 patients, transabdominal esophageal transection (TAET) in 3 patients, and Hassabs procedure in 6 patients. Rates of postoperative variceal eradication were: 78.4% by Sugiuras procedure; 100% by TAET; and 50% by Hassabs procedure. The cumulative rates for recurrent varices and recurrent bleeding were 3.9%, and 5.1%, respectively, at 5 years, and 8.9% and 9.8% at both 10 and 15 years. Only 3 patients required additional endoscopic injection sclerotherapy to treat recurrent varices. Although 3 patients developed upper gastrointestinal bleeding, the source of hemorrhage was esophageal varices in 1, and portal hypertensive gastropathy in 2; none of the patients died from bleeding. Actuarial survival for all patients was 87.5% at 5 years, 77.9% at 10 years, and 58.8% at 15 years. There were no deaths within the first 30 days after surgery. These results show that non-shunt operation is useful in preventing bleeding from esophageal varices in patients with IPH.

Early Diagnosis of Postoperative Infection : Assessment of Whole Blood Chemiluminescence

Abstract: Whole blood chemiluminescence (CL), which allows for the evaluation of both the oxygen radical release by phagocytes and the serum opsonin activity using very small amounts of blood, is considered to be a useful means of assessing the host defense against infection. We measured the whole blood chemiluminescence in 59 patients before and after open surgery (surgery by a laparotomy) for gastrointestinal disease. Early postoperative infection was detected in 12 (20.3%) of the 59 patients. These 12 patients all had significantly higher white blood cell counts compared with the noninfected patients on the third and subsequent days after surgery ( P < 0.01). The peak CL in the early postoperative infected group was also significantly higher than that in the noninfected group on the day of surgery ( P < 0.0001), 1 day after surgery ( P <≧0.0001), and 3 days after surgery ( P < 0.01). Whole blood CL may therefore be a useful modality for the early detection of postoperative infection in the future.

Immunohistochemistry of p53, Bcl-2, and Ki-67 as predictors of chemosensitivity.

Chemosensitivity is affected by molecular biological factors, including factors related to the induction of apoptosis and the activity of proliferation. We analyzed immunohistochemically the expression of p53, Bcl-2, and Ki-67 in various types of cancers and assessed the correlation between this expression and chemosensitivity. Moreover, we investigated whether the expression of these factors could be a useful predictor for the clinical response to chemotherapy. Study subjects comprised 63 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 12 with stomach cancer, 12 with colon cancer, 16 with liver cancer, and 14 with breast cancer). Immunohistochemical staining (the labeled streptavidin biotin technique: LSAB method) was used to assess expression of p53 protein, Bcl-2 protein, and Ki-67. A chemosensitivity test was carried out with the histoculture drug response assay method using four drugs: mitomycin C, 5-fluorouracil, doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical studies for p53 were found to be useful for predicting chemosensitivity.