Gene Expression Profile Prospectively Predicts Peritoneal Relapse After Curative Surgery of Gastric Cancer

Background

Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction.

Methods

RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity.

Results

In the retrospective phase, repeated random validation yielded ~68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis of peritoneal-relapse-free survival showed a significant difference between the “good signature group” and “poor signature group” (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse.

Conclusions

Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.     

The giant schwannoma in the pelvic cavity: a case report

A 62-year-old man presented with a giant tumor in the pelvic cavity that was incidentally revealed by abdominal ultrasonography. Abdominal magnetic resonance imaging showed the heterogenous tumor in the pelvis with cystic components. The tumor was 10.8 × 10.5 × 11.7 cm in diameter and adhered to the sacral wall. The tumor was extirpated following diagnosis as a benign neurogenic tumor by needle biopsy. The pelvic cavity was occupied by the tumor rigidly adhered to the sacrum. The histopathological diagnosis of the specimen was benign schwannoma, type Antoni A.     

Hepatocyte transplantation through the hepatic vein: a new route of cell transplantation to the liver

The efficiency of hepatocyte transplantation into the liver varies with the method of administration. This study investigated whether retrograde infusion via the hepatic vein provides a sufficient number of donor cells for the liver. Donor hepatocytes were isolated from dipeptidyl peptidase IV (DPPIV(+)) rats and transplanted into DPPIV(-) rat livers either by antegrade portal vein infusion or retrograde hepatic vein infusion. Hepatocyte engraftment ratios and localization were evaluated by histological DPPIV enzymatic staining at 1 week and 8 weeks after the transplantation. No significant differences in engraftment efficiency were observed at either 1 week or 8 weeks after transplantation by either route. However, the localization of the transplanted hepatocytes differed with the administration route. Portal vein infusion resulted in predominantly periportal engraftment, whereas hepatic vein infusion led to pericentral zone engraftment. Immunohistochemical analysis showed that the transplanted hepatocytes engrafted in the pericentral zone after retrograde infusion displayed intense CYP2E1 staining similar to the surrounding native hepatocytes. CYP2E1 staining was further enhanced by administration of isosafrole, an inducing agent for various cytochrome P450 enzymes, including CYP2E1. This study demonstrates a novel approach of transplanting hepatocytes into the liver through retrograde hepatic vein infusion as the means to target cell implantation to the pericentral zone.     

A case of large bladder hemangioma successfully treated with endoscopic yttrium aluminium garnet laser irradiation

Bladder hemangioma is a rare benign tumor. While partial cystectomy remains an effective treatment option for large bladder hemangioma, the combined method of neodymium:yttrium aluminium garnet and holmium:yttrium aluminium garnet laser irradiation is an effective and less invasive treatment option. We report a case of large bladder hemangioma in an otherwise healthy 4-year-old boy, successfully treated with serial endoscopic yttrium aluminium garnet laser irradiation. There was no recurrence, and normal bladder function was preserved. Serial yttrium aluminium garnet laser irradiation is thus a useful, less invasive method for cases of large tumors.     

A patient with hypophosphatemic rickets and ossification of posterior longitudinal ligament caused by a novel homozygous mutation in ENPP1 gene

X-linked hypophosphatemic rickets/osteomalacia (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets/osteomalacia (ARHR1 or ARHR2) are hereditary fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets showing similar clinical features. We here show a patient with hypophosphatemic rickets and widespread ossification of posterior longitudinal ligament (OPLL). The proband is a 62-year-old female. Her parents are first cousins and showed no signs of rickets or osteomalacia. She showed hypophosphatemic rickets with elevated FGF23 level and had been clinically considered to be suffering from XLH. However, direct sequencing of all coding exons and exon–intron junctions of phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX), FGF23 and dentin matrix protein 1 (DMP1) genes, responsible genes for XLH, ADHR and ARHR1, respectively, showed no mutation. A novel homozygous splice donor site mutation was found at the exon–intron junction of exon 21 of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene responsible for ARHR2 (IVS21 + 1_3(GTA > CACC)). Subsequent analysis of mRNA revealed that this mutation caused skipping of exon 21 which created a premature stop codon in exon 22. These results indicate that genetic analysis is mandatory for the correct diagnosis of hereditary FGF23-related hypophosphatemic rickets. Because Enpp1 knockout mouse is a model of OPLL, this case also suggests that OPLL is associated with ARHR2.     

Scintigraphic demonstration of renal cell carcinoma with I-131-6β-iodomethyl-19-norcholesterol: A case report

Extraadrenal abnormal uptake on adrenocortical scintigraphy has been reported rarely in the normal gallbladder, lipid cell tumor of the ovary, or in clear cell type renal cell carcinoma. Clear cell type renal cell carcinoma contains glycogen and cholesterol like the adrenal gland, but the uptake of the radionuclide I-131 cholesterol has been reported to be low and not sufficient to image it. Right renal and adrenal masses were incidentally discovered on abdominal CT scan in a patient with chronic renal failure resulting in bilateral acquired cystic kidney disease. Adrenocortical scintigraphy done to know the nature of the adrenal mass showed high uptake corresponding to the right renal mass and the right adrenal mass. Clear cell type renal cell carcinoma and adrenal adenoma with prominent clear cells were histologically confirmed on hematoxylin-eosin stain and in an immunohistochemical study with renal cell antibody. Not only low-density lipoprotein receptors mediated uptake but also overall replacement of the right non-tumorous renal parenchyma by acquired cysts may have played a role in imaging the renal cell carcinoma on adrenocortical scintigraphy.     

Pulmonary Resection for Metastases from Hepatocellular Carcinoma

BACKGROUND: Pulmonary metastasectomy has become the standard therapy for various metastatic malignancies to the lungs; however, few data have been available about lung metastasectomy for hepatocellular carcinoma. To confirm the role for resection of pulmonary metastases for such tumors, we reviewed our institutional experience. METHODS: Between 1993 and 2005, 12 patients with pulmonary metastases from hepatocellular carcinomas underwent complete pulmonary resection. All patients had undergone curative resection of their primary hepatocellular carcinomas and also had obtained or had obtainable locoregional control of their primaries. Various perioperative variables were investigated retrospectively to analyze the possible prognostic factors for overall survival and pulmonary metastases-free survival after pulmonary metastasectomy. RESULTS: Nine patients were male and three were female (median age, 53 (range, 43-80) years). Overall survival rate after metastasectomy was 80.8%, 57.7%, and 28.9% at 1, 2, and 5 years, respectively. Pulmonary metastases-free survival rate was 64.2%, 32.1%, and 21.4% at 1, 2, and 5 years, respectively. Five patients presented recurrences in the remaining liver before pulmonary metastases, but hepatic recurrences at this interval did not affect an overall survival after pulmonary metastasectomies. Two patients had undergone living-related liver transplantation. The maximum tumor size of the pulmonary metastasis < 3 cm was the only favorable prognostic factor for overall survival (P = 0.0006), whereas there was no significant prognostic factor for pulmonary metastases-free survival. CONCLUSIONS: Pulmonary metastasectomy for hepatocellular carcinoma in selected patients was well justified when the maximum tumor size was <3 cm.     

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.     

Prediction of the need for mechanical ventilation after transsternal thymectomy in patients with myasthenia gravis]

Between June 1992 and May 2000, transsternal extended thymectomy was performed for 70 patients with myasthenia gravis in our hospital. We were able to evaluate 64 of them in terms of prediction of the need for postoperative mechanical ventilation using the score systems reported by Leventhal et al., Kimura et al. and the criteria of Adachi et al.. For these systems, the rates of agreement between predictions and results were 85.9%, 82.8%, and 64.1%, respectively. The two former systems had some false negative cases (i.e., they predicted that ventilation would not be needed when in fact it was), but the last one gave no false negatives. We recommend Adachi's criteria for clinical safety. In our cases the patients whose value of %VC multiplied by FEV1.0% was less than 7,000 (Adachi's criterion is less in 8,300), especially, needed careful management with regard to respiratory crisis.