Diagnostic validity of CT gastrography versus gastroscopy for primary lesions in gastric cancer: evaluating the response to chemotherapy, a retrospective analysis.

BACKGROUND: This retrospective study was carried out to compare computed tomographic (CT) gastrography and conventional optical gastroscopy (GS) in order to evaluate the effectiveness of chemotherapy in primary gastric lesions. METHODS: Patients with unresectable advanced and unresected early gastric cancer who had primary lesions and had received chemotherapy were enrolled. For primary lesions, CT gastrography and endoscopic assessment were done after chemotherapy, based on the Japanese Classification of Gastric Carcinoma (JCGC) criteria, 13th edition, and the Response Evaluation Criteria in Solid Tumors (RECIST). For metastatic solid lesions including lymph nodes, CT assessment was done based on the RECIST criteria. RESULTS: Data from 23 patients were analyzed. With median follow-up of 9.4 months (range 2-23 months), 58 examinations were assessed by GS and CT gastrography. Setting optical endoscopic results as the gold standard, the accuracy of CT gastrography for primary gastric lesions was 77.6 % (45 of 58) (weighted κ = 0.72; P < 0.01) according to the JCGC 13th edition criteria and 90.0 % (52 of 58) (weighted κ = 0.75; P < 0.01) according to the RECIST. When all results were divided into two groups [the non-progressive disease (non-PD) group and PD group], accuracy was 93.1 % (52 of 58) (κ = 0.81; P < 0.01), sensitivity was 100 %, and specificity was 75.0 % (12 of 16). In addition, the predictability of PD was 100 % (12 of 12). The four cases of failure in specification were the following: a case of gastric remnant cancer, a case with insufficient distension of the stomach, a healed case with stenosis and scarring, and a case in which the wrong position had been selected for the examination. The average period until PD was 9.9 months (range 5-18 months), and the concordance period between GS and CT gastrography was 7.2 months in both non-PD and PD cases. CONCLUSIONS: There was good concordance between the evaluations of GS and CT gastrography. CT gastrography exhibited favorable results in accuracy as well as 100 % PD predictability, which implied the possibility of using CT gastrography as a substitute for endoscopic assessments at post-chemotherapy assessments.

[Advanced poorly differentiated adenocarcinoma of the colon with micropapillary carcinoma components except specific cytokeratin expressions, report of a case].

A 53-year-old woman had a tumor in the ascending colon. CT revealed tumor invasion to the surrounding tissue and also showed multiple swollen lymph nodes, liver metastases and ascites. Colonic tumor with severe stenosis was diagnosed by colonoscopy and the obtained biopsy specimen revealed poorly differentiated adenocarcinoma. Immunohistochemically, the tumor was positive for CEA, CK7, MUC2, MUC5AC·MUC6 (spotty) and negative for CK20, CDX2, TTF-1, GCDFP-15. Cytology of ascites also showed malignant cells. Although these protein expressions were specific for not primary colonic cancer but metastasis from ovarian cancer, the case was clinically and pathologically diagnosed as poorly differentiated adenocarcinoma of the colon with peritoneal metastases composed of micropapillary carcinoma. MLH1 and MSH2 protein expressions were normal. Even though modified FOLFOX6 chemotherapy was administered, the patient rapidly worsened due to pulmonary carcinomatous lymphangiosis and died a month after diagnosis. To determine the high-risk group of metastases, it seems necessary to require the accumulation of further cases evaluated by a precise immunohistochemistrical approach.

A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine.

A 64-year-old man had been admitted to a previous hospital because of melena and a diagnosis of ulcerative colitis (UC, pancolitis type) had been made. He had received prednisolone and 5-ASA but steroid-induced hyperamylasemia had developed. Prednisolone had been tapered and halted, but it had resulted in UC relapse and thrombocytopenia. Then, he was referred to our hospital due to severe melena with hypovolemic shock. However, he was also positive for CMV antigen. Thus, we attempted to treat him with ganciclovir for CMV and intravenous cyclosporine (CsA) for UC. According to his clinical course, a reduction of CsA blood concentration induced leukocytopenia. Myelodysplastic syndrome (MDS, RAEB-1) was then revealed after bone marrow biopsy. A high blood CsA concentration may cause the improvement of UC and MDS conditions.

[Cholangiocarcinoma with bile duct adenoma and hamartoma-like lesion in the bile duct].

A 76-year-old man presented with fever of unknown origin. Diagnostic imaging showed a liver tumor measuring 3cm in maximum dimension. The tumor was subsequently resected, and histopathology showed a moderately differentiated adenocarcinoma. This showed a number of bile ductules with variable amounts of stroma, well circumscribed but not encapsulated, so the lesion was diagnosed as a cholangiocarcinoma. Within the tumor there was also a cholangiolocarcinoma-like lesion. In addition, cystically dilated ductules resembling bile duct hamartoma and bile duct adenoma adjacent to the tumor were found, but with no area of transition among them. In the Glisson's capsule around the tumor, there was also a bile duct hamartoma.

[A case of solitary fibrous tumor of the pancreas].

A 58-year-old woman without any clinical symptoms had a routine health check-up, during which a mass in the head of the pancreas was detected by US. Abdominal US showed a round, hypoechogenic nodule of the pancreatic head. The tumor measured 3cm in diameter and contained an anechoic area. CT revealed a well-demarcated tumor in the pancreatic head. The tumor was partially enhanced by contrast medium, but the left portion of the tumor, which US had shown to be an anechoic area was not enhanced. Imaging findings suggested an endocrine tumor with cystic changes. A pylorus-preserving pancreatoduodenectomy was performed. The tumor was composed of spindle-shaped cells. There was a typical patternless growth of short fascicles and a short storiform arrangement of cells in the stroma with varying degrees of collagenization. Immunohistochemically, the tumor cells were positive for CD34 and Bcl-2. Based on the light microscopic morphology and immunostaining profile, the tumor was classified as a solitary fibrous tumor (SFT) of the pancreas.

[Clinical administration of oxaliplatin for patients previously treated for refractory advanced or recurrent colorectal cancer].

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5. The response rate was 22.2%. Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer. It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.

Augmentation of antitumor effects of p53 gene therapy by combination with HDAC inhibitor.

We have previously shown that the HDAC inhibitors (HDACI) activate the p53 molecule through acetylation of 320 and 373 lysine residues, upregulate PIG3 and NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type p53 genes (Terui T, et al. Cancer Res 2003; 63:8948-54). It has also been reported that expression of the Coxsackie adenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI treatment. In this study, we extended these observations to explore the combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first confirmed an increased expression of Coxsackie adenovirus receptors with an associated increment of transgene (X-gal) expression by SB treatment in KATO-III cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7 combined with intraperitoneal administration of SB and found a significantly higher growth suppressive effect than single treatments of each. Even a complete regression of tumors was observed in three of five mice treated with this combination while with single treatment no tumor regression was observed. Tumors treated with the combination showed higher numbers of TUNEL positive cells than those treated with a single modality. Moreover, necrotic changes were more evident in tumors treated with the combination than separately, a compatible finding to the observation that vascularity revealed by CD34 staining was poorer in tumors treated with the combination than those treated with p53 gene or SB alone. This was further supported by the finding that BAI-1 (brain specific angiogenesis inhibitor-1), an inhibitor of vascularization, was induced by SB treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown to be an efficient potentiator of p53 gene therapy for cancer.

[Successful treatment with antiviral agents for human herpesvirus type 6 encephalitis following reduced intensity stem cell transplantation in a patient with myelodysplastic syndrome].

We report here a patient who suffered from PCR-confirmed human herpesvirus type 6 (HHV-6) encephalitis following reduced intensity stem cell transplantation (RIST) from her HLA-matched sibling donor. A 66-year-old woman with MDS-RA underwent RIST from her HLA-matched brother. Engraftment was favorable and grade 2 GVHD (skin and intestine) was observed with good response to 60 mg of prednisolone. On day 162, she developed fever, headache, diplopia, disorientation and abnormal neurological findings including cervical stiffness and nystagmus. An analysis of cerebrospinal fluid (CSF) revealed 80 cells/microl, a glucose level of 50 mg/dl and a protein level of 97 mg/dl on day 162. Although computed tomography (CT) of the brain and electroencephalography (EEG) were nonspecific, HHV-6 was detected in the CSF using polymerase chain reaction (PCR) techniques and the patient was diagnosed as having encephalitis due to local reactivation of HHV-6. Administration of ganciclovir (GCV) and acyclovir (ACV) were started from day 162. Treatment with antiviral agents was effective, with total resolution of her symptoms and the DNA of this virus disappeared from the CSF after 23 days of treatment. This case shows that HHV-6 infection has to be considered in patients with neurological symptoms following stem cell transplantation, and suggests the necessity of PCR for HHV-6 virus from the CSF.

Ethanol induces transforming growth factor-alpha expression in hepatocytes, leading to stimulation of collagen synthesis by hepatic stellate cells.

BACKGROUND: Liver fibrosis often develops in alcoholic liver diseases without accompanying inflammation; however, the underlying mechanism is unclear. Using ethanol-exposed human HepG2 hepatoblastoma cells as a model for alcoholic liver diseases, we previously found that ethanol exposure causes HepG2 cells to secrete an approximately 6,000 Da nonheparin-binding polypeptide that stimulates collagen synthesis in human IMR-90 fibroblasts. The aim of the current study was to characterize and identify this factor. METHODS: Concentration of type I procollagen peptide and transforming growth factor (TGF)-alpha was assessed by enzyme-linked immunosorbent assay. TGF-alpha protein expression was examined by Western blot. Type I collagen messenger RNA expression in rat hepatic stellate cells was assessed by reverse transcription-polymerase chain reaction. RESULTS: The collagen-stimulating activity in conditioned media from ethanol-exposed HepG2 cells to stimulate type I procollagen peptide synthesis of IMR-90 cells was specifically inhibited by addition of anti-TGF-alpha antibodies. Western blot analysis showed increased TGF-alpha protein expression in ethanol-treated HepG2 cells. TGF-alpha in conditioned medium from ethanol-exposed HepG2 cells stimulated type-I collagen messenger RNA expression in rat hepatic stellate cells. CONCLUSIONS: These results suggest that TGF-alpha derived from ethanol-exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.

Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura.

The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 ITP patients (62.5%) and in two secondary AITP (25%). H.pylori eradication was obtained in 19 of 19 infected ITP patients (100%), who were not in remission (platelets < 100 x 109/l) at the time of infection assessment. During follow-up (median 14.8 months), 12 of 19 H. pylori-eradicated patients (63.2%) showed a significant increase in platelet count accompanied by a significant decrease of platelet-associated immunoglobulin G (IgG). This response was maintained in all responding patients throughout the follow-up period. However, two infected patients with secondary AITP did not show platelet increase after eradication. The assessment of H. pylori infection and its eradication should be attempted in ITP as this approach could be an effective strategy, at least for some of these patients.