Clinical utility of sequential imaging of hepatocellular carcinoma by contrast-enhanced power Doppler ultrasonograpy

The aim of this study was to investigate the clinical utility of sequential imaging of hepatocellular carcinoma (HCC) by contrast-enhanced power Doppler ultrasonograpy (CE-PDUS) to differentiate hepatocellular carcinoma from adenomatous hyperplasia (AH) and regenerated nodule (RN) and to predict the degree of differentiation of HCC. Fifty-one patients with 62 hepatic lesions including 33 moderately and poorly differentiated HCCs, 19 well-differentiated HCCs, seven AHs and three large RNs were examined by CE-PDUS. The imaging patterns during early arterial phase (tumor vessel image), late vascular phase (tumor perfusion image) and post-vascular phase (liver perfusion image) were classified as diffuse, basket, peripheral, central and no enhancement; as whole tumor, partial tumor and no enhancement; as whole tumor, partial tumor and no defect, respectively. The diffuse pattern in the tumor vessel image, the whole enhancement pattern in the tumor perfusion image and the whole defect pattern in the liver perfusion image were observed in moderately and poorly differentiated HCCs only. The basket pattern in the tumor vessel image and the partial defect pattern in the tumor perfusion image were observed in HCCs only. All AH/RNs showed no defect pattern in the liver perfusion image. The sequential imaging of HCC during early arterial, late vascular and post-vascular phases by CE-PDUS is clinically useful to differentiate HCC from AH/RN and to predict the degree of differentiation of HCC.     

The accuracy of transcutaneous carbon dioxide monitoring during laparoscopic surgery

BACKGROUND: Laparoscopic procedures are considered relatively low-invasive. However, there exists a small but important risk of developing complications related to carbon dioxide (CO2) insufflation. End-tidal CO2 (PetCO2) monitoring may not be a sufficient guide to adjust pulmonary ventilation during laparoscopic surgery, and arterial CO2 (PaCO2) monitoring is not always indicated. We evaluated the accuracy and feasibility of transcutaneous CO2 (PtcCO2) monitoring during laparoscopic surgery. METHODS: Thirty adult patients undergoing abdominal or gynecological laparoscopic surgery were studied. PtcCO2, PaCO2 and PetCO2 were measured before laparoscopy, and 30 and 60 minutes after beginning of CO2 insufflation. PtcCO2 and PaCO2 were also measured in the recovery room under spontaneous respiration. RESULTS: During operation, the PtcCO2 values demonstrated a high degree of correlation with PaCO2 (r = 0.92), and PetCO2 values also demonstrated generally a good correlation with PaCO2 (r = 0.85). The PtcCO2 PaCO2 gradient was -0.6 +/- 2.2 mmHg, while the PetCO2-PaCO2 gradient was -3.9 +/- 2.7 mmHg. In the recovery room, PtcCO2 values still demonstrated a high correlation with PaCO2 (r = 0.91). CONCLUSIONS: The transcutaneous devices provide an effective method for non-invasive monitoring of PCO2 in situations where continuous monitoring of CO2 levels is desired such as peri-operative period of laparoscopic surgery.     

Four cases of gastric cancer with multiple hepatic metastases successfully treated with TS-1 in combination with low-dose cisplatinum

We treated five cases for multiple hepatic metastases from gastric cancer with a novel combination of TS-1 and low-dose cisplatinum (CDDP). TS-1 was orally administered at 100 mg/body/day every day or only on weekdays, and 10 mg of CDDP was infused once or twice a week. The efficacy was evaluated by body CT after the treatment. The CT showed more than a 60% reduction of hepatic tumors in four patients. The tumor markers, CEA and CA19-9, were reduced to 10%. The response rate was 80%. Adverse reactions of grade 1 anemia were observed in two patients and grade 1 leucopenia in one patient. The liver function normalized in one patient. The hemoglobin level was increased from 6.8 g/dl to 11.8 g/dl in one patient. In conclusion, this combined chemotherapy of TS-1 and low-dose CDDP proved useful for advanced gastric cancer patients with multiple hepatic metastases, in view of its therapeutic efficacy, patients' quality of life and low toxicity.     

A case of advanced gastric cancer attaining histological CR of paraaortic lymph node after TS-1/CDDP neoadjuvant chemotherapy

A 60-year-old male complaining of anemic symptoms went through examinations and was diagnosed with gastric cancer (cardia, type 3', cT2, cN3, cH0, cP0, cM0, cStage IV). Further inspection showed multiple lymph node metastases, including, No. 1, 3, 7, 11, and 16 (paraaortic LNs). Poor prognosis was predicted, yet we tried neoadjuvant chemotherapy (NAC) expecting down staging of the tumor. With the efficacy and safety previously proven, we chose TS-1 + CDDP as NAC regimen. TS-1 (tegafur gimestat otastat potassium, = 80 mg/m2) was administered orally for 21 days, followed by CDDP (cisplatin, = 60 mg/m2) i.v. on day 9. One course was completed without any significant adverse effects. The tumor itself showed PR-MR to the chemotherapy, but all the lymph nodes were expected to attain PR from CT findings. Total gastrectomy, lymph node dissection (D3) with Roux-en-Y reconstruction was performed, and histological re-evaluation was made. Macroscopically, the stomach seemed to be penetrated into serosa by the tumor, i.e., se invasion was suggested, yet histologically no cancerous cells were detected within mp and ss layer. Many of the lymph nodes were replaced with fibrosis, some with normal lymph node structure remained. Definitely no malignant cells were detected throughout all the lymph node specimens (Grade 3). Because pathological CR of paraaortic lymph nodes has never been reported previously, this case shows TS-1 + CDDP as a promising NAC regimen for advanced gastric cancer, in a sense that tumors once diagnosed as inoperable would still have the possibility of CR.     

Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutation

The aim of the present study was to clarify differences in genetic events between primary breast cancers and asynchronous metastatic/recurrent lesions, by examining HER2 gene amplification and p53 mutation. The subjects were 44 breast cancer patients with asynchronous metastasis or recurrence. Synchronous metastases were excluded. HER2 overexpression and gene amplification were examined using immunohistochemistry and fluorescent in situ hybridization (FISH). P53 point mutation was examined by immunohistochemistry, laser-captured microdissection, PCR-single-strand conformation polymorphism, and a direct sequencing method. Immunohistochemistry showed that, for HER2, p53, ER and PgR, discordance rates between primary and recurrent tumor were 2 (4.5%), 1 (2.3%), 7 (15.9%) and 10 (22.7%), respectively. Two primary tumors with discordant HER2 overexpression were composed of at least two populations of carcinoma cells, with and without HER2 gene amplification. Distribution of HER2 gene amplification was consistent with protein overexpression. Corresponding recurrent tumors consisted of carcinoma cells without HER2 gene amplification. Of 6 recurrent tumors in which the primary carcinoma had a p53 point mutation, 3 tumors had identical mutations, 1 tumor had a different point mutation, and 2 tumors had no mutation. It was suspected that the latter 3 recurrent tumors comprised a minor component of the primary tumor. In the present study, we examined a large series of asynchronous recurrent tumors. A limited number of these tumors showed discordance between primary and recurrent tumors. Detailed observations revealed that cell populations present in recurrent tumors were also present in the primary tumors, although they comprised a minor component of the primary tumor. Heterogeneity of the primary tumor apparently contributed to discordance.     

Roles of histamine receptors in pain perception: a study using receptors gene knockout mice

To study the participation of histamine H1- and H2-receptors in pain perception, H1 and H2 receptor knockout (KO) mice were examined for pain threshold by means of three kinds of nociceptive tasks. These included assays for thermal, mechanical, and chemical nociception. H1KO mice showed significantly fewer nociceptive responses to the hot-plate, tail-flick, tail-pressure, paw-withdrawal, formalin, capsaicin, and abdominal constriction tests. Sensitivity to noxious stimuli in H1KO mice was significantly decreased when compared to wild-type mice. The antinociceptive phenotypes of H2KO were relatively less prominent when compared to H1KO mice. We also examined the antinociceptive effects of intrathecally-, intracerebroventricularly-, and subcutaneously-administered morphine in H1KO and H2KO mice. In these nociceptive assays, the antinociceptive effects produced by morphine were more enhanced in both H1KO and H2KO mice. The effects of histamine H1- and H2-receptor antagonists on morphine-induced antinociception were studied in ICR mice. The intrathecal, intracerebroventricular and subcutaneous co-administrations of d-chlorpheniramine enhanced the effects of morphine in all nociceptive assays examined. In addition, intrathecal co-administrations of cimetidine enhanced the antinociception of morphine in the hot plate tests. These results suggest that existing H1 and H2 receptors play an inhibitory role in morphine-induced antinociception in the spinal and supra-spinal levels.     

Control of liposidomycin production through precursor-directed biosynthesis

Liposidomycin, a potent inhibitor of bacterial peptidoglycan biosynthesis, represents the main component of a group of over 24 closely related, fatty acyl nucleoside antibiotics produced by Streptomyces. Exogeneously supplied myristic acid or palmitic acid resulted in the almost exclusive production of liposidomycin C-(III) and/or M-(III). Exogeneously supplied [1-13C]-palmitic acid was incorporated directly into liposidomycin M-(III) as judged by the FAB-MS and 13C NMR spectra.     

A case of superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus

We hereby reported a case of 60-year old man with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus. Endoscopic ultrasonography and CT showed the thickness of esophageal muscular layer, but the accurate diagnosis could not be entertained before operation. Idiopathic muscular hypertrophy of the esophagus is an entity rarely encountered, and most cases are diagnosed at postmortem examination. Only a few cases have been reported regarding its clinical symptoms and images. The etiology remains to be elucidated, and the pathologic features are characterized by significant thickness of inner circular muscular layer of esophagus without degeneration of plexus and ganglionic cells. This case report deals with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of esophagus. Literature review is also included.     

Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity,Th1/Th2 balance,and granulocyte function

The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF+G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.     

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

Because of the paucity of primate experimental models, the precise molecular mechanism of ischemic neuronal death remains unknown in humans. This study focused on nonhuman primates to determine which cascade necrosis or apoptosis is predominantly involved in the development of delayed (day 5) neuronal death in the hippocampal CA1 sector undergoing 20 min ischemia. We investigated expression, activation, and/or translocation of micro-calpain, lysosome-associated membrane protein-1 (LAMP-1), caspase-3, and caspase-activated DNase (CAD), as well as morphology of the postischemic CA1 neurons and DNA electrophoresis pattern. Immunoblotting showed sustained (immediately after ischemia until day 5) and maximal (day 3) activation of micro-calpain. The immunoreactivity of activated micro-calpain became remarkable as coarse granules at lysosomes on day 2, while it translocated throughout the perikarya on day 3. The immunoreactivity of LAMP-1 also showed a dynamic and concomitant translocation that was maximal on days 2-3, indicating calpain-mediated disruption of the lysosomal membrane after ischemia. In contrast, immunoblotting demonstrated essentially no increase in the activated caspase-3 at any time points after ischemia, despite upregulation of pro-caspase-3. Although expression of CAD was slightly upregulated on day 1 or 2, or both, it was much less compared with lymph node or intestine tissues. Furthermore, light and electron microscopy showed eosinophilic coagulation necrosis and membrane disruption without apoptotic body formation, while DNA electrophoresis did not show a ladder pattern, but rather a smear pattern. Sustained calpain activation and the resultant lysosomal rupture, rather than CAD-mediated apoptosis, may cause ischemic neuronal necrosis in primates.