Preoperative and postoperative prognostic factors of patients with stage II/III lower rectal cancer without neoadjuvant therapy in the clinical trial (JCOG0212).

BACKGROUND: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial. METHODS: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment. RESULTS: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival. CONCLUSIONS: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes.

Prospective multicenter study of reduced port surgery combined with transvaginal specimen extraction for colorectal cancer resection.

PURPOSE: The relevance of transvaginal specimen extraction (TVSE) combined with reduced port surgery (RPS) remains unknown. This study investigated the feasibility of TVSE with RPS according to short-term outcomes and cosmesis. METHODS: This prospective multicenter study enrolled ten patients at three institutions. For the semi-quantification of each parameter, we administered questionnaires to assess pain (visual analogue scale), subjective/objective wound healing esthetics [photo series questionnaires (PSQ)], and quality of life (QOL). RESULTS: No operative complications occurred, except one case of urinary tract infection, which was promptly cured with antibiotics. On day 0, pain was rated at 2.3 ± 0.67 at rest and 4.9 ± 0.82 during sneezing; these ratings gradually declined over time. The PSQ showed that the patient ratings of wound esthetics after TVSE were not inferior to ratings from patients after conventional laparoscopy or single incision laparoscopic surgery, and they were significantly higher than the patient ratings of wounds after laparotomy (P < 0.05). The QOL scores showed that, in comparison to before surgery, after surgery, patients reported significant deterioration of their physical function (96.67 ± 1.49 vs. 87.33 ± 2.71), emotional function (93.33 ± 2.72 vs. 86.67 ± 2.22), fatigue (7.78 ± 3.72 vs. 26.67 ± 8.31), and pain (6.67 ± 3.69 vs. 18.33 ± 4.61). CONCLUSION: TVSE with RPS for colorectal cancer was feasible and was associated with a low degree of postoperative pain.

Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone.

Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the alpha-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 62 Fabry patients in Japan and found 24 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 24 mutant GLAs and analyzed the alpha-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease.

[Renal pelvic cancer representing G-CSF production and hypercalcemia simultaneously: a case report].

A 73-year-old man was admitted to the hospital complaining of gross hematuria and left flank pain. Abdominal ultrasonography and computed tomography revealed a left renal tumor with extracapsular extension. Laboratory data showed marked leukocytosis of 121,000/mm3 and hypercalcemia of 12.3 mg/dl without any findings of inflammatory disease or bone metastasis. Enzyme immunoassay of the serum demonstrated a high level of granulocyte colony-stimulating factor (250 pg/ml) and parathyroid hormone-related protein (1,069 pmol/l). Pathological diagnosis of needle biopsy specimen of the primary tumor was transitional cell carcinoma which was suspected to have originated from renal pelvis. Immunohistochemical examination with anti-granulocyte colony-stimulating factor monoclonal antibody demonstrated granulocyte colony-stimulating factor production in cancer cells. The patient underwent a course of systemic chemotherapy, but died two months after diagnosis. To our knowledge, this is the first report of renal pelvic cancer representing granulocyte colony-stimulating factor production and hypercalcemia simultaneously.

[Sarcomatoid carcinoma of the renal pelvis: a case report].

A 65-year-old man visited our hospital with the complaint of left hypochondrial pain. Since he had left giant hydronephrosis due to ureteral stone, we performed left nephrectomy. Unexpectedly, macroscopic examination of the resected kidney revealed multiple yellowish nodules located in the renal pelvis and calyces. Histopathologically the nodules consisted of two pattern of malignancy, transitional cell carcinoma and spindle sarcomatous tumor. Immunohistochemical examination showed that spindle cells were stained positive for cytokeratin, and the final diagnosis was sarcomatoid carcinoma of left renal pelvis. Postoperatively, the patient underwent two courses of adjuvant chemotherapy, but metastases to retroperitoneal lymph nodes were noted two months after operation. He died of the disease eight months postoperatively.

Kinetics of electron transfer between soluble cytochrome c-554 and purified reaction center complex from the green sulfur bacterium Chlorobium tepidum.

Soluble cytochrome c-554 (M (r) approximately 10 kDa) is purified from the green sulfur bacterium Chlorobium tepidum. Its midpoint redox potential is determined to be +148 mV from redox titration at pH 7.0. The kinetics of cytochrome c-554 oxidation by a purified reaction center complex from the same organism were studied by flash absorption spectroscopy at room temperature, and the results indicate that the reaction partner of cytochrome c-554 is cytochrome c-551 bound to the reaction center rather than the primary donor P840. The second-order rate constant for the electron donation from cytochrome c-554 to cytochrome c-551 was estimated to be 1.7x10(7) M(-1) s(-1). The reaction rate was not significantly influenced by the ionic strength of the reaction medium.

Localization of Type IV Collagen in the Myotome Cells during the Somite Differentiation in the Chick Embryo: (type IV collagen/chick embryo/myotome/dermatome/immunohistochemistry).

Type IV collagen is a major structural component of basement membranes which play various roles upon their adjacent cells. In order to better understand roles of type IV collagen during the somite differentiation, we produced anti-rat type IV collagen polyclonal antibodies and demonstrated spacial and temporal distribution of type IV collagen in somites of the chick embryo by immunohistochemical procedure. Type IV collagen was detected in the basal surface and the cytoplasm of epithelial dermatome cells at early stage of the somite differentiation, and then detected in myotome cells overlying apical surface of dermatomes, but not in migratory mesenchymal dermatome cells. With the appearance of type IV collagen-expressing myotome cells, epithelial dermatome cells showed the decrease in immunoreaction with anti-type IV collagen antibodies, the disappearance of their basal-apical polarity and their epithelial shape. From these results, it was suggested that type IV collagen is an early marker for myotome cells, and that type IV collagen and/or other factors co-expressed by myotome cells might provide an accelerative signal for epithelial/mesenchymal conversion of dermatome cells.