The prognosis of patients with advanced diffuse‐type gastric cancer (
GC)
, especially scirrhous gastric cancer (
SGC
) remains extremely poor. Peritoneal carcinomatosis is a frequent form of ...metastasis of
SGC
. With survival rates of patients with peritoneal metastasis at 3 and 5 years being only 9.8% and 0%, respectively, development of a new treatment is urgently crucial. For such development, the establishment of a therapeutic mouse model is required. Among the 11
GC
cell lines we examined,
HSC
‐60 showed the most well‐preserved expression profiles of the Hedgehog and epithelial‐mesenchymal transition pathways found in primary
SGC
s. After six cycles of harvest of ascitic tumor cells and their orthotopic inoculation in scid mice, a highly metastatic subclone of
HSC
‐60, 60As6 was obtained, by means of which we successfully developed peritoneal metastasis model mice. The mice treated with small interfering (si)
RNA
targeting
NEDD
1
, which encodes a gamma‐tubulin ring complex‐binding protein, by the atelocollagen‐mediated delivery system showed a significantly prolonged survival. Our mouse model could thus be useful for the development of a new therapeutic modality. Intraperitoneal administration of si
RNA
s of targeted genes such as
NEDD
1
could provide a new opportunity in the treatment of the peritoneal metastasis of
SGC
.
Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We ...previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre- and post-treatment biopsy specimens of 30 ESCC patients and 121 pre-treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-activation associated genes such as IFNG, PRF1, and GZMB, were found in post-treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-activated cases, designating them as I-type, from other cases. However, despite the better CR rate in the I-type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-type was significantly better than that of the CDH2-positive cases in the I-type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested to cooperatively enhance the effect of CRT in the CDH2-negative I-type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics.
New laparoscopic double-stapling technique Hamada, Madoka; Nishioka, Yutaka; Kurose, Yohei ...
Diseases of the colon & rectum,
2007-December, Volume:
50, Issue:
12
Journal Article
Peer reviewed
Laparoscopic surgery for colon cancer has been shown by several randomized, controlled trials to be an acceptable alternative to open surgery; however, laparoscopic rectal surgery has not been ...evaluated in a randomized trial. One of the most serious problems associated with laparoscopic rectal surgery are bowel clamping, irrigation, and transection of the rectum, and laparoscopic rectal surgery has not been as reliable as open rectal surgery.
We present our new technique, the laparoscopic double-stapling technique, which eliminates these problems. This technique uses curved Doyen forceps introduced through the wound just above pubis symphysis for clamping the rectal wall at the anal side of the tumor. An endolinear stapler (length 60 mm) is inserted through the same wound, applied at the rectal wall parallel and caudal to the Doyen forceps, and transects the rectum under pneumoperitoneum. We used this technique for eight cases of rectal surgery.
The laparoscopic double-stapling technique provided secure bowel clamping and rectal irrigation. The number of cartridges used in laparoscopic double-stapling technique cases was not more than 2, with an average of 1.6 per patient. None of the laparoscopic double-stapling technique cases experienced major complications.
We consider that many cases of rectal cancer that are suitable for laparoscopic low anterior resection can undergo laparoscopic surgery by using this technique, which will improve the quality of rectal surgery.
Abstract A prospective naturalistic multicentre study for deep sedation was conducted in intensive care with continuous electrocardiogram (ECG) monitoring. Clinical purpose was enough sedation, which ...made uncooperative and disrupted patients receive brain computed tomography (CT), magnetic resonance imaging (MRI), or fluid therapy, with minimum drug doses. A first infusion was either haloperidol (HAL group) or flunitrazepam (FNP group). If enough sedation was not achieved, a second infusion, which was the opposite drug to the first infusion, was given. The proportion requiring a second infusion was higher in the HAL group than in the FNP group (82% vs. 36%, P < 0.0001). The mean reduction of the Excited Component for Positive and Negative syndrome scale at 15 min was greater for the FNP first group (FNP + HAL group) than the HAL first group (HAL + FNP group) (68% S.D. 17 vs. 54% S.D. 31, P = 0.02). The mean dose of flunitrazepam in the HAL + FNP group was significantly lower than that in the FNP + HAL-group (1.3 mg vs. 3.5 mg, P = 0.0003). Thus, in terms of monotherapy and speed of action, flunitrazepam has advantages over haloperidol as a first infusion for deep sedation. Regarding drug dosages, haloperidol has an advantage over flunitrazepam as a first infusion in safety.
Diffuse-type solid tumors are often composed of a high proportion of rarely proliferating (i.e., dormant) cancer cells, strongly indicating the involvement of cancer stem cells (CSCs) Although ...diffuse-type gastric cancer (GC) patients have a poor prognosis due to high-frequent development of peritoneal dissemination (PD), it is limited knowledge that the PD-associated CSCs and efficacy of CSC-targeting therapy in diffuse-type GC. In this study, we established highly metastatic GC cell lines by in vivo selection designed for the enrichment of PD-associated GC cells. By microarray analysis, we found C-X-C chemokine receptor type 4 (CXCR4) can be a novel marker for highly metastatic CSCs, since CXCR4-positive cells can grow anchorage-independently, initiate tumors in mice, be resistant to cytotoxic drug, and produce differentiated daughter cells. In clinical samples, these CXCR4-positive cells were found from not only late metastasis stage (accumulated ascites) but also earlier stage (peritoneal washings). Moreover, treatment with transforming growth factor- beta enhanced the anti-cancer effect of docetaxel via induction of cell differentiation/asymmetric cell division of the CXCR4-positive gastric CSCs even in a dormant state. Therefore, differentiation inducers hold promise for obtaining the maximum therapeutic outcome from currently available anti-cancer drugs through re-cycling of CSCs.
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