Axillary reverse mapping using fluorescence imaging is useful for identifying the risk group of postoperative lymphedema in breast cancer patients undergoing sentinel node biopsies.

BACKGROUND: Axillary reverse mapping (ARM) is a novel technique for preserving the upper extremity lymphatic pathways during axillary lymph node surgery. However, there is no evidence of the usefulness of ARM for patients undergoing sentinel lymph node biopsy (SNB). METHODS: Between August 2009 and July 2012, 372 patients who underwent the SNB procedure for breast cancer were enrolled in this study. Using the indocyanine green fluorescence technique and indigocarmine blue dye method, we studied the relationship between the upper extremity lymphatic flow and breast sentinel node (SN). Our aim of this study was the probability of postoperative lymphedema with respect to whether the upper extremity lymphatics corresponded to the breast SN. RESULTS: Among the 327 patients who underwent the SNB procedure, the upper extremity lymphatics drainage into the breast SN in 76 (23.2%; corresponding group), and only 5 patients in this group developed lymphedema. In contrast, none of the patients in the noncorresponding group developed lymphedema. CONCLUSIONS: ARM during SN biopsy can identify the group of patients who are at high risk for developing lymphedema. More risk-focused guidance should be used for these patients.

Sentinel node mapping for gastric cancer: a prospective multicenter trial in Japan.

PURPOSE: Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique. PATIENTS AND METHODS: Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines. RESULTS: Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure. CONCLUSION: The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition.

Marimastat is a broad-spectrum matrix metalloproteinase (MMP) inhibitor that inhibits almost all major MMPs, key enzymes in gastric cancer invasion and metastasis. We investigated the ability of marimastat to inhibit tumor angiogenesis in the severe combined immuno-deficient (SCID) mouse/human gastric cancer model of peritoneal dissemination. A human stomach adenocarcinoma cell line, TMK-1, was injected intraperitoneally into SCID mice. On the 7th day after tumor inoculation, the administration of marimastat (27 mg/kg/day) was initiated and the treatment was continued for 2 weeks using subcutaneously-inoculating mini-osmotic pumps. On the 21st day, the mice were killed and the disseminated nodules were evaluated. Total weights, numbers, and the microvascular density of the disseminating nodules were significantly lower in mice treated with marimastat compared to the control group. Film in situ zymography demonstrated that net gelatinolytic activity in the tissues was weaker in treated-group nodules than in control-group nodules. Thus, our results suggested that marimastat inhibited peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis, possibly involving the down-regulation of gelatinases, in SCID mice injected with human gastric cancer cells.

Complete response of a highly advanced gastric carcinoma to preoperative chemoradiotherapy with S-1 and low-dose cisplatin.

S-1 has been developed as a new oral anticancer drug, based on the biological modulation of 5-fluorouracil. We report a patient with highly advanced gastric carcinoma who was treated successfully with a new combination chemoradiotherapy using S-1 and cisplatin (CDDP). The patient was a 37-year-old man who was diagnosed with advanced gastric carcinoma (T4N3M0) that had invaded the diaphragm and the paraaortic tissues. Remarkable tumor reduction was observed in the primary tumor and metastatic lymph nodes around the stomach after three cycles of the therapy. Radiological examination before surgery determined that a partial response (PR) had been achieved by the initial therapy. Adverse effects included only a gastrointestinal disorder that was limited to grade 2 when low-dose CDDP was utilized in the regimen, while an initial high dose of CDDP resulted in grade 3 toxicity, due to myelosuppression. The patient underwent curative surgery, including total gastrectomy, D2 lymph node dissection, and splenectomy, after completion of the radiochemotherapy regimen. No surgical complication was observed. No tumor cells were detected by pathological evaluation of the resected stomach and all the regional lymph nodes, confirming a pathological complete response (CR; grade 3). This regimen is a potent treatment for advanced gastric carcinoma, especially when used as preoperative chemotherapy to control cancer cells.

Matrix metalloproteinase inhibitor, marimastat, decreases peritoneal spread of gastric carcinoma in nude mice.

Marimastat, a matrix metalloproteinese inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK-1. Even with novel approaches such as molecular targeting of cancer chemotherapy, peritoneal dissemination of gastric cancer has little sensitivity to anticancer drugs, and it is impossible to inhibit its growth completely. Intraperitoneal injection of TMK-1 into nude mice at 5 x 10( 5) cells / body resulted in carcinomatous peritonitis that mimicked clinical cases. Continuous administration of marimastat (18 mg / kg / day) from 24 h after the tumor inoculation successfully inhibited the growth of peritoneal dissemination nodules. Combined administration of marimastat (18 mg / kg / day) and mitomycin C (MMC, 2 mg / kg) showed synergistic inhibition of growth of peritoneal dissemination, being superior to MMC alone (2 mg / kg). Although marimastat alone could not increase survival time with statistical significance, combined administration of marimastat and MMC had a survival benefit with statistical significance. The combination of marimastat and MMC increased the preventive effect on peritoneal dissemination. Marimastat seems to be a candidate for the prevention of peritoneal spread of gastric carcinoma.