Michihiro Koizumi

Antiangiogenic effect of Octreotide inhibits the growth of human rectal neuroendocrine carcinoma

Background: Somatostatin and its analogues have antitumor effects on foregut and midgut neuroendocrine (NE) tumors, but their effect on hindgut NE tumors is unclear. We examined the effect of the somatostatin analogue, octreotide, on human rectal NE carcinoma. Materials and Methods: Expression of somatostatin receptor (sst) on NE carcinoma was examined by immunohistochemical staining. Octreotide was added in cell culture medium in order to investigate antiproliferative effect toward NE carcinoma in vitro. Octreotide was administered for 6 weeks to nude mice xenografted with NE carcinoma. We investigated the effect of octreotide on the tumor histologically. The plasma levels of VEGF and bFGF were measured. Results: The NE carcinoma and endothelial cells expressed sst. Octreotide induced NE carcinoma to apoptosis in vitro and in vivo. Octreotide-treated tumors had a massive necrotic area (62.7 ± 19.3% treated vs. 39.7 ± 20.34% untreated, p < 0.05). Microvessels in the treated tumor were decreased (264.0 ± 48.2/mm2 treated vs. 341.4 ± 56.6/mm2 untreated, p < 0.05). The plasma levels of VEGF and bFGF were reduced by octreotide. Conclusions: Octreotide induces rectal NE carcinoma to apoptosis and inhibits angiogenesis in the tumor. These result in tumor necrosis. Octreotide has an antitumor effect on rectal NE carcinoma.

Utility of KRAS mutation detection using circulating cell‐free DNA from patients with colorectal cancer

In this study, we evaluated the clinical utility of detecting KRAS mutations in circulating cell‐free (ccf)DNA of metastatic colorectal cancer patients. We prospectively recruited 94 metastatic colorectal cancer patients. Circulating cell‐free DNA was extracted from plasma samples and analyzed for the presence of seven KRAS point mutations. Using the Invader Plus assay with peptide nucleic acid clamping method and digital PCR, KRAS mutations were detected in the ccfDNA in 35 of 39 patients previously determined to have primary tumors containing KRAS mutations using the Luminex method, and in 5 of 55 patients with tumors containing wild‐type KRAS. Curative resection was undertaken in 7 of 34 patients with primary and ccfDNA KRAS mutations, resulting in the disappearance of the mutation from the cell‐free DNA in five of seven patients. Three of these patients had tumor recurrence and KRAS mutations in their ccfDNA reappeared. Epidermal growth factor receptor blockade was administered to 24 of the KRAS tumor wild‐type patients. Of the 24 patients with wild‐type KRAS in their primary tumors, three patients had KRAS mutations in their ccfDNA and did not respond to treatment with epidermal growth factor receptor (EGFR) blockade. We also detected a new KRAS mutation in five patients during chemotherapy with EGFR blockade, before disease progression was detectable with imaging. The detection of KRAS mutations in ccfDNA is an attractive approach for predicting both treatment response and acquired resistance to EGFR blockade, and for detecting disease recurrence.

Successful Treatment of Necrotizing Fasciitis after Rectal Surgery with the Application of a Negative-pressure Wound Therapy: A Case Study

INTRODUCTION Necrotizing fasciitis (NF) is an aggressive soft tissue infection that involves the deep fascia and is characterized by the extensive deterioration of the surrounding tissue. Immediate recognition and aggressive treatment, including debridement and systemic antibiotics, are mandatory for the successful management of NF. Following radical debridement, closure of the remaining wound can pose significant reconstructive challenges. Accumulating evidence indicates that application of negative-pressure wound therapy (NPWT) is useful in the treatment of patients with severe acute complex wounds, including NF. CASE PRESENTATION A 58-year-old man who had undergone surgical resection for rectal carcinoma followed by chemo-radiation therapy developed NF of the pelvis and thigh three years after the surgical procedure. Following extensive debridement, a VAC system was applied to the large open wound and successfully contributed to wound bed cleansing, which was followed by surgery for skin grafting. CONCLUSION This case demonstrates the successful management of a complex and potentially lethal wound of the perineum to lower leg with debridement and skin grafting as well as with the application of the VAC system.

Superior mesenteric artery syndrome treated with single-incision laparoscopy-assisted duodenojejunostomy

Superior mesenteric artery (SMA) syndrome is an uncommon disease resulting from compression and partial obstruction of the third portion of the duodenum from the SMA. A 77‐year‐old man, who did not have a history of surgery, experienced repeated vomiting and developed abdominal distension. Abdominal CT showed a narrowed third portion of the duodenum, with a distended stomach and proximal duodenum. The patient was diagnosed as having SMA syndrome and was initially treated conservatively, but his condition did not improve. Single‐incision laparoscopy‐assisted duodenojejunostomy was performed. The patient recovered well and was discharged from hospital on postoperative day 8. Laparoscopic treatment is feasible for the treatment of SMA syndrome given its safety and minimal invasiveness. This is a report of the first case of single‐incision laparoscopy‐assisted duodenojejunostomy. This procedure is safer and less invasive than a conventional laparoscopic approach in a patient with SMA syndrome.

Complete response of a patient with advanced gastric cancer, showing Epstein-Barr virus infection, to preoperative chemotherapy with S-1 and cisplatin

Here we report the case of a patient with advanced gastric cancer with esophageal invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP) preoperatively. The patient was a 72-year-old woman who was diagnosed with advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally administered at 80 mg/day (60 mg/m2 per day) on days 1–14 and CDDP was infused at 80 mg/day (60 mg/m2 per day) on day 8, followed by a 1-week rest. Marked reductions in the sizes of the primary tumor and metastatic lymph nodes around the stomach were observed after two cycles of the therapy. Adverse reactions occurring during the therapy were only grade 2 gastrointestinal disorder and grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery showed that a partial response (PR) had been achieved. The patient underwent curative surgery consisting of total gastrectomy, D2 lymph node dissection, and splenectomy. Her postoperative course was uneventful, without surgical complications. No gastric cancer cells were detected in the primary lesion or lymph nodes by immunohistochemical staining with cytokeratin, confirming a histological complete response (CR). As Epstein-Barr virus-encoded small RNA (EBER) had been detected by in-situ hybridization in the gastric cancer cells of a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and cisplatin chemotherapy.

Intraperitoneal Migration of a Mesh Plug from a Hernioplasty Forming a Colocutaneous Fistula with the Cecum: Report of a Case.

Tension-free hernia repair with a mesh plug causes relatively low postoperative pain and allows an earlier return to work, as well as a low recurrence rate. Occasionally, however, hernioplasty can result in complications including mesh migration and invasion of intra-abdominal organs. This report describes the case of a 57-year-old man who had undergone a right inguinal hernioplasty 13 years previously. Recovery was uneventful until he experienced inflammation of the groin, and required open drainage three times for a refractory abscess in his right groin. Additional colonoscopy and x-ray examinations with contrast medium clearly demonstrated a mesh plug that had migrated and penetrated the cecum, forming a colocutaneous fistula. The mesh was successfully removed under general anesthesia, and the inflammation in the groin resolved.

Surgical Specimens of Colorectal Cancer Fixed with PAXgene Tissue System Preserve High-Quality RNA.

BACKGROUND RNA analysis of surgical specimens is one of the most useful methods for exploring biomarkers of advanced cancer. The most readily available source for RNA is formalin-fixed, paraffin-embedded (FFPE) specimens, but RNA isolated from FFPE tissue is of limited use. The PAXgene Tissue (PAX) system is a formalin-free system designed to improve the quality of molecular analysis without diminishing the quality of histopathological analysis. In this human colorectal cancer tissue study, we aimed to evaluate whether surgical specimens fixed with PAX can preserve high-quality RNA in comparison with FFPE and fresh-frozen tissue specimens. METHODS Ten consecutive advanced colorectal cancer patients undergoing colectomy were examined. Each specimen was processed in three ways: as frozen tissue, as PAX-fixed tissue, and as formalin-fixed tissue. RNA integrity numbers (RINs) were assessed using an Agilent Bioanalyzer. RNA transcript levels and stability were investigated by quantitative real-time PCR. We also evaluated the immunohistochemical intensity of Ki-67, CEA, and EGFR in the PAX samples. RESULTS The average RINs of RNA extracted from frozen and PAX samples were significantly higher than those from FFPE samples (p < 0.001). The cycle threshold (Ct) values were similar in PAX and frozen samples, but significantly increased in FFPE samples (p < 0.001). Most of the ΔCt values in the PAX samples did not differ significantly from those in the matched frozen samples. On the other hand, most of the ΔCt values in the FFPE samples differed significantly from those in the matched frozen samples. The immunohistochemical intensity in the PAX samples was well preserved. CONCLUSIONS The quality of RNA extracted from PAX samples may be slightly inferior to that from frozen samples, but is greatly superior to that from FFPE samples.

Gene profiling and bioinformatics analyses reveal time course differential gene expression in surgically resected colorectal tissues

It has previously been reported that gene profiles in surgically-resected colorectal cancer tissues are altered over time possibly due to the different tissue-acquisition methods and sample extraction timing that were used. However, the changes that occur are still not clearly understood. In the present study, time-dependent changes in gene expression profiling in colorectal surgical specimens were analyzed. Normal and tumor tissues at several time-points (0, 30, 60 and 120 min) were extracted, and RNA quality, microarray experiments, quantitative PCR and bioinformatics clustering were performed. Although RNA integrity was preserved 2 h after resection, inherent increased/decreased gene expression was observed from 30–120 min in approximately 10% of genes. Bioinformatics clustering could not distinguish case-by-case, probably due to gene profiling changes. Irregular changes in gene expression after surgical resection were found, which could be a crucial confounding factor for quantitative analyses.

Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX

Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy‐related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy.

Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer

Background/Aim: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). Patients and Methods: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. Results: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). Conclusion: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.