Norio Yukawa

Serum miR-21, miR-29a, and miR-125b Are Promising Biomarkers for the Early Detection of Colorectal Neoplasia.

Purpose: Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms. Experimental Design: A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR. Results: Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (≤5 mm) than in healthy subjects. Conclusions: Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia. Clin Cancer Res; 21(18); 4234–42. ©2015 AACR.

A prospective validation study to diagnose serosal invasion and nodal metastases of gastric cancer by multidetector-row CT.

BackgroundMultidetector-row CT (MDCT) may provide accurate preoperative staging of resectable gastric cancer. However, the standard methods and criteria to diagnose the T and N stages to select the patients who are good candidates for neoadjuvant chemotherapy have not been established yet.MethodsThe aim of this prospective study was to evaluate the accuracy of MDCT to diagnose the serosal invasion and nodal metastases of gastric cancer. Patients who had gastric adenocarcinoma underwent MDCT scanning using a standardized method. The T and N stage were diagnosed by prespecified criteria. The analyses were performed in the patients who had cN0–2 and M0 tumors and underwent curative gastrectomy as a primary treatment. The accuracy was calculated by comparing the results of MDCT with the histopathological findings.ResultsA total of 315 patients were analyzed. The overall diagnostic accuracy (95 % confidence interval) of T staging was 71.4 % (225 of 315, 66.2–76.1). The accuracy, sensitivity, and specificity for serosal invasion were 85.7 % (81.4–89.1), 54.5 % (42.6–66.0), and 94.0 % (90.3–96.3), respectively. The false-positive rate for serosal invasion was 6.0 % (2.9–7.7). The overall diagnostic accuracy of N staging was 75.9 % (239 of 315, 70.9–80.3). The accuracy, sensitivity, and specificity for nodal metastases were 81.3 % (76.6–85.2), 46.4 % (36.8–56.3), and 96.8 % (93.5–98.4), respectively. The false-positive rate for nodal metastases was 3.2 % (1.6–6.5 %).ConclusionsThese results suggest that MDCT provides an accurate diagnosis with high specificity and a low false-positive rate and can be used to select the patients who are candidates for preoperative chemotherapy.

Impact of Plasma Tissue Inhibitor of Matrix Metalloproteinase-1 on Long-Term Survival in Patients with Colorectal Cancer

Tissue inhibitor of metalloproteinase-1 (TIMP-1) not only inhibits matrix metalloproteinases but also stimulates tumor growth. In this study, long-term follow-up results were analyzed to clarify the prognostic value of plasma TIMP-1. Preoperative plasma TIMP-1 was measured from peripheral blood samples of 87 Japanese patients with colorectal carcinoma. All the patients underwent surgical resection and were followed for 5 years prospectively. The median follow-up period was 70 months (60–79 months). The cutoff value of plasma TIMP-1 was set at 170 ng/ml based on the ROC curve. Sensitivity and specificity to predict 5-year survival was 66.7 and 55.0% with this cutoff value. In univariate analyses for overall survival, lymph node metastasis, serosal invasion, peritoneal metastasis, liver metastasis, metastasis to other distant organs and TIMP-1 were significant. In multivariate analyses, lymph node and liver metastases, metastasis to other distant organs and plasma TIMP-1 were independent prognosticators, but p values of TIMP-1 did not reach statistical significance. Our results suggested that the preoperative plasma TIMP-1 concentration could be a useful prognosticator of long-term survival in patients with colorectal carcinoma.

Clinical significance of SPARC gene expression in patients with gastric cancer.

Secreted protein acidic and rich in cysteine (SPARC) is one of the first known matricellular proteins that modulates interactions between cells and extracellular matrix. Recent studies investigated the clinical significance of SPARC gene expression in the development, progression, and metastasis of cancer. The present study examined the relations of the relative expression of the SPARC gene to clinicopathological factors and overall survival in patients with gastric cancer.

Superior vena cava (SVC) reconstruction using autologous tissue in two cases of differentiated thyroid carcinoma presenting with SVC syndrome

Herein, we report two extremely rare cases of differentiated thyroid carcinoma (DTC) with extended tumor thrombus or mediastinum lymph node metastasis (LNM) involving the superior vena cava (SVC), causing SVC syndrome. Both of these patients were successfully treated with radical resection and reconstruction of the SVC using autologous tissue instead of an expanded polytetrafluoroethylene (ePTFE) graft. The left brachiocephalic vein was used to reconstruct the SVC in a papillary thyroid carcinoma patient with mediastinum LNM and a pericardial patch was used in a follicular thyroid carcinoma patient with tumor thrombus. Our search of the English-language literature found sporadic reports of SVC resection with reconstruction by vascular graft (ePTFE), interposed between the brachiocephalic vein and the right atrium. However, SVC reconstruction using autologous tissue in thyroid carcinoma has not been reported to date. To our knowledge, this is the first report describing such an unusual technique in DTC patients.

Laparoscopic esophagojejunostomy using the EndoStitch and a circular stapler under a direct view created by the ENDOCAMELEON

Laparoscopic esophagojejunostomy using a circular stapler is associated with technical difficulties in the purse-string sutures used to insert the anvil head and in obtaining an adequate visual field to prevent rolling the mesentery and the wall of the jejunum on the mesenteric side into the anastomosis. To overcome these difficulties, we used the EndoStitch to create the purse-string suture and the ENDOCAMELEON to create the visual field to stretch the jejunum. After resecting the esophagus, purse-string sutures were placed using the EndoStitch. A total of five to six needle deliveries were performed. Next, the anvil head was inserted into the esophagus. The main unit of the EEA was inserted from the end of the resected jejunum. Then, the scope was changed to the ENDOCAMELEON. The main unit was slowly moved toward the anvil head. After making sure that the mesentery and the wall of the jejunum on the mesenteric side were not rolled into the anastomosis under the visual field created by the ENDOCAMELEON, the main unit was then fired. Thereafter, esophagojejunostomy was successfully completed. This technique was applied in 20 patients between April 2010 and May 2012. Laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer was completed in all 20 patients. No case required conversion to open surgery. Neither anastomotic leakage nor stenosis was observed. This method is simple and useful for laparoscopic esophagojejunostomy after total gastrectomy for gastric cancer.

Laparoscopy-Assisted Distal Gastrectomy for an Early Gastric Cancer Patient With Situs Inversus Totalis

Situs inversus totalis (SIT) is a congenital condition in which there is complete right to left reversal of the thoracic and abdominal organs. This report describes laparoscopy-assisted distal gastrectomy (LADG) for an early gastric cancer patient with SIT. The preoperative diagnosis was c-stage IA (cT1a cN0 cH0 cP0 cM0). LADG with D1+ dissection and Billroth-I reconstruction was successfully performed by standing at the opposite position. The operating time was 234 minutes and blood loss was 5 mL. Although a mechanical obstruction occurred after surgery, the patient recovered after re-operation with Roux-en-Y bypass.

Perivascular epithelioid cell tumor of the rectum: report of a case and review of the literature

We report a case of perivascular epithelioid cell tumor arising in the rectum of a 55-year-old woman. The tumor was treated by transanal endoscopic microsurgery. After 1 year follow-up, the patient is alive with no radiologic or endoscopic evidence of recurrence. Perivascular epithelioid cell tumor is a rare mesenchymal tumor characterized by co-expression of melanocytic and smooth muscle markers. This rare tumor can arise in various organs, including the falciform ligament, uterus, uterine cervix, liver, kidney, lung, breast, cardiac septum, pancreas, prostate, thigh, and gastrointestinal tract. Perivascular epithelioid cell tumor of the gastrointestinal tract is very rare, with only 23 previously reported cases. We review the literature on perivascular epithelioid cell tumors arising in the gastrointestinal tract.

Gallbladder herniation into the lesser sac through the foramen of Winslow: report of a case.

We report a case of gallbladder hernia into the lesser sac through the foramen of Winslow. The patient was a 90-year-old woman, admitted to hospital with obstructive jaundice. Computed tomography (CT) showed a left-deviated and remarkably enlarged gallbladder dragging the liver, and a dilated intrahepatic bile duct. The deviated gallbladder was thought to compress the common bile duct, causing the obstruction. Laparoscopic examination revealed gallbladder herniation into the lesser sac without a floating gallbladder; thus, we performed laparoscopic cholecystectomy. Herniation of the gallbladder is the rarest of all internal hernias and most reported cases have involved a floating gallbladder. The case we report here is therefore considered especially unusual.

Primary placement technique of jejunostomy using the entristar™ skin-level gastrostomy tube in patients with esophageal cancer

BackgroundWe developed a skin-level jejunostomy tube (SLJT) procedure for patients undergoing esophagectomy using a skin-level gastrostomy tube (G-tube) (Entristar™; Tyco Healthcare, Mansfield, Mass), in order to improve their nutrition status and quality of life (QOL). We describe the procedure and the adverse effects of SLJT in patients with esophageal cancer (EC).MethodsOver a 24-month period (March 2008 to March 2010), there were 16 patients (mean age: 61.8 years; age range: 49-75 years; 15 men, 1 woman) who had Stage II or III EC. Primary jejunostomy was performed under general anesthesia during esophagectomy. The technical success and the immediate and delayed complications of the procedure were recorded.Jejunostomy techniquesSLJT placement using the G-tube (20Fr) was performed 20 cm from the Treitz ligament on the side opposing the jejunal mesenterium. The internal retention bolster was exteriorized through an incision in the abdominal wall. A single purse string suture using a 4-0 absorbable suture was performed. The internal retention bolster was then inserted into the jejunal lumen via the small incision. The intestine adjacent to the tube was anchored to the peritoneum using a single stitch.ResultsThe SLJT was successfully inserted in all 16 patients. No early complications were documented. Follow-up for a median of 107 days (range, 26-320 days) revealed leakage to the skin in four patients, including superficial wound infections in two patients. There were no cases of obstruction of the tube or procedure-related death.ConclusionsThis SLJT placement technique using the G-tube is a safe procedure in patients with EC and allows the creation of a long-term feeding jejunostomy.