Akinari Nomura

Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma†

Intrahepatic cholangiocarcinoma is a neoplasm arising in the liver, and its incidence is increasing in Japan as well as in Western countries. Prognosis of patients with this type of tumor remains unsatisfactory because no effective chemotherapeutic drugs are available, we have no sensitive tumor markers to detect this tumor in its early stage, and it is difficult to identify a high‐risk group for the disease. To clarify the molecular mechanism of tumorigenesis and identify molecular targets for diagnosis and treatment, we analyzed global gene‐expression profiles of 25 intrahepatic cholangiocarcinomas using tumor cell populations purified by laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 52 genes that were commonly upregulated and 421 that were downregulated in intrahepatic cholangiocarcinomas compared with noncancerous biliary epithelial cells. From the 52 upregulated genes, we selected P‐cadherin and survivin for further investigation and corroborated enhanced expression of their products in cancer tissues by immunohistochemical staining. Furthermore, comparison between tumors with lymph node metastasis and those without metastasis identified 30 genes that were associated with lymph node involvement. In conclusion, these data should be helpful for a better understanding of the tumorigenesis of intrahepatic cholangiocarcinoma and should contribute to the development of diagnostic and therapeutic strategies for this type of tumor. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270‐9139/suppmat/index.html). (HEPATOLOGY 2005.)

Intracorporeal esophagojejunal anastomosis after laparoscopic total gastrectomy for patients with gastric cancer

BackgroundTo facilitate acceptance of laparoscopic total gastrectomy (LTG) for patients with upper gastric cancer, a simple, secure technique of reconstruction is necessary. The authors developed a new technique for intracorporeal esophagojejunal anastomosis that does not require hand sewing.MethodsFrom September 2006 to January 2008, 16 patients (11 men and 5 women) with gastric cancer underwent LTG at the authors’ institution. Laparoscopic esophagojejunal anastomosis using the following method was attempted for all patients. The esophagus was transected while being rotated by about 45° counterclockwise to make the subsequent anastomosis easier. After the Y-anastomosis was created, an endoscopic linear stapler was applied to create a side-to-side anastomosis between the left dorsal side of the esophagus and the jejunal limb. The entry hole was first closed roughly with hernia staplers. Subsequently, an endoscopic linear stapler was applied so that all hernia staplers could be removed and the closure completed.ResultsLaparoscopic esophagojejunal anastomosis was successfully performed for 15 patients. Intracorporeal anastomosis failed for one patient because a nasogastric tube was caught between the jaws of an endostapler, which resulted in a conversion to open procedure. No postoperative anastomotic complications occurred.ConclusionsUsing the new technique, intracorporeal linear-stapled esophagojejunal anastomosis can be performed easily and securely. This technique could become one of the standard methods for reconstruction after LTG, facilitating the acceptance of LTG as a surgical option for patients with upper gastric cancer.

Long-term outcomes of peripheral arm ports implanted in patients with colorectal cancer

BackgroundVenous ports are mandatory for chemotherapy in cancer patients because prolonged infusions are required. The aim of this study was to assess the safety of peripheral arm ports for chemotherapy in patients with colorectal cancer.MethodsA peripheral venous access port was placed in the upper arm in 113 consecutive patients with metastatic colorectal cancer (MCRC). All patients received modifi ed FOLFOX (5-fl uorouracil [5-FU]/l-leucovorin [LV]/oxaliplatin [L-OHP]) 6 or FOLFIRI (5-FU/LV/irinotecan hydrochloride [CPT-11]) regimens at least once via the venous access port. All patients were followed up at least once every 2 weeks.ResultsPuncture of the basilic veins was successfully completed under real-time sonographic guidance or radiographic guidance in all patients. The median operative time was 30 min. The cumulative follow-up period was 29 886 catheter days (range, 9–560 days; mean, 264 days). No procedural complications, such as pneumothorax, hemothorax, arterial puncture, or cardiovascular problems, occurred in our series. A total of nine patients (8.0%) had complications. Port-site infection occurred in six patients (5.3%; 0.20 infections per 1000 catheter-days). One patient (0.9%) had an episode of ultrasound-documented deep vein thrombosis in the ipsilateral upper extremity (0.03/1000 catheter-days). Dislocation or migration of the catheter tip occurred in two patients (0.07/1000 catheter-days). A second port was placed in six patients (5.3%) after removal of the fi rst port.ConclusionPeripheral arm ports can be maintained with excellent short-and long-term outcomes. Peripheral arm ports are considered to be a good alternative to central venous ports implanted in the chest in patients with MCRC.

SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas

Accumulation of loss of heterozygosity (LOH) on chromosome 16 is frequently observed in human hepatocellular carcinomas (HCCs). To identify tumor‐suppressor genes (TSGs) involved in hepatocarcinogenesis, we performed deletion mapping of chromosome 16 in 59 HCCs. Three commonly deleted regions, located in 16q12.1, 16q22.1, and 16q24.2, were observed. Because there has been no study on LOH at locus 16q12.1 in HCCs, we focused on this region. By searching the Human Genome Database at the National Center for Biotechnology Information web site, we identified 14 known genes in 16q12.1 as TSG candidates. Among these, the expression of SIAH1 was markedly downregulated in HCCs, and inactivation of SIAH1 expression was associated with LOH at 16q12.1. A mutation analysis of SIAH1 revealed no somatic mutations, but one single nucleotide polymorphism was found among the 35 HCCs investigated. Subsequently, we evaluated the relation between SIAH1 expression, confirmed by semiquantitative RT‐PCR, and clinicopathological parameters in HCCs. SIAH1 was significantly downregulated in advanced HCCs, including poorly differentiated tumors, larger tumors, and tumors in advanced stages. These findings suggest that inactivation of SIAH1 plays an important role in HCC progression.

Esophagojejunostomy through minilaparotomy after laparoscopic total gastrectomy

Although laparoscopic distal gastrectomy (LDG) has been accepted as a surgical option for the treatment of early gastric cancer, laparoscopic total gastrectomy (LTG) has been adopted less often, because a more difficult surgical technique is required for reconstruction. To reduce the technical difficulties, we made some modifications to the functional end-to-end anastomosis technique and performed esophagojejunal anastomosis through a minilaparotomy. First, for easier handling of the esophagus, the first application of the linear stapler to create the esophagojejunal anastomosis was performed before transection of the esophagus. Second, the jejunal limb was anastomosed to the left side of the esophagus, which, compared with the right side, made available more free space, sufficient to operate the stapling device. Third, to close the entry hole and complete the gastrectomy concurrently, a linear stapler was applied through the left lower trocar. With this technique, the closure of the access opening was performed easily and was monitored directly through the minilaparotomy. We successfully performed LTG with Roux-en-Y reconstruction using our modified procedure in seven patients without any anastomotic complications. We believe our procedure is a secure and reliable method for reconstruction after LTG and will facilitate adoption of LTG as a surgical option for patients with early upper gastric cancers.

Medially approached radical lymph node dissection along the surgical trunk for advanced right-sided colon cancers.

Although laparoscopic surgery is one of the treatment options for colorectal cancer, certain technical problems remain unresolved for the radical dissection of regional lymph nodes (LNs), which is essential to improve treatment outcome. We present a safe procedure for laparoscopic right hemicolectomy to dissect the regional LNs along the superior mesenteric vein (SMV). The key characteristic of our procedure is that all right and middle colic vessels are cut along the surgical trunk using only a medial approach. First, the pedicle of ileocolic vessels is identified and the mesocolon is dissected between the pedicle and the periphery of the SMV to expose the second portion of the duodenum. The ileocolic vessels are then cut at their roots. The ascending mesocolon is separated from the retroperitoneal tissues, duodenum, and pancreatic head up to the hepatocolic ligament cranially. The important detail in this procedure is the wide separation between the pancreatic head and the transverse mesocolon. This procedure uncovers the course of the right colic artery, veins, and the gastrocolic trunk [1]. The right colic artery and veins can then be safely cut at their roots. For an extended right hemicolectomy, the middle colic vessels can easily be identified below the lower edge of the pancreas and cut at their roots [2]. We performed curative resections in this manner for 16 consecutive patients with advanced right-sided colon cancer without any serious intraoperative complications. The median number of retrieved lymph nodes was 31 (range = 9–57). The median operative time and intraoperative blood loss were 274 min (range = 147–431 min) and 45 g (range = 0–120 g), respectively. The postoperative course of all patients was uneventful. Four of 16 patients had node-positive disease. With a median follow-up period of 272 days, all patients are alive without recurrence. We consider this a safe method for radical LN dissection during laparoscopic right hemicolectomy.

Autonomic Nerve-Preserving Total Mesorectal Excision in the Laparoscopic Era

PurposeAlthough technically demanding, laparoscopy may be advantageous in magnifying the anatomy of the pelvic autonomic nervous system when performing total mesorectal excision for rectal cancer. We present our method for laparoscopic total mesorectal excision for men.MethodsWe performed laparoscopic total mesorectal excision for 36 men with middle or low rectal cancer. The rectum was mobilized through a medial approach down to the pelvic floor without minilaparotomy or hand assist. Anteriorly, the dissection plane was in front of Denonvilliers fascia. Anterolaterally, to preserve the pelvic plexus and neurovascular bundle, Denonvilliers fascia must be cut at its lateral continuity. We found that the most important factor in obtaining a good surgical view is keeping adequate tension in the dissection plane by coordination between the surgeon and assistant. Dissection was performed by using only electrocautery without an ultrasonic dissector or vessel sealing device.ResultsNo case was converted to open surgery. The short-term feasibility was acceptable.ConclusionsOur method of laparoscopic total mesorectal excision is a feasible approach and may be beneficial for the standardization and popularization of laparoscopic total mesorectal excision. Long-term results, including survival data and urogenital function, are needed to evaluate the true efficacy of this procedure.

Oral and Parenteral Versus Parenteral Antibiotic Prophylaxis in Elective Laparoscopic Colorectal Surgery (JMTO PREV 07-01): A Phase 3, Multicenter, Open-label, Randomized Trial.

Objective:To confirm the efficacy of oral and parenteral antibiotic prophylaxis (ABX) in the elective laparoscopic colorectal surgery. Background:There is no evidence for the establishment of an optimal ABX regimen for laparoscopic colorectal surgery, which has become an important choice for the colorectal cancer patients. Methods:The colorectal cancer patients scheduled to undergo laparoscopic surgery were eligible for this multicenter, open-label, randomized trial. They were randomized to receive either oral and parenteral prophylaxis (1 g cefmetazole before and every 3 h during the surgery plus 1 g oral kanamycin and 750 mg metronidazole twice on the day before the surgery; Oral-IV group) or parenteral prophylaxis alone (the same IV regimen; IV group). The primary endpoint was the incidence of surgical site infections (SSIs). Secondary endpoints were the incidence rates of Clostridium difficile colitis, other infections, and postoperative noninfectious complications, as well as the frequency of isolating specific organisms. Results:Between November 2007 and December 2012, 579 patients (289 in the Oral-IV group and 290 in IV group) were evaluated for this study. The incidence of SSIs was 7.26% (21/289) in the Oral-IV group and 12.8% (37/290) in the IV group with an odds ratio of 0.536 (95% CI, 0.305–0.940; P = 0.028). The 2 groups had similar incidence rates of C difficile colitis (1/289 vs 3/290), other infections (6/289 vs 5/290), and postoperative noninfectious complications (11/289 vs 12/290). Conclusions:Our oral-parenteral ABX regimen significantly reduced the risk of SSIs following elective laparoscopic colorectal surgery.

Male sexual function after laparoscopic total mesorectal excision

Aim  The aim of this prospective study was to clarify the frequency of male sexual dysfunction after laparoscopic total mesorectal excision (LTME) and to examine the relationship between pelvic autonomic nerve (PAN) preservation status and functional outcomes.

A novel laparoscopic approach for safe and simplified suprapancreatic lymph node dissection of gastric cancer

BackgroundLymph node dissection is a crucial procedure for curative resection of gastric cancer [1]. To avoid portal vein injury during laparoscopic extended lymph node dissection for gastric cancer, taping of the common hepatic artery and subsequent confirmation of the portal vein have been recommended [2, 3]. This taping method, however, makes laparoscopic nodal dissection technically complicated. This study introduces a novel procedure for safe and simple laparoscopic suprapancreatic nodal dissection without taping of the common hepatic artery.MethodsThe authors’ novel, simplified method consists of four steps: (1) dissection along the cranial edge of the pancreas from right to left, (2) dissection along the splenic artery with exposure of the left renal fascia, (3) dissection along the left gastric and the common hepatic arteries, and (4) retraction of the lymph nodes surrounding the common and proper hepatic arteries and their complete dissection from the portal vein. This procedure is reversely directed compared with conventional open gastrectomy (i.e., the nodal dissection is from left to right). For this study, the lymph node stations and groups were defined according to the 13th edition of the Japanese Classification for Gastric Carcinoma. The described procedures were performed for 58 consecutive patients with gastric cancer. The indication for this operation is primary T1/T2 gastric cancer without clinical nodal metastasis.ResultsIn all cases, safely extended suprapancreatic lymph node dissection was successfully accomplished using the described technique. A total of 43.5 ± 18 lymph nodes were retrieved, including 14.4 ± 6.3 second-tier lymph nodes. The overall number of retrieved lymph nodes in this study was similar to that reported previously [4]. Postoperative morbidity occurred at a rate of 22.3%, and the mortality rate was 0%. There was no conversion to open surgery. The mean blood loss was 127 ml (range, 0–490 ml), and the mean operative time was 289 min (range, 104–416 min) in the last 20 consecutive cases. To date, no tumor recurrence has been observed. The median postoperative observation period was 1.4 years (range, 0.4–2.4 years).ConclusionThe described novel procedure would be sufficient and convenient for dissection of the suprapancreatic lymph nodes.