Atsushi Takeno

Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis

Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21WAF1/CIP1) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage.

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

Background:Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression.Methods:We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis.Results:Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (P<0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P=0.020), pN number (P=0.001), and CK18 expression (P=0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P=0.045).Conclusion:CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.

Lymph Node Dissection in Curative Gastrectomy for Advanced Gastric Cancer

Gastric cancer is one of the most common causes of cancer-related death worldwide. Surgical resection with lymph node dissection is the only potentially curative therapy for gastric cancer. However, the appropriate extent of lymph node dissection accompanied by gastrectomy for cancer remains controversial. In East Asian countries, especially in Japan and Korea, D2 lymph node dissection has been regularly performed as a standard procedure. In Western countries, surgeons perform gastrectomy with D1 dissection only because D2 is associated with high mortality and morbidity compared to those associated with D1 alone but does not improve the 5-year survival rate. However, more recent studies have demonstrated that western surgeons can be trained to perform D2 lymphadenectomies on western patients with a lower morbidity and mortality. When extensive D2 lymph node dissection is preformed safely, there may be some benefit to D2 dissection even in western countries. In this paper, we present an update on the current literature regarding the extent of lymphadenectomy for advanced gastric cancer.

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

BackgroundThis pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy.MethodsSixteen patients were enrolled. Paclitaxel was administered at 120 mg/m2 on day 1 and S-1 was administered orally at 80 mg/m2 for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit.ResultsPartial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively.ConclusionThis chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.

Efficacy of endoscopic gastroduodenal stenting for gastric outlet obstruction due to unresectable advanced gastric cancer: a prospective multicenter study.

Gastroduodenal stents for gastric outlet obstruction due to unresectable advanced gastric cancer are increasingly used; however, their effects have not been fully evaluated.

Thoracoscopic enucleation of esophageal schwannoma exhibiting 18F-fluorodeoxyglucose uptake on positron emission tomography

Schwannoma is a benign neurogenic tumor that can arise from the esophagus, but this is extremely rare. We report thoracoscopic resection of benign esophageal schwannoma that showed Ffluorodeoxyglucose (FDG) uptake. An esophageal submucosal tumor (2.3 ¥ 2.8 cm in size) was found incidentally on computed tomography (CT), dorsal to the bifurcation of the trachea organs (Fig. 1A), in a 72-year-old man with aneurysm of the abdominal aorta. Endoscopy showed a submucosal tumor with negative iodine staining in the posterior esophageal wall (24 cm from the incisors), covered with smooth normal mucosa (Fig. 1C). Although endoscopic ultrasound-guided, fine-needle aspiration biopsy (Fig. 1D) was not helpful in establishing the diagnosis, positron emission tomography-CT showed increased FDG uptake (SUVmax 4.7), implying GIST or schwannoma as a possible diagnosis (Fig. 1B). The patient underwent thoracoscopic enucleation of tumor through the right chest approach without any perioperative complications. The tumor was Address correspondence to: Dr Tomoki Makino, MD, PhD, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan. Email: tmakino@gesurg.med.osaka-u.ac.jp (A) (C)

A suspected [18F]fluorodeoxyglucose positron emission tomography-negative metastatic lymph node successfully diagnosed by laparoscopic staging in esophageal cancer: Report of two cases

An accurate preoperative staging is important for selecting an appropriate therapy for esophageal cancer. In particular, diagnosis of lymph node metastases influences the indication for radical surgery. [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely applied primarily as a useful tool for initial staging of esophageal cancer. However, false-negative cases sometimes make it difficult to select the appropriate treatment. We report two patients with esophageal cancer and PET-negative enlarged lymph node successfully diagnosed by laparoscopic sampling. This procedure did not only allow accurate histopathological staging, but also helped to select the optimal minimally invasive management. This technique can be recommended for patients with esophageal cancer in whom the diagnosis of enlarged lymph node cannot be confirmed by preoperative imaging.

Elective laparoscopic surgery for sigmoid colon carcinoma incarcerated within an inguinal hernia: report of a case.

Primary colon carcinoma within an inguinal hernia sac is very rare and most reported cases were found at emergency open surgery for an incarcerated hernia. We report a case of incarcerated sigmoid colon carcinoma diagnosed preoperatively and treated with elective laparoscopic surgery. A 67-year-old man with a 2-year history of swelling of the scrotum and a breast lump was referred to us for surgical treatment of an irreducible left inguinal hernia and a right breast tumor. Blood examination results showed severe anemia. Computed tomography scan and endoscopic biopsy confirmed sigmoid colon carcinoma incarcerated in the left inguinal hernia. Thus, we performed definitive laparoscopic sigmoidectomy and conventional hernia repair for preoperatively diagnosed sigmoid colon carcinoma within an inguinal hernia.

Single-site laparoscopic right hemicolectomy for acute cecal volvulus: a case report

BackgroundCecal volvulus is an uncommon cause of acute abdomen in patients. Cecal volvulus is currently treated mostly with right hemicolectomy with laparotomy, which is an invasive surgical procedure. Less invasive techniques, such as endoscopic decompression, have a poor success rate.Case presentationWe report a case of cecal volvulus in a 35-year-old male patient. He was successfully treated with single-site laparoscopic decompression by inserting a catheter through the amputated appendix, detorsion, and hemicolectomy. This approach was less invasive than the traditional approach and resulted in satisfactory outcomes and cosmesis.ConclusionsApplication of single-site laparoscopic colectomy to acute cecal volvulus is feasible using decompression of the dilated colon by inserting a catheter through the amputated appendix. To the best of our knowledge, this is the first report of this treatment.

Evaluation of the effects of postoperative oral nutrition support on body weight in gastric cancer patients by using an elemental diet: A randomized study.

110 Background: Postoperative weight loss causes deterioration in the patient’s quality of life and influences long-term prognosis in gastric cancer patients who have undergone gastrectomy. Moreover, recent retrospective studies indicated postoperative weight loss as a risk factor for premature interruption of S-1 adjuvant chemotherapy. We conducted a prospective randomized controlled study to examine whether the early institution of nutritional support comprising an oral elemental diet (ED) prepared for post-gastrectomy patients with depressed digestive/absorptive function would help prevent postoperative weight loss. Methods: After surgery, patients were randomly assigned to the ED or control groups. The groups were divided according to the surgical methods used (total/distal gastrectomy), clinical stage (≤Ia/>Ia), and patients’ body mass index ( 18.5). In patients assigned to the ED group (Elental, 300 kcal) was provided in addition to the regular diet from the day starting soft rice diet or equi...