East Versus West: Differences in Surgical Management in Asia Compared with Europe and North America.

In recent decades, there has been considerable worldwide progress in the treatment of gastric cancer. Gastrectomy with a modified D2 lymphadenectomy (sparing the distal pancreas and spleen) has increasingly gained acceptance as a preferable standard surgical approach among surgeons in the East and the West. Despite growing consensus significant differences still exist in surgical techniques in clinical trials and clinical practices secondary to variations in epidemiology, clinicopathologic features, and surgical outcomes among geographic regions. In addition, Western physicians tend to prefer adjuvant chemotherapy and radiotherapy after surgery instead of using S-1 chemotherapy, as is the preference in the East.

Prediction of Anastomotic Leakage After Laparoscopic Low Anterior Resection in Male Rectal Cancer by Pelvic Measurement in Magnetic Resonance Imaging.

OBJECTIVE: Anastomotic leakage after laparoscopic low anterior resection in male rectal cancer patients with a narrow pelvis cannot be easily resolved. The objective of this study is to assess numerical information of narrow pelvis and to determine whether prediction of morbidity can be possible. METHODS: Retrospective medical record review was performed. From July 2007 to January 2013, 43 consecutive male patients with low rectal cancer who underwent laparoscopic low anterior resection were divided into the anastomotic leakage-negative group and anastomotic leakage-positive group. Eleven anatomic parameters were measured from preoperative magnetic resonance imaging of pelvis and a new index called "pelvic index" was calculated. RESULTS: The pelvic index (difference between the interspinous distance and the diameter of the mesorectum divided by the depth of the cavity of the lesser pelvis) in the leakage-positive group was significantly smaller than that in the negative group (P=0.038). Comparison between those 2 groups at the border of the cut-off value of the pelvic index (13.0) showed a significant difference. CONCLUSIONS: Preoperative assessment by the pelvic index can predict the narrow pelvis and risk of anastomotic leakage.

Laparoscopic right hemicolectomy for ascending colon cancer with persistent mesocolon.

Persistent ascending or descending mesocolon is an embryological anomaly that occurs during the final process of intestinal development in organogenesis. Specifically, the primitive dorsal mesocolon fails to fuse with the parietal peritoneum in the fifth month of gestation. Herein, we describe a case of ascending colon cancer with persistent ascending and descending mesocolon treated by laparoscopic right hemicolectomy. Preoperative computed tomography imaging of the abdomen demonstrated that the descending colon shifted at the midline of the abdomen and the sigmoid colon was located under the ascending colon. The detailed preoperative imaging examination revealed malpositioning of the large intestine and aided in the procedural planning. Because persistent mesocolon may result in the formation of abnormal adhesions, an accurate preoperative diagnosis is essential. We propose that it is important to consider this anomaly when making the preoperative imaging diagnosis to ensure a safe operation.

Eicosapentaenoic acid modifies cytokine activity and inhibits cell proliferation in an oesophageal cancer cell line.

BACKGROUND/AIM: The present study investigated the effect of eicosapentaenoic acid (EPA) on nuclear factor-kappa B (NF-κB) activation, inflammatory interleukin-6 (IL-6) production, and cell proliferation in a human oesophageal carcinoma cell line (TE-1). MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced IL-6 production in TE-1 cells in the presence or absence of EPA was determined using enzyme-linked immunosorbent assay (ELISA). The proliferation of TE-1 cells was determined by the WST-1 assay. TE-1 cells were stained with Hoechst 33342 and propidium iodide to observe apoptosis. Immunohistochemical staining of NF-κB in TE-1 cells was performed. RESULTS: LPS increased IL-6 production in TE-1 cells, and EPA treatment prevented this effect. EPA treatment inhibited NF-κB activation and induced apoptosis of TE-1 cells. CONCLUSION: EPA inhibits NF-κB activation and IL-6 production in oesophageal cancer cells, their inducing apoptosis. These effects of EPA may be of benefit in improving the outcome of cancer surgery.

Minimally invasive surgery using intraoperative real-time capsule endoscopy for small bowel lesions.

BACKGROUND: The small bowel has been considered the "black box" of gastroenterology. Identifying the exact site of small bowel hemorrhage is often difficult, thus complicating surgical treatment. We report two cases of small bowel bleeding lesions that were successfully managed by intraoperative real-time capsule endoscopy and minimally invasive surgery. METHODS: We developed a double-lumen tube similar to, but thinner and longer than, the Miller-Abbott tube. We insert the tube nasally, 3 or 4 days preoperatively, such that its balloon tip reaches the anus by the operative day. During surgery, the endoscopic capsule is connected to the balloon tip of the tube that protrudes from the anus. An assistant pulls on the nasal end of the tube, bringing the balloon tip and capsule back into the bowel. Capsule endoscopic images are displayed in a real-time video format. RESULTS: We employed this procedure in two patients with repeated melena. Various examinations including gastroendoscopy and total colonoscopy showed bleeding confined to the small bowel, but the exact lesion site was unknown. Minimally invasive surgery was successfully performed in both patients: open minilaparotomy in one and laparoscopy in the other. The small bowel and capsule endoscope were easily controlled during minilaparotomy, and real-time capsule endoscopic images clearly identified the bleeding lesion. Control of the small bowel was more difficult in the laparoscopic case; however, real-time capsule endoscopic images identified a small tumor that was successfully resected. CONCLUSIONS: Intraoperative capsule endoscopy combined with the tube provides surgeons real-time images indicating the exact site of lesions. The tube also helps surgeons control the position of the capsule endoscope and enables suction of intraluminal fluid or inflation of the lumen to allow clearer views during the operation. We conclude that combined use of capsule endoscopy and the tube facilitates management of bleeding lesions in the small bowel.

Current status of multichannel electrogastrography and examples of its use.

Electrogastrography (EGG) is a non-invasive diagnostic motility for recording gastric myoelectrical activity. Gastric myoelectrical activity was first recorded in 1922. Advances in recording equipment enabled widespread use of cutaneous EGG after 1985. Later, introduction of multichannel EGG (M-EGG) enabled measurement of electrical activity transmission. At present, M-EGG findings are used as objective indicators of gastric motility disorders caused by various diseases. EGG measures two categories of gastric electrical activity: electrical response activity, or spike potentials; and electrical control activity, or slow waves. The appearance of abnormal rhythmic electrical activity is indicative of abnormalities in gastric motility. The normal frequency range of gastric electrical activity (normogastria) is around 3 cycles per?min. Multiple EGG parameters assist in the assessment of gastric myoelectrical activity, and significant correlations between EGG and other gastric motility tests have been demonstrated in many studies. In Japan, however, EGG remains in the exploratory stage, and its clinical use is limited. There are large variations in procedures and systems used in previous studies, thus there is a need for standardization of EGG procedures and technical terminology. Here, we outline the current status of EGG and report the M-EGG procedures used in our department in addition to our M-EGG findings.

Evaluation of 5-FU plasma concentration by 13C breath test in patients treated with oral 5-FU analogs.

BACKGROUND/AIM: The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests. PATIENTS AND METHODS: Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min (AUC0-480 min), time-of-drug concentration peak (T(max)), maximum drug concentration (C(max)) and the half-life period (t(1/2)) of 5-FU were investigated. Simultaneously, a continuous (13)C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the (13)CO(2) excretion rate curve between 0-4 h (AUC(0-4h)), peak (13)CO(2) value and elimination rate constant (K(el)) value. RESULTS: The AUC(0-8h) and C(max) of 5-FU were significantly correlated with K(el) (p=0.012 and p=0.024, respectively), and the 5-FU C(max) value was significantly correlated with the peak value of (13)CO(2) (p=0.037). Multivariate regression analysis also found the C(max) of 5-FU to be associated with K(el) (p=0.0118). The C(max) and AUC(0-8h) of 5-FU were also significantly correlated (p<0.0001). CONCLUSION: The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.

An immunoassay method for the pharmacokinetics of 5-fluorouracil in patients with gastric cancer administered adjuvant chemotherapy.

Conventional gas chromatography-mass spectrometry (GC-MS) was compared with a new immunoassay method for measuring plasma (5-FU) concentrations in adjuvant chemotherapy with TS-1 for patients with gastric cancer. TS-1 was administered orally to patients after gastrectomy. Blood samples for pharmacokinetic analysis were collected on the seventh day of treatment. The mean area under the time concentration curve (AUC)(0-8), half-life (t(1/2)), and maximum drug concentration (C(max)) obtained by the two methods were as follows: GC-MS, 847.9 µg/ml/hr, 2.76 h, and 186.6 ng/ml; and immunoassay, 1311.2 µg/ml/hr, 3.5 h, and 259.8 ng/ml. Significant correlations were observed for AUC(0-8) (p=0.0001), C(max) (p=0.0007), and changes in the 5-FU concentration in blood over time (p=0.018) for the two methods. Compared with the conventional GC-MS method, the new immunoassay method provides similar results, but is simpler and results can be obtained earlier. This method will be useful for monitoring the 5-FU concentration in serum from patients with gastric cancer receiving TS-1.

[A case of chemo-radiation therapy with high degree of efficacy for esophageal cancer with liver metastasis].

A 78-year-old man underwent a radical resection for esophageal cancer (Stage III) and cardiac gastric cancer (Stage IA) at another hospital 2 years ago. After the operation, he was followed at that hospital. In 2008, abdominal CT scan and FDG-PET/CT revealed a liver tumor. He was referred to our hospital and was diagnosed as esophageal cancer with liver metastasis. He received chemo-radiation therapy (CRT). The regimen was docetaxel hydrate (30 mg/m2, day 1, 8, 29 and 36) and S-1 (60 mg/m2, day 1-14 and day 29-45) with radiation (45 Gy) for liver metastasis. He finished the CRT without any hematotoxicity, liver disorder and non-hematotoxic adverse event (grade 3). Abdominal CT was done 2 months after the end of CRT and revealed that the tumor lesion disappeared completely. The patient is alive for 11 months after the CRT without any evidence of recurrence. The tumor disappeared completely for the last 11 months. We conclude that CRT is safe and very effective for esophageal cancer with liver metastasis.

[A resected case of postoperative liver metastasis of a gastrointestinal stromal tumor showing complete response after imatinib treatment].

A 71-year-old man visited the hospital complaining of nausea in December 2002. Following a diagnosis of a gastrointestinal stromal tumor (GIST), partial resection of the stomach was performed in January 2003. The tumor was immunohistochemically positive for c-kit and CD34. The tumor size was 6.5 x 5.0 x 4.5 cm with a mitotic index of 25 out of 50 in the high-power field. The pathological diagnosis indicated a high-risk GIST. Treatment with imatinib at a dose of 400 mg/day was started because of liver metastasis of the GIST in January 2004. The liver metastasis was gradually reduced and exhibited cystic change. We considered that there was a complete response without accumulation by FDG-PET in June 2007. An hepatic segmentectomy was performed and imatinib was discontinued in July 2007. Most intratumorale in the specimen underwent hyaline degeneration after pathological examination, but there were viable cells in a portion of the tumor border. Imatinib treatment was resumed because of recurrence in the remnant stomach four months postoperatively owing to imatinib withdrawal. In making a diagnosis at the cell level by FDG-PET, it was difficult to determine the effectiveness of imatinib, and therefore, it is suggested that imatinib treatment must be continued after surgical resection.

[Results of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for unresectable liver metastases from colorectal cancer].

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.

Alterations of the Dutt1/Robo1 gene in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.

Abnormalities of tumor suppressor genes (TSGs) on chromosome 3p are known to be important for the development of human lung cancers. In the present study, we investigated alterations of the Dutt1/Robo1 gene, as a possible tumor suppressor in this region, in rat lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP). Male Wistar rats, 6-wk-old, were given 2000 ppm BHP in their drinking water for 12 wk and maintained without further treatment until killed at wk 25. A total of 12 lung adenocarcinomas were obtained and total RNAs were extracted from each for assessment of aberrant transcripts of the Dutt1/Robo1 gene by reverse transcription (RT)-polymerase chain reaction (PCR) analysis. Aberrant transcripts bearing deletions of nucleotides (nt) 55-4318, 89-4346, 605-4221, and 929-4318 were detected in four of 12 adenocarcinomas (33.3%). Loss or reduced expression of the Dutt1/Robo1 gene was not found in any of the adenocarcinomas. Genomic DNAs extracted from six adenocarcinomas for Southern blot analysis did not show any evidence of deletion or gross rearrangement of the Dutt1/Robo1 gene. These results suggest that alterations of the Dutt1/Robo1 gene may be involved in the development of some lung adenocarcinomas induced by BHP in rats.

Alterations of the M6p/Igf2 receptor gene in hepatocellular carcinomas induced by N-nitrosodiethylamine and a choline-deficient L-amino acid-defined diet in rats.

To elucidate whether the M6p/Igf2 receptor (M6p/Igf2r) gene might be involved in exogenous and endogenous liver carcinogenesis, we investigated its alteration in hepatocellular carcinomas (HCCs) induced by N-nitrosodiethylamine (DEN) and by a choline-deficient L-amino acid-defined (CDAA) diet in rats. Male F344 rats, 6 wk old, received a single intraperitoneal (i.p.) injection of DEN at a dose of 10 mg/kg body weight, followed by combined treatment with partial hepatectomy and colchicine to induce cell cycle disturbance, and a selection procedure regimen, HCCs being obtained after 42 wk. With continuous CDAA diet feeding, tumors were sampled after 75 wk. Total RNA was extracted from individual HCCs for assessment of mutations within exons 27, 28, 31, 33, and 34, and aberrant transcript of the M6p/Igf2r gene by reverse transcription (RT)-polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and RT-PCR analyses, respectively. Mutations were detected in three of 15 HCCs (20%) induced by the CDAA diet, a TTT to TTG (Phe to Leu) transversion at codon 1516 and two AAG to AGG (Lys to Arg) transitions at codon 1620, but in none of those caused by DEN. Aberrant transcripts were found in seven of 15 HCCs after DEN treatment (46.7%) and in two of 15 HCCs induced by the CDAA diet (13.3%). These results suggest that alterations of the M6p/Igf2r gene may be involved in both exogenous and endogenous liver carcinogenesis with the different patterns and frequencies.

Fhit gene alterations in hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats.

Alterations of the fragile histidine triad (Fhit) gene were investigated in rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet. Males of the F344 strain, 6 wk of age, were fed a CDAA diet, and subgroups were killed at 2, 4, 12, 20, and 75 wk after the beginning of the experiment. Fifteen hepatocellular carcinomas (HCCs) were noted in rats by the last time point; they were dissected free from the surrounding tissue. Normal control liver specimens were obtained from 6-wk-old rats. Total RNAs were extracted from whole livers of animals fed the CDAA diet for 2, 4, 12, and 20 wk and from HCCs, for assessment of aberrant transcription of the Fhit gene by reverse transcription-polymerase chain reaction. Aberrant transcripts were detected in livers of rats fed the CDAA diet for 4, 12, and 20 wk, but not 2 wk, as well as in 11 of 15 HCCs (73.3%). Southern blot analysis showed a genomic DNA abnormality in one of seven informative HCCs (14.3%), while Western blot analysis showed reduction of Fhit protein expression in seven of nine HCCs (77.8%). No abnormal expression was evident in the livers after exposure to the CDAA diet for 2-20 wk. These results suggest that Fhit alterations may play important roles in hepatocarcinogenesis due to choline deficiency in rats.

Double common bile duct: a case report and a review of the Japanese literature.

BACKGROUND: A double common bile duct (DCBD) is a rare congenital anomaly. We report the case of a 60-year-old Japanese female, whose common bile duct divided into 2 channels and both channels opened individually into the second portion of the duodenum. This is the fourth reported case of DCBD with a choledochal cyst and pancreaticobiliary maljunction (PBM). METHODS: A review of the literature revealed that DCBD is more frequently diagnosed in Oriental people. We reviewed 47 cases of DCBD reported in the Japanese literature. RESULTS: Among these, cholelithiasis was found in 27.7%, a choledochal cyst in 10.6%, PBM in 29.8%, and cancers in 25.5%. Cancer and PBM were the 2 most serious concomitant conditions. The incidence and type of complicating cancer and PBM varied according to the site of the opening of the accessory common bile duct (ACBD). Concomitant gastric cancer was frequently noted when the ACBD opened into the stomach, whereas cancer of the biliary system was common when the ACBD opened into the second portion of the duodenum or the pancreatic duct. PBM was observed only in those patients in whom the ACBD opened into the second portion of the duodenum or the pancreatic duct. Therefore the treatment and prognosis of DCBD is influenced by the site of opening of the ACBD. CONCLUSIONS: In DCBD, the opening site of the ACBD was considered to have close implications for the type of concomitant cancer and concomitant PBM that would appear.