Hangeshashinto-Associated Mesenteric Phlebosclerosis and Highly Atypical Adenoma Requiring Laparoscopic Right Hemicolectomy.

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

Three semi-selective media for Pseudomonas syringae pv. maculicola and P. cannabina pv. alisalensis.

Three semi-selective media, DTarTA, SPbc, and SPamt, were developed and tested to isolate Pseudomonas syringae pv. maculicola (Psm) and P. cannabina pv. alisalensis (Pca) from Raphanus sativus seeds. DTarTA contained D-tartaric acid as a carbon source and potassium tellurite, ampicillin sodium, and methyl violet as antibiotics. DTarTA suppressed growth in 19 of the 24 pathovars from the P. syringae complex, whereas Psm and Pca grew and formed gray to black colonies. SPamt contained sucrose and peptone as nutrient sources and was supplemented with bromothymol blue and the same antibiotics present in DTarTA and Psm and Pca formed yellowish to dark brown colonies on the SPamt medium. SPbc contained sucrose and peptone and was supplemented with cephalexin and boric acid as antibiotics and Psm and Pca formed semi-translucent to white colonies on the SPbc medium. SPamt and SPbc suppressed the growth of several plant-associated bacteria (except the P. syringae complex). The growth of saprophytic bacteria in seeds on the different media was compared with that on King's B medium, using five types of commercially available Raphanus sativus seeds. The suppression rate of DTarTA was 85-99% and was lower for seeds with more saprophytic bacteria. The suppression rates of SPamt and SPbc were 90-99%. In detection tests using 10,000 seed samples mixed with Pca or Psm-contaminated seeds, it was possible to selectively isolate Psm and Pca using SPamt and SPbc, even when the colony numbers of the target bacterium constituted less than 10% of the total colonies. KEY POINTS: • Bacterial leaf spot and blight pathogens were selectively isolated from seeds. • DTarTA medium distinguishes these pathogens from P. syringae complex pathovars. • SPamp and SPbc media have different selectivity for plant-associated bacteria.

[Primary Small Bowel Tumor with Simultaneous Lung Metastases from Rectal Cancer - A Case Report].

A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage IV), and underwent low anterior resection and laparoscopic partial hepatectomy. The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed multiple lung metastases 11 months later. Before undergoing a pulmonary resection, the patient presented with acute small bowel obstruction. Abdominal computed tomography showed small bowel stenosis due to a tumor, and we suspected peritoneal metastases from the rectal tumor. We performed partial resection of the small intestine, and histopathological examination revealed a primary small bowel tumor. The patient was discharged to her home without complications, and later underwent pulmonary resections for bilateral lung metastases. We usually suspect that small bowel obstruction is due to peritoneal metastases in patients with advanced colorectal tumors, but must consider the rare possibility of a separate primary small bowel tumor, especially in patients with a solitary lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a patient with Stage IV rectal cancer.

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia.

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

Puborectal sling interposition combined with seton drainage for pouch-vaginal fistula after rectal cancer surgery with colonic J pouch-anal reconstruction: report of a case.

The management of postoperative rectovaginal fistula (RVF) after rectal cancer surgery is difficult and requires reconstruction of the anastomotic site and fistula. Though various surgical procedures have been reported for the repair of RVFs, the results of surgical repair are often unsatisfactory, and failure of the initial repair leads to difficulty in the later operations. Furthermore, it has been reported that cases associated with local infection result in low success rates. We report a case of an 80-year-old woman with a recurrent colonic J pouch-vaginal fistula after anoabdominal rectal resection with partial internal sphincteric resection, who achieved a good outcome following a repair using a puborectal sling interposition combined with seton drainage. It may be a useful option for RVF management in repair of such pouch-vaginal fistula after coloanal anastomosis with intersphincteric resection.

Podoplanin and SOX2 expression in esophageal squamous cell carcinoma after neoadjuvant chemo-radiotherapy.

Neoadjuvant chemo-radiotherapy (CRT) followed by surgery are the standard approaches for locally advanced esophageal cancer. However, the overall cure rate is very low. The aim of this preliminary study was to evaluate the expression of podoplanin and SOX2 known as stemness markers for esophageal squamous cell carcinoma (ESCC) and their association with clinical outcome. We obtained a total of 20 specimens from patients with ESCC who underwent neoadjuvant CRT (30-40 Gy; 5-fluorouracil plus cisplatin) followed by surgery. Podoplanin and SOX2 expression was evaluated using immunohistochemistry and the association of their expressions with clinicopathological variables was investigated. Podoplanin and SOX2 staining was detected not only in residual cancer cells, but also in the basal layer of adjacent normal mucosa after neoadjuvant CRT. High expression of podoplanin was correlated with lymph node metastasis, advanced postoperative stage and vascular invasion (P<0.05), while, high expression of SOX2 was correlated with lymphatic, vascular invasion, poor differentiated tumor and incomplete resection (P<0.05). High expression of podoplanin was significantly associated with poor overall survival (P<0.05). In conclusion, the expression levels of podoplanin and SOX2 expression may be useful prognostic markers for ESCC treated with neoadjuvant CRT.

Pure tone auditory thresholds can change according to duration of interrupted tones in patients with psychogenic hearing loss.

CONCLUSION: Pure tone auditory thresholds can change according to duration of interrupted tones in patients with mild to severe psychogenic hearing loss (PHL). OBJECTIVES: To examine how the duration of stimulus tones affects the hearing thresholds of patients with PHL. METHODS: Twelve patients with PHL (21 ears) were enrolled in this study. We initially measured their hearing thresholds using interrupted tones with a duration of 2 s and equal length of on-time and off-time, 225 ± 35 ms, respectively. After a 10 min interval, we measured their hearing thresholds using the same interrupted tones conditions lasting 5 s. The average threshold gains (2 s thresholds minus 5 s thresholds) were compared to those of 15 control subjects with normal hearing (25 ears), 15 patients with cochlear hearing loss (23 ears), and 4 patients with retrocochlear lesions (4 ears). Patients with profound PHL (4 patients, 6 ears) were analyzed separately. RESULTS: The average threshold gain of PHL patients (excluding profound PHL patients) at all frequencies was 18.3 dB, which was significantly larger than that of other groups: 0.3 dB (profound PHL patients), 3.8 dB (controls with normal hearing), 3.0 dB (patients with cochlear hearing loss), and 3.2 dB (patients with retrocochlear lesions).

Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for colon cancer.

To evaluate the feasibility of paclitaxel (PTX) radiosensitization for colon cancer, we investigated the cytotoxic and G2/M checkpoint protein (Chk1, Wee1, Bub1, MAD2) effects of 5-fluorouracil (5-FU) or PTX combined with radiation in the human colon cancer cell line LoVo. Cytotoxicity and radiocytotoxicity were evaluated for each drug by the WST-8 colorimetric assay. The IC20 for each drug was determined as a cytotoxic concentration from a survival curve. LoVo cells were exposed to the IC20 of each drug for 24 h and then irradiated. Expressions of the G2/M checkpoint proteins were confirmed by Western blot analysis. Cytotoxicity was induced by 5-FU or PTX alone in a time- and dose-dependent manner. The IC20 of PTX caused higher radiosensitivity than the IC20 of 5-FU (P<0.05). Western blot analysis revealed different expression patterns of the G2/M checkpoint proteins between 5-FU and PTX pre-treatments. 5-FU combined with radiation tended to decrease the expressions of all G2/M checkpoint proteins in a time-dependent manner. PTX combined with radiation maintained high expressions of Chk1 and MAD2 proteins for 24 h post-radiation and, in particular, MAD2 protein was strongly induced by PTX with high-dose radiation. PTX showed higher radio-sensitization than 5-FU for the colon cancer cell line LoVo and may be an alternative radiosensitizer to 5-FU in the clinical setting.

Preoperative C-reactive protein as a prognostic and therapeutic marker for colorectal cancer.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the significance of preoperative C-reactive protein (CRP) as a prognostic marker for carcinoembryonic antigen (CEA)-independent stage I or II colorectal cancer (CRC) patients. METHODS: Preoperative CRP was measured in 300 CRC patients to assess its relationships with clinicopathological factors and long-term survival. Based on the results of the initial study, the relationship between preoperative CRP and long-term survival was evaluated with reference to adjuvant 5-fluorouracil (5-FU)-based chemotherapy in a further 128 stage II patients. RESULTS: CRP was associated with disease progression and factors reflecting nutritional depletion such as serum albumin, lymphocyte count and body weight loss ratio. In stage I or II patients, CRP could predict early disease recurrence, even when a CEA test could not. Multivariate analyses revealed that CRP was an independent prognostic variable in stage I or II patients. In the additional 128 stage II patients, CRP-positive patients showed a 3-year survival rate of only 55% without adjuvant chemotherapy, but this increased to 90% with adjuvant chemotherapy. CONCLUSIONS: CRP may be a potent prognostic and therapeutic indicator that provides valuable information for determining the need for adjuvant chemotherapy in stage II CRC patients.

Mechanism of resistance to chemoradiation in p53 mutant human colon cancer.

To understand one of the mechanisms of resistance to chemoradiation in colon cancer cells, we investigated whether 5-fluorouracil (5-FU) mediated the expression of epidermal growth factor receptor (EGFR) and modified repair of radiation-induced DNA damage, especially in a p53 independent pathway. Cytotoxicity was determined for 5-FU combined with radiation for three colon cancer cell lines that contain mutant p53 (SW480, HT29 and WiDr), using the WST-8 colorimetric assay. EGFR and the excision repair cross complementation group 1 (ERCC1) proteins during chemoradiation were measured by Western blot analysis. SW480 cells were significantly resistant to chemoradiation compared to the other mutant p53 cell lines. The alteration of EGFR and ERCC1 proteins during chemoradiation in SW480 was apparently inversely related to that of the other radiosensitive cell lines. 5-FU-induced activation of EGFR followed by radiation in SW480 cells resulted in up-regulation of ERCC1. In contrast, 5-FU-induced degradation of EGFR followed by radiation in the other radiosensitive cell lines resulted in down-regulation of ERCC1. This suggested a complementary interaction between EGFR and ERCC1, and that 5-FU-induced EGFR activation conferred protection against radiation, through activation of DNA repair. Interaction of EGFR and ERCC1 might correlate with radiation-induced DNA damage when p53 mutant colon cancer cell lines are exposed to 5-FU followed by radiation.

Gene expression profiles of colorectal carcinoma in response to neo-adjuvant chemotherapy.

The combination of irinotecan and a fluoropyrimidine has been widely accepted as a treatment for advanced colorectal carcinoma. However, there have been no evaluable data on the feasibility of these combinations. To assess the significance of such combinations, we attempted to identify gene expression patterns in response to irinotecan and two different types of fluoropyrimidines. In 12 patients dispositioned to receive preoperative chemotherapy for colorectal carcinoma, pre-therapy tumor biopsies and final resected specimens were available for analysis. Patients were randomly assigned to receive one of the following four regimens: (I), oral doxifluridine; (II), intravenous infusion of 5-FU; (III), intravenous infusion of irinotecan; (IV), combination of doxifluridine and irinotecan (I+III). To identify genes whose expressions changed, we analyzed the gene expression profiles prior to and after these therapies using an oligonucleotide microarray consisting of 12,000 genes. Next, we focused on the genes that demonstrated similar kinetics of altered expression in all patients in each of the regimens. We identified two proto-oncogenes, nuclear receptor of T-cells (NOT) and c-fos, that were up-regulated in doxifluridine- and irinotecan-related regimens but unchanged in the 5-FU-related regimen. Moreover, group IV tumors showed the highest apoptotic rate and lowest proliferation activity following the combined chemotherapy. These results suggest that doxifluridine has a synergistic impact on the therapeutic effect of irinotecan by up-regulating proto-oncogenes such as NOT and c-fos, and thus justify the use of one of the irinotecan and fluoropyrimidine combinations.

[Changes in Japanese cedar sensitization rates of Japanese allergic children during the last 15 years].

In order to evaluate the changes in Japanese Cedar (JC) sensitization rates of allergic children, serum samples from 88 patients about 15 years ago (past group) and those from 91 current patients (present group) were randomly selected, and their JC specific IgE were measured with the CAP-RAST system. Sensitivity rate (class 2 or more) for JC of the present group was 65.9%, which was significantly higher than that of the past group, which was 46.6%. However, there was no significant difference between these two groups for children aged 6 or younger. For children aged 7 or older, the sensitivity rate of the present group was significantly higher than that of the past group. Thus, protection against JC sensitization, especially during early childhood, should be given serious attention.