Baba H

Polymorphisms of GSTP1, ERCC2 and TS‑3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients

The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5′-untranslated region (UTR) and 6-bp deletions in the 3′-UTR of thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S-transferase π (GSTP1; IIe105Val), GST θ1 (GSTT1; deletion) and GST μ1 (GSTM1; deletion) and the two DNA-repair genes, excision repair cross-complementing-1 (ERCC1; Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and the clinical outcome, including drug response, progression-free survival (PFS), overall survival (OS) and the incidence of peripheral neuropathy, were evaluated. Patients with the GSTP1-105 A/A genotype had poor responses to mFOLFOX6 treatment compared with those with the GSTP1-105 A/G and G/G genotypes (P=0.01). The median PFS of patients with the ERCC2-751 A/A genotype tended to be longer than that of patients with the ERCC2-751 A/C genotype (P=0.05). Patients with the TS-3′-UTR −6/−6 genotype had a significantly longer OS compared with patients with other genotypes (P=0.003). A statistically significant association between the incidence of peripheral neuropathy higher than grade 2 and the GSTP1-105 (P=0.03) and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression analyses. Results demonstrated that polymorphisms in GSTP1-105, ERCC2-751 and the 3′-UTR of TS may be a statistically significant predictors of clinical outcome. GSTP1-105 and GSTM1 genotypes may be useful markers of severe peripheral neuropathy in MCRC patients treated with 5-FU/oxaliplatin as first-line chemotherapy.

Angiogenesis in Superficial Esophageal Squamous Cell Carcinoma: Assessment of Microvessel Density Based on Immunostaining for CD34 and CD105

OBJECTIVE The esophagus is the only organ where changes in the superficial microvasculature from normal squamous epithelium to invasive cancer are evident by magnifying endoscopy. We investigated in detail the features of angiogenesis in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also the correlation between angiogenesis and mononuclear cell infiltration. MATERIALS AND METHODS Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer, we determined the microvessel density at hot spots showing positive staining for CD34 and CD105. We observed the histological features of CD34- and CD105-positive microvessels that corresponded to observations made by magnifying endoscopy. We then investigated the correlation between microvessel density and each histological situation or the grade of mononuclear cell infiltration. RESULTS The histological features of CD34- and CD105-positive microvessels were able to explain the morphological changes in the microvasculature during cancer progression observed by magnifying endoscopy. The microvessel density for CD34 or CD105 was significantly correlated with each of the histological types (P < 0.001, rS = 0.51 and 0.76, respectively). Mononuclear cell infiltration at CD105 hot spots was most frequent in M1 and M2 cancer (94.7%). The correlation between the degree of mononuclear cell infiltration and microvessel density for CD105 staining was also significant (P < 0.001, rS = 0.49). CONCLUSIONS The microvessel density based on CD34 and CD105 immunostaining can be used to corroborate observations of superficial esophageal squamous cell carcinoma made by magnifying endoscopy. Mononuclear cell infiltration may play an important role in angiogenesis at the early stage of cancer progression.

Usefulness of indocyanine green angiography for evaluation of blood supply in a reconstructed gastric tube during esophagectomy.

We report a case of necrosis of a reconstructed gastric tube in a 77-year-old male patient who had undergone esophagectomy. At the time of admission, the patient had active gastric ulcers, but these were resolved by treatment with a proton pump inhibitor. Subtotal esophagectomy with gastric tube reconstruction was performed. Visually, the reconstructed gastric tube appeared to be well perfused with blood. Using indocyanine green (ICG) fluorescence imaging the gastroepiploic vessels were well enhanced and no enhancement was visable 3 to 4 cm from the tip of the gastric tube. Four days after esophagectomy, gastric tube necrosis was confirmed, necessitating a second operation. The necrosis of the gastric tube matched the area that had been shown to lack blood perfusion by ICG angiography imaging. It seems that ICG angiography is useful for the evaluation of perfusion in a reconstructed gastric tube.

Heterotopic Mesenteric Ossification After a Ruptured Abdominal Aortic Aneurism: Case Report With a Review of Literatures

Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240 cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation.

Clinicopathologic Characteristics and Clinical Outcomes of Esophageal Basaloid Squamous Carcinoma: Experience at a Single Institution

This retrospective study investigated the clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma (BSC). Among 190 patients with esophageal carcinoma treated surgically between 1998 and 2011, we identified 9 (4.7%) with BSC. All of the patients were male, with a median age of 65 years. The frequencies of venous invasion, lymphatic invasion, and lymph node metastasis were 56%, 89%, and 67%, respectively. A total of 2 patients were pathologic stage 1, 5 were stage 2, and 2 were stage 3. Tumor recurrence was observed in 56% of the patients. The 5-year survival rate for patients with esophageal BSC was 40%, which was compatible with the figure of 53.8% for control patients (n = 18) with typical squamous cell carcinoma matched for sex, age, tumor location, and pathologic stage (P = 0.45). Although esophageal BSC shows aggressive lymph-vascular invasion and has a high likelihood of recurrence, its prognosis seems identical to that of typical squamous cell carcinoma.

Prognostic Factors for Stage IV Gastric Cancer

recommend selectionfrom among 5 treatments for stage IV patients inclinical practice: surgery (extended or palliative),chemotherapy, radiation therapy or palliative care.Principles are still controversial, and clinical study isadvocated. The nature of the disease does not allowus to conduct prospective studies; however, retro-spective study plays an important role by means ofclinical study.This study is a retrospective study based onclinical practice and aims to clarify the favorablefactors contributing to better prognosis of stage IVgastric cancer patients. Furthermore, we aim toassess the optimal treatment strategies.

Prognostic role of gastrectomy in patients with gastric cancer with positive peritoneal cytology.

This retrospective study identified the optimal treatment strategy for patients with gastric cancer with positive peritoneal cytology. We analyzed clinicopathologic and survival data for 54 patients who had undergone gastrectomy and/or chemotherapy for treatment of gastric cancer with positive peritoneal cytology with (n = 40) or without (n = 14) metastatic disease. The median overall survival did not differ significantly between patients with gastric cancer with positive peritoneal cytology with and without metastatic disease (19 versus 13 months, respectively). Among 14 clinicopathologic variables, the lack of gastrectomy was the only significant independent unfavorable factor for survival (odds ratio, 1.64; 95% confidence interval, 1.04-2.57; P = 0.03). The median overall survival significantly differed among patients who had undergone gastrectomy plus chemotherapy, chemotherapy alone, and gastrectomy alone (25, 10, and 17 months, respectively; P < 0.01). Gastrectomy may be optimal for patients with (gastric cancer with positive peritoneal cytology), considering its favorable prognostic effect with respect to perioperative chemotherapy.

Primary papillary hyperplasia of the gallbladder mimicking gallbladder cancer.

Primary papillary hyperplasia of the gallbladder (PPHG) is a rare entity. PPHG is a benign diffuse mucosal projection without any background chronic inflammation-related disease of the gallbladder or bile ducts. Reported cases of PPHG are limited in that its characteristics are not well defined. We herein report a case of PPHG mimicking gallbladder cancer in radiologic investigations and present a review of the literature. Also coincident erythroderma is discussed.

Unusual bleeding from hepaticojejunostomy controlled by adult variable stiffness colonoscopy: report of a case and literature review.

We herein present a case of a 59-year-old man who had undergone pylorus preserving pancreaticoduodenectomy with regional lymph node dissection prior to episodes of melena. Series of conventional endoscopic investigations failed to identify the bleeding source. Enhanced computed tomography scan revealed complete obstruction of the main portal vein with numerous collateral veins running towards the hepatic hilus. Comprehensively, hemorrhage from the jejunal varices caused by postoperative portal hypertension was highly suspected. As the jejunal loop was out of reach, adult variable-stiffness colonoscope (AVSC) was utilized to solve the Roux-en-Y anatomy. Numerous telangiectasis and small varices at hepaticojejunostomy were observed and in the mean time, bleeding was noticed and endoclips were placed without any delay. Ectopic variceal bleeding in jejunal loop after pancreaticoduodenectomy is difficult to manage. We believe that AVSC is an alternative device when specialized jejunal endoscopy is not available.

Production of Intraperitoneal Interleukin-6 Following Open or Laparoscopic Assisted Distal Gastrectomy

The interleukin (IL)-6 concentration in plasma or serum has been considered to represent the degree of stress resulting from surgery. However, IL-6 in peritoneal fluid has rarely been considered. The aim of this study was to assess the concentration and amount of IL-6 in peritoneal fluid as indicators of surgical stress. To obtain basic data on peritoneal release of IL-6 during gastric cancer surgery, we measured IL-6 in peritoneal drainage samples, stored for up to 72 hours postoperatively, from patients who had undergone conventional open (ODG group, n = 20) and laparoscopic-assisted (LADG group, n = 19) distal gastrectomy. Within 24 hours, 61 and 77% of the IL-6 was released into the peritoneal cavity in the LADG and ODG groups, respectively. In both groups, the concentration and amount of peritoneal fluid IL-6 were significantly correlated with each other (LADG group: Spearmans rank correlation test [rS] = 0.48, P = 0.04; ODG group: rS = 0.58, P = 0.01). The concentration and amount of IL-6 in peritoneal fluid was 2.8- and 3.6-fold higher in the ODG than in the LADG group, respectively (P < 0.01). With regard to the relationship between the serum C-reactive protein (CRP) peak and the concentration or amount of peritoneal fluid IL-6 released within 24 hours, only the concentration of peritoneal fluid IL-6 in the LADG group was significantly correlated (rS = 0.60, P = 0.01) with the serum CRP peak. Our findings suggest that the amount and concentration of IL-6 released into the peritoneal cavity for up to 24 hours after surgery can each be a reliable parameter for assessment of surgical stress.