[show abstract][hide abstract] ABSTRACT: Purpose
We compared biweekly irinotecan plus cisplatin (BIRIP) with irinotecan alone as the second-line chemotherapy (SLC) for advanced gastric cancer (AGC).
Patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy were randomly assigned to receive BIRIP (irinotecan 60 mg/m2 plus cisplatin 30 mg/m2, every 2 weeks) or irinotecan alone (irinotecan 150 mg/m2, every 2 weeks). The primary end-point was to show the superiority of BIRIP to irinotecan in terms of progression free survival (PFS).
130 patients were enrolled. PFS was significantly longer in the BIRIP group (3.8 months [95% confidence interval (CI) 3.0–4.7]) than in the irinotecan group (2.8 months and ; hazard ratio 0.68, 95% CI 0.47–0.98; P = 0.0398). Median overall survival was 10.7 months in the BIRIP group and 10.1 months in the irinotecan group (HR 1.00, 95% CI 0.69–1.44, P = 0.9823). The objective response rate was 22% in the BIRIP group and 16% in the irinotecan group (P = 0.4975). However, the disease control rate was significantly better in the BIRIP group (75%) than in the irinotecan group (54%, P = 0.0162). The incidences of grade 3 or worse adverse events did not differ between the two groups. Any grade elevation of serum creatinine was more common in the BIRIP group (25% versus 8%, P = 0.009), but any grade diarrhoea (17% versus 42%, P = 0.002) was more common in the irinotecan group.
BIRIP significantly prolonged PFS as compared with irinotecan alone and was tolerated as SLC, but did not demonstrate the survival benefit in this trial.
European journal of cancer (Oxford, England: 1990) 01/2014; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Approximately 80%-95% of gastrointestinal stromal tumors (GISTs) show positive staining for KIT, while the other 5%-20% show negative staining. If the tumor is negative for KIT, but is positive for CD34, a histological diagnosis is possible. However, if the tumor is negative for KIT, CD34, S-100, and SMA, a definitive diagnosis is often challenging. Recently, Discovered on GIST-1 (DOG1) has received considerable attention as a useful molecule for the diagnosis of GIST. DOG1, a membrane channel protein, is known to be overexpressed in GIST. Because the sensitivity and specificity of DOG1 are higher than those of KIT, positive staining for DOG1 has been reported, even in KIT-negative GISTs. KIT-negative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically. We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia. Our findings suggest that immunohistochemical staining for DOG1, in addition to gene analysis, is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.
World Journal of Gastroenterology 12/2013; 19(47):9133-6. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lemur tyrosine kinase-3 (LMTK3) was recently identified as estrogen receptor (ER) -α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Since different predominant ERs distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was conducted to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and one-hundred and thirty-seven United States (US) patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival (HR 4.37; 95% CI, 2.08-9.18; p<0.0001) and overall survival (OS) (HR 3.69; 95% CI, 1.65-8.24; p=0.0014) in the Japanese males and time to recurrence (HR 7.29; 95% CI, 1.07-49.80; p=0.043) in the US females. Meanwhile, harboring rs8108419 G/G genotype was associated with OS in the Japanese females (HR 3.04; 95% CI, 1.08-8.56; p=0.035) and the US males (HR 3.39; 95% CI, 1.31-8.80; p=0.012). The prognostic role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patient with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.
Molecular Cancer Therapeutics 08/2013; · 5.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Most previous studies of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms were retrospective; prospective studies are scant. OBJECTIVE: To prospectively assess the efficacy and safety of ESD for superficial esophageal neoplasms. DESIGN: Phase II study. SETTING: University hospital. PATIENTS: Fifty-two patients (median age 68 years; 48 men) who had a histologic diagnosis of superficial esophageal cancer without metastasis on CT or high-grade intraepithelial neoplasia (HGIN) were enrolled from April 2009 through November 2011. INTERVENTION: ESD was used to treat 56 lesions. All procedures were done by 4 endoscopists who each had previously performed ESD in more than 100 patients with gastric tumors. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the R0 resection rate, and secondary endpoints were the safety and the rate of accurately diagnosing tumor depth on endoscopic examination. RESULTS: The median treatment time was 69 minutes (24-168 minutes). The histopathologic diagnosis was squamous cell carcinoma in 49 lesions, HGIN in 5, and tubular adenocarcinoma in 2. The en bloc resection rate and R0 resection rate were 100% and 94.6%, respectively. The rates of adverse events during ESD and after ESD were 22.2% and 53.8%, respectively, but most events were mild. One patient (1.9%) had mediastinal emphysema without perforation. The rate of accurately diagnosing tumor depth on endoscopic examination was 76.8%. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our study showed that ESD was an effective and relatively safe treatment for superficial esophageal neoplasms. ESD may be a useful treatment option for superficial esophageal neoplasms in hospitals with endoscopists who are experts in performing ESD for gastric tumors. (Clinical trial registration number: UMIN000002047.).
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Percutaneous transesophageal gastrotubing (PTEG) was developed as an alternative route to access the gastrointestinal tract when percutaneous endoscopic gastrostomy is contraindicated. PTEG was originally performed without endoscopy. However, endoscopy may enhance safety. MATERIALS AND METHODS: A percutaneous rupture-free balloon is inserted under ultrasonographic control into an upper esophageal puncture site with a specialized needle. A guidewire is inserted through the needle into the rupture-free balloon, followed by a dilator and sheath. A placement tube is then inserted through the sheath. PTEG was performed in 85 patients (56 men and 29 women, mean age 70.5 years), 30 under fluoroscopic guidance and 55 under endoscopic guidance. These groups were subdivided into the nutrition subgroup (fluoroscopy, 20 patients; endoscopy, 23) and the decompression subgroup (fluoroscopy, 10 patients; endoscopy, 32) according to the purpose of PTEG. RESULTS: Nine (30%) of the 30 patients in the fluoroscopy group required endoscopic assistance to complete the procedure. None of the patients in the endoscopy group required fluoroscopy (P<0.05). The overall complication rate of PTEG was 16.4%. Complication rates in the nutrition and decompression subgroups were, respectively, 20.0 and 20.0% in the fluoroscopy group and 17.4 and 12.5% in the endoscopy group (NS). No patient required surgery or died because of the procedure. Survival rates did not differ significantly between the groups. CONCLUSION: Endoscopically assisted PTEG is a feasible, safe, and useful procedure. The use of endoscopy enhances visual information, may increase the safety of the procedure, and allows better confirmation of each step involved, without radiation exposure.
European journal of gastroenterology & hepatology 05/2013; · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Few studies have compared the outcomes of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in patients with early gastric cancer. METHODS: We studied 780 lesions for which endoscopic treatment was indicated according to the Japanese Gastric Cancer Association (JGCA) criteria or the extended National Cancer Center (NCC) criteria from April 1995 to December 2007. A total of 359 lesions were treated by endoscopic aspiration mucosectomy (EAM) between April 1995 and March 2003 (EAM group), and 421 lesions were treated by ESD between April 2003 and December 2007 (ESD group). Long-term outcomes (local recurrence rate, overall survival) were compared between the groups. RESULTS: The median follow-up was 73 months in the EAM group and 65 months in the ESD group. Overall, the local recurrence rate was significantly lower in the ESD group (0.2 %, 1/421) than in the EAM group (4.2 %, 15/359) (p < 0.05). For lesions meeting the JGCA criteria, the local recurrence rate was 2.9 % in the EAM group and 0 % in the ESD group (p < 0.05). For lesions meeting the NCC criteria, the local recurrence rate was 12.5 % in the EAM group and 0.6 % in the ESD group (p < 0.05). There was no significant difference between the groups in overall survival. CONCLUSIONS: On long-term follow-up, ESD was associated with a lower rate of local recurrence than EAM for lesions that met the JGCA or the NCC criteria. From the point of view of radical curability, ESD can be recommended for the management of lesions that meet either set of criteria.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric cancer accompanied by an ulcer scar remains challenging. Several counter-traction techniques have been attempted to facilitate ESD, but a standard procedure remains to be established. OBJECTIVE: To evaluate the efficacy and safety of double-endoscope ESD by using a single light source in patients with early gastric cancer accompanied by an ulcer scar. DESIGN: Single center, retrospective study. SETTING: Kitasato University East Hospital. PATIENTS: A total of 30 early gastric cancers with ulcer scars were treated by double-endoscope ESD in 30 patients from October 2008 through May 2012. INTERVENTION: Double-endoscope ESD. MAIN OUTCOME MEASUREMENTS: En bloc resection rate, complete resection rate, treatment time, and adverse events. RESULTS: The use of two endoscopes for ESD provided a good field of vision and allowed counter-traction to be applied to the lesion, clearly facilitating submucosal dissection. Because only a single light source was used, the working space of the endoscope room was not compromised. Moreover, it was unnecessary to prepare another light source or to coordinate image filing. The en bloc resection rate and complete resection rate were 100% and 90%, respectively, and the median treatment time was 80 minutes. As compared with historical control data obtained before the introduction of double-endoscope ESD, the rate of cutting into the specimen was significantly lower (7% vs 35%; P = .01). No serious adverse events occurred during the procedure. Postoperatively, however, 3 patients (10%) had delayed hemorrhage, and 1 (3.3%) had a delayed perforation. LIMITATIONS: Single-center, nonrandomized study. CONCLUSION: Our experience indicates that our procedure for double-endoscope ESD is useful and feasible in patients with early gastric cancer accompanied by an ulcer scar.
[show abstract][hide abstract] ABSTRACT: Endoscopic submucosal dissection is associated with a longer treatment time and a higher risk of patient discomfort than conventional procedures. Adequate, safe sedation is therefore essential. Sedation can cause adverse effects such as hypoxemia and hypotension, requiring continuous intraoperative and postoperative monitoring of blood pressure, use of the electrocardiogram, and arterial blood oxygen saturation by pulse oximetry. A physician and a nurse solely responsible for sedating and monitoring the patient should be present during treatment.A combination of benzodiazepines and analgesics are generally used for sedation, but new sedatives such as propofol and dexmedetomidine hydrochloride are expected to be useful agents. Endoscopists should become more familiar with sedatives, analgesics, and emergency procedures in the future.
[show abstract][hide abstract] ABSTRACT: To evaluate the usefulness and safety of argon plasma coagulation (APC) for superficial esophageal squamous-cell carcinoma (SESC) in high-risk patients.
We studied 17 patients (15 men and 2 women, 21 lesions) with SESC in whom endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and open surgery were contraindicated from March 1999 through February 2009. None of the patients could tolerate prolonged EMR/ESD or open surgery because of severe concomitant disease (e.g., liver cirrhosis, cerebral infarction, or ischemic heart disease) or scar formation after EMR/ESD and chemoradiotherapy. After conventional endoscopy, an iodine stain was sprayed on the esophageal mucosa to determine the lesion margins. The lesion was then ablated by APC. We retrospectively studied the treatment time, number of APC sessions per site, complications, presence or absence of recurrence, and time to recurrence.
The median duration of follow-up was 36 mo (range: 6-120 mo). All of the tumors were macroscopically classified as superficial and slightly depressed type (0-IIc). The preoperative depth of invasion was clinical T1a (mucosal cancer) for 19 lesions and clinical T1b (submucosal cancer) for 2. The median treatment time was 15 min (range: 10-36 min). The median number of treatment sessions per site was 2 (range: 1-4). The median hospital stay was 14 d (range: 5-68 d). Among the 17 patients (21 lesions), 2 (9.5%) had recurrence and underwent additional APC with no subsequent evidence of recurrence. There were no treatment-related complications, such as bleeding or perforation.
APC is considered to be safe and effective for the management of SESC that cannot be resected endoscopically because of underlying disease, as well as for the control of recurrence after EMR and local recurrence after chemoradiotherapy.
World Journal of Gastroenterology 10/2012; 18(38):5412-7. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.
Diseases of the Esophagus 09/2012; · 1.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: The phase III CONFIRM clinical trials demonstrated that metastatic colorectal cancer patients with elevated serum lactate dehydrogenase (LDH) had improved outcome when the vascular endothelial growth factor receptor (VEGFR) inhibitor PTK/ZK (Vatalanib) was added to FOLFOX4 chemotherapy. We investigated the hypothesis that high intratumoral expression of genes regulated by hypoxia-inducible factor-1 alpha (HIF1α), namely LDHA, glucose transporter-1 (GLUT-1), VEGFA, VEGFR1, and VEGFR2, were predictive of outcome in CONFIRM-1. Tumor tissue was isolated by laser-capture microdissection from 85 CONFIRM-1 tumor specimens; FOLFOX4/placebo n=42, FOLFOX4/PTK/ZK n=43. Gene expression was analyzed using quantitative RT-PCR. In univariate analyses, elevated mRNA expression of LDHA, GLUT-1, and VEGFR1 were associated with response to FOLFOX4/PTK/ZK. In univariate and multivariate analyses, elevated LDHA and VEGFR1 mRNA levels were associated with improved progression-free survival in FOLFOX4/PTK/ZK patients. Furthermore, increased HIF1α and VEGFR2 mRNA levels were associated with decreased survival in FOLFOX/placebo patients but not in patients who received FOLFOX4/PTK/ZK. These are the first data suggesting intratumoral mRNA expression of genes involved in angiogenesis/HIF pathway may predict outcome to VEGFR-inhibitors. Biomarkers that assist in directing VEGFR-inhibitors toward patients with an increased likelihood of benefit will improve the cost-effectiveness of these promising agents.The Pharmacogenomics Journal advance online publication, 5 June 2012; doi:10.1038/tpj.2012.23.
The Pharmacogenomics Journal 06/2012; · 5.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endoscopic submucosal dissection (ESD) has become a standard treatment. However, the treatment time tends to be relatively long and insufflation and manipulation of the endoscope can increase pain and discomfort. We aimed to find an optimal method for sedation during ESD.
Patients scheduled to undergo ESD for early gastric cancer or adenoma were randomly assigned to sedation with midazolam or propofol, and consciousness level was evaluated by bispectral index (BIS) monitoring. Primary end points of effectiveness (three parameters) and secondary end points of safety during ESD and after return to the ward were compared between the groups. Study registration was in the UMIN Clinical Trial Registry (UMIN 000001497), and the institutional trial number was KDOG 0801.
From June 2008 through June 2009, we enrolled 178 patients (90 midazolam, 88 propofol). Regarding safety after ESD, recovery was significantly better in the propofol group immediately after and at 1 hour and 2 hours after return to the ward (P < 0.001). The number of patients who required a continuous supply of oxygen 2 hours after returning to the ward was significantly lower in the propofol group (midazolam 18; propofol 6; P = 0.010). Though propofol seemed to be better for effectiveness and safety, there were no statistically significant differences for all three primary end points and the safety parameters (hypotension, hypoxia, bradycardia).
Propofol with BIS monitoring improved recovery of patients after ESD, though this study was underpowered to prove the effectiveness and safety of propofol.
[show abstract][hide abstract] ABSTRACT: Multicentric squamous dysplasia in the esophagus can be visualized by Lugol chromoendoscopy as multiple Lugol-voiding lesions (LVLs). Narrow-band imaging combined with magnifying endoscopy (NBI-ME) facilitates the detection of superficial squamous cell carcinoma within the head and neck region (HNSCC). We investigated risk factors for superficial HNSCC in patients with esophageal squamous cell carcinoma (ESCC).
We studied 71 patients with synchronous or former ESCC. All patients underwent screening of the head and neck by NBI-ME and Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Genetic polymorphisms of aldehyde dehydrogenase type 2 (ALDH2) were identified by the sequence-specific primer polymerase chain reaction. Clinical factors related to superficial HNSCC were analyzed.
All patients with superficial HNSCC were drinkers. On univariate analysis, multiple LVLs (odds ratio [OR], 56.92; 95% confidence interval [CI] 6.93-467.38; P < .001), ALDH2-2 allele (OR, 14.48; 95% CI, 1.8-116.56; P = .01), current smoker (OR, 4.25; 95% CI, 1.44-12.57; P = .009), and smoking index ≥ 1,000 (OR, 3.45; 95% CI, 1.19-9.99; P = .02) were associated with superficial HNSCC. On multivariate analysis, multiple LVLs (OR, 61.12; 95% CI, 5.4-691.64; P = .001), ALDH2-2 allele (OR, 16.19; 95% CI, 1.15-228.06; P = .04), and current smoker (OR, 8.02; 95% CI, 1.09-59.22; P = .04) were associated with superficial HNSCC.
Patients with ESCC, particularly drinkers, current smokers, and those with the ALDH2-2 allele and multiple LVLs, have an increased risk of superficial HNSCC.
The Laryngoscope 06/2012; 122(6):1291-6. · 1.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Estrogen replacement therapy in women has shown a protective effect on the development of colonic carcinomas. Gender-related differences in the development of colonic carcinomas have also been reported. Estrogen receptor-β (ERβ) is expressed in colon carcinomas and has shown prognostic value in colon cancer patients. This study investigated an ERβ 3' non-coding polymorphism associated with transcriptional activity to determine clinical outcome in patients with metastatic colon cancer. Genomic DNA from 318 metastatic colon cancer patients, 177 males and 141 females, were collected from 1992 to 2003. These patients were analyzed for CA repeat polymorphism of the ERβ gene. Gender-related survival differences were associated with an ERβ (CA)n repeat polymorphism (P for interaction=0.003, the likelihood ratio test). Female patients with any short<22 (CA)n repeat alleles had shorter overall survival (OS) compared with female patients who had both long≥22 (CA)n repeat alleles. In the male patients, the opposite OS difference was found. This study supports the role of an ERβ (CA)n repeat polymorphism as a prognostic marker in metastatic colon cancer; however, this prognostic factor had opposite implications based on gender.
The Pharmacogenomics Journal 10/2011; 11(5):375-82. · 5.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: We conducted a phase II study to evaluate the efficacy and safety of a triplet regimen of docetaxel, cisplatin, and S-1 in patients with unresectable or recurrent gastric cancer.
Docetaxel (40 mg/m(2)) and cisplatin (70 or 60 mg/m(2)) were given on day 1 of a 28-day cycle. S-1 (40 mg/m(2)) was given twice daily on days 1-14. Treatment with this regimen was continued for a maximum of 6 cycles. Subsequently, patients with no disease progression received a combination of docetaxel and S-1.
Fifty-nine patients were enrolled. The median number of administered cycles was 8 (range, 1-25). Because some patients had serious myelosuppression and renal dysfunction with 70 mg/m(2) of cisplatin, dose of cisplatin was reduced to 60 mg/m(2) after 19 patients had been treated. Common severe toxic effects of grade 3 or 4 were leukocytopenia (44%), neutropenia (72%), anemia (15%), and febrile neutropenia (14%). The overall response rate of this group was 81% (95% confidence interval (CI), 71-91%). The median overall survival and progression-free survival were 18.5 (95% CI, 15.6-21.5) and 8.7 (95% CI, 6.7-10.7) months, respectively.
Triplet of docetaxel, cisplatin, and S-1 is a well-tolerated and highly active regimen for advanced or recurrent gastric cancer. A 60 mg/m(2) of cisplatin is as effective as 70 mg/m(2) of cisplatin.
Cancer Chemotherapy and Pharmacology 07/2011; 69(2):407-13. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: In patients with carcinomatous peritonitis caused by the invasion and peritoneal dissemination of gastrointestinal cancer, disease progression can trigger complications such as ileus, ascites, and hydronephrosis.Anorexia, impaired oral intake, nausea, vomiting, abdominal pain, abdominal bloating, anuria, and other symptoms can develop, negatively affecting patients' general condition and quality of life.The treatment of carcinomatous peritonitis is an important determinant of outcomes, but the guidelines for its diagnosis, the evaluation of its response to chemotherapy, and the question of which standard therapy to apply remain unestablished.In recent years, however, clinical trials have attempted to evaluate the benefits of systemic chemotherapy and the intraperitoneal administration of drugs such as cisplatin and paclitaxel in patients with advanced or recurrent gastric cancer who have peritoneal dissemination.In the field of palliative therapy, octreotide has been approved in Japan for the amelioration of symptoms associated with gastrointestinal obstruction.Such treatment is expected to contribute substantially to improving patients' quality of life.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2011; 38(4):509-14.
[show abstract][hide abstract] ABSTRACT: In Japan, gastric cancer is the second leading cause of cancer-related mortality after lung cancer. Many randomized trials of various chemotherapeutic regimens have been conducted, contributing to improved outcomes in patients with advanced gastric cancer (AGC). The standard regimen for AGC is a combination of S-1 and cisplatin in Japan. Recently, new drug development has focused on molecular target agents, and personalized therapy for AGC has just begun. In patients with human epidermal growth factor receptor 2-positive AGC, trastuzumab in combination with chemotherapy improves survival. Furthermore, abundant information about the heterogeneity and biological backgrounds of AGC patients has been compiled. New strategies for the development of personalized therapy should be studied in the future.
[show abstract][hide abstract] ABSTRACT: We describe a 54-year-old man who presented with right subcostal pain. Minocycline had been prescribed to treat pruritus, and the symptoms resolved. Subsequently, the patient consulted a local physician because of right subcostal pain. Giant folds were found in the greater curvature of the gastric body, and he was referred to the Department of Gastroenterology, Kitasato University East Hospital. Upper gastrointestinal endoscopy revealed markedly enlarged folds in the greater curvature of the stomach, with redness and edematous mucosa in the lesser curvature. Biopsy showed marked inflammatory cell infiltration (mainly eosinophils), but no atypical cells. Blood tests showed marked eosinophilia and elevated immunoglobulin E levels in the serum. The results of various allergic examinations were negative, but the clinical course suggested drug-induced eosinophilic gastroenteritis, and treatment was started. Minocycline was withdrawn without adequate resolution of symptoms. Because the leukocyte and eosinophil counts continued to increase, the patient was given suplatast, an anti-allergic agent. The symptoms and hematological values improved promptly. The patient recovered uneventfully, with no recurrence.
[show abstract][hide abstract] ABSTRACT: To test whether intratumoral gene expression levels and germline polymorphisms predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab and bevacizumab plus irinotecan (CBI) vs. cetuximab and bevacizumab (CB)(BOND2).
Genomic DNA was extracted for genotyping from 65 patients (31: CBI arm and 34: CB arm). Thirty five patients had tissue samples available for the gene expression assay (18: CBI arm and 17: CB arm).
High intratumoral gene expression levels of EGFR, VEGFR2 and NRP1 were associated with longer overall survival (OS) in patients receiving combined monoclonal antibodies with or without irinotecan. FCGR3A V158F, CyclinD1 A870G and EGFR R497K polymorphisms are associated with clinical outcome in patients received combined cetuximab and bevacizumab.
Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.
Anticancer research 10/2010; 30(10):4209-17. · 1.71 Impact Factor