Purpose: Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC). Materials and Methods: Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity. Results: RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D. Conclusion A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3, and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III–IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of severe toxicity such as intense diarrhea or neutropenia.

OBJECTIVES: The purpose of this study was to investigate whether the neural activity of autism spectrum disorder (ASD) patients is different from that of normal individuals when performing aesthetic judgments. METHODS: We recruited typical ASD patients without savant skills (ASD group, n=17) and healthy controls (HC group, n=19) for an functional magnetic resonance imaging study. All subjects were scanned while performing aesthetic judgment tasks on two kinds of artwork (magnificent landscape images and fractal images). Differences in brain activation between the two groups were assessed by contrasting neural activity during the tasks. RESULTS: The aesthetic judgment score for all images was significantly lower in the ASD group than in the HC group. During the aesthetic judgment tasks, the ASD group showed less activation than the HC group in the anterior region of the superior frontal gyrus, and more activation in the temporoparietal area and insula, regardless of the type of images being judged. In addition, during the aesthetic judgment task for the fractal images, the ASD group exhibited greater neural activity in the amygdala and the posterior region of the middle/inferior temporal gyrus (Brodmann area 37) than the HC group. CONCLUSION: The results of this study suggest that the brain activation patterns associated with aesthetic experiences in ASD patients may differ from those of normal individuals.
Amygdala ; Autism Spectrum Disorder* ; Autistic Disorder* ; Beauty* ; Brain ; Fractals ; Humans ; Judgment ; Magnetic Resonance Imaging ; Prefrontal Cortex ; Temporal Lobe

OBJECTIVES: Individuals with autism spectrum disorder (ASD) are considered to have problems with empathy. It has recently been suggested that there are two systems for empathy; cognitive and emotional. We aimed to investigate the neural response to cognitive and emotional empathy and elucidate the neurobiological aspects of empathy in patients with ASD. METHODS: We recruited patients with ASD (N=17, ASD group) and healthy controls (HC) (N=22, HC group) for an functional magnetic resonance imaging study. All of the subjects were scanned while performing cognitive and emotional empathy tasks. The differences in brain activation between the groups were assessed by contrasting their neural activity during the tasks. RESULTS: During both tasks, the ASD group showed greater neural activities in the bilateral occipital area compared to the HC group. The ASD group showed more activation in the bilateral precunei only during the emotional empathy task. No brain regions were more activated in the HC group than in the ASD group during the cognitive empathy task. While performing the emotional empathy task, the HC group exhibited greater neural activities in the left middle frontal gyrus and right anterior cingulate gyrus than the ASD group. CONCLUSION: This study showed that the brain regions associated with cognitive and emotional empathy in ASD patients differed from those in healthy individuals. The results of this study suggest that individuals with ASD might have defects both in cognitive empathy and in emotional empathy.
Autism Spectrum Disorder* ; Autistic Disorder* ; Brain ; Empathy* ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging

PURPOSE: This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m2) or docetaxel (DFL; 75 mg/m2) on day 1, followed by a bolus of LV (20 mg/m2 days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m2 days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. RESULTS: Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade > or =3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. CONCLUSION: Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.
Adenocarcinoma ; Diarrhea ; Disease-Free Survival ; Fluorouracil ; Follow-Up Studies ; Humans ; Leucovorin ; Mucositis ; Neutropenia ; Paclitaxel ; Peripheral Nervous System Diseases ; Prospective Studies ; Stomach Neoplasms ; Taxoids

Malignant obstruction develops frequently in advanced gastric cancer. Although it is primarily the gastric outlet that is obstructed, there are occasional reports of colonic obstruction. Treating intestinal obstruction usually requires emergency surgery or stent insertion. There are several kinds of complications with stent insertion, such as bowel perforation, stent migration, bleeding, abdominal pain and reobstruction. Nevertheless, endoscopic stent insertion could be a better treatment than emergency surgery in cases of malignant bowel obstruction in cancer patients with poor performance status. We report a case of advanced gastric cancer with carcinomatosis in which a recurrent colonic stent was inserted at the same site because of cancer growth into the stent. The patient maintained a good condition for chemotherapy, thus improving their chances for survival.
Aged ; Female ; Humans ; Intestinal Obstruction/etiology/radiography/*surgery ; Neoplasm Recurrence, Local ; Prosthesis Implantation/*methods ; *Stents ; Stomach Neoplasms

PURPOSE: The aim of this study was to determine the prognosis of pN3 stage gastric cancer patients after they have undergone curative resection, and we also wanted to identify the prognostic factors according to the clinico-pathologic features. MATERIALS AND METHODS: Between January 2000 and December 2004, we retrospectively reviewed the medical records of the patients with histologically confirmed pN3 stage gastric cancer. They underwent both gastrectomy and lymphadenectomy with a curative aim. We categorized the pN3 stage patients into 2 groups; one with pN3 only (pN3M0) and the other with pN3 combined with M1 stage (pN3M1) that included peritoneal seeding, hepatic metastasis or para-aortic LN metastasis. RESULTS: Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 78 patients were classified as the pN3/M1 stage. For all the patients, the median follow-up period was 19 months (range: 1~108 months) and the median overall survival time was 16.2 months (95% CI, 14.1~18.3%). The 5-year survival rate of the pN3/M0 group was significantly higher than that of the pN3/M1 group (12.6% vs. 2.6%, respectively, p<0.0001). The identified predictor for a worse prognosis was an advanced T4 stage (HR: 3.38, 95% CI, 1.4~8.3, p=0.008) for the pN3 patients. CONCLUSION: The survival for the pN3 gastric cancer patients after curative gastrectomy was significantly longer in the pN3/M0 group as compared to that of the pN3/M1 group. An advanced T stage was a predictor for a poor prognosis for the pN3 patients. Therefore, diverse treatment strategies for these heterogeneous pN3 gastric cancer patients are needed for improving their survival.
Adenocarcinoma ; Follow-Up Studies ; Gastrectomy ; Humans ; Lymph Node Excision ; Medical Records ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Seeds ; Stomach Neoplasms ; Survival Rate

S-1, a novel oral fluoropyrimidine, is an effective therapeutic agent for gastric cancer. Herein, we report a case with locally advanced gastric cancer that achieved a curative resection after S-1 monotherapy as neoadjuvant treatment. A 68-year-old man was diagnosed with gastric cancer and massive lymphadenopathy involving the perigastric, celiac axis and splenic hilum. His clinical stage was cT3N2H0P0M0. Considering his relatively poor performance (ECOG 2, severe weight loss) and advanced age, we started the patient on S-1 monotherapy at a dose of 35 mg/m2 bid for 4 consecutive weeks followed by a 2-week rest. Follow-up study after 4 treatment cycles revealed disappearance of the lymphadenopathy of the perigastric and celiac axis with diminished extension of the stomach mass. The patient had a partial response (PR) with a 72% tumor reduction, according to the Response Evaluation Criteria in Solid Tumors (RECIST). His performance status was improved to an ECOG 1 and he gained 7 kg. A curative (R0) resection was achieved with a radical total gastrectomy and D2 dissection. The pathological stage was pT3N2M0, stage IIIB. In conclusion, S-1 neoadjuvant chemotherapy aided in the treatment of gastric cancer in this patient.
Adenocarcinoma/*drug therapy/pathology/surgery ; Aged ; Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use ; Drug Combinations ; Gastrectomy ; Humans ; Male ; *Neoadjuvant Therapy ; Neoplasm Staging ; Oxonic Acid/administration & dosage/*therapeutic use ; Stomach Neoplasms/*drug therapy/pathology/surgery ; Tegafur/administration & dosage/*therapeutic use

Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.
Breast Neoplasms* ; Breast* ; Carcinoma, Medullary* ; Carcinosarcoma* ; Diagnosis ; Diagnosis, Differential* ; Drug Therapy* ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Paclitaxel ; Prognosis

PURPOSE: The diverse experimental environments in microarray technology, such as the different platforms or different RNA sources, can cause biases in the analysis of multiple microarrays. These systematic effects present a substantial obstacle for the analysis of microarray data, and the resulting information may be inconsistent and unreliable. Therefore, we introduced a simple integration method for combining microaray data sets that are derived from different experimental conditions, and we expected that more reliable information can be detected from the combined data set rather than from the separated data sets. MATERIALS AND METHODS: This method is based on the distributions of the gene expression ratios among the different microarray data sets and it transforms, gene by gene, the gene expression ratios into the form of the reference data set. The efficiency of the proposed integration method was evaluated using two microarray data sets, which were derived from different RNA sour-ces, and a newly defined measure, the mixture score. RESULTS: The proposed integration method intermixed the two data sets that were obtained from different RNA sources, which in turn reduced the experimental bias between the two data sets, and the mixture score increased by 24.2%. A data set combined by the proposed method preserved the inter-group relationship of the separated data sets. CONCLUSION: The proposed method worked well in adjusting systematic biases, including the source effect. The ability to use an effectively integrated microarray data set yields more reliable results due to the larger sample size and this also decreases the chance of false negatives.
Bias (Epidemiology) ; Dataset* ; Gene Expression* ; RNA ; Sample Size