The Molecular Landscape of Gastric Cancers for Novel Targeted Therapies from Real-World Genomic Profiling.

BACKGROUND: Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known. OBJECTIVE: We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups. METHODS: This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/< 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low < 10 Muts/Mb), Epstein-Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate's correction. RESULTS: Genes with frequent alterations included TP53 (60.1%), ARID1A (19.6%), CDKN2A (18.2%), KRAS (16.6%), and CDH1 (15.8%). Differences in comprehensive genomic profiling were observed according to molecularly defined or age-stratified subgroups. Druggable genomic alterations were detected in 31.4% of patients; ATM (4.4%), BRAF V600E (0.4%), BRCA1 (1.5%), BRCA2 (2.9%), ERBB2 amplification (9.2%), IDH1 (0.2%), KRAS G12C (0.7%), microsatellite instability-high (4.8%), NTRK1/2/3 fusion (0.13%), PIK3CA mutation (11.4%), and tumor mutational burden-high (9.4%). CDH1 alterations and MET amplification were significantly more frequent in patients aged < 40 years (27.7 and 6.2%) than in those aged ≥ 40 years (14.7 and 4.0%). CONCLUSIONS: Real-world datasets from clinical panel testing revealed the genomic landscape in gastric cancer by subgroup. These findings provide insights for the current therapeutic strategies and future development of treatments in gastric cancer.

Predictive value of CDC37 gene expression for targeted therapy in metastatic colorectal cancer.

BACKGROUND: CDC37 is a key determinant of client kinase recruitment to the HSP90 chaperoning system. We hypothesized that kinase-specific dependency on CDC37 alters the efficacy of targeted therapies for metastatic colorectal cancer (mCRC). MATERIAL AND METHODS: Two independent mCRC cohorts were analyzed to compare the survival outcomes between CDC37-high and CDC37-low patients (stratified by the median cutoff values): the CALGB/SWOG 80405 trial (226 and 207 patients receiving first-line bevacizumab- and cetuximab-containing chemotherapies, respectively) and Japanese retrospective (50 refractory patients receiving regorafenib) cohorts. A dataset of specimens submitted to a commercial CLIA-certified laboratory was utilized to characterize molecular profiles of CDC37-high (top quartile, N = 5055) and CDC37-low (bottom quartile, N = 5055) CRCs. RESULTS: In the bevacizumab-treated group, CDC37-high patients showed significantly better progression-free survival (PFS) (median 13.3 vs 9.6 months, hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.79, p < 0.01) than CDC37-low patients. In the cetuximab-treated group, CDC37-high and CDC37-low patients had similar outcomes. In the regorafenib-treated group, CDC37-high patients showed significantly better overall survival (median 11.3 vs 6.0 months, HR 0.24, 95% CI 0.11-0.54, p < 0.01) and PFS (median 3.5 vs 1.9 months, HR 0.51, 95% CI 0.28-0.94, p = 0.03). Comprehensive molecular profiling revealed that CDC37-high CRCs were associated with higher VEGFA, FLT1, and KDR expressions and activated hypoxia signature. CONCLUSIONS: CDC37-high mCRC patients derived more benefit from anti-VEGF therapies, including bevacizumab and regorafenib, but not from cetuximab. Molecular profiles suggested that such tumors were dependent on angiogenesis-relating pathways.

Clinical utility of geriatric assessment tools in older patients with gastrointestinal cancer.

Background: Geriatric 8 (G8) and instrumental activities of daily living (IADL) are recommended to predict overall survival (OS) or risk of serious adverse events (SAEs) in older cancer patients. However, the clinical utility is relatively unknown in older patients suffering malnutrition with gastrointestinal (GI) cancer, including gastric cancer (GC) and pancreatic cancer (PC). Materials and methods: We retrospectively included patients aged ≥65 years with GC, PC, and colorectal cancer (CRC) who received a G8 questionnaire at first visit from April 2018 to March 2020. The associations between G8/IADL and safety or OS were assessed in patients with advanced/unresectable tumors. Results: Of 207 patients (median age: 75 years), the median G8 score was 10.5 and normal G8 score rate was 6.8%. Both the median G8 score and normal G8 (>14) score rate numerically increased in the order of GC < PC < CRC. There was no clear association between the G8 standard cutoff value of 14 and SAEs or OS. However, OS was significantly longer in patients with G8 >11 than in those with G8 ≤11 (19.3 vs. 10.5 months, p = 0.0017). Furthermore, OS was significantly better in patients with normal IADL than in those with abnormal IADL (17.6 vs. 11.4 months, p = 0.049). Conclusion: The G8 cutoff value of 14 would not be clinically useful in patients with GI cancer for predicting OS or SAEs; however, the cutoff value of 11 and IADL may be useful to predict OS for older patients with GI cancers including GC and PC.

Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study.

BACKGROUND: We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer. METHODS: Patients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m2, intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2). RESULTS: Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively. CONCLUSIONS: Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.

The Molecular Landscape of Pancreatobiliary Cancers for Novel Targeted Therapies From Real-World Genomic Profiling.

BACKGROUND: Chemotherapies have limited efficacy in pancreatic cancer (PC) and biliary tract cancer (BTC), underscoring the need for new regimens. Recently, tumor-agnostic approaches have been developed for some targeted therapies in advanced solid tumors; however, the frequency of alterations by clinical and genomic background is unclear in PC and BTC. METHODS: To assess the frequencies of druggable gene alterations and investigate new potential therapeutic targetable genomic alterations, advanced PC and BTC patients were tested with comprehensive genomic profiling at Foundation Medicine during the course of clinical care. RESULTS: A total of 16 913 PC patients and 3031 BTC patients were available for analyses, and frequencies of genomic alterations were stratified by age (≥40 years or <40 years), microsatellite instability status, tumor mutational burden status (high ≥10 or low <10 Muts/Mb), and select genomic alterations. Alterations in BRCA2, BRAF, ERBB2, CDK12, PIK3CA, FGFR2, EGFR, and other potential targets were seen across cohorts, with enrichment observed within particular subsets such as in PC patients lacking a KRAS mutation. In BTC patients, the rate of ERBB2 amplification was statistically significantly higher in the tumor mutational burden-high population (23.3% vs 13.7%). Interestingly, CDK12 rearrangement was observed in BTC patients with ERBB2 amplification tumors. In patients younger than 40 years, FGFR2 rearrangement (4%) was observed in PC: GATA6 amplification (11.1%) and rearrangement of BRAF (2.8%)FGFR2 (5.6%) was observed in BTC patients. CONCLUSIONS: We identified an appreciable frequency of immunotherapy biomarkers and targetable gene alterations in both PC and BTC, with notable frequencies in PC samples lacking KRAS mutations and children or adolescent and young adult populations, that should encourage comprehensive genomic profiling testing.

Clinical Utility of Genomic Profiling Tests in Patients with Advanced Gastrointestinal Cancers.

BACKGROUND: Comprehensive analyses of cancer-related genomic alterations are expected to lead to increased availability of targeted therapies. However, in patients with gastrointestinal (GI) cancers, the utility of genomic profiling is unclear because of common non-druggable alterations and rapid disease progression that prevent a sufficient time period to seek targets. OBJECTIVE: The aim of this study was to determine the utility of genomic profiling tests in patients with GI cancers. METHODS: The subjects of this retrospective study were patients with GI cancers and patients with non-GI cancers who underwent tissue-based genomic profiling at a single institution from April 2017 to October 2020. The profile of gene alterations, frequency of tumor mutational burden-high (≥ 10 Muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers. RESULTS: In all, 133 patients with GI cancers and 63 patients with non-GI cancers were included. The genomic profiles of GI cancers showed the highest frequencies of TP53, KRAS, and APC mutations and a significantly lower frequency of PIK3CA mutations than those of non-GI cancers. Tumor mutational burden-high was significantly less prevalent in GI cancers (4% vs 20%, p = 0.008). Twenty-nine patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies based on the findings. Among them, seven patients each with GI cancers and non-GI cancers received the recommended therapy on their genomic findings, which showed similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%, p = 0.791). HER2-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers. CONCLUSIONS: Although their genomic profiles revealed fewer druggable sites, patients with GI cancers accessed targeted therapies similarly to patients with non-GI cancers. The utility of genomic profile testing in patients with GI cancers was highlighted to determine if patients can receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.

Impact of Body Weight Loss on Survival in Patients with Advanced Gastric Cancer Receiving Second-Line Treatment.

Limited information is available regarding the impact of body weight loss (BWL) in patients with advanced gastric cancer (AGC) who receive second-line chemotherapy. We retrospectively reviewed data for consecutive AGC patients who received second-line treatment with taxane-based chemotherapy at our institution between January 2014 and September 2018. We calculated variables, including percent BWL per month during chemotherapy (%BWL/m), and analyzed the correlations between BWL and other clinicopathological parameters with survival. Forty-four AGC patients were registered (median age, 67.5 years; females, n = 16 [36.3%]; severe ascites, n = 12 [27.3%]). The median overall survival was significantly shorter among patients with a %BWL/m of 1% or more, compared with patients with less weight loss (6.3 mo, vs. 12.3 mo, P = 0.038). The %BWL/m (≥1% vs. <1%) was significantly correlated with survival in a univariate analysis (HR = 2.11, P = 0.04), and the survival period was shorter for patients with severe ascites (HR = 1.92; 95% CI, 0.90-3.90) and if their %BWL/m was 1% or more (HR = 2.01; 95% CI, 0.98-4.10) in a multivariate analysis. In conclusion, BWL during second-line chemotherapy was associated with a poor prognosis among patients with AGC.

Inferior mesenteric arteriovenous fistula during treatment with bevacizumab in colorectal cancer patient: A case report.

BACKGROUND: Fistula formation is a severe adverse event related to antiangiogenetic agents such as bevacizumab and inferior mesenteric arteriovenous fistula (IMAVF) is a result of acquired factor, especially colon surgery. However, IMAVF occurs very rarely and there are few reports in patients during chemotherapy. We report a case of a patient who developed IMAVF during treatment with bevacizumab in metastatic colorectal cancer (mCRC) after colon surgery. CASE SUMMARY: An 81-year-old man was diagnosed with descending colon cancer and underwent left hemicolectomy without any complications. He was definitely diagnosed with high-risk stage 2 and received tegafur-uracil plus leucovorin as adjuvant chemotherapy. Three years and 6 mo after the operation, the cancer relapsed with peritoneal dissemination. The patient underwent CyberKnife radiosurgery targeting the recurrent tumor and received chemotherapy with S-1 plus bevacizumab. At 1 year after chemotherapy, he complained of severe diarrhea, which is suspected drug-induced colitis. As diarrhea worsened despite the termination of treatment, he underwent colonoscopy and computed tomography (CT) scans that revealed edematous change from sigmoid to rectosigmoid colon. CT scans also revealed an aneurysm adjacent to the inferior mesenteric vein and multidetector CT angiography showed the IMAVF. Elective angiography confirmed the diagnosis of an IMAVF and it was successfully treated by arterial embolization. The patient resumed chemotherapy with only S-1 6 mo after embolization. CONCLUSION: Clinicians should keep in mind the probability of severe diarrhea arose from IMAVF in mCRC patients treated with bevacizumab.

Analysis of fistula formation of T4 esophageal cancer patients treated by chemoradiotherapy.

BACKGROUND AND AIM: Fistula is one of the known complications of T4 esophageal cancer (T4-EC). The standard treatment for T4-EC is chemoradiotherapy, but detailed data about fistula resulting from chemoradiotherapy in this condition are limited. In particular, radiographic findings of T4-EC with fistula have not been reported. This study assessed the risk factors of fistula based on clinical information on patients with chemoradiotherapy for T4-EC. METHODS: We retrospectively reviewed the clinical data of 59 T4-EC patients who had squamous cell carcinoma without any fistula before receiving definitive or palliative chemoradiotherapy. RESULTS: A fistula was observed in 18 patients (31%) throughout their clinical course. The overall survival in the fistula group was significantly shorter than that in the non-fistula group (259 vs. 346 days; p = 0.0341). The axial tumor size on computed tomography (CT) was confirmed as an independent risk factor for esophageal fistula in multivariate analysis of stepwise methods [OR 1.226; 95% CI 1.109-1.411; p < 0.0001]. Twelve out of 14 patients with an axial tumor size of 50 mm or greater had developed a fistula. CONCLUSIONS: A large tumor size on the axial plane on CT is a risk factor for fistula formation.

Phase I study of the anti-heparin-binding epidermal growth factor-like growth factor antibody U3-1565 with cetuximab in patients with cetuximab- or panitumumab-resistant metastatic colorectal cancer.

KRAS wild-type colorectal cancers initially responsive to anti-endothelial growth factor receptor (EGFR) antibodies [cetuximab (Cetu)/panitumumab (Pani)] develop acquired resistance. Overexpression of EGFR ligands such as heparin-binding EGF-like growth factor (HB-EGF) may be one resistance mechanism. This phase I study of U3-1565, anti-HB-EGF antibody, and Cetu combination therapy enrolled patients with KRAS wild-type metastatic colorectal cancer who had received two ≤ regimens with fluoropyrimidine, oxaliplatin, irinotecan, and Cetu/Pani and had disease progression on Cetu/Pani. Recommended dose (RD) was determined in the 1st stage, followed by evaluation of efficacy at the RD level in the 2nd-stage. Cetu was given at a loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2 in levels 1 and 0. U3-1565 was administered at a loading dose of 24 mg/m2 followed by biweekly infusions of 16 mg/m2 in level 1 and 16-12 mg/m2 in level 0. Twenty-two patients were enrolled. No dose-limiting toxicities were observed among three patients in level 1 in the first stage, which was determined as RD. Grade 3 or higher adverse events occurred in 59.1%; those in ≥5% of patients were anemia, γ-GTP elevation, and acneiform rash. Overall response rate was 0.0% [95% confidence interval (CI): 0.0%-15.4%] and disease control was achieved in 17 patients (77.3%, 95% CI: 54.6%-92.2%). Median progression-free survival time was 85.0 days (95% CI: 54.0-91.0) and median survival time was 196 days (95% CI: 113.0-306.0). RD was determined as level 1. The efficacy of this combination therapy after progression on Cetu/Pani was negligible. Trial Registration: UMIN000013006.

[A Patient Surviving More Than Five Years Due to the Effect of Sequential Alternating Chemotherapy Administered to Metachronous Overlapping Cancer of Multiple Myeloma and Stageâ £ EGFR Positive Non-Small Cell Lung Cancer].

A woman in her late 50s visited our department because an abnormal shadow of her right lung was seen on her chest radiographs. She was diagnosed with Stage ⅠA primary lung adenocarcinoma with EGFR exon 19 deletion mutation by performing thoracoscopic middle lobe resection and lymph node dissection. After 1 and a half years, the lung metastasis recurred and she received gefitinib(GEF)monotherapy for 9 months and withdrew because of the sustained complete response(CR). Three years and 7 months after the first visit, she was diagnosed as having complication of revised international staging system(R-ISS)Ⅱ multiple myeloma with anemia, retinal vein occlusion, and M proteinemia. It was decided that treatment for myeloma should be given priority and hence, Bd, high dose chemotherapy with auto-peripheral blood stem cell transplantation(aPBSCT), Ld, ELd and Pd therapy were performed sequentially until progressive disease(PD)and survival benefit were evident. As lung metastasis of adenocarcinoma also progressed, myeloma treatment was terminated, GEF was administered intermittently and consequently, shrinkage of the lung metastasis was confirmed. Depending on sequential alternating chemotherapy for both malignancies, a relatively long survival time of 5.4 years from the initiation of treatment for myeloma and 7.5 years from the recurrence of lung adenocarcinoma was achieved.

[A Case of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Achieving Complete Molecular Response with Ponatinib Therapy despite the Development of Hemorrhagic Stroke during Remission Induction Chemotherapy].

A man in his late 50s had lumbago and thrombocytopenia. He was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph plus ALL). Remission induction chemotherapy was initiated with JALSG Ph plus ALL 208 protocol, but cerebral infarction in the right occipital lobe developed on day 2 and, to make matters worse, was accompanied by hemorrhagic cerebral infarction in the left occipital lobe on day 9. We decided that chemotherapy with multiple drugs was difficult to continue, and it was stopped. After improvement of the general condition, dasatinib therapy was started on day 52. After about 5 months, Ph plus ALL relapsed. Although mild disorientation and visual field defects remained due to old cerebral infarction, organ function was maintained, and patient performance status(PS)was classified as 1. Introduction of ponatinib was considered feasible, and ponatinib was started from a dose of 15mg/day to prevent the occurrence of vaso- occlusive adverse events. It was gradually increased to 30mg /day and continued about 4 months without recurrence of cerebral infarction. Complete molecular response was achieved with ponatinib therapy. It was suggested that, in patients with Ph plus ALL with a history of cerebral infarction, ponatinib could be a treatment option under careful risk management.

Clinical Implications of Decreased Computed Tomography Value after Ramucirumab in Advanced Gastric Cancer.

OBJECTIVES: This study aimed to evaluate whether a decrease of computed tomography (CT) value for tumors serves as a predictive marker in patients with advanced gastric cancer (aGC) who have undergone chemotherapy with vascular epithelial growth factor receptor 2 inhibitor (ramucirumab). METHOD: We retrospectively analyzed 44 patients with aGC who received taxane alone (TAX arm; n = 33), ramucirumab alone, or ramucirumab in combination with taxane (RAM arm; n = 11) as second-line or later chemotherapy between July 2010 and October 2016. In all patients, tumor size and tumor CT value were evaluated at two timepoints: pretreatment and first evaluation. We calculated the change of the tumors' CT value. The associations of these factors with tumor response, progression-free survival (PFS), and overall survival were investigated. RESULTS: Ten (90.9%) of 11 patients in the RAM arm and 18 (54.5%) of 33 patients in the TAX arm showed decreased CT values. The rate of CT value change in the RAM arm (median -32.80%, range -53.63 to 6.84%) was higher than that in the TAX arm (median -0.44%, range -37.47 to 40.64%; p = 0.0005). When using the median value of CT value change as a cut-off, PFS was significantly longer in patients with a high rate of CT value change (decrease ≥32.80%) than in those with a low rate (decrease <32.80%) in the RAM arm (median 292 and 112 days; p = 0.045), while no significant difference of this kind was found in the TAX arm (median 91 and 125 days; p = 0.45). CONCLUSIONS: Patients with aGC treated with ramucirumab experienced a significant decrease of CT value of tumors and had an association between the rate of CT value change and PFS. Our study suggests that CT value changes of tumors may be a predictor for the efficacy of ramucirumab in aGC.

[Azacitidine for Therapy-Related Myelodysplastic Syndrome Following Oxaliplatin (L-OHP)Therapy for Metastatic Rectal Cancer].

Therapy-related myelodysplasticsyndrome(t-MDS)has been reported to occur after treatment with cytotoxic agents and radiation. Here, we report a case of t-MDS following oxaliplatin(L-OHP)exposure, which was successfully treated with azacitidine(AZA). A 71-year-old man was referred to our department because of pancytopenia. He had been diagnosed with rectal cancer(cT4aNXM0, stage II B-III C, RAS gene status wild-type)3 years ago and had received 8 courses of capecitabine(CAP)and L-OHP(XELOX regimen), followed by 48 courses of CAP and bevacizumab. Before referral, recurrence of rectal cancer was detected using CT after the last course of chemotherapy. A bone marrow examination revealed multilineage dysplasia and 9.0%myeloblasts. Cytogenetic analysis disclosed a chromosome 7 abnormality. The diagnosis of t- MDS was made and treatment with AZA was initiated. Subsequently, temporary but significant hematological improvements were observed, which enabled the patient to receive additional palliative radiation therapy against the locally relapsed rectal cancer. AZA might be useful in t-MDS because of its efficacy and low toxicity.

Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.

OBJECTIVES: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists. METHODS: This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ≥6 mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated. RESULTS: Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ≥6 mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ≥10 mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8 min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ≥10 mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists. CONCLUSIONS: CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ≥6 mm than did radiologists, although their interpretation time was longer than that of radiologists.

Double Extramedullary Plasmacytoma of the Stomach with a Long-term Endoscopic Follow-up.

A 56-year-old woman was referred to our hospital with a growing gastric submucosal tumor. An upper endoscopic examination revealed two gastric tumors, an original polypoid tumor and a newly diagnosed superficial tumor. Boring biopsied specimens of the submucosal tumor showed gastric plasmacytoma; however, the other specimens showed no malignancy. Blood diseases were ruled out using various examinations; therefore, we diagnosed the tumor as extramedullary gastric plasmacytoma. The patient underwent laparoscopic distal gastrectomy, and both tumors were thus revealed to be plasmacytomas. We experienced a rare case with two differently shaped extramedullary gastric plasmacytomas without significant morphologic change during the follow-up.

Efficacy of palonosetron and 1-day dexamethasone in moderately emetogenic chemotherapy compared with fosaprepitant, granisetron, and dexamethasone: a prospective randomized crossover study.

BACKGROUND: Although palonosetron (PALO) and NK1 receptor antagonist both reduce chemotherapy-induced nausea and vomiting, no comparison trial in moderately emetogenic chemotherapy (MEC) had been reported. The purpose of this study was to find out which drug combinations are preferable for patients receiving MEC. METHODS: Chemotherapy-naive patients receiving MEC were randomized to two groups; group A first received PALO therapy [PALO plus 1-day dexamethasone (DEX)], and group B first received fosaprepitant (FAPR) therapy [FAPR, granisetron (GRAN), and DEX]. Patients were re-allocated to the other therapy, respectively, for the second cycle of chemotherapy. We administered intravenous PALO (0.75 mg) and DEX (9.9 mg) to the PALO therapy group, and FAPR (150 mg), DEX (4.95 mg), and GRAN (3 mg) to the FAPR therapy group, on Day 1. Complete response (CR) was the primary endpoint; complete control (CC), total control (CT), and the therapy chosen by the patients for their third and following cycles of antiemetic therapy were the secondary endpoints. We evaluated CR, CC, and TC in the acute phase, in the delayed phase, and over the whole period. RESULTS: A total of 35 patients and 70 cycles of therapy was evaluable for analysis. No significant difference was found at all evaluation points. Overall CR rates for PALO and FAPR therapy were 74 vs 69 % (P = 0.567), CC rates 66 vs 69 % (P = 0.521), and TC rates 46 vs 60 % (P = 0.235), respectively. Patients also showed no clear preference for their third and following cycles of chemotherapy, choosing both regimens almost equally often (PALO 10 vs FAPR 13). CONCLUSIONS: PALO and 1-day DEX is almost equivalent to FAPR, GRAN, and DEX for MEC.

A novel method based on curvature analysis for estimating the dietary vitamin K requirement in adolescents.

BACKGROUND & AIMS: Few studies have investigated the association between vitamin K status and bone health in adolescents. We established a novel method for estimating the vitamin K status in adolescents by curvature analysis using the serum concentrations of undercarboxylated osteocalcin (ucOC)-a sensitive biomarker of vitamin K status in the bone. We also compared the vitamin K concentrations required for good bone health and for normal blood coagulation. METHOD: We enrolled 1183 healthy adolescents. For the curvature analysis, we used a logarithmic regression equation obtained from vitamin K intake and serum ucOC or plasma abnormal prothrombin (PIVKA-II) concentrations (marker for blood coagulation). The cut-off point was determined to be the vitamin K intake that showed the highest curvature. RESULTS: In adolescents, the serum ucOC concentration was negatively correlated with vitamin K intake. In the curvature analysis, requirement of vitamin K intake for good bone health and normal blood coagulation were 155-188 µg/d and 62-54 µg/d [1 µg/(kg d)], respectively; the latter result was consistent with that of a previous report. CONCLUSION: Our novel method is useful for estimating the vitamin K status; moreover, this method showed that bone metabolism requires more vitamin K than blood coagulation.