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This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM).In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS).A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p.05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms.FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM.• In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine and induces immune tolerance in tumor cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. Therefore, the present study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. An immunohistochemical microarray analysis of IDO1 expression was performed for 76 surgically resected cases of EHBDC. CD8

Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic bile duct carcinoma (EBDC) are distinct entities with different clinicopathological implications. Therefore, research to differentiate between the two diseases is compulsory. In this study, four biomarkers were selected (Hippocalcin-like 1 (HPCAL1); annexin A10 (ANXA10); MUC5AC; sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1)) and focus was placed on clarifying the diagnostic performance of each biomarker and pioneering novel-combined biomarker panels to discriminate between PDAC and EBDC.An immunohistochemical microarray analysis of HPCAL1, ANXA10, MUC5AC, and ATP1B1 was conducted for surgically resected 55 PDACs and 77 EBDCs. The diagnostic performance discriminating between PDAC and EBDC was evaluated using four biomarkers and the combined biomarker panels.PDACs exhibited more positive expressions for HPCAL1, ANXA10, and MUC5AC, whereas EBDCs exhibited more ATP1B1-positive expressions. The PDAC panel with the best diagnostic performance was the profile of (+ in ≥ 2 among HPCAL1, ANXA10, MUC5AC)/ATP1B1-. The immunophenotype pattern of (- in ≥ 1 among HPCAL1, ANXA10, MUC5AC)/ATP1B1+ is the EBDC panel with the most excellent discriminating power.The suggested combined biomarker panels demonstrate the distinguishing diagnostic ability between PDAC and EBDC is better than previous studies. Therefore, for differentiation between PDAC and EBDC, these panels are expected to help unravel the clinicopathological enigma as promising biomarker panels in the future.

In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin. This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m2/day on days 1–14; oxaliplatin 130 mg/m2 on day 1; every 3 weeks) or SP (S-1 80 mg/m2/day on days 1–14; cisplatin 60 mg/m2 on day 1; every 3 weeks [SP3]). Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67–1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66–1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX. SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC. ClinicalTrials.gov: NCT01671449

Background: Indoleamine 2, 3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme that catalyzes the degradation of tryptophan to kynurenine (Kyn) and induces immune tolerance in tumour cells. The effects of IDO1 on extrahepatic bile duct carcinoma (EHBDC) are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO1 in EHBDC. Methods: An immunohistochemical microarray analysis of IDO1 expression was performed for 77 surgically resected cases of EHBDC, and the results were compared with various clinicopathologic variables including survival data. CD8+ tumour infiltrating lymphocytes (TILs) were also investigated to elucidate their relationship with IDO1 expression and prognosis through a combination analysis with IDO1 expression. Results: IDO1 was highly expressed in 25 of 76 (32.9%) cases. High expression of IDO1 was associated with decreased numbers of CD8+ TILs (P=0.008), a higher pN category (P=0.007), an advanced overall stage (P=0.001), and frequent recurrence (P=0.018). When IDO1 expression was further stratified with CD8+ TIL state, the IDO1high /CD8low subgroup showed the worst prognosis in terms of overall survival (P = 0.025, Cox risk ratio = 2.168) and disease-free survival (P = 0.015, Cox risk ratio = 2.460) in a multivariate analysis. Conclusions: Our study confirmed that high IDO1 expression was correlated with a decreased number of CD8+ TILs and associated with a poor prognosis. As IDO1 may be a new target of immunotherapy applications, IDO1/CD8+ TIL subgrouping can be a useful prognostic prediction tool in the patients with EHBDC.

Background Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study. Results We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher’s exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P –6) and two suggestive functional loci on HLA-C and NUTM1 (10–6 ≤ P –4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways. Conclusions Exome array CRC case–control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.

Purpose BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. Results p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. Conclusion The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Advanced breast cancer frequently metastasizes to the skeleton causing major mobility issues and hazards to quality of life. To manage osteolytic bone metastasis, bone-modifying agents and chemotherapy are recommended as the standard of care. Here, we investigated serologic biomarkers that might be associated with prognosis in breast cancer patients treated with zoledronic acid (ZA) and taxane-based chemotherapy. We collected serum samples from breast cancer patients with bone metastasis who received taxane plus ZA as palliative treatment. Fourteen biomarkers of angiogenesis, immunogenicity, and apoptosis were assessed, and the correlation between serum cytokine levels and patient's prognosis was statistically analyzed. Sixty-six patients were enrolled, and samples from 40 patients were analyzed after laboratory quality control. Patients with low baseline PDGF-AA, high IFN-γ, low MCP-2, low TGF-β1, and low TNF-α were significantly associated with longer progression-free survival (PFS). Decreasing VEGF and TNF-α and increasing FGF-2 and PDGF-AA in the early treatment phase indicated longer PFS. In univariate and multivariate analyses, low TGF-β1 and TNF-α and high IFN-γ at baseline were associated with a significantly low hazard ratio for disease progression. Further, we designed a risk score with TGF-β1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-β1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.

The goal of palliative care is to maximize the quality of life and thus maintain the dignity of patients facing problems associated with a life-threatening illness. The Patient Dignity Inventory (PDI) is an instrument used to measure various sources of distress that can impact patients' sense of dignity at the end of life.We aimed to obtain a Korean translation of the PDI (PDI-K) and evaluate its psychometric properties in patients with advanced cancer.Translation and cultural adaptation of the PDI were performed to obtain the Korean version. In a sample of 131 inpatients and outpatients with advanced cancer, psychometric properties, including factor structure, internal consistency, and concurrent validity, were examined. Concurrent validity was evaluated using the Edmonton Symptom Assessment System, the Hospital Anxiety and Depression Scale, and the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being.Cronbach's α for the PDI-K was 0.96. Four factors were identified by exploratory factor analysis, accounting for 68.7% of the overall variance: Dependency and Physical Symptoms, Psychological Distress, Existential Distress, and SocialSupport. Concurrent validity was confirmed by significant correlations between PDI-K and Edmonton Symptom Assessment System (r = 0.40 to 0.59, P 0.001), Hospital Anxiety and Depression Scale (r = 0.78 to 0.81, P 0.001), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (r = -0.32 to -0.57, P 0.001).Our findings indicate that the PDI-K is a valid and reliable instrument to measure dignity-related distress in patients with advanced cancer. This tool provides a four-factor Korean language alternative to the PDI.

BACKGROUND Irinotecan-based chemotherapy is a standard backbone of therapy in patients with metastatic colorectal cancer (CRC) or gastric cancer (GC). However, there is still a paucity of information concerning the efficacy and safety of irinotecan-based regimens in elderly patients. PATIENTS AND METHODS Using the patient cohort (n = 1,545) from the UGT1A1 genotype study, we compared the efficacy and safety between elderly and nonelderly patients with metastatic CRC (n = 934) or GC (n = 611) who received first- or second-line FOLFIRI (irinotecan, leucovorin, and 5-fluorouracil) chemotherapy. RESULTS Despite lower relative dose intensity in elderly patients, progression-free survival and overall survival were similar between elderly (age ≥70 years) and nonelderly (

Objective. To compare efficacy and safety of intravenous continuous infusion of oxycodone with morphine in patients with cancer pain.Methods. A 5-day, randomized, open-label, exploratory study at 6 sites in the Republic of Korea. Sixty-six adults aged ≥19 years with moderate-to-severe cancer pain (Numeric Rating Scale [NRS] ≥ 4) were enrolled. The study group received intravenous (IV) oxycodone, and the comparator group received IV morphine which were titrated depending on pain intensity. The efficacy endpoint is change in average NRS score from baseline to Day 5. Other assessments included worst, current, and average pain intensity; patient satisfaction; medication dose; and adverse events.Results. Both groups achieved >50% reduction in average pain intensity: from “moderate” at baseline (oxycodone versus morphine: 6.0 ± 1.8 versus 5.9 ± 1.4) to “mild” at Day 5 (2.5 ± 1.8 versus 2.8 ± 1.6). While this reduction was similar between groups (3.5 ± 2.2 versus 3.1 ± 1.8,Pvalue = 0.562), oxycodone achieved faster pain relief (average pain: 3.0 ± 1.6 versus 3.9 ± 1.6,Pvalue = 0.020) on Day 2 and significant NRS reductions for worst pain on Day 2 (Pvalue = 0.045) and current pain on Day 2 (Pvalue = 0.035) and Day 5 (Pvalue = 0.020) compared to morphine. Patient satisfaction, adverse events, and adverse drug reactions were similar for both groups.Conclusions. For Asian patients with cancer pain, IV oxycodone is faster acting and showed similar analgesic efficacy and safety profiles as IV morphine. This trial is registered with Clinicaltrials.govNCT02660229.

To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP. This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1–3), moderate (4–6), and severe (7–10) groups. Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0–8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p

Although there have been some reports that hyperbaric oxygen therapy (HBOT) is effective in treating breast cancer-related lymphedema (BCRL), controversy regarding its therapeutic effects remains. We sought to evaluate the efficacy of HBOT in addition to conventional complex decongestive therapy (CDT) for BCRL. A prospective observational study was conducted on 10 patients with BCRL. After screening, the subjects were stratified into a CDT-only group and a CDT and HBOT combination (CDT–HBOT) group. All patients received a total of 10 treatments over 2 weeks. Changes in the circumference of the upper limbs, quality-of-life questionnaire results, and bioelectrical impedance values were compared between the 2 groups. Between both groups, there were no significant differences in demographic or clinical characteristics and in the quality-of-life outcomes for lymphedema of the limbs. The parameters measured by bioimpedance spectroscopy showed more significant improvements in the CDT–HBOT group than in the CDT-only group. In patients with BCRL, HBOT may be recommended as an adjunct treatment to the existing therapies.

10106 Background: A decision aid (DA) increases knowledge, decreases decisional conflicts and regrets and improves post-decision satisfaction, emotional distress. However, few DA trials have revealed whether decisional role preferences have an impact on patient-reported outcomes by decision making. The objective of this study was to investigate the impact of caregiver’s decisional role preference on decisional conflicts and psychiatric distresses in decision making. Methods: 406 of 444 caregivers of terminally ill cancer patients enrolled onto a previous trial determining the efficacy of the decision aid about disclosure of terminal disease status were included in this analysis. The analysis outcomes were change score of decisional conflicts using the Decision Conflict Scale (DCS) and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) at 1 and 3 months from baseline. Participants were divided into 4 groups: active caregiver who received DA (active-DA), active caregiver in control group (active-control), passive caregiver who received DA (passive-DA), and passive caregiver in control group (passive-control). Linear mixed model was conducted to find out the impact of caregiver’s decisional role preference on the DCS and the HADS. Results: Among 406 caregivers, 137 (33.7%) showed active role preference, and 269 (66.3%) showed passive role preference. In post-hoc analysis of adjusted differences of change scores between passive-DA and active-DA groups, non-significant differences were observed in DCS. However, at 3 months, change scores of HADS depression subscale increased as 4.43 (95% confidence interval (CI), 0.78-8.07; P< 0.007; effect size (ES) 0.71) and those of HADS anxiety subscales increased as 4.14 (95% CI, 0.37-7.91; P= 0.021; ES 0.61) in passive-DA group than in active-DA group, showing moderate to large difference. Conclusions: These findings suggest that information about decision making might be provided with tailored format for how much individual wish to involve in decision making.

Guillain-Barré syndrome (GBS) is defined as an acute, autoimmune polyradiculoneuropathy. It is a rare disease that occurs at a rate of 1.11 cases per 100,000 person-years. However, once infected, up to 20% of patients develop severe disability, and approximately 5% die. There have been reports of GBS in different cancers. Among them, there are 6 previous reports of GBS in small cell lung cancer. Here, we report a case of a 52-year-old man who was diagnosed with GBS in the setting of small cell lung cancer with chemotherapy.

Objectives: Crystal-storing histiocytosis (CSH) is an uncommon finding in plasma cell neoplasms. CSH is thought to be an intralysosomal deposition of secreted paraproteins or immunoglobulins, which usually express κ immunoglobulin light chains that finally aggregate in crystals. Because of its rarity, CSH in bone marrow often makes diagnosis difficult. Methods: A 57-year-old woman had IgA κ monoclonal proteinemia and monoclonal proteinuria. In the bone marrow aspirate, plasma cells were initially counted less than what would be expected, whereas histiocytes with intracellular crystals were increased. Then, we used α–naphthyl acetate esterase (ANAE) staining to distinguish between true histiocytes and plasma cells. Immunostaining for κ, CD138, CD56, and CD68 was performed on a bone marrow biopsy specimen. Results: True histiocytes containing crystalline inclusions were stained strongly for ANAE, while unstained cells with intracytoplasmic crystals represented plasma cells. The biopsy specimen revealed diffuse infiltration of CD138-positive plasma cells. We also confirmed the presence of plasma cells, histiocytes, and their crystallized inclusions with the immunostaining. The patient was finally diagnosed with plasma cell myeloma. Conclusions: The diagnosis was challenging; the bone marrow findings resembled features of other histiocytic disorders. The use of immunohistochemistry enabled the diagnosis of CSH in the presence of plasma cell myeloma.

A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m2 intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m2 oral S-1 on days 1–14 of each cycle. The treatment was repeated every 3 weeks. Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6 %), intrahepatic and extrahepatic bile ducts in 23 (60.5 %), and the ampulla of Vater in 3 (7.9 %) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6 % (95 % CI 8.5–36.7] in the per-protocol (PP) population, and 18.4 % (95 %CI 6.1–30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5 % (95 %CI 60.6–87.6) in the PP population. The median progression-free survival was 4.4 months (95 %CI 1.8–6.9), and the median overall survival was 9.0 months (95 %CI 4.0–13.9) with a 1-year survival rate of 44.7 % (95 %CI 29.0–61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1 %), 9 (25.7 %), 2 (5.7 %), and 2 (5.7 %) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4 %), anorexia (2.9 %), and renal toxicity (2.9 %). Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

Purpose Preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME) in locally advanced rectal cancer is the standard of care. To date, the role of consolidation chemotherapy after CRT has rarely been addressed through randomized trials. This study aimed to evaluate the efficacy of CRT followed by consolidation chemotherapy compared with CRT alone. Methods and Materials This study enrolled patients with adenocarcinoma of the rectum and cT3 or cT4 disease with any N category and no metastasis. In arm A (control arm), we planned CRT (50.4 Gy in 28 fractions) with capecitabine followed by TME. In arm B, 2 cycles of capecitabine and oxaliplatin were administered 1 week after the completion of CRT before TME (capecitabine, 1700 mg/m2 per day from day 1 to 14, and oxaliplatin, 100 mg/m2 on day 1, every 3 weeks). The downstaging rate (the proportion of ypT0 to ypT2 and ypN0M0) was the primary endpoint, which was to be tested with a 1-sided type I error of 15% and with 85% power. Results From September 2014 to February 2016, 110 patients (56 in arm A and 54 in arm B) were randomized and 108 (55 in arm A and 53 in arm B) started CRT. TME was conducted per protocol in 96 patients (52 in arm A and 44 in arm B). In arms A and B, downstaging was achieved in 21.2% and 36.4% (P = .077), respectively, and the pathologic complete response rate was 5.8% and 13.6% (P = .167), respectively. Grade ≥3 adverse events occurred in 3.6% of patients in arm A and 9.4% of patients in arm B during the preoperative treatment phase and in 1.9% and 9.0%, respectively, during the postoperative recovery phase. Conclusions Consolidation chemotherapy with 2 cycles of capecitabine and oxaliplatin demonstrated a marginal improvement in the downstaging rate. However, a phase 3 trial of this strategy is discouraged because of the high dropout rate and safety issues.

Purpose The aim of this study was to identify prognostic factors in stage IVB colorectal cancer in elderly patients, focusing on the influence of treatment modalities, including palliative chemotherapy and primary tumor resection. Methods A cohort of 64 patients aged over 65 years who presented with stage IVB colorectal cancer at the Gangneung Asan Hospital between July 1, 2001, and December 31, 2009, was analyzed. Demographics, tumor location, tumor grade, performance status, levels of carcinoembryonic antigen (CEA), level of aspartate aminotransferase (AST), and distant metastatic site at diagnosis were analyzed. Using the treatment histories, we analyzed the prognostic implications of palliative chemotherapy and surgical resection of the primary tumor retrospectively. Results The cohort consisted of 30 male (46.9%) and 34 female patients (53.1%); the median age was 76.5 years. Primary tumor resection was done on 28 patients (43.8%); 36 patients (56.2%) were categorized in the nonresection group. The median survival times were 12.43 months in the resection group and 3.58 months in the nonresection group (P < 0.001). Gender, level of CEA, level of AST, Eastern Cooperative Oncology Group performance status, tumor location, and presence of liver metastasis also showed significant differences in overall survival. On multivariate analysis, male gender, higher level of CEA, higher AST level, and no primary tumor resection were independent poor prognostic factors. In particular, nonresection of the primary tumor was the most potent/poor prognostic factor in the elderly-patient study group (P = 0.001; 95% confidence interval, 2.33 to 21.99; hazard ratio, 7.16). Conclusion In stage IVB colorectal cancer in elderly patients, resection of the primary tumor may enhance survival.

Daurinol, a lignan from the ethnopharmacological plant Haplophyllum dauricum, was recently reported to be a novel topoisomerase II inhibitor and an alternative to the clinical anticancer agent etoposide based on a colorectal cancer model. In the present study, we elucidated the detailed biochemical mechanism underlying the inhibition of human topoisomerase IIα by daurinol based on a molecular docking study and in vitro biochemical experiments. The computational simulation predicted that daurinol binds to the ATP-binding pocket of topoisomerase IIα. In a biochemical assay, daurinol (10-100 µM) inhibited the catalytic activity of topo-isomerase IIα in an ATP concentration-dependent manner and suppressed the ATP hydrolysis activity of the enzyme. However, daurinol did not inhibit topoisomerase I activity, most likely because topoisomerase I does not contain an ATP-binding domain. We also evaluated the anti-proliferative activity of daurinol in ovarian, small cell lung and testicular cancer cells, common target cancers treated with etoposide. Daurinol potently inhibited SNU-840 human ovarian cancer cell proliferation through cell cycle arrest in S phase, while etoposide induced G2/M phase arrest. Daurinol induced the increased expression of cyclin E, cyclin A and E2F-1, which are important proteins regulating S phase initiation and progression. Daurinol did not induce abnormal cell and nuclear enlargement in SNU-840 cells, in contrast to etoposide. Based on these data, we suggest that daurinol is a potential anticancer drug candidate for the treatment of human ovarian cancer with few side effects.

Introduction: Adenoid cystic carcinoma (ACC) of the breast is a rare condition, and cases in male patients are even less common. Case: We describe a case of ACC of the breast with axillary lymph node metastasis, disseminated osteolytic bone metastasis and bone marrow involvement in a 41-year-old man. Conclusion: Male breast ACC is an extremely rare malignancy; there can be difficulty in obtaining a final diagnosis. We report this case because of its rarity.

The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection.In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III gastric cancer patients who underwent curative surgery.Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P 0.001) and intestinal type (P = 0.002).HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.

Gastric cancer patients with acute disseminated intravascular coagulation experiences a rare but severe complication resulting in a dismal prognosis. We report a case of advanced gastric cancer complicated with disseminated intravascular coagulation with intractable tumor bleeding which was successfully treated with chemotherapy consisting of 5-fluorouracil and oxaliplatin. The patient was a 63-year-old man who complained of abdominal pain, melena, and dyspnea on 24 November 2010. We diagnosed stage IV gastric cancer complicated by disseminated intravascular coagulation. Gastric tumor bleeding was not controlled after procedures were repeated three times using gastrofiberscopy. With the patient's consent, we selected the 5-fluorouracil and oxaliplatin combination chemotherapy for treatment. After one cycle of 5-fluorouracil and oxaliplatin therapy, symptoms of bleeding improved and the disseminated intravascular coagulation process was successfully controlled. The primary tumor and multiple metastatic bone lesions were remarkably shrunken and metabolically remitted after eight cycles of chemotherapy. In spite of progression, systemic chemotherapy is effective in disease control; further, the patient gained the longest survival time among cases of gastric cancer with disseminated intravascular coagulation.

Direct sequencing and reverse hybridization are currently the main methods for detecting drug-resistance mutations of hepatitis B virus (HBV). However, these methods do not enable haplotype analysis so they cannot be used to determine whether the mutations are co-located on the same viral genome. This limits the accurate identification of viral mutants that are resistant to drugs with a high genetic barrier. In our current study, ultra-deep pyrosequencing (UDPS) was used to detect HBV drug-resistance mutations in 25 entecavir-treated and five treatment-naive patients. Of the 25 entecavir-treated patients, 18 had experienced virological breakthrough and two exhibited reduced susceptibility to entecavir. The results obtained by UDPS were compared with those of direct sequencing, and the haplotypes of the drug-resistant HBV mutants were analysed. The average number of reads per patient covering the region in which drug-resistance mutations are located was 1735 (range 451-4526). UDPS detected additional drug-resistance mutations not detected by direct sequencing in 19 patients (mutation frequency range 1.1-23.8%). Entecavir-resistance mutations were found to be co-located on the same viral genome in all 20 patients displaying virological breakthrough or reduced susceptibility to entecavir. In conclusion, UDPS was not only sensitive and accurate in identifying drug-resistance mutations of HBV but also enabled haplotype analysis of the mutants. This method may offer significant advantages in explaining and predicting the responses of patients with HBV to antiviral therapy.

PURPOSE Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement. RESULTS Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients.

Purpose We tested whether a decision aid explaining how to discuss the approach of death with a family member with cancer would help family caregivers decide to discuss a terminal prognosis. Patients and Methods We randomly assigned caregivers of terminally ill patients with cancer to a group that received a video and a companion workbook that showed either how they can discuss the prognosis with their patient (experimental arm) or how cancer pain can be controlled (control arm). At baseline and 1 month, we evaluated the decision to discuss terminal prognosis as the primary outcome. At 0, 1, 3, and 6 months, we assessed the caregivers' decisional conflict and satisfaction as secondary outcomes using a Decision Conflict Scale (DCS). Results We found no difference in changes in the decision to discuss terminal prognosis between the two groups. Conflict (P = .003), uncertainty (P = .019), and value clarity (P = .007) subscale scores and total DCS score (P = .008) improved from baseline to 1 month significantly more in the experimental arm than in the control arm. Over 6 months, the significant between-group differences continued for the conflict (P = .031), uncertainty (P = .014), and value clarity (P = .039) subscale scores and total DCS score (P = .040). Conclusion Decision aids can help caregivers, with the aid of trained professionals, to communicate with patients about their terminal illness.

Crystal-storing histiocytosis (CSH) is an uncommon finding in plasma cell neoplasms. CSH is thought to be an intralysosomal deposition of secreted paraproteins or immunoglobulins, which usually express κ immunoglobulin light chains that finally aggregate in crystals. Because of its rarity, CSH in bone marrow often makes diagnosis difficult.A 57-year-old woman had IgA κ monoclonal proteinemia and monoclonal proteinuria. In the bone marrow aspirate, plasma cells were initially counted less than what would be expected, whereas histiocytes with intracellular crystals were increased. Then, we used α-naphthyl acetate esterase (ANAE) staining to distinguish between true histiocytes and plasma cells. Immunostaining for κ, CD138, CD56, and CD68 was performed on a bone marrow biopsy specimen.True histiocytes containing crystalline inclusions were stained strongly for ANAE, while unstained cells with intracytoplasmic crystals represented plasma cells. The biopsy specimen revealed diffuse infiltration of CD138-positive plasma cells. We also confirmed the presence of plasma cells, histiocytes, and their crystallized inclusions with the immunostaining. The patient was finally diagnosed with plasma cell myeloma.The diagnosis was challenging; the bone marrow findings resembled features of other histiocytic disorders. The use of immunohistochemistry enabled the diagnosis of CSH in the presence of plasma cell myeloma.

Background Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder. Methods We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003. Results Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70,040/mm3, 83,960/mm3, and 62,680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage. Conclusion Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications

Vascular endothelial growth factor (VEGF) is considered a potent stimulator of angiogenesis. In multiple myeloma (MM), it has been reported that bone marrow angiogenesis parallels tumor progression and correlates with a poor prognosis. To investigate the role of angiogenesis in MM, we investigated VEGF expression and microvessel density (MVD) in the bone marrow of 75 MM patients by immunohistochemical methods. VEGF expression was observed in 87.3% (62 of 71) of patients. MVD was 69.42 +/- 9.67 (mean +/- SE) compared with the normal control values of 26.81 +/- 2.85. MVD values were 73.98 +/- 11.27 and 36.04 +/- 6.99 in the VEGF-positive and VEGF-negative groups, respectively. The MVD of patients in the VEGF-positive group was significantly higher than in the VEGF-negative group (P = .045). However, there were no significant differences in various clinical parameters, such as age, sex, hemoglobin, platelet count, serum levels of albumin, calcium, creatinine, and beta2-microglobulin, and bone marrow plasma cell percentage, between the VEGF-positive and VEGF-negative groups. Multivariate analysis revealed that age, hemoglobin, platelet count, serum levels of albumin and creatinine, and bone marrow plasma cell percentage were correlated with overall survival, whereas VEGF expression or MVD was not. In conclusion, our results suggest that VEGF is highly expressed and that MVD is increased in MM, indicating that angiogenesis may play a role in MM. Although MVD in the bone marrow of the VEGF-positive group is significantly higher compared with the VEGF-negative group (P = .045), VEGF is not correlated with overall survival. Further studies that include other angiogenic factors are needed to determine the functional role of angiogenesis in MM.

Bone marrow angiogenesis has been reported to increase in several hematologic malignant diseases, including multiple myeloma. Because high-dose chemotherapy combined with autologous stem cell transplantation (SCT) improves the response rate, event-free survival, and overall survival in patients with multiple myeloma (MM), we studied the changes in bone marrow microvessel density (MVD) in 21 patients who underwent high-dose chemotherapy combined with autologous SCT to determine whether there was persistently increased angiogenesis at the time of response. Bone marrow biopsy specimens were obtained before and after SCT for each patient and immunostained with anti-CD34 antibodies for the identification of microvascular endothelial cells. The mean value of MVD in 21 MM patients at initial diagnosis was 46.0 ± 24.0 and in healthy controls was 26.8 ± 8.54 (P = .046). The mean MVD at initial diagnosis was 46.0 ± 24.0 compared with 29.0 ± 12.5 after achievement of response with SCT, and there was a statistically significant difference (P = .004). Sixteen of 21 patients (76.2%) had decreased MVD after SCT, and 5 patients were found to have a greater than 50% decrease in MVD after SCT. However, there was no difference in overall survival between the patient group with decreased MVD after SCT and that without decreased MVDP = .9370). These results suggest that angiogenesis plays an important role in MM. In addition, the persistence of MVD at the time of response indicates continuous stimulus of microvessels by minimal residual disease even after SCT. Int J Hematol. 2002;76:465-470.

3606 Background: In LARC, preop CRT followed by total mesorectal excision (TME) is a standard of care. Recently consolidation chemotherapy after CRT was shown to be safe and to improve pathologic complete response (pCR) rate in LARC. We aimed to evaluate downstaging (DS) rate (the proportion of ypT0-2N0M0) of CRT followed by consolidation chemotherapy (capecitabine and oxaliplatin: CapOx) compared to that of CRT alone. Methods: Patients (pts) with adenocarcinoma of rectum(≤ 12cm from anal verge), ECOG PS 0 or 1, and cT3-4NxM0 were enrolled. CRT (50-50.4Gy/25-28fx) with Cap (825mg/m2/day for 5 days per week throughout CRT) followed by TME was planned in Arm A (control arm). In Arm B, 2 cycles of CapOx was given a week after completion of CRT before TME (Cap 850mg/m2/day from day 1 to day 14; Ox 100mg/m2on day 1; q 3w). 110 pts (55 per arm) were needed to show improvement of DS rate in per-protocol population (PP set) from 30% to 50% in arm B with one-sided α = 0.15, 1- β = 0.85, and follow-up loss in 5%. Results: From 9/2014 Sep to 2/2016, 110 (56 in arm A; 54 in arm B) were enrolled; 108 (55 in arm A; 53 in arm B) were randomized and started study treatment. Median age was 56 years; male/ECOG PS 1/cT4 was 76%/70%/18%. 100 pts (54 in arm A; 46 in arm B) completed CRT ± CapOx and surgery (R0 or R1 resection), while 8 (1 in arm A, 7 in arm B) dropped out mainly due to consent withdrawal. 2 of each arm underwent non-TME; that leaves 96 (52 in arm A and 44 in arm B) in PP set. Relative dose intensity of CapOx was 96% (Cap) and 95% (Ox). The main treatment outcome is described in table. The mean interval days between completion of CRT and surgery was significantly longer in arm B (52.9 vs 61.3, p < 0.0001). Conclusions: 2 cycles of CapOx after completion of CRT was feasible and safe, and it showed improvement in DS rate, even with high dropout rates (13%). Clinical trial information: NCT01952951. [Table: see text]

The aim of this study was to determine the prognostic factors and treatment outcome of for elderly patients (ageor=60 at time of diagnosis) with aggressive non-Hodgkin's lymphoma (NHL).We analyzed 52 patients diagnosed with aggressive NHL between January 1990 and May 2000.The patient's median age was 69 years (range: 60~92). Thirty-two (61.5%) patients were male. Patients included those with diffuse large B cell (53.8%), peripheral T cell (23.1%), AILD-like T-cell (3.8%), angiocentric (3.8%), mantle cell (3.8%), Burkitt's lymphoma (3.8%), and others (7.9%). International prognostic index (IPI) parameters were as follows: elevated LDH (60.8%), ECOG performance statusor=2 (32.7%), advanced stage (III/IV, 62.7%), and extranodal siteor=2 (11.5%). Twenty-six (50.0%) patients demonstrated a high and high-intermediate IPI. The median follow-up for surviving patients was 26.6 months. The overall median survival was 22.7 months and the 2-year survival rate was 46.9%. Among the 49 patientstreated with chemotherapy, 28 (57.1%) patients achieved complete remission (CR). Univariate analysis identified 8 prognostic factors for overall survival: age70 (P=0.04), low/low-intermediate IPI (P=0.02), good performance (P= 0.04), normal WBC (P=0.008), normal Hb (P=0.02), normal LDH (P=0.04), CR on first line therapy (P0.001), and absence of B symptom (P=0.001). In the multivariate analysis, the independent prognostic factors for improved overall survival were age70 (P=0.03), low/low-intermediate IPI (P=0.03), normal WBC (P=0.006), and CR on first line therapy (P0.001).In our experience, even elderly patients (or=60 years) with aggressive NHL can be successfully treated with conventional chemotherapy and the important prognostic factors for survival are age, IPI, initial WBC, and CR on first line treatment.

The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics.In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29 ± 7 and 57 ± 7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID).In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P 0.0001 for both visit 1-visit 2 and visit 1-visit 3). However, this pain relief was not associated with improved quality of life (P = 0.326 and P = 0.055 for visit 1-visit 2 and visit 1-visit 3, respectively).This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.

4015Background: S-1 plus cisplatin (SP) is one of the standard first-line chemotherapies for AGC in the East Asia. Oxaliplatin is generally less toxic and more convenient than cisplatin. This study...

Micropapillary carcinoma (MPC) is an aggressive variant of adenocarcinoma, with a high incidence of lymph node (LN) metastasis in several organs, although not yet well described in the stomach. Thus, we compared the clinicopathologic characteristics, including survival data and immunohistochemical profiles of cell adhesion molecules (E-cadherin, β-catenin, IQGAP-1, and CD44v6), of MPCs with those of adenocarcinomas lacking MPC components (non-MPC) in the stomach. We compared 72 MPC cases with 160 non-MPC cases. Most gastric MPCs arose from tubular or papillary adenocarcinomas, and the proportion of MPC components ranged from 5% to 80%. MPCs were characterized by more frequent lymphovascular invasion and LN metastasis (P0.0001), higher tumor node metastasis (TNM) stage (P=0.019), advanced age (65 y; P0.0001), and more frequent CD44v6 and aberrant β-catenin expression (P0.0001). The overall 5-year survival rates for patients with MPC were significantly worse than those with non-MPC (30% vs. 67%; P=0.002). Furthermore, when it was stratified by TNM stages, the survival rates were distinguished between MPC and non-MPC groups in TNM stages I to II (P=0.0003), but not in TNM stages III to IV. The presence of the MPC component was associated with a significantly worse patient survival by univariate (P=0.0003) and multivariate (P=0.04) analyses in patients with stages I to II gastric carcinoma. In conclusion, recognition of the MPC component in gastric carcinoma is critical, because the MPC component is associated with more frequent LN metastasis and a worse prognosis, especially in stages I to II gastric cancer.

The purpose of this study is to determine whether the prognosis can be more precisely gauged by the revised 6th AJCC staging system and if this is suitable for Korean colorectal cancer patients, and especially for those patients in the Youngdong district.Between September 1996 and December 2003, 365 patients with histologically confirmed colorectal cancer were analyzed. Kaplan-Meier analyses were used to compare the overall and stage-specific 5-year survival. All the statistical tests were two-sided.The overall 5-year survival for the entire cohort was 62%. According to the stages defined by the AJCC fifth edition system, the 5-year stage-specific survival was 91% for stage I, 82% for stage II, 51% for stage III and 4% for stage IV. According to the stages defined by the AJCC sixth edition system, the 5-year stage-specific survival was 91% for stage I, 81% for stage IIa, 83% for stage IIb, 100% for stage IIIa, 64% for stage IIIb, 37% for stage IIIc and 4% for stage IV. The 5-year survival was significantly better for the patients with stage IIIb (64%) than those patients with stage IIIc (37%) (p.001).It is widely known that the AJCC sixth edition system for colorectal cancer stratifies survival more distinctly than does the fifth edition system by providing more substages. Our study showed that stage IIIb disease had better survival than stage IIIc disease, but we couldn't confirm that this new staging system is relevant in our Korean clinical practice due to the small study population. Therefore, further study is required in a larger population.

Extramedullary plasmacytoma may originate in any organ, either as a primary tumor or as a facet of systemic multiple myeloma. These solid lesions most commonly affect the upper respiratory tract, gastrointestinal and urogenital tract, skin, and lung. Primary plasmacytoma of the lymph node is a rare hematologic neoplasm, which usually manifests as an enlargement of the cervical lymph nodes with no evidence of any other plasma cell dyscrasia. A 56-year-old man was admitted, due to the presence of multiple palpable masses in the right cervical and submandibular areas. Surgical resection revealed plasmacytoma of the lymph nodes. According to our full work-up, no evidence of the systemic involvement of plasma cell dyscrasia was discovered and thus, the diagnosis of primary plasmacytoma of the lymph node was made. Radiotherapy was administered, and the remnant mass was reduced substantially, to 1×2 cm in size. The patient was scheduled to be monitored by a PET CT scan, as well as by a neck CT scan.

Myelodysplastic syndrome (MDS) is a heterogenous group of stem cell disorders usually characterized by progressive refractory cytopenias, which could progress to acute myeloid leukemia. MDS may be associated with a wide spectrum of skin lesions, including neoplastic cell infiltration, Sweet's syndrome, pyoderma gangrenosum, erythema elevatum diutinum, vasculitis, and panniculitis. However, erythema nodosum is rarely associated with MDS. Unusual rheumatologic manifestations in patients with MDS also have been reported, which range from asymptomatic serological abnormalities to classic connective tissue disorders such as Sjogren's syndrome, relapsing polychondritis, systemic lupus erythematosus, rheumatoid arthritis and mixed connective tissue disease. However, concurrent erythema nodosum and serositis has rarely been reported. We describe a case of MDS with erythema nodosum and immune-mediated pericardial effusion in a 34-year-old woman.

Vascular endothelial growth factor (VEGF) is known to play a key role in tumor angiogenesis. The tumor-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on esophageal carcinoma and the correlation between VEGF and p53. Tissue samples were taken from 81 patients with esophageal carcinoma after surgery. VEGF and p53 expressions were examined by immunohistochemical staining. Microvessels in the tumor stained for CD34 antigen were also counted. VEGF and p53 expressions were observed in 51.3% (41/80) and 51.9% (41/79), respectively. The microvessel density was 70.9+/-6.7 (mean+/-SE) in VEGF-positive group and 68.7+/-5.1 in VEGF-negative group. However, no correlation was noted between VEGF and p53 expression. Whereas the tumor size, nodal status, depth of invasions, and tumor stage were associated with poor overall survival, VEGF expression or p53 expression was not. These results indicate that VEGF and p53 are highly expressed in esophageal carcinomas. Since the VEGF expression is not correlated with the p53 expression, microvessel density or clinicopathological findings, further studies with other angiogenic molecules are needed to determine the role in esophageal carcinomas.

595 Background: Combination oxaliplatin and S-1 or oxaliplatin and capecitabine chemotherapy have shown significant efficacy in advanced colorectal cancer. To evaluate those efficacy and safety, we performed a randomized phase II study in patients with metastatic or recurrent colorectal cancer. Methods: Eligible patients were those who had measurable lesions and had no previous history of chemotherapy except adjuvant chemotherapy. The patients of age greater than 18 were enrolled to this study. Oxaliplatin 130 mg/m2 was administered intravenously on day 1 and S-1 80 mg/m2 (OS, Arm A) or capecitabine 2,000 mg/m2 (XELOX, Arm B) was administered orally on days 1-14. Cycles were repeated every 21 days. Patients were treated until proved to have disease progression or unacceptable toxicity. The primary endpoint of the study was to assess the overall response rate (ORR). Results: Eight-two patients (male/ female 57/ 31; median age 67, range 29-83; median ECOG PS 1; Arm A/ B 43/45) were enrolled to this study. Twenty-five patients had recurred cancer after surgery and 63 patients were diagnosed as metastatic diseases. A total of 268 cycles (median 5, range 1-34) in Arm A; 278 cycles (median 5, range 1-18) in Arm B were administered. Eighty-two (41 for each arm) patients were evaluated for toxicity and response. The main toxicities were thrombocytopenia [grade 1/ 2/ 3/ 4 = 11/ 7/ 6/ 1 patients (A); 9/ 10/ 7/ 5 (B)], neutropenia [grade 1/ 2/ 3/ 4 = 8/ 6/ 1/ 0 (A); 9/ 9/ 5/ 2 (B)], anemia [grade 1/ 2/ 3/ 4 = 21/ 13/ 3/ 1 (A); 20/ 10/ 3/ 0 (B)], peripheral neuropathy [grade 1/ 2/ 3 = 11/ 8/ 0 (A); 10/ 8/ 2 (B)], and hand-foot syndrome [grade 1/ 2/ /3 = 2/ 0/ 0 (A); 7/ 1/ 2 (B)]. There were 3 CR, 10 PR, 27 SD and 1 PD (A); 3 CR, 15 PR, 17 SD and 6 PD (B). The confirmed ORR in the intention-to-treat population was 30.2 (95% CI: 16.5-43.9) % (A); 40.0 (95% CI, 25.7-54.3) % (B). The median time to progression was 6.6 (95% CI, 4.4-8.8) months (A); 8.1 (95% CI, 6.3-10.0) months (B). The median survival time was 19.0 (95% CI, 7.3-30.8) months (A); 22.0 (95% CI, 12.1-32.0) months in (B). Conclusions: These data suggest that both OS and XELOX regimen are active and are well tolerated regimens in patients with advanced colorectal cancer.

Purpose: The 7th edition UICC/AJCC TNM classification for gastric cancer has several changes from the previous edition. Especially, the classification of the number of lymph node metastases (LNM) is reorganized. According to the new TNM system, N stage was categorized to N0 (no LNM), N1 (1∼2 LNM), N2 (3∼6 LNM), N3 (7 or more LNM). The aim of our study was to compare the prognostic significance of the new (7th) UICC/AJCC N stage with the old (6th). Methods: From 2000 to 2005 a total of 425 patients who underwent curative resections with D2 and with 15 or more lymph nodes retrieved were studied retrospectively. Results: According to the 7th UICC/AJCC N stage, the 5-year cumulative survival rates (5YSR) of N0, N1, N2, N3 were 96.0%, 79.2%, 58.5% and 24.3%, respectively (P＜0.001). Using univariate analysis, the N stage of 7th and 6th UICC/AJCC TNM classification, 7th UICC/AJCC T stage, differentiation of tumor, type of gastrectomy (subtotal and total gastrectomy), size of primary tumor (≤5, 5＜≤10, 10＜) were associated with 5YSR. However, Cox regression multivariate analysis showed the 7th UICC/AJCC N stage to bean independent factor for predicting the 5YSR instead of the 6th UICC/AJCC N stage (P＜0.001, hazard ratio (HR) 1.859, 95% confidence interval (CI) 1.576∼2.194), including depth of tumor invasion (P＜0.001, HR 1.673, 95% CI 1.351∼2.073). Conclusion: The new (7th) UICC/AJCC N stage is a more reliable prognostic factor of gastric cancer than the old (6th) N stage.