Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

A preliminary study on rectal dose reduction associated with hyaluronic acid implantation in brachytherapy for prostate cancer

Objectives: Hydrogel spacer (HS) was developed to reduce rectal toxicities caused by radiotherapy, but has been reported to cause major adverse events. Our institute has attempted to introduce a hyaluronic acid (HA) as an alternative spacer. This study aimed to compare rectal doses and geometric distributions between the HS and HA implantation in prostate cancer.Methods: HS and HA were inserted in 20 and 18 patients undergoing high-dose brachytherapy, respectively. The rectum spacer volumes injected were 10 mL and 22 mL, respectively. In the treatment planning system, 13.5 Gy was administered with common catheter positions. The rectal dose indices were assessed between the spacer groups for dosimetry evaluation. Distances between the prostate and rectum and configurations of the spacers were compared.Results: The mean doses irradiated to 0.1 and 2 mL of the rectum were 10.45 Gy and 6.71 Gy for HS, and 6.73 Gy and 4.90 Gy for HA (p<0.001). The mean minimum distances between the prostate and rectum were 1.23 cm and 1.79 cm for HS and HA, respectively (p<0.05). Geometrical configuration comparisons revealed that HA has a higher ability to expand the space than HS.Conclusion: The rectal dose reduction ability of HA is significantly greater than that of HS, suggesting its potential as a new spacer.

Genomic medicine in clinical practice:national genomic medicine program in Japan

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

Current and future trends in whole genome sequencing in cancer

Cancer remains a formidable global health challenge affecting millions of lives annually.For decades,conventional cancer treatments used a one-size-fits-all approach,overlooking the intricate genetic variations that drive tumors.The emergence of cancer genomics has ushered in a new era of personalized and targeted cancer therapies.The Human Genome Project,which was launched in 1990 and completed in 2003。

Gastric cancer incidence based on endoscopic Kyoto classification of gastritis

BACKGROUND Gastric cancer(GC)incidence based on the endoscopic Kyoto classification of gastritis has not been systematically investigated using time-to-event analysis.AIM To examine GC incidence in an endoscopic surveillance cohort.METHODS This study was retrospectively conducted at the Toyoshima Endoscopy Clinic.Patients who underwent two or more esophagogastroduodenoscopies were enrolled.GC incidence was based on Kyoto classification scores,such as atrophy,intestinal metaplasia(IM),enlarged folds(EFs),nodularity,diffuse redness(DR),and total Kyoto scores.Hazard ratios(HRs)adjusted for age and sex were calculated using a Cox hazard model.RESULTS A total of 6718 patients were enrolled(median age 54.0 years;men 44.2%).During the follow-up period(max 5.02 years;median 2.56 years),GC developed in 34 patients.The average frequency of GCs per year was 0.19%.Kyoto atrophy scores 1[HR with score 0 as reference:3.66,95%confidence interval(CI):1.06 to 12.61],2(11.60,3.82-35.27),IM score 2(9.92,4.37-22.54),EF score 1(4.03,1.63-9.96),DR scores 1(6.22,2.65-14.56),and 2(10.01,3.73-26.86)were associated with GC incidence,whereas nodularity scores were not.The total Kyoto scores of 4(HR with total Kyoto scores 0-1 as reference:6.23,95%CI:1.93 to 20.13,P=0.002)and 5-8(16.45,6.29-43.03,P<0.001)were more likely to develop GC,whereas the total Kyoto scores 2-3 were not.The HR of the total Kyoto score for developing GC per 1 rank was 1.75(95%CI:1.46 to 2.09,P<0.001).CONCLUSION A high total Kyoto score(≥4)was associated with GC incidence.The endoscopy-based diagnosis of gastritis can stratify GC risk.

Long-term survival of the Sister Mary Joseph nodule originating from breast cancer:A case report

BACKGROUND A Sister Mary Joseph nodule(SMJN)is an uncommon cutaneous metastasis found in the umbilicus,indicating an advanced malignancy.SMJNs typically originate from intra-abdominal sources,rarely from breast cancer.Diagnosis suggests a poor prognosis with a median survival of approximately 8 mo after detection.Managing patients with SMJNs is challenging,as most receive limited palliative care only.The optimal strategy for long-term survival of these patients remains unclear.CASE SUMMARY A 58-year-old female,previously diagnosed with right breast cancer 17 years ago and underwent breast-conserving surgery,adjuvant radiotherapy,and endocrine therapy,presented with a 2-cm umbilical nodule.Thirteen years previously,metastases were detected in the right supraclavicular,infraclavicular,hilar,and mediastinal lymph nodes.An umbilical nodule emerged four years before the date of presentation,confirmed as a skin metastasis of primary breast cancer upon excisional biopsy.Despite initial removal,the nodule recurred and grew,leading to her referral to our hospital.The patient underwent extensive excision of the umbilical tumor and immediate abdominal wall reconstruction.Endocrine therapy was continued postoperatively.Five years later,no local recurrence was observed,and the patient continued to work full-time,achieving over 9 years of survival following SMJN diagnosis.CONCLUSION This case study aimed to identify the optimal strategy for achieving extended survival outcomes in patients with SMJN through comprehensive treatment.We presented a case of the longest survival in a patient after undergoing a multidisciplinary treatment regimen.Our findings underscore the significance of adopting a multimodal treatment approach comprising timely and wide excision along with adjunctive therapy.This approach can control the disease,prolong survival,and improve the quality of life in patients with SMJN.

Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

Precision surgery for primary liver cancer

Liver resection remains the best curative option for primary liver cancer, such as hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma.In particular, in liver resection for HCC, anatomical resection of the tumor-bearing segments is highly recommended to eradicate the intrahepatic metastases spreading through portal venous branches.Anatomical liver resection,including anatomical segmentectomy and subsegmentectomy using the dye-injection method, is technically demanding and requires experience for completion of a precise procedure.The recent development of imaging studies and new computer technologies has allowed for the preoperative design of the operative procedure, intraoperative navigation, and postoperative quality evaluation of the anatomical liver resection.Although these new technologies are related to the progress of artificial intelligence, the actual operative procedure is still performed as human-hand work.A precise anatomical liver resection still requires meticulous exposure of the boundary of hepatic venous tributaries with deep knowledge of liver anatomy and utilization of intraoperative ultrasonography.

Clinical impact of surveillance for head and neck cancer in patients with esophageal squamous cell carcinoma

AIM To evaluate the clinical impact of surveillance for head and neck(HN) region with narrow band imaging(NBI) in patients with esophageal squamous cell carcinoma(ESCC).METHODS Since 2006, we introduced the surveillance for HN region using NBI for all patients with ESCC beforetreatment, and each follow-up. The patients with newly diagnosed stage Ⅰ to Ⅲ ESCC were enrolled and classified into two groups as follows: Group A(no surveillance for HN region); between 1992 and 2000), and Group B (surveillance for HN region with NBI; between 2006 and 2008). We comparatively evaluated the detection rate of superficial head and neck squamous cell carcinoma (HNSCC), and the serious events due to metachronous advanced HNSCC during the follow-up.RESULTS A total 561 patients(group A: 254, group B: 307) were enrolled. Synchronous superficial HNSCC was detected in 1 patient (0.3%) in group A, and in 12 (3.9%) in group B (P=0.008). During the follow up period, metachronous HNSCC were detected in 10 patients(3.9%) in group A and in 30 patients(9.8%) in group B(P = 0.008). All metachronous lesions in group B were early stage, and 26 patients underwent local resection, however, 6 of 10 patients (60%) in group A lost their laryngeal function and died with metachronous HNSCC.CONCLUSION Surveillance for the HN region by using NBI endoscopy increase the detection rate of early HNSCC in patients with ESCC, and led to decrease serious events related to advanced metachronous HNSCC.

Size does not determine the grade of malignancy of early invasive colorectal cancer

AIM:To clarify the clinicopathological characteristics of small and large early invasive colorectal cancers(EI-CRCs),and to determine whether malignancy grade depends on size.METHODS:A total of 583 consecutive EI-CRCs treated by endoscopic mucosal resection or surgery at the National Cancer Center Hospital between 1980 and 2004 were enrolled in this study.Lesions were classified into two groups based on size:small(≤10mm) and large(>10mm).Clinicopathological features,incidence of lymph node metastasis(LNM) and risk factors for LNM,such as depth of invasion,lymphovascular invasion(LVI) and poorly differentiated adenocarcinoma(PDA) were analyzed in all resected specimens.RESULTS:There were 120(21%) small and 463(79%) large lesions.Histopathological analysis of the small lesion group revealed submucosal deep cancer(sm:≥1000 μm) in 90(75%) cases,LVI in 26(22%) cases,and PDA in 12(10%) cases.Similarly,the large lesion group exhibited submucosal deep cancer in 380(82%) cases,LVI in 125(27%) cases,and PDA in 79(17%) cases.The rate of LNM was 11.2% and 12.1% in the small and large lesion groups,respectively.CONCLUSION:Small EI-CRC demonstrated the same aggressiveness and malignant potential as large cancer.

Metastatic bone cancer as a recurrence of early gastric cancer - characteristics and possible mechanisms

The surgical outcome of most early gastric cancer (EGC)is usually satisfactory. Some cases show bone metastasis even though the depth of cancer invasion is confined to the mucosa. The most frequent site for recurrence of EGC is the liver. Cases of EGC with bone metastasis are reviewed to clarify the clinicopathological characteristics of EGC giving rise to bone metastasis. Possible mechanisms and risk factors underlying this rare condition are proposed.Forty-six cases of bone metastasis from EGC are reviewed from published reports and meeting proceedings in Japan.This investigation suggests that risk factors for bone metastasis from EGC include depressed-type signet-ring cell carcinoma, poorly differentiated carcinoma, and/or the likely involvement of lymph node metastasis, even though the cancer is confined to the gastric mucosa. The risk factors do not include recurrence of EGC in the liver. We speculate that the mechanism of bone metastasis from EGC is via lymphatic channels and systemic circulation. Postoperative follow-up of cases should consider the development of bone metastasis from EGC. We propose the use of elevated alkaline phosphatase levels for the detection of bone metastasis and recommend bone scintigraphy in positive cases.

Sphingosine kinase 1 is upregulated with lysophosphatidic acid receptor 2 in human colorectal cancer

AIM: To examine the expression of Sph K1, an oncogenic kinase that produces sphingosine 1-phosphate(S1P), and its correlation with the expression of LPAR2, a major lysophosphatidic acid(LPA) receptor overexpressed in various cancers, in human colorectal cancer.METHODS: Real-time reverse-transcription polymerase chain reaction was used to measure the m RNA expression of Sph K1, LPAR2, and the three major S1 P receptors in 27 colorectal cancer samples and corresponding normal tissue samples. We also examined the correlation between the expression of Sph K1 and LPAR2.RESULTS: C o l o r e c t a l c a n c e r t i s s u e i n 2 2 o f 2 7 patients had higher levels of Sph K1 m RNA than in normal tissue. In two-thirds of the samples, Sph K1 m RNA expression was more than two-fold higher than in normal tissue. Consistent with previous reports, LPAR2 m RNA expression in 20 of 27 colorectal cancer tissue samples was higher compared to normal tissue samples. Expression profiles of all three major S1 P receptors, S1PR1, S1PR2, and S1PR3, varied without any trend, with no significant difference in expression between cancer and normal tissues. A highly significant positive correlation was found between Sph K1 and LPAR2 expression [Pearson's correlation coefficient(r) = 0.784 and P < 0.01]. The m RNA levels of Sph K1 and LPAR2 did not correlate with TNM stage.CONCLUSION: Our findings suggest that S1 P andLPA may play important roles in the development ofcolorectal cancer via the upregulation of Sph K1 andLPAR2, both of which could serve as new therapeutictargets in the treatment of colorectal cancer.

HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer

BACKGROUND The clinical significance of intratumoral human epidermal growth factor receptor 2(HER2)heterogeneity is unclear for HER2-positive gastric cancer,although it has been reported to be a significant prognosticator for HER2-positive breast cancer,which has received trastuzumab-based chemotherapy.AIM To clarify the clinical significance of intratumoral HER2 heterogeneity for HER2-positive gastric cancer,which has received trastuzumab-based chemotherapy.METHODS Patients with HER2-positive unresectable or metastatic gastric cancer who received trastuzumab-based chemotherapy as a first line treatment were included.The patients were classified into two groups according to their intratumoral HER2 heterogeneity status examined by immunohistochemistry(IHC)on endoscopic biopsy specimens before treatment,and their clinical response to chemotherapy and survival were compared.RESULTS A total of 88 patients were included in this study,and HER2 heterogeneity was observed in 23(26%)patients(Hetero group).The overall response rate was significantly better in patients without HER2 heterogeneity(Homo group)(Homo vs Hetero:79.5%vs 35.7%,P=0.002).Progression-free survival of trastuzumab-based chemotherapy was significantly better in the Homo group(median,7.9 vs 2.5 mo,HR:1.905,95%CI:1.109-3.268).Overall survival was also significantly better in the Homo group(median survival time,25.7 vs 12.5 mo,HR:2.430,95%CI:1.389-4.273).Multivariate analysis revealed IHC HER2 heterogeneity as one of the independent poor prognostic factors(HR:3.115,95%CI:1.610-6.024).CONCLUSION IHC of HER2 heterogeneity is the pivotal predictor for trastuzumab-based chemotherapy.Thus,HER2 heterogeneity should be considered during the assessment of HER2 expression.

Comparison of Effectiveness of Gefitinib, Erlotinib, and Afatinib in Advanced Non-small Cell Lung Cancer Patients with EGFR Mutation Positive in Indonesian Population

Background and objective EGFR-tyrosine kinase inhibitors(EGFR-TKIs) were used to treat non-small cell lung cancer(NSCLC) patients with EGFR mutation positive. This study aims to compare the effectiveness of first line TKIs;gefitinib, erlotinib, and afatinib in the treatment of advanced stage NSCLC patients with EGFR mutation positive in the Indonesian population.Methods A retrospective cohort study of 88 NSCLC patients with EGFR mutation positive treated with gefitinib(n=59), erlotinib(n=22), and afatinib(n=7) was performed in national cancer hospital in Indonesia.Inclusion criteria were stage IIIb or IV NSCLC with adenocarcinoma subtype. Subjects less than 18 years or with a history of other malignancy were excluded. Outcomes were treatment response, progression-free survival(PFS), and mortality rate. Results Complete response, partial response, and stable disease were shown in 1.1%, 35.2%, and 31.8% of subjects, respectively. There were 31.8% of subjects developed progressive disease during treatment. Regarding EGFR mutation positive profile, a total of 56.8% subjects had deletion in exon 19, 42% subjects had mutation in exon 21, and rare mutation in exon 18 was found in 3.4% of total subjects. Demography and clinical characteristics had no significant association with the risk of progressive disease. The median PFS of subjects was 11 months(95%CI: 6.8-15.2 months). There was no statistical difference of PFS between treatment groups.Conclusion Gefitinib, erlotinib, and afatinib have similar effectiveness in advanced stage NSCLC with EGFR mutation positive. Afatinib tends to be associated with longer PFS but further investigation is required.

Bone metastasis from early gastric cancer following non-curative endoscopic submucosal dissection

A 67-year-old male underwent endoscopic submucosal dissection(ESD)to treat early gastric cancer(EGC)in 2001.The lesion(50 mm × 25 mm diameter)was histologically diagnosed as poorly differentiated adenocarcinoma,with an ulcer finding.Although the tumor was confined to the mucosa with no evidence of lymphovascular involvement,the ESD was regarded as a noncurative resection due to the histological type,tumor size,and existence of an ulcer finding(as indicated by the 2010 Japanese gastric cancer treatment guidelines,ver.3).Despite strong recommendation for subsequent gastrectomy,the patient refused surgery.An alternative follow-up routine was designed,which included five years of biannual clinical examinations to detect and measure serum tumor markers and perform visual assessment of recurrence by endoscopy and computed tomography scan after which the examinations were performed annually.The patient's condition remained stable for eight years,until a complaint of back pain in 2010 prompted further clinical investigation.Bone scintigraphy indicated increased uptake.Histological examination of biopsy specimens taken from the lumbar spine revealed adenocarcinoma resembling the carcinoma cells from the EGC that had been treated previously by ESD,and which was consistent with immunohistochemical findings of gastrointestinal tract cancer.Thus,the diagnosis of bone metastasis from EGC was made.The reported rates of EGC recurrence in surgically resected cases range 1.4%-3.4%,but among these bone metastasis is very rare.To our knowledge,this is the first reported case of bone metastasis from EGC following a non-curative ESD and occurring after an eight-year disease-free interval.

Performance of 18-fluoro-2-deoxyglucose positron emission tomography for esophageal cancer screening

AIM To evaluate the performance of 18-fluoro-2-deoxyglucose positron emission tomography(FDG-PET) for esophageal cancer(EC) screening.METHODS We retrospectively analyzed the data of consecutive asymptomatic individuals who underwent FDG-PET and esophagogastroduodenoscopy(EGD) simultaneously for cancer screening at our institution from February 2004 to March 2013. In total, 14790 FDG-PET and EGD procedures performed for 8468 individuals were included in this study, and the performance of FDGPET for EC screening was assessed by comparing the results of FDG-PET and EGD, considering the latter as the reference.RESULTS Thirty-two EC lesions were detected in 28 individuals(31 squamous cell carcinomas and 1 adenocarcinoma). The median tumor size was 12.5 mm, and the depths of the lesions were as follows: Tis(n = 12), T1a(n = 15), and T1b(n = 5). Among the 14790 FDG-PET procedures, 51 examinations(0.3%) showed positive findings in the esophagus; only 1 was a true-positive finding. The screen sensitivity, specificity, positive predictive value, and negative predictive value of FDGPET for ECs were 3.6%(95%CI: 0.1-18.3), 99.7%(95%CI: 99.6-99.7), 2.0%(95%CI: 0.0-10.4), and 99.8%(95%CI: 99.7-99.9), respectively. Of the 50 FDG-PET false-positive cases, 31 were observed in the lower esophagus, and gastroesophageal reflux disease was observed in 17 of these 31 cases.CONCLUSION This study is the first to clarify the FDG-PET performance for EC screening. Based on the low screen sensitivity, FDG-PET is considered to be difficult to use as a screening modality for ECs.

Effectiveness of narrow-band imaging magnification for invasion depth in early colorectal cancer

AIM: To evaluate the surface microvascular patterns of early colorectal cancer (ECC) using narrow-band imaging (NBI) with magnification and its effectiveness for invasion depth diagnosis. METHODS: We studied 112 ECC lesions [mucosal/ submucosal superficial (m/sm-s), 69; sm-deep (sm-d), 43] ≥ 10 mm that subsequently underwent endoscopic or surgical treatment at our hospital. We compared microvascular architecture revealed by NBI with magnification to histological findings and then to magnifi- cation colonoscopy pit pattern diagnosis. RESULTS: Univariate analysis indicated vessel density: non-dense (P < 0.0001); vessel regularity: negative (P < 0.0001); caliber regularity: negative (P < 0.0001); vessel length: short (P < 0.0001); and vessel meandering: positive (P = 0.002) occurred significantly more often with sm-d invasion than m/sm-s invasion. Multivariate analysis showed sm-d invasion was independently associated with vessel density: non-dense[odds ratio (OR) = 402.5, 95% confidence interval (CI): 12.4-13 133.1] and vessel regularity: negative (OR = 15.9, 95% CI: 1.2-219.1). Both of these findings when combined were an indicator of sm-d invasion with sensitivity, specificity and accuracy of 81.4%, 100% and 92.9%, respectively. Pit pattern diagnosis sensitivity, specificity and accuracy, meanwhile, were 86.0%, 98.6% and 93.8%, respectively, thus, the NBI with magnification findings of non-dense vessel density and negative vessel regularity when combined together were comparable to pit pattern diagnosis. CONCLUSION: Non-dense vessel density and/or negative vessel regularity observed by NBI with magnification could be indicators of ECC sm-d invasion.

Effect of dietary vitamin C on gastric cancer risk in the Korean population

AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest(< 80.14 mg/d) intake category [OR(95%CI): 0.64(0.46-0.88)], with a significant trend across the three intake categories(P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

Alpha-fetoprotein-producing colon cancer with atypical bulky lymph node metastasis

Alpha-fetoprotein (AFP)-producing colorectal cancer is extremely rarely reported until now. All of the reported cases harboring synchronous hematogenous spread including liver and/or lung metastasis had a poor prognosis and died within 12 mo. We here describe a 71-year old man with AFP-producing colon cancer who presented with an unusual bulky lymph node metastasis instead of hematogenous spread. He underwent adjuvant chemotherapy in addition to curative surgical resection, which prolonged his survival.