• Journal of Preventive Medicine and Public Health
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• 제49권3호
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• pp.143-152
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• 2016

Objectives: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. Methods: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. Results: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. Conclusions: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

• 한국간담췌외과학회지
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• 제27권1호
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• pp.70-75
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• 2023

Backgrounds/Aims: Locally advanced gallbladder cancer (GBC) is associated with survival limited to a few months. Extended resections (ER) are occasionally performed in this group and outcomes remain inconclusive. This study assessed outcomes after ER for locally advanced GBC. Methods: Patients who underwent ER for GBC between 2011 and 2020 were reviewed. ER was defined as a major hepatectomy alone (n = 9), a pancreaticoduodenectomy (PD) with or without minor hepatectomy (n = 3), a major hepatectomy with PD (HPD) (n = 3) or vascular resection and reconstruction (n = 4). We assessed 30-day morbidity, mortality, and 2-year overall survival (OS). Results: Among 19 patients, negative margins were achieved in 14 (73.6%). The 30-day mortality was 1/9 (11.1%) for a major hepatectomy, 0/3 (0%) for a minor HPD, 2/3 (66.7%) for a major HPD, and 1/4 (25.0%) for vascular resection. All short term survivors (< 6 months) (n=8) had preoperative jaundice and 6/8 (75.0%) underwent a major HPD or vascular resection. There were five (26.3%) long term survivors. The median OS in patients with and without preoperative jaundice was 4.1 months (0.7-11.1 months) and 13.7 months (12-30.4 months), respectively (p = 0.009) (2-year OS = 7% vs. 75%; p = 0.008). The median OS in patients who underwent a major hepatectomy alone or a minor HPD was 11.3 months (6.8-17.3 months) versus 1.4 months (0.3-4.1 months) (p = 0.02) in patients who underwent major HPD or vascular resection (2 year OS = 33% vs. not reached) (p = 0.010) respectively. Conclusions: In selected patients with GBC, when ER is limited to a major hepatectomy alone, or a minor HPD, acceptable survival can be achieved.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1441-1446
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• 2014

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC ($P_{SC/ASC}$ =0.000) or AC ($P_{AC}$ =0.000 or $P_{AC}$ =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1963-1969
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• 2012

Objectives: Recent data show that the metabolic syndrome may play a role in several cancers, but the etiology for biliary tract cancer is incompletely defined. The present aim was to evaluate risk factors for biliary tract cancer in China. Methods: A case-control study in which cases were biliary tract cancer patients referred to Peking Union Medical College Hospital (PUMCH). Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on the metabolic syndrome, liver diseases, family history, and history of diabetes and hypertension were collected by retrospective review of the patients' records and health examination reports or by interview. Results: A total of 281 patients (102 intrahepatic cholangiocarcinoma (ICC), 86 extrahepatic cholangiocarcinoma (ECC) and 93 gallbladder carcinoma (GC)) and 835 age- and sex-matched controls were enrolled. $HBsAg^+/anti-HBc^+$ (P=0.002), history of diabetes (P=0.000), cholelithiasis (P=0.000), TC (P=0.003), and HDL (P=0.000) were significantly related to ICC. Cholelithiasis (P=0.000), Tri (P=0.001), LDL (P=0.000), diabetes (P=0.000), Apo A (P=0.000) and Apo B (P=0.012) were significantly associated with ECC. Diabetes (P=0.017), cholelithiasis (P=0.000) and Apo A (P=0.000) were strongly inversely correlated with GC. Conclusion: Cholelithiasis, HBV infection and metabolic symptoms may be potential risk factors for the development of biliary tract cancer.

• Journal of Digestive Cancer Research
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• 제1권2호
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• pp.104-107
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• 2013

담낭암은 진행된 상태에서 발견되었을 경우 예후가 매우 불량한 암으로 전신항암화학요법으로 치료를 하게 되나 일반적으로 고식적인 역할에 그치는 경우가 대부분이다. 본 증례는 원위부 림프절 전이가 있어서 수술적 절제가 불가능한 담낭암 환자에서 gemcitabine과 cisplatin을 병합한 전신항암화학요법으로 여섯 주기 치료 후 부분 관해를 얻어서 확대 담낭절제술이 가능하였던 증례로 매우 드문 증례를 경험하였기에 보고하는 바이다. 담낭암에서 수술 전 항암화학요법의 효과는 아직까지 확립되어 있지 않으나, 최근 양호한 종양 반응률과 종양 억제율을 보이는 항암화학요법이 개발됨에 따라서 그 가능성이 기대되고 있다.

• Journal of Gastric Cancer
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• 제19권4호
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• pp.417-426
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• 2019

Purpose: Although an increased incidence of gallbladder (GB) stone formation after gastrectomy has been reported, its etiology remains uncertain. The goal of this study was to explore the incidence of gallstone formation after gastrectomy in gastric cancer patients and investigate the risk factors therein. Materials and Methods: Medical records of patients who underwent curative gastrectomy, performed by a single surgeon between August 2012 and December 2015 at the Asan Medical Center, were retrospectively reviewed. Baseline characteristics and surgical outcomes, including GB stone gallstone formation after gastrectomy, were analyzed. Results: Of 561 patients included in the study, 36 presented with GB stone formation after gastrectomy for gastric cancer. The incidence of gallstone formation was 6.4%. The mean interval between gallstone formation and gastrectomy was 21.9 months. In multivariate analyses, the incidence of gallstone formation increased in patients 63 years or older, with greater than 6.2 kg weight loss in the first 6 months after the procedure, a preoperative serum total bilirubin level greater than 0.5 mg/dL, and in patients who did not receive adjuvant chemotherapy. Conclusions: This study presented risk factors for GB stone formation after gastric cancer surgery, and special attention should be afforded to patients with such risk factors.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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• pp.32-33
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• 2006

There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5449-5454
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• 2014

Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4791-4795
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• 2015

Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapy in treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy. Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer, 19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advanced gallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer in Jiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated with pemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results: For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligible for inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD, progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexed based regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made use of this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 of them got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients used this regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last 14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among 17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-line treatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients could not be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%. Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as first-line treatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patients accepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD. Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-line treatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment. Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment, the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed based regimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bone marrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers such as breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify the results.

• 한국간담췌외과학회지
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• 제27권2호
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• pp.180-188
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• 2023

Backgrounds/Aims: The present study looked at the role of radical surgery in gallbladder cancers (GBC) with limited metastatic disease. Methods: The retrospective observational study was conducted to screen the database from 1st January 2010 to 31st December 2019. Patients of GBC found to have low-volume metastatic disease upon surgical exploration were included. Results: Of the 1,040 patients operated for GBC, 234 patients had low-volume metastatic disease (microscopic disease in station 16b1 node or N2 disease isolated port-site metastases, or low burden peritoneal disease with deposits less than 1 cm, in adjacent omentum or adjacent diaphragm or Morrison's pouch or a solitary discontinuous liver metastasis in adjacent liver parenchyma) detected intraoperative. Of these, 62 patients underwent radical surgery for R-0 metastatic disease followed by systemic therapy, while the remaining 172 patients did not undergo radical surgery and were given palliative systemic chemotherapy. Patients who underwent radical surgery had significantly superior overall survival (19 months versus 12 months, p < 0.01) and superior progression-free survival (10 months versus 5 months, p < 0.01) when compared to the rest. This difference in survival was more significant amongst patients when operated on after neoadjuvant chemotherapy. Regression analysis showed that a sub-group of patients with incidental GBC with limited metastases showed more favorable outcomes with radical surgery. Conclusions: Authors suggest a possible role for radical treatment of advanced GBC with a limited metastatic burden. Neoadjuvant chemotherapy can be used for preferentially selecting patients of favorable disease biology for curative treatment.