Long-term survival differences for bronchiolo-alveolar carcinoma patients with ipsilateral intrapulmonary metastasis at diagnosis.

BACKGROUND: It has been suggested that the current staging system does not accurately reflect survival outcomes for advanced bronchiolo-alveolar carcinoma (BAC) patients. METHODS: We conducted a case-only analysis of US Surveillance, Epidemiology, and End Results (SEER) data (1998-2002). Overall survival (OS) and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: 2345 incident cases of BAC were analyzed, including 707 patients with stage IIIB or IV BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n=93) had significantly improved median OS (46m) and LCSS (>58m) compared to other stage IIIB BAC patients (n=111; OS=9m, P<0.0001; LCSS=10m, P<0.0001). Among stage IV BAC patients, those with intrapulmonary metastasis (n=278) had significantly improved median OS (13m) and LCSS (15m) compared to those with distant metastasis (n=225; OS=7m, P<0.0001; LCSS=7m, P=0.0001). These survival differences persisted after adjustment for age, gender, ethnicity, and surgical treatment status. CONCLUSIONS: Among stage IIIB and IV BAC patients, those presenting with ipsilateral intrapulmonary metastasis have improved survival outcomes. Our results add further support for modification to the current staging system for BAC.     

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.     

A retrospective analysis of second-line chemotherapy or best supportive care in patients with advanced-stage non-small-cell lung cancer

BACKGROUND: We retrospectively evaluated the clinical characteristics and outcome of patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) enrolled in first-line chemotherapy trials conducted by our group with respect to receiving or not receiving subsequent treatment. PATIENTS AND METHODS: Data were collected from 634 patients with stage IIIB/IV NSCLC treated with platinum and nonplatinum agent-based first-line regimens. Patient survival was calculated from the day of registration to first-line chemotherapy trials (OS1) as well as from the day of first-line treatment failure or the initiation of second-line chemotherapy (OS2) until death. The decision for administering second-line chemotherapy was, in all cases, at the discretion of the physician. Two hundred twenty-four patients (35.3%) received second-line chemotherapy (second-line group) in the context of second-line clinical trials run by the same group, and 410 (64.7%) received best supportive care (BSC group). There were significant differences between second-line and BSC groups in terms of age, histology, early discontinuation of first-line chemotherapy, and performance status after first-line treatment. RESULTS: Three (1.3%) complete and 25 (11.2%) partial responses to second-line chemotherapy were observed for an overall response rate of 12.5% (95% confidence interval, 8.2%-16.8%). The median OS1 was 13 months and 7 months (P < 0.001) and the OS2, 7 months and 3 months (P < 0.001) for the second-line and BSC groups, respectively. Multivariate analysis revealed that good performance status, disease stage IIIB, response to first-line treatment, and late termination of first-line chemotherapy were significantly associated with increased survival. The administration of second-line chemotherapy was also independently correlated with better outcome. CONCLUSION: The second-line chemotherapy and BSC groups represent different populations of patients with NSCLC. Factors indicative of increased probability of survival could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy.     

Clinical outcome and prognosis of patients with inflammatory breast cancer

This report analyzes clinical factors affecting outcome in 26 patients with inflammatory breast cancer. Peau d'orange was the most common clinical finding at diagnosis (65%). A palpable breast mass (PBM) was noted in 65% with axillary lymph node involvement in 81% of patients. Eighteen patients were staged as stage IIIB and eight as stage IV. Initial metastases included supraclavicular nodes (five of eight), bones (one of eight), skin (one of eight), and liver (one of eight). All patients were treated with neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil, 18 patients; other, 8 patients). Partial response was the best clinical response attained in 38% of patients. Only one patient was treated with total mastectomy after neoadjuvant chemotherapy, and 19 patients received radiotherapy followed (2 patients) or not (17 patients) by mastectomy. The progression rate in stage IIIB patients was 78%, with distant sites of progression in 93% of patients and only 7% with local progression. Mean time-to-progression was 13 months (Kaplan-Meier estimates of 45% and 11% at 24 and 48 months, respectively). The median overall survival (OS) value of the entire population was 13.2 months (Kaplan-Meier estimates at 24 and 48 months of 21% and 12.5%). By Kaplan-Meier method and log-rank test, a better OS was correlated with stage IIIB (p = 0.002), a PBM at diagnosis (p = 0.01), and a favorable response to initial chemotherapy (p = 0.03). Our results confirm the better clinical outcome of patients with stage IIIB and PBM at diagnosis. They also support the role for combined treatment as the best modality approach for this disease. However, overall prognosis remained poor, with recurrence and death resulting from the disease.     

Helicobacter pylori infection-negative gastric cancer in Japanese hospital patients: incidence and pathological characteristics

We used Helicobacter pylori sero-positivity and mucosal atrophy as detected by the serum pepsinogen method to identify H. pylori infection-negative gastric cancer patients with or without atrophy. One hundred and six of 748 (14.2%) primary gastric cancer patients were infection-negative by a serum antibody detection system. Further, 121 (16.2%) of the 748 were negative for gastric mucosal atrophy by the pepsinogen method, of whom 15/748 (2.0%) were H. pylori-negative by pepsinogen I level (>70 ng/mL) and pepsinogen I/II ratio (>3.0). Twenty-seven of 782 (3.6%) gastric cancer patients were H. pylori-negative by antibodies and severe atrophy as determined by pepsinogen I level (<30 ng/mL) and pepsinogen I/II ratio (<2.0). H. pylori-negative gastric cancer patients with severe atrophy likely had a previous infection. These results indicate that the actual number of H. pylori-negative patients is 2.0% at minimum and 10.6% (14.2% minus 3.6%) at maximum in the general Japanese population. Five of 15 (33%) cases displaying neither anti-H. pylori antibodies nor atrophy were intestinal-type and 10 (67%) were diffuse-type adenocarcinomas. Thirteen surgical patients with primary gastric cancer displaying neither antibodies nor mucosal atrophy were further analyzed for pathological and phenotypic characteristics. The mucin phenotype was divided into four gastric, five gastric and intestinal, two intestinal and two null types, independent of histological classification. Intestinal phenotype elements were detected by Cdx2 immunohistochemical methods in nine of 13 (70%) cases examined. We conclude that a small fraction of gastric cancer patients displayed multifactorial carcinogenesis without H. pylori infection, indicating that gastric cancer risk still exists in the absence of H. pylori infection, at an incidence of 2.0% at minimum and 10.6% at maximum in the general Japanese population.     

Tobacco smoking and vitamin C concentration in gastric juice in healthy subjects and patients with Helicobacter pylori infection.

Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori infection probably plays a role in gastric carcinogenesis. Vitamin C plays a role in the neutralization of various pathogenic factors connected with H. pylori infection, including the destruction of free radicals, which damage tissues and cell DNA, and inhibition of the formation of N-nitroso compounds, which have a strong carcinogenic activity. The aim of the study was to determine whether tobacco smoking had any effect on gastric juice vitamin C concentration in healthy subjects and in patients infected with H. pylori. Eighty-six patients with dyspeptic symptoms undergoing routine endoscopy entered the study after giving informed consent. In all patients plasma and gastric juice total vitamin C levels were measured by a spectrophotometric method. They were entered into four groups: group I (controls) - H. pylori-negative non-smokers (n = 17), group II - H. pylori-negative smokers (n = 16), group III - non-smokers with H. pylori infection (n = 21), and group IV - H. pylori-infected smokers (n = 32). In the control group (I) the mean gastric juice total vitamin C concentration was 17.1 microg/ml (range 5.3-40.0 microg/ml), which was significantly higher (P < 0.05) than in group II (12.6 microg/ml, range 5.1-21.0 microg/ml), group III (5.8 microg/ml range 2.1-13.7 microg/ml) and group IV (3.9 microg/ml, range 1.1-10.6 microg/ml) (P < 0.001). Statistically significant differences also were noted between groups II and III (P < 0.01) and groups II and IV (P < 0.001) and between groups III and IV (P < 0.05). These results demonstrate that the concentration of vitamin C in gastric juice is significantly lower in smokers than in non-smokers. This was observed in healthy subjects as well as H. pylori-infected patients. This phenomenon may be one of the mechanisms whereby smoking contributes to the production of gastric lesions, impairs healing of peptic ulcers and also increases the recurrence rate of peptic ulcers in cases with H. pylori infection.     

Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers.

BACKGROUND: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori-negative cases with a gastric cancer had higher methylation levels than those of H. pylori-negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers. METHODS: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands. RESULTS: In H. pylori-negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori-positive individuals were increased to various degrees in all the three groups. CONCLUSIONS: In H. pylori-negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers.     

Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study

To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 920 subjects with precancerous gastric lesions. H. pylori status was determined by 13C-urea breath test and the density of H. pylori in biopsy specimens used for detecting methylation status was assessed by the modified Giemsa stain. The frequency of p16 methylation was significantly higher in subjects with H. pylori positive than those with H. pylori negative in each category of gastric lesion (p<0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) of p16 methylation were markedly elevated in subjects with H. pylori positive for superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94-30.41), chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60-33.36), intestinal metaplasia (OR, 4.46; 95%CI: 2.44-8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90-7.10), and dysplasia (OR, 2.48; 95%CI: 1.02-5.99). Moreover, the frequencies of p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02-16.13 times higher in subjects with mild H. pylori infection, and 2.69-38.73 times higher in those with moderate/severe infection, respectively. Our findings indicate that p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island.     

Clinical Characteristics and Helicobacter pylori Status of Gastric Cancer in Thailand

Background: Gastric cancer is the second leading course of cancer death worldwide and H. pylori infectionis an important risk factor for gastric cancer development. This study was design to evaluate the clinical,pathological features, survival rate and prevalence of H. pylori infection in gastric cancer in Thailand. Materialsand Methods: Clinical information, histological features, endoscopic findings and H. pylori status were collectedfrom gastric cancer patients from Thammasat university hospital during June 1996-December 2011. H. pyloriinfection was assessed by histological evaluation, rapid urease test and serological test. Clinical information,endoscopic findings and histopathology of all patients were recorded and compared between patients with activeor non-active H. pylori infection. Results: A total of 100 gastric cancer patients (55 men and 45 women withmean age of 55±16.8 years) were enrolled in this study. Common presenting symptoms were dyspepsia (74%),weight loss (66%), anemia (63%) and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98days. Overall prevalence of H. pylori infection was 83% and active H. pylori infection was 40%. 1-year and5-year survival rates were 43% and 0%. There was no significant difference between active H. pylori infectionin different locations (proximal vs non-proximal: 47.1% vs 48.5%; P-value = 0.9, OR=0.9; 95%CI =0.3-3.1) andhistology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P-value= 0.8, OR=0.9, 95%CI=0.3-2.7).However, linitis plastica was significantly more common in non-active than active H. pylori infection (27.9% vs0%; P-value <0.0001, OR =13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was higher in non-active thanactive H. pylori infection (93% vs 50%, P-value<0.001). Conclusions: Prevalence of H. pylori infection in Thaigastric cancer patients was high but active infection was low. Most gastric cancer patients presented in advancestage and had a grave prognosis. Screening for gastric cancer in high risk individuals might be an appropriatetool for early detection and improve the treatment outcome for this particular disease in Thailand.     

Association between Gastric Pathology and Hepatitis B Virus Infection in Patients with or without Helicobacter Pylori

Background: In the recent years, hepatitis B virus (HBV) infection has been considered as a risk factor for gastriccancer, but further studies are required to confirm these claim. The present study was aimed to evaluate the correlationbetween gastric pathology (precancerous and cancerous conditions) with HBV infection in Helicobacter pylori (H. pylori)positive or negative patients. Methods: In this cross-sectional study, 728 patients under endoscopy examination in YazdShaheed Sadoughi Hospital between 2017 and 2018 were participated. Histopathological analysis was performed ongastric specimens. Hepatitis B surface antigen (HBsAg) in sera was detected by the enzyme-linked immunosorbent assay(ELISA). The relationship between gastric pathology and HBV infection were explored by logistic regression analysis.Results: Of 728 patients, HBsAg and H. pylori infection were detected in 83 and 408 patients, respectively. Sixty ninepatients were co-infected with H. pylori/HBV. H. pylori infection detected in patients with HbsAg positive significantlymore than those were negative for HbsAg (p=0.029). None of HBV/H. pylori co-infected patients did not have normalgastric tissue. A significant difference was seen in histopathology of gastric tissue between HBsAg positive patientswith and without H. pylori infection (p<0.0001). The HBsAg was associated with histopathology of gastric (OR=21.56,95℅CI=7.070-65.741, p<0.001) and as a risk factor for gastritis (OR=12.457, 95℅CI= 3.007-51.614, P=0.001) but nocancer (OR=2.127, 95℅CI=0.242-18.704, P=0.496). Conclusion: The HBV infection alone is associated with someprecancerous lesions but is not correlated with gastric cancer. It can increase development of premalignant conditionsand carcinoma significantly in H. pylori positive patients.     

A Retrospective Analysis of Second-Line Chemotherapy or Best Supportive Care in Patients with Advanced-Stage Non–Small-Cell Lung Cancer

BackgroundWe retrospectively evaluated the clinical characteristics and outcome of patients with stage IIIB/IV non–small-cell lung cancer (NSCLC) enrolled in first-line chemotherapy trials conducted by our group with respect to receiving or not receiving subsequent treatment.Patients and MethodsData were collected from 634 patients with stage IIIB/IV NSCLC treated with platinum and nonplatinum agent–based firstline regimens. Patient survival was calculated from the day of registration to first-line chemotherapy trials (OS1) as well as from the day of first-line treatment failure or the initiation of second-line chemotherapy (OS2) until death. The decision for administering second-line chemotherapy was, in all cases, at the discretion of the physician. Two hundred twenty-four patients (35.3%) received second-line chemotherapy (second-line group) in the context of second-line clinical trials run by the same group, and 410 (64.7%) received best supportive care (BSC group). There were significant differences between second-line and BSC groups in terms of age, histology, early discontinuation of first-line chemotherapy, and performance status after first-line treatment.ResultsThree (1.3%) complete and 25 (11.2%) partial responses to second-line chemotherapy were observed for an overall response rate of 12.5% (95% confidence interval, 8.2%–16.8%). The median OS1 was 13 months and 7 months (P < 0.001) and the OS2, 7 months and 3 months (P < 0.001) for the second-line and BSC groups, respectively. Multivariate analysis revealed that good performance status, disease stage IIIB, response to first-line treatment, and late termination of first-line chemotherapy were significantly associated with increased survival. The administration of second-line chemotherapy was also independently correlated with better outcome.ConclusionThe second-line chemotherapy and BSC groups represent different populations of patients with NSCLC. Factors indicative of increased probability of survival could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy.     

Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study

BACKGROUND: The effect of Helicobacter-pylori status on survival after curative resection for gastric adenocarcinoma is unknown. We aimed to follow-up patients who were positive or negative for infection with H pylori who had curative (ie, R0) resection for gastric adenocarcinoma to assess differences in relapse-free survival and overall survival. METHODS: Before surgery, we assessed the H pylori status of 166 patients who had R0 resection for gastric adenocarcinoma between 1992 and 2002 with bacterial culture, histological analyses (ie, staining with haematoxylin and eosin and with Warthin-Starry), and serological analyses. FINDINGS: At a median follow-up of 53.0 months (range 1-146), relapse-free survival was 56.7 months (95% CI 4.7-108.7) and overall survival was 61.9 months (13.0-110.9) in patients positive for H pylori, compared with 19.2 months (12.7-25.6) and 19.2 months (7.1-31.3), respectively, in patients negative for H pylori (p=0.0009 for difference in relapse-free survival between groups, and p=0.0017 for difference in overall survival between groups). In multivariate analyses, H pylori was an independent prognostic factor for relapse-free survival (hazard ratio 2.16 [95% CI 1.33-3.49]) and overall survival (2.00 [1.22-3.27]). Depth of tumour invasion (2.60 [1.66-4.08]), lymph-node metastasis (2.11 [1.25-3.57]), and patient age 67.5 years or older (1.75 [1.11-2.75]) were also independent prognostic factors for overall survival. INTERPRETATION: Tumour-specific immune responses might be downregulated in patients who are negative for H pylori, and these patients should be followed up carefully because of a poor outlook.     

Association between CagA+ Helicobacter pylori infection and p53, bax and transforming growth factor-beta-RII gene mutations in gastric cancer patients

We assessed the possible association between CagA+ Helicobacter pylori infection and gastric carcinogenesis in gastric cancer patients. Gastric biopsy specimens were obtained from 64 patients with gastric cancer and were histologically classified into intestinal and diffuse types. H. pylori infection was determined by cultivation, flaA-PCR and serum antibody against CagA. p53, BAX and transforming growth factor-beta-RII (TGFbeta-RII) gene mutations were analyzed by PCR-SSCP and direct sequencing. Intestinal and diffuse types of cancer were detected in 45 and 19 patients, respectively. H. pylori infection was found in 55 (85.9%) of 64 patients. There was no significant difference in H. pylori positivity between intestinal and diffuse types. However, the CagA antibody was positive in 15 (78.9%) of 19 patients with the diffuse type and in 22 (48.9%) of 45 patients with the intestinal type (p = 0.030). Among the 55 H. pylori-positive cases, 11 (29.7%) of the 37 patients in the CagA+ group were found to have p53 alterations, compared with 2 (11.1%) in the 18 CagA- group (p = 0.182). Moreover, among the 64 gastric cancer patients, p53 alterations were more frequently found in the CagA+ group (29.7%) than in the H. pylori-positive CagA- and H. pylori-negative groups (7.4%; p = 0.033). BAX gene mutations were found in 19 (29.7%) of 64 patients and there was no relationship among CagA seropositivity, cancer stages and histopathological phenotypes. In contrast, the TGFbeta-RII gene mutation was only detected in one CagA- patient. The results suggest that CagA+ H. pylori infection may have an important role in the development of gastric cancer patients with p53 mutations Copyright 2001 Wiley-Liss, Inc.     

Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients.

Recent studies (K. Komoto et al., Am. J. Gastroenterol., 93: 1271-1276, 1998) have shown that Helicobacter pylori infection is associated with gastric cancer. However, the mechanism of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to a sustained production of reactive nitrogen species that may contribute to cause DNA damage. In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in gastric mucosa. The expression of iNOS and nitrotyrosine was examined by immunohistochemistry in 93 patients who initially underwent gastric biopsies between 1975 and 1992. Thirty-four individuals were later found to have gastric cancer at least 2 years after the initial biopsies (group A). The other 59 subjects have shown no evidence of gastric cancer during long-term follow-up. Fifty-one of these patients were positive for H. pylori (group B), and eight were negative for H. pylori (group C). The expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive groups A and B than in H. pylori-negative group C. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine was significantly higher in group A than in group B. These results suggest that high production of iNOS and nitrotyrosine in the gastric mucosa infected with H. pylori may contribute to the carcinogenesis of gastric cancer.     

FLEP chemotherapy for alpha-fetoprotein-producing gastric cancer

OBJECTIVE: This study aimed at comparing the efficacy of FLEP chemotherapy in the treatment of stage IV AFP-producing gastric cancer and stage IV non-AFP-producing gastric cancer. METHODS: Between 1989 and 2002, 57 patients with stage IV inoperable gastric cancer were given a combination of chemotherapy with 5-fluorouracil (5-FU), leucovorin (LV), etoposide (VP-16) and cis-diamminedichloroplatinum (CDDP) (designated as FLEP). In the two groups classified histologically according to AFP positivity, the rate of response and conversion to surgery, disease-free and overall survival were compared. The disease-free and overall survival in the two groups was compared by a log-rank test. RESULTS: Patients of the AFP-producing group had a significantly better response rate (70 vs. 31.9%, p = 0.03) and a better conversion rate (40 vs. 12.8%, p = 0.04) than those of the non-AFP-producing group. Patients of the AFP-producing group also had a significantly better disease-free and overall survival (p = 0.02) than those of the non-AFP-producing group. AFP-producing gastric cancer was identified as an independent prognostic factor. CONCLUSION: FLEP chemotherapy was more effective for stage IV AFP-producing gastric cancer than in stage IV non-AFP-producing gastric cancer. Preoperative FLEP chemotherapy improved the prognosis of AFP-producing gastric cancer because of downstaging.     

Survivin mRNA-circulating tumor cells predict treatment efficacy of chemotherapy and survival for advanced non-small cell lung cancer patients

The purpose of this prospective study was to evaluate the prognostic and predictive value of survivin mRNA-circulating tumor cells (CTCs) in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) who received first-line chemotherapy. Blood samples were collected from 78 patients with stage IIIB and IV NSCLC before (C0) and after 1 cycle (C1) and 3 cycles (C3) of chemotherapy. Survivin mRNA-CTCs were detected by real-time quantitative-PCR and correlated with treatment response and survival. The results showed that the presence of survivin mRNA-CTCs before and during chemotherapy was associated with histology type, tumor stage, and number of sites of metastasis. Moreover, the detection of survivin mRNA-CTCs after 1 and 3 cycles of chemotherapy was significantly associated with imaging response to treatment. Patients with positivity for survivin mRNA-CTCs at C0, C1, and C3 time points had significantly shorter progressive-free survival (PFS) and overall survival (OS) compared with patients without. Multivariate analysis using a Cox proportional hazards model revealed that the presence of survivin mRNA-CTCs after one and three chemotherapy cycles was a significant independent factor for worse PFS and OS. In conclusion, the detection of survivin mRNA-CTCs before and during chemotherapy is a prognostic and predictive factor correlated with poor PFS and OS in patients with advanced NSCLC.     

Lung Cancer in Women,a Different Disease: Survival Differences by Sex in Turkey

Purpose: In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC)varieties on survival rates. Materials and Methods: A retrospective study was performed in patients with NSCLCwho were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used tocompare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Of the 844patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in womenthan in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statisticallysignificant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women andmen. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs10.0 months; p=0.006) and who had a hemoglobin level ≥12g/dL (18.0 vs 12.0 months; p=0.01) were found to havea better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 monthsin males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months inmales (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, themedian OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapywas higher in women than in men (p=0.03). Conclusions: In our study, we found that survival duration is longerand chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and whoare mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences mayprovide clarity on this subject.     

Neoadjuvant chemotherapy in the combined modality approach of locally advanced nonmetastatic breast cancer

We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control.     

Advanced ovarian carcinoma. Factors influencing survival

One hundred ten patients with advanced ovarian carcinoma (Stages IIIA, IIIB, and IV) were evaluated for survival. They received as first treatment one of the following regimens: melphalan (L-PAM) (41 patients), cyclophosphamide plus methotrexate plus 5-fluorouracil (CMF) (16 patients), cyclophosphamide plus doxorubicin plus 5-fluorouracil (CAF) (17 patients), cyclophosphamide plus doxorubicin plus hexamethylmelamine plus cisplatin (CHAD) (13 patients, thiotepa plus methotrexate (TM) with fixed rotation with CAF (TM/CAF) (17 patients), and 6 patients received other chemotherapy as first treatment. There was no significant difference in survival time with the various treatment arms despite differences in response rates. Patients with Stage IIIA had significantly longer survival than those with Stages IIIB and IV (P less than 0.01). Patients with good performance status (PS 0) had significantly better survival than those with poor performance status (PS 3-4) (P less than 0.02). At this time the improved response rates on combination chemotherapy has not given improved survival rates, and disease stage and performance status remain of prime importance in survival prediction.