The association between neighborhood socioeconomic status and ovarian cancer tumor characteristics

Purpose

Higher pathologic grade, suboptimal debulking surgery, and late-stage are markers of more aggressive and advanced ovarian cancer. Neighborhood socioeconomic status (SES) has been associated with more aggressive and advanced tumors for other cancer sites, and this may also be true for ovarian cancer.

Methods

We examined the association between neighborhood SES and ovarian cancer tumor characteristics using data on 581 women diagnosed with epithelial ovarian cancer in Cook County, Illinois. Two complementary measures (concentrated disadvantage and concentrated affluence) were used to estimate neighborhood SES. Prevalence differences and 95 % confidence intervals were estimated in logistic regression models adjusted for age and race.

Results

Greater disadvantage was associated with higher grade tumors (p = 0.03) and suboptimal debulking (p = 0.05) and marginally associated with later tumor stage (p = 0.20). Greater affluence was inversely associated with stage at diagnosis (p = 0.004) and suboptimal debulking (p = 0.03) and (marginally) with tumor grade (p = 0.21).

Conclusion

Our findings suggest that lower SES, estimated by neighborhood SES, is associated with ovarian cancer tumor characteristics indicative of more advanced and aggressive disease.     

ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association Consortium

Purpose

Previous studies have examined the association between ABO blood group and ovarian cancer risk, with inconclusive results.

Methods

In eight studies participating in the Ovarian Cancer Association Consortium, we determined ABO blood groups and diplotypes by genotyping 3 SNPs in the ABO locus. Odds ratios and 95?% confidence intervals were calculated in each study using logistic regression; individual study results were combined using random effects meta-analysis.

Results

Compared to blood group O, the A blood group was associated with a modestly increased ovarian cancer risk: (OR: 1.09; 95 %?CI: 1.01–1.18; p?=?0.03). In diplotype analysis, the AO, but not the AA diplotype, was associated with increased risk (AO: OR: 1.11; 95 %?CI: 1.01–1.22; p?=?0.03; AA: OR: 1.03; 95 %?CI: 0.87–1.21; p?=?0.76). Neither AB nor the B blood groups were associated with risk. Results were similar across ovarian cancer histologic subtypes.

Conclusion

Consistent with most previous reports, the A blood type was associated modestly with increased ovarian cancer risk in this large analysis of multiple studies of ovarian cancer. Future studies investigating potential biologic mechanisms are warranted.     

Prognostic significance of breast cancer subtype and p53 overexpression in patients with locally advanced or high-risk breast cancer treated using upfront modified radical mastectomy with or without post-mastectomy radiation therapy

Background

Although post-mastectomy radiation therapy (PMRT) has shown benefits, its effects in patient subpopulations remain uncertain. Therefore, we assessed whether breast cancer subtype and p53 overexpression were associated with outcome after modified radical mastectomy (MRM), with or without PMRT.

Methods

We retrospectively analyzed the records of patients who underwent MRM, with or without PMRT, between January 1991 and December 2008. Patients were considered eligible if they had T3 or T4 stage disease; any T stage with N2 or N3 stage; any T or N stage with positive, close (<1?mm) resection margins; or skin, nipple, or pectoral muscle invasion. We used immunohistochemistry and/or fluorescent in situ hybridization to determine breast cancer subtypes and p53 overexpression status.

Results

We found that 104 patients were eligible, including 59 (56.7%) who underwent PMRT and 45 (43.3%) who did not. Median follow-up duration was 61.3?months (range 16.1–232.7). Overall survival (OS) was significantly longer in patients who underwent PMRT (P?=?0.029). This trend was evident in the subgroup of luminal type A breast cancer (P?=?0.017) and non-p53 overexpression (P?=?0.026) patients. However, there was no significant survival benefit from PMRT in the subgroup of triple negative (TN) breast cancer (P?=?0.528) and p53 overexpression (P?=?0.189) patients.

Conclusions

The benefit of PMRT differed among subgroups with different breast cancer subtype and p53 overexpression. More efficacious systemic treatment strategies are needed, especially in patients at high risk for distant metastasis, to obtain optimal therapeutic gain.     

Expression of COX-2 in Stomach Carcinogenesis

Backgrounds

Gastric cancer is a frequent cause of cancer in Brazil. The understanding of gastric carcinogenesis is not completely known but the progress of the molecular biology has provided that the initiation and progression of gastric cancer process is a consequence of a cumulative series of multiple gene alterations.

Aim

The aim of the study is to investigate the relationship among cytoplasmatic COX-1 and COX-2, Bcl-2 and nuclear P53 in chronic gastritis, metaplasia, and intestinal and gastric cancer.

Patients and Methods

COX-1, COX-2, P53, and Bcl-2 were evaluated by immunohistochemistry in 34 gastric adenocarcinoma (GA) tissues obtained from gastric resection, 21 tissues of patients with chronic gastritis (CG), and 34 with intestinal metaplasia (IM) obtained from endoscopic biopsies.

Results

COX-1 and COX-2 were expressed in more than 85% of the tissues. A correlation between COX-1 and COX-2 were observed (r?=?0.66). P53 was positive in 29% CG, 20% of IM and in 59 % of GA. Bcl-2 was negative in all the CG, in 88% of IM, and in 85% of GA. P53 staining was expressed more frequently in gastric cancer when compared to CG (p?=?0.05) or IM (p?=?0.003). The expression of Bcl-2 was also higher in gastric cancer (p?=?0.002) and in intestinal metaplasia (p?=?0.04) when compared to CG. There were no difference between metaplasia and chronic gastritis for P53 or Bcl-2. The imunoreactivity of COX-2 in gastric cancer was higher in the intestinal type (58%) than in diffuse type. A higher expression of COX-2 was found in advanced gastric cancer (p?=?0.019). P53 was also more frequent in node positive cancer (p?=?0.04).

Conclusion

COX-2 is probably involved in gastric carcinogenesis, being an early alteration in cancer. Although we observed in this study a correlation between COX-2 and depth of cancer, this association as a prognostic marker is not well defined. P53 and Bcl-2 was expressed mainly in gastric cancer, being probably a latest alteration in gastric development.     

PIK3CA kinase domain mutation identifies a subgroup of stage III colon cancer patients with poor prognosis

Background

PIK3CA mutations in the helical domain (in exon 9) and in the kinase domain (exon 20) cause tumor formation by different means. We aimed to determine the effects of each of these mutations on survival of colon carcinoma patients.

Methods

A large cohort of 685 colon carcinoma patients was tested for PIK3CA mutations in exons 9 and 20 by single nucleotide primer extension (N?=?428) or by real time PCR (N?=?257).

Results

PIK3CA mutation rate was 13%. 66 of 83 (79.5%) were in exon 9 and 17 of 83 (20.5%) in exon 20. In survival analysis, PIK3CA mutations in exon 9 and 20 had different effects on patient outcome. The PIK3CA exon 20 mutation conferred a poorer disease free survival compared to patients with wild type alleles and exon 9 mutations (Log rank p?=?0.04 and p?=?0.03 respectively) and cancer specific survival (Log rank p?=?0.03 and p?=?0.056 respectively) in stage III patients. In stage I and II this negative effect on outcome was not seen.

Conclusions

PIK3CA mutation in exon 20 is a negative prognostic factor in stage III colon cancer patients. Moreover, this negative effect is not present in stage I and II patients.     

Skin Rash During Cetuximab Treatment in Advanced Colorectal Cancer: is Age a Clinical Predictor?

Purpose

The aim of this study is to evaluate the intensity and the duration of skin rash in young and elderly patients treated with cetuximab for advanced colorectal cancer, in order to define a possible relationship between age and skin toxicity.

Methods

We retrospectively analyzed all consecutive patients with advanced colorectal cancer who developed skin rash during cetuximab treatment at the Clinical Oncology Unit from June 2006 to May 2011. We divided the general case study into two subgroups: young and elderly patients (≥65 years old), and we compared clinical, pathological, and therapeutical characteristics of both subgroups.

Results

Among the 31 patients affected by advanced colorectal cancer (64.5 % with colon cancer and 35.5 % with rectal cancer) treated with cetuximab, 19 patients (61.3 %) developed skin toxicities: seven patients (36.8 %) had grade 1 skin rash, nine patients (47.4 %) had grade 2, three patients (15.8 %) had grade 3, and no grade 4 was found. Ten (52.6 %) out of 19 patients were elderly (>65 years). Concerning skin rash, grading was substantially comparable between the two subgroups, but median duration of skin rash was higher in the first subgroup for all grades. The univariate analysis showed no statistical significant difference in overall survival between young and elderly patients (p?=?0.171), such as age that does not seem to statistically influence the appearance (p?=?0.386), duration (p?=?0.455), and grade of skin rash (p?=?0.765).

Conclusions

Age is an insufficient predictor of skin toxicity during cetuximab treatment in advanced colorectal cancer and does not seem to statistically influence the appearance, duration, and grade of skin rash.     

Lung metastases in metastatic gastric cancer: pattern of lung metastases and clinical outcome

Background

There are only limited data regarding pulmonary metastasis from gastric cancer. Therefore, we analyzed large series of gastric cancer with pulmonary metastasis and analyzed their clinical characteristics and treatment outcome to enhance perception of metastatic gastric cancer.

Methods

Of 20,187 advanced gastric cancer patients treated between 1995 and 2007, 193 (0.96%) were identified to have pulmonary metastasis from gastric cancer. The pulmonary lesions were detected at chest computed tomography (CT) scan or plain chest X-ray and/or abdominal pelvic CT scan covering the lower part of the lungs, and were divided into three patterns: lymphangitic, hematogenous, and pleural.

Results

The most frequently observed pattern of lung metastasis was hematogenous metastasis (52.3%) followed by pleural (35.2%) and lymphangitic (26.4%). Patients who had hematogenous pulmonary metastasis were significantly associated with hepatic metastasis (p?=?0.004) and male sex (p?=?0.012). Patients with lymphangitic metastasis were significantly associated with concomitant bone (p?=?0.010) and bone marrow (p?=?0.029) metastasis. In case of pleural metastasis, it was positively correlated with gastrectomy history (p?=?0.015) and the presence of peritoneal metastasis (p?=?0.020). After a median follow-up duration of 87 (9–162)?months, the median survival after diagnosis of pulmonary metastasis was 4 (0–67)?months.

Conclusion

The most frequently observed pattern of lung metastasis was hematogenous metastasis (52.3%) followed by pleural (35.2%) and lymphangitic (26.4%) in gastric cancer patients. Among gastric cancer patients with lung metastases, patients with pleural metastasis or lymphangitic metastasis had shorter survival with 1.5–2-fold increased risk of deaths.     

Synchronous endometrial and ovarian carcinomas: predictors of risk and associations with survival and tumor expression profiles

Purpose

Synchronous endometrial and ovarian tumors (SEOs) are diagnosed in 10% of ovarian cancer patients. We examined predictors of SEOs, evaluated associations of SEOs with survival and characterized ovarian tumor profiles using immunohistochemistry.

Methods

We included patients with endometrioid (n?=?180) and clear cell (n?=?165) ovarian carcinoma identified from the Alberta Cancer Registry between 1979 and 2010 for whom we abstracted medical records and constructed tumor tissue microarrays (TMAs). A concurrent diagnosis of endometrial cancer was obtained from the medical chart. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs. Protein expression in ovarian tumors of patients with and without SEOs was evaluated using Fisher’s exact test.

Results

Comparing 52 patients with SEO tumors to 293 patients with endometrioid or clear cell ovarian carcinomas, endometriosis at the ovary (OR?=?0.45, 95% CI?=?0.23–0.87, p?=?0.02) was the strongest predictor of decreased risk in multivariable models. Premenopausal status (OR?=?2.17, 95% CI?=?0.92–5.13, p?=?0.08) and lower pre-treatment CA125 levels (OR?=?0.17, 95% CI?=?0.02–1.32, p?=?0.09) showed weaker associations. There were no significant differences in survival between patients with or without SEO tumors. More patients with SEO tumors compared to endometrioid ovarian carcinoma were deficient in MLH1, PMS2 and PTEN (p?≤?0.03).

Conclusions

Endometriosis may not be the mechanism by which SEO cancers arise. Altered tumor oncoprotein expression between women with and without SEOs indicates important biological differences although this did not translate into prognostic differences.

     

Imunoexpression of Ki-67 and p53 in Rectal Cancer Tissue After Treatment with Neoadjuvant Chemoradiation

Introduction

Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice.

Aim

The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment.

Patients and Methods

Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG).

Results

Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p?=?0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p?=?0.052. We have not found any difference among metastasis development in the groups (p?=?0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p?=?0.041). Patients with positive or negative p53 tumors had similar survival (p?=?0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p?=?0.069).

Conclusion

The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.     

Body Mass Index and Body Surface Area and Their Associations with Outcomes in Stage II and III Colon Cancer

Background

Our study aims were to measure the associations between body mass index (BMI) and body surface area (BSA) with outcomes for stage II and III colon cancer and to evaluate if the effect of obesity is modified by disease stage and receipt of adjuvant therapy.

Methods

Using a prospective cohort of stage II and III colon cancer patients who were referred between 2001 and 2005, we compared 3-year relapse-free survival (3-year RFS), 5-year cancer-specific survival (5-year CSS), and 5-year overall survival (5-year OS) rates among different BMI and BSA categories. Cox proportional-hazards models were constructed to explore the relationships between different body compositions and outcomes while adjusting for confounders.

Results

Postoperative height and weight were used to classify 913 patients as normal weight (n?=?424, BMI <25 kg/m²), overweight (n?=?319, BMI 25–30 kg/m²), and obese (n?=?170, BMI >30 kg/m²). Using Mosteller formula, 684 subjects had normal BSA (≤2.0 m²) and 229 had high BSA (>2.0 m²). Obese subjects experienced similar 3-year RFS (61.9 vs. 66.5 vs. 63.6 %, p?=?0.51), 5-year CSS (65.6 vs. 72.4 vs. 68.0 %, p?=?0.22), and 5-year OS (60.8 vs. 64.0 vs. 62.2 %, p?=?0.69) when compared to overweight subjects and those with normal BMIs, respectively. Likewise, individuals with high BSA had similar outcomes as those with normal BSA (66.2 vs. 63.6 %, p?=?0.64 for 3-year RFS, 70.3 vs. 68.6 %, p?=?0.62 for 5-year CSS, and 64.5 vs. 61.9 %, p?=?0.48 for 5-year OS). In Cox models, advanced age, male gender, stage III disease, and poor performance status correlated with inferior RFS, CSS, and OS, but BMI and BSA did not.

Conclusions

Obesity as measured by either BMI or BSA was not associated with differences in outcomes in stage II and III colon cancer.     

Adjuvante Therapiekonzepte beim Ovarialkarzinom

Background

The overall survival of patients with advanced ovarian cancer after optimal cytoreductive surgery and adjuvant chemotherapy could be improved over the last four decades but is still limited with 35–45?%. Thus ovarian cancer is still the deadliest of all genital cancers. There is a great need for optimization in efficacy of the current adjuvant treatment standard of carboplatin and paclitaxel and a reduction of acute and long-term side effects.

Objective

This article presents an evidence-based review of the current state of the art therapy as well as new developments

Material and methods

A systematic literature search was carried out and relevant publications, congress reports as well as current clinical trials are summarized.

Results

Management of early stage ovarian cancer requires an adequate intraoperative staging. For all patients other than FIGO stage Ia, G1 chemotherapy should be recommended following the individual risk situation. Inhibition of angiogenesis is a new and highly effective treatment strategy for treatment of advanced ovarian cancer. Bevacizumab has been approved since 2011 for the adjuvant therapy of advanced stage disease FIGO stages IIIb-IV in combination with carboplatin and paclitaxel.

Conclusion

The long-term focus of management of ovarian cancer aims at the implementation of targeted strategies to reduce toxicity and optimize the therapeutic index. Currently running clinical trials are focusing on additional inhibitors of angiogenesis. The great challenge for clinicians is to identify subgroups of patients who may benefit of different targeted treatment strategies.     

Impact of the number of removed lymph nodes on recurrence-free survival in stage I ovarian clear cell carcinoma

Background

Although there have been several reports regarding the significance of staging lymphadenectomy for early stage ovarian clear cell carcinoma (CCC) patients, there have been few reports focusing on the number of removed lymph nodes. The aim of this study was to evaluate the impact of the number of removed lymph nodes on recurrence-free survival (RFS) in stage I ovarian CCC.

Methods

The subjects were patients with ovarian CCC who underwent surgery between January 1988 and December 2013. Clinicopathological variables were obtained from the medical records retrospectively. Statistical analysis using Kaplan–Meier method, log-rank test, and Cox proportional hazards model was performed.

Results

A total of 68 patients were entered into this study. The median number of removed lymph nodes was 56.5 (21–135). We calculated that the cutoff value of the number of removed lymph nodes for predicting recurrence was 35. RFS of the group with ≥?35 removed lymph nodes was significantly better than that of the group with <?35 removed lymph nodes (p?=?0.001). Similarly, RFS of stage IA and PS 0 or 1 was significantly better than that of stage IC (p?=?0.029) and PS 2 or 3 (p?=?0.001), respectively. Multivariate analysis revealed that the number of removed lymph nodes, stage, and PS was independent predictors for RFS.

Conclusions

This study showed that the number of removed lymph nodes ≥?35 was an independent predictor for improved RFS for stage I ovarian CCC. Sufficient lymphadenectomy may improve prognosis for stage I ovarian CCC.

     

Correlates of depressive symptomatology in African-American breast cancer patients

Purpose

This study assessed the levels of depressive symptomatology in African-American women with breast cancer compared to those of women without breast cancer and examined demographic, psychosocial, and clinical factors correlated with depression.

Methods

A total of 152 African-American women were recruited from Washington, DC and surrounding suburbs. Breast cancer patients (n?=?76 cases) were recruited from a health care center and women without cancer were recruited from health fairs (n?=?76 comparison). We assessed depression, psychosocial variables (ego strength and social support), and sociodemographic factors from in-person interviews. Stage and clinical factors were abstracted from medical records. Independent sample t test, chi square test, analyses of variance, and multiple regression models were used to identify differences in depression and correlates of depression among the cases and comparison groups.

Results

Women with breast cancer reported significantly greater levels of depression (m?=?11.5, SD?=?5.0) than women without breast cancer (m?=?3.9, SD?=?3.8) (p?<?0.001). Higher cancer stage (beta?=?0.91) and higher age (beta?=?0.11) were associated with depression in the breast patients, explaining 84 % of the variance. In the comparison group, ego strength and tangible support were inversely associated with depressive symptoms, accounting for 32 % of the variance.

Conclusions

Women with more advanced disease may require interdisciplinary approaches to cancer care (i.e., caring for the whole person).

Implications for Cancer Survivors

Depression is often underrecognized and undertreated in African-American breast cancer patients. Understanding the factors related to depression is necessary to integrate psychosocial needs to routine cancer care to improve survivors’ quality of life.     

A 4-week versus a 3-week schedule of gemcitabine monotherapy for advanced pancreatic cancer: a randomized phase II study to evaluate toxicity and dose intensity

Background

This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 3 consecutive weeks every 4?weeks) or a 3-week schedule (gemcitabine at 1000?mg/m2 as a 30-min infusion weekly for 2 consecutive weeks every 3?weeks). The primary endpoint was the compliance rate during the first 8?weeks between the two groups.

Results

A total of 90 patients were enrolled. The compliance rate during the first 8?weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p?=?0.92), median progression free survival was 112 and 114?days (p?=?0.82), and median overall survival was 206 and 250?days (p?=?0.84), respectively. Grade 3?? neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p?=?0.82). In contrast, thrombocytopenia (platelet count <70000/mm3) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p?=?0.008). The mean received dose intensity was equal: 588 and 550?mg/m2/week (p?=?0.14).

Conclusions

The 3-week schedule of gemcitabine did not improve the compliance rate during 8?weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. Clinical trial registration number: UMIN ID 974.     

Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes: A collaborative re-analysis from the Ovarian Cancer Cohort Consortium

Purpose

Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results.

Methods

We pooled and harmonized data from 6 case–control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results

Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [OR_log2?=?0.82; CI 0.72–0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p _het?=?0.62), menopausal status at blood collection (p _het?=?0.79), or age at diagnosis (p _het?=?0.60).

Conclusions

These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.

     

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests

Background

We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer.

Methods

545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing.

Results

The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%.

Conclusion

No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.     

Feasibility and efficacy of a supervised exercise intervention in de-conditioned cancer survivors during the early survivorship phase: the PEACH trial

Purpose

This study aims to evaluate the feasibility and efficacy of an 8-week supervised exercise program in de-conditioned cancer survivors within 2–6 months of chemotherapy completion.

Methods

Participants were randomly assigned to an 8-week, twice-weekly, supervised aerobic exercise training regime (n?=?23) or a usual care group (n?=?20). Feasibility was assessed by recruitment rate, program adherence and participant feedback. The primary outcome was aerobic fitness assessed by the Modified Bruce fitness test at baseline (0 weeks), post-intervention (8 weeks) and at 3-month follow-up. Secondary outcomes included physical activity, waist circumference, fatigue and quality of life.

Results

The recruitment rate was 81 % and adherence to the supervised exercise was 78.3 %. Meaningful differences in aerobic fitness between the exercise and usual care groups at both the 8-week [mean 3.0 mL kg^?1 min^?1 (95 % CI ?1.1–7.0)] and 3-month follow-up [2.1 mL kg^?1 min^?1 (?2.3–6.6)] were found, although these differences did not achieve statistical significance (p values >0.14). Self-reported physical activity increased in the exercise group (EG) compared to the usual care group at both 8-week (p?=?0.01) and 3-month follow-up (p?=?0.03) and significant differences in favour of the EG were found for physical well-being at both the 8-week (p?=?0.03) and 3-month follow-up (p?=?0.04). Improvements in fatigue (p?=?0.01), total quality of life plus fatigue (p?=?0.04), and a composite physical functioning score (p?=?0.01) at the 3-month follow-up were also found.

Conclusion

The PEACH trial suggests that 8 weeks of supervised aerobic exercise training was feasible and may improve aerobic fitness, fatigue and quality of life in de-conditioned cancer survivors during the early survivorship phase.

Implications for Cancer Survivors

Exercise interventions commenced in the early survivorship phase appear safe, feasible and may lead to improvements in QOL and fatigue.     

Phosphodiesterases in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia

Background

Intracellular signaling through cyclic nucleotides, both cyclic AMP and cyclic GMP, is altered in colorectal cancer. Accordingly, it is hypothesized that an underlying mechanism for colorectal neoplasia involves altered function of phosphodiesterases (PDEs), which affects cyclic nucleotide degradation. Here we present an approach to evaluate the function of selected cyclic nucleotide-PDEs in colonic endoscopic biopsies from non-neoplastic appearing mucosa.

Methods

Biopsies were obtained from patients with and without colorectal neoplasia. Activities of PDEs were characterized functionally by measurements of transepithelial ion transport and their expression and localization by employing real-time qPCR and immunohistochemistry.

Results

In functional studies PDE subtype-4 displayed lower activity in colorectal neoplasia patients (p?=?0.006). Furthermore, real-time qPCR analysis showed overexpression of subtype PDE4B (p?=?0.002) and subtype PDE5A (p?=?0.02) in colorectal neoplasia patients. Finally, immunohistochemistry for 7 PDE isozymes demonstrated the presence of all 7 isozymes, albeit with weak reactions, and with no differences in localization between colorectal neoplasia and control patients. Of note, quantification of PDE subtype immunostaining revealed a lower amount of PDE3A (p?=?0.04) and a higher amount of PDE4B (p?=?0.02) in samples from colorectal neoplasia patients.

Conclusion

In conclusion, functional data indicated lower activity of PDE4 subtypes while expressional and abundance data indicated a higher expression of PDE4B in patients with colorectal neoplasia. We suggest that cyclic nucleotide-PDE4B is overexpressed as a malfunctioning protein in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia. If a predisposition of reduced PDE4B activity in colonic mucosa from colorectal neoplasia patients is substantiated further, this subtype could be a potential novel early diagnostic risk marker and may even be a target for future medical preventive treatment of colorectal cancer.

     

Quality of life beyond the early postoperative period after laparoscopy-assisted distal gastrectomy: the level of patient expectation as the essence of quality of life

Background

The aim of this study was to compare the quality of life after the early postoperative period and before reaching 5?years postoperatively between patients who underwent laparoscopy-assisted distal gastrectomy (Group A) and patients who underwent open distal subtotal gastrectomy (Group B).

Methods

The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and a gastric cancer-specific module, the EORTC QLQ-STO22, were used to assess the quality of life of 80 patients who underwent laparoscopy-assisted distal gastrectomy or open distal subtotal gastrectomy for gastric cancer. The postoperative period ranged between 6?months and 5?years.

Results

The global health status/quality of life scores of Groups A and B were 56.0?±?19.0 and 57.4?±?18.2, respectively (p?=?0.729). Group A experienced worse quality of life in role functioning (p?=?0.026), cognitive functioning (p?=?0.034), fatigue (p?=?0.039), eating restrictions (p?=?0.009), and anxiety (p?=?0.033). Group A showed a trend to experience worse quality of life in physical functioning, emotional functioning, social functioning, insomnia, and body image, albeit without statistical significance.

Conclusion

After the early postoperative period and before achieving long-term survival, patients who underwent laparoscopy-assisted distal gastrectomy appeared to experience lower quality of life compared to patients who underwent open distal subtotal gastrectomy. This finding may be associated with the patients’ erroneously high expectations of laparoscopy-assisted distal gastrectomy.