Outcomes and adverse factors for endoscopic mucosal resection (EMR) of colorectal polyps in elderly patients.

INTRODUCTION: Endoscopic mucosal resection (EMR) is an invaluable technique, however it is associated with significant risks. In the elderly in particular, the long-term survival benefits of polyp resection with EMR are unknown. The aim of this study was to determine the long-term outcomes in elderly patients who had undergone EMR and to identify any adverse factors. METHOD: A retrospective observational study on patients of 75 years of age or greater, who underwent EMR of colorectal polyps, in a single tertiary centre, from 2005 to 2014. Demographics of the patients, including Charlson Comorbidity Index (CCI), endoscopic and histological data, were reviewed to identify potential factors predicting outcomes. RESULTS: The patients' median age was 80 years. In total 239 procedures were performed in 206 unique patients. The complication rate was 1.6%. Mean overall survival was 6.7 years with only one patient dying from metastatic colorectal cancer (0.5%) and 49 dying from non-colorectal cancer conditions (24%). Age more than 79 years and CCI more than 2 were independent predictors of significantly shorter survival (p=<0.01). Gender, size of the removed polyps and total number of polyps were not statistically significantly affecting survival. Patients who had more than two colonoscopies were found to have a survival benefit (p=0.02). CONCLUSION: EMR of colonic polyps is safe even for elderly patients. However, the decision to proceed to complex endoscopic therapy should be individualised considering the patients' age and comorbidities. CCI can help to objectively assess the comorbid state of a patient prior to such decisions.

Evaluation and long-term outcomes of the different modalities used in colonic endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) has been used in western countries to remove colonic polyps for at least the last two decades. Significant experience has been accumulated and the efficacy of the method has recently been evaluated in a large meta-analysis. A number of variations to modify the technique, including knife-assisted, cap-assisted, ligation devices, and underwater EMR, have been developed in an attempt to improve outcomes. However, to date there are only limited data comparing these techniques or demonstrating the superiority of any one of them. This article reviews the current evidence on the efficacy of each of these modified techniques.

Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation.

BACKGROUND AND AIM: Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling dietary fiber with a wide range of uses in clinical nutrition. The aim of this prospective study was to investigate the effect of guar gum on colonic transit time (CTT) and symptoms of chronic constipation. METHODS: We enrolled patients fulfilling Rome III criteria for chronic constipation. CTT was measured before and at the end of treatment. After a 2-week run-in period, patients received 5 mg PHGG daily for 4 weeks. During study period, patients kept daily symptoms, stool and laxative usage diaries. They also recorded their symptom-related satisfaction weekly and treatment adverse events. RESULTS: Forty-nine patients received treatment; 39 (80 %) completed the study. Treatment significantly reduced colon transit time, from 57.28 ± 39.25 to 45.63 ± 37.27 h (p = 0.026), a reduction more prominent in slow transit patients (from 85.50 ± 27.75 to 63.65 ± 38.11 h, p = 0.016). Overall, the weekly number of complete spontaneous and spontaneous bowel movements increased significantly (p < 0.001); the latter correlated significantly with the acceleration of CTT in the overall population and in slow transit patients (B = 0.382; p = 0.016 and B = 0.483; p = 0.023, respectively). In addition, the number of bowel movements with straining decreased (p < 0.001) and stool form improved (p < 0.001), while days with laxative intake and days with abdominal pain decreased (p = 0.001 and p = 0.027, respectively). CONCLUSION: Four-week PHGG use accelerates colon transit time in patients with chronic constipation, especially in those with slow transit, and improves many of their symptoms including frequency of bowel movements.

Clinical characteristics in patients with non-cardiac chest pain could favor gastroesophageal reflux disease diagnosis.

BACKGROUND: In patients with non-cardiac chest pain (NCCP), gastroesophageal reflux disease (GERD) is thought to be the commonest cause. Ambulatory pH monitoring and/or endoscopy are usually performed in order to confirm GERD diagnosis. At present, clinical diagnosis of reflux in patients with NCCP is uncertain.The aim of the study was to determine clinical characteristics that could identify GERD in patients with NCCP. METHODS: A total of 52 (age 52.8±1.8 yrs, 29 women) patients with NCCP underwent combined impedance-pH monitoring and gastroscopy. GERD diagnosis was based on the presence of esophagitis and/or a positive impedance-pH study (symptom index >50% and/or esophageal acid exposure time >4.0%). Patients were then divided into 2 groups: GERD- and non-GERD-related NCCP. Demographic and clinical parameters were compared between these two groups. RESULTS: GERD-related NCCP was found in 30 (58%) patients. Demographic characteristics were similar in both groups. Chest pain showed no difference in severity, radiation, relation to exercise and relation to sleep between the two groups. In the GERD-related NCCP group, chest pain was more prevalent during the postprandial period (P<0.05) and was relieved by spontaneous use of antireflux drugs (P<0.05). The presence of typical reflux symptoms favored a GERD diagnosis (P<0.05). CONCLUSIONS: A proportion of patients with NCCP showed clinical characteristics suggesting a GERD diagnosis. Typical reflux symptoms, postprandial chest pain and use of anti-reflux drugs for pain relief were the best predictors for GERD-related NCCP.

Bravo 48-hour Wireless pH Monitoring in Patients With Non-cardiac Chest Pain. Objective Gastroesophageal Reflux Disease Parameters Predict the Responses to Proton Pump Inhibitors.

BACKGROUND/AIMS: In patients with non-cardiac chest pain (NCCP), gastroesophageal reflux disease (GERD) is the commonest cause and ambulatory pH is of great value in identifying these patients. However, parameters in the context of predicting therapeutic response are still unknown. By extending the monitoring period, we could better evaluate the best evidence for GERD association. Our aims were (1) to compare the outcomes of 48-hour pH monitoring to 24-hour and (2) to determine whether objective parameters could predict the treatment success in patients with NCCP using Bravo pH system. METHODS: Pathological esophageal acid reflux (PEAR) and positive symptom index (SI) were calculated after 24-hour and compared to the 48-hour study. Evidence suggestive of GERD diagnosis was considered if PEAR and/or SI (+) were present on each different day. After pH study, all patients received proton pump inhibitor twice a day for 4 weeks. Treatment success was determined at the end of therapy. RESULTS: Thirty-two patients with NCCP participated. GERD was identified in 20 (62.5%) patients; 17 (53.1%) had PEAR, 3 (9.4%) SI (+) and 7 (22%) both. Twelve (41%) patients exhibited PEAR values on day 1, while 17 after 2 days; a 12.1% gain. SI (+) was found in 6 patients (18.8%) on day 1 and in 4 more on day 2, a gain of 12.5%. Significantly higher proportion of patients with GERD indicators showed improvement compared to those without (90% vs 16.7%, P < 0.005). CONCLUSIONS: In patients with NCCP, 48-hour pH measurement identified GERD as the cause of NCCP with an increased yield by almost 12% compared to 12 hours. Objective GERD parameters could predict response to antireflux therapy.

Yield of combined impedance-pH monitoring for refractory reflux symptoms in clinical practice.

BACKGROUND/AIMS: In patients with gastroesophageal reflux disease, persistent symptoms on proton pump inhibitor (PPI) therapy may be due to residual acid or non-acid reflux. Combined impedance-pH has been suggested to be superior to pH alone in the management of refractory patients to PPI. The utility of implementation of this technique in every day clinical practice is still unknown. The aim of this study was to investigate the outcomes of patients studied with combined impedance-pH and to evaluate the yield of additional impedance monitoring over pH alone in patients with persistent gastroesophageal reflux disease symptoms. METHODS: Seventy-one patients (31 men; mean age, 49.1 ± 15.5 years) on PPI therapy underwent combined impedance-pH for persistent typical (76%) or atypical (49%) symptoms. RESULTS: During impedance-pH study, 44 (62%) patients reported symptoms. A positive symptom index (SI) was found in 21 (48%) patients: 8 (18.2%) had a positive SI for acid reflux, 9 (20.5%) for non-acid reflux and 4 (9.1%) for mixed reflux. Addition of impedance allowed association between reflux and symptoms in 20.5% of patients who would have been missed by pH study alone. Heartburn was the most prevalent symptom associated with acid reflux, whereas regurgitation and ear, nose and throat symptoms were associated with non-acid reflux. CONCLUSIONS: The use of combined impedance-pH monitoring substantially increased the diagnostic yield compared to pH alone. With SI analysis, 20.5% of patients received a diagnosis that could not have been achieved with pH testing alone.

New endoscopy devices to improve population adherence to colorectal cancer prevention programs.

Despite recent advances in medicine, colorectal cancer (CRC) remains one of the greatest hazards for public health worldwide and especially the industrialized world. It has been well documented with concrete data that regular screening colonoscopy aimed at early detection of precancerous polyps can help decrease the incidence of CRC. However, the adherence of the general population to such screening programs has been shown to be lower than that expected, thus allowing CRC to remain a major threat for public health. Various reasons have been suggested to explain the disappointing compliance of the population to CRC screening programs, some of them associated with colonoscopy per se, which is viewed by many people as an unpleasant examination. Governments, medical societies, individual gastroenterologists, as well as the medical industry are working in order to improve endoscopic devices and/or to improve standard colonoscopy. The aim is to improve the acceptance of the population for this method of CRC screening, by providing a painless and reliable examination of the colon. This review focuses on some of the latest improvements in this field.

Gemcitabine and pegylated liposomal doxorubicin alternating with cisplatin plus cyclophosphamide in platinum refractory/resistant, paclitaxel-pretreated, ovarian carcinoma.

OBJECTIVES: This phase II study conducted to investigate the efficacy and toxicity of the combination of gemcitabine (GEM) and pegylated liposomal doxorubicin (LDOX) alternating with cisplatin (CDDP) and cyclophosphamide (CTX) in platinum-resistant/refractory, paclitaxel pretreated epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Forty-eight patients with CDDP-resistant/refractory and paclitaxel pretreated patients were treated with 8 cycles of GEM 800 mg/m2 days 1 and 8 and LDOX 30 mg/m2 day 1, alternating with CDDP 60 mg/m2 and CTX 600 mg/m2 every 3 weeks. RESULTS: Objective responses were observed in 37.5% of patients (4 complete and 11 partial responses) with measurable disease (n=40). CA125 response occurred in 30 (71.4%) of patients with elevated CA125 (n=42). After a median follow-up of 23 months, the median progression-free survival (PFS) was 6.9 months (95% confidence interval, CI: 5.2-8.5), while the median overall survival (OS) was 18.2 months (95% CI: 12.7-23.6). A progression-free interval (PFI) of 0-3 months was associated with lower objective responses (10% versus 46.6%, p=0.06). Chemotherapy was well tolerated. The most frequent toxicities were myelosuppression, neurotoxicity, nephrotoxicity, nausea/vomiting, fatigue and palmar-plantar erythrodysesthesia (PPE). Overall 31 (65%) patients received G-CSF and 13 (27%) antibiotics because of neutropenia and/or febrile neutropenia. CONCLUSION: This alternating combination chemotherapy is feasible for patients with platinum-resistant EOC and is associated with encouraging outcomes and a favorable toxicity profile.

Dermatomyositis associated with breast cancer.

An increased risk of underlying malignancy has been found in patients with dermatomyositis (DM). The risk is increased even in patients with DM aged 45 or younger and remains high for many years after diagnosis. Breast carcinoma does not represent the most common solid tumor associated with this autoimmune disorder. In the present report, two new cases of DM associated with breast cancer are described, together with an extensive literature review.

Two cases of complete response after imatinib mesylate treatment of advanced GIST.

BACKGROUND: Imatinib mesylate has undoubted efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), but complete responses have only been reported rarely. CASE REPORT: A 47-year-old man with liver metastasis from GIST achieved a complete response after 7 months of treatment with imatinib and a 47-year old woman with local relapse of GIST on the stomach after gastrectomy, showed complete remission, 9 months after treatment with imatinib. CONCLUSION: Although the response rate is high in patients with advanced GIST treated with imatinib mesylate, complete responses remain rare. Several issues concerning its optimal administration need to be clarified, in order to improve its efficacy.

Clinical value of bone remodelling markers in patients with bone metastases treated with zoledronic acid.

BACKGROUND: Bisphosphonates have an established role in the treatment of bone metastases from a variety of solid tumours. The objective response to anti-resorptive treatment cannot be evaluated by imaging techniques. A number of bone remodelling markers have been associated with bone metastases status; among them, urine and serum levels of N-terminal telopeptide of collagen type I (NTx) seem to have the best diagnostic accuracy. However, serum NTx has not yet been properly evaluated. PATIENTS AND METHODS: Seventy-one consecutive patients with newly diagnosed skeletal metastases were enrolled in this prospective study. All of them were treated with zoledronic acid at 4 mg, every 3 or 4 weeks. Serum NTx and bone-isoform of alkaline phosphatase (BAP) were measured by enzyme-linked immunosorbent assays at baseline and every 2 months thereafter. RESULTS: At baseline, serum NTx and BAP levels were significantly higher in patients with blastic than lytic bone lesions and in those with multiple rather than few bone site involvement. Forty-seven patients were followed for a median period of 139 days. Zoledronic acid resulted in a significant NTx reduction at first and second post-treatment evaluations (mean reduction of 43% at first evaluation); thereafter, mean NTx levels remained suppressed. In contrast, BAP levels did not show any significant changes. Bone disease progression resulted in a significant NTx elevation by an average of 69%. The initial response of NTx to zoledronic acid was correlated with the long-term clinical outcome of bone disease: patients with an initial NTx elevation had a significantly higher rate of bone disease progression compared to those with an initial NTx decline (66.7% versus 18.8%, p=0.001). Extraskeletal disease or bone irradiation did not influence NTx response. CONCLUSION: Serum NTx appears to be a useful marker in monitoring patients with skeletal metastases, as it is correlated with the type and bulk of bone disease and reflects bone disease progression. It is also useful in monitoring bisphosphonate therapy, while the initial response to this therapy seems to bear a prognostic significance for bone disease outcome.

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study.

OBJECTIVE: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients, with a median age of 58 years (range 33-77), were treated with oxaliplatin 85 mg m(-2) as a 2-h infusion on day 1, LV 200 mg m(-2) day(-1) as a 2-h infusion followed by bolus 5-FU 400 mg m(-2) day(-1) and a 22-h infusion of 5-FU 600 mg m(-2) day(-1) for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The vast majority of patients had performance status 0 or 1 and 76.3% had > or = 2 metastatic sites. A median number of four cycles per patient (range, 1-8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5-17), the median time to tumor progression was 4.8 months (range 0.6-19), and the median overall survival was 10.1 months (range 0.2-36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea-vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.

Oxaliplatin and irinotecan plus granulocyte-colony stimulating factor as third-line treatment in relapsed or cisplatin-refractory germ-cell tumor patients: a phase II study.

OBJECTIVE: To investigate the efficacy and tolerability of the combination of oxaliplatin and irinotecan in patients with relapsed or cisplatin-refractory germ cell tumors (GCT). PATIENTS AND METHODS: Eighteen patients with relapsed or cisplatin-refractory GCT were treated with oxaliplatin 85 mg/m(2) on days 1 and 15, followed by irinotecan 80 mg/m(2) on days 1, 8 and 15, every four weeks for a maximum of six cycles. RESULTS: All patients were assessable for response and toxicity. Overall, 7 patients (40%) achieved a favorable response (4 complete and 3 partial responses). One of the complete responders relapsed after 2.5 months and despite further treatment with high dose chemotherapy, he died two months later. The remaining 3 patients are continuously disease free for 11+, 14+ and 19+ months. The partial responders subsequently progressed and died after 2, 3 and 4.5 months, respectively. None of the patients with extragonadal mediastinal GCT responded to oxaliplatin and irinotecan chemotherapy. The investigated combination has a good tolerance. Neutropenia related toxicity (grade 3/4, 17%), neutropenic infections and sepsis were not common probably due to prophylactic use of hematopoietic colony stimulating factor (G-CSF). Thrombocytopenia and anemia were not a serious problem. Gastrointestinal side effects, specifically grade 3/4 diarrhea and nausea/vomiting were noted in 22% and 28% of patients, respectively. Oxaliplatin-associated neurotoxicity was rather low; grade 3 peripheral sensory neuropathy was recorded in 11% of patients. CONCLUSION: The combination of oxaliplatin and irinotecan is feasible and associated with significant clinical antitumor activity, mild and manageable toxicity and easy outpatient administration in patients with relapsed or cisplatin-refractory germ cell cancer. This combination seems to offer a possibility for long-term disease-free status (17%), despite the poor prognostic features of the study patient group.

Irinotecan and gemcitabine in patients with advanced non-small cell lung cancer, previously treated with cisplatin-based chemotherapy. A phase II study.

BACKGROUND: To evaluate the efficacy and tolerability of irinotecan plus gemcitabine administered every two weeks in patients with advanced non-small cell lung cancer (NSCLC) previously treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: Fifty patients with advanced NSCLC, refractory or resistant to cisplatin derivatives, were treated on an out-patient basis with irinotecan 150 mg/m2 intravenously (i.v.) and gemcitabine 1,800 mg/m2 i.v. on days 1 and 15, every two weeks. The response to treatment was evaluated every two cycles. The patients' median age was 59 years, 44 were men and 92% had a performance status (PS) of 0-1. RESULTS: On an intent-to-treat analysis, 8 (16%) patients, [95% confidence interval (CI), 7.2% to 29.1%] achieved partial response (PR), 19 (38%) stable disease (SD) and 23 (46%) progressive disease (PD). The median time to tumor progression (TTP) was 5.5 months (range, 0.1 to 16.5 months), the median survival time was 8.1 months (range, 0.8 to 22.1 months) and the 1-year survival 36% (95% CI, 22.9% to 50.8%). Clinical benefit response, including improvement of PS, dyspnea, anorexia and fatigue, cessation of hemoptysis and fever and reduction of cough and pain, was observed in 10% to 44% of patients. No patient experienced grade 3/4 anemia. Grade 3/4 neutropenia and thrombocytopenia occurred in 7 (14%) and 8 (16%) patients, respectively. Five (10%) patients were hospitalized due to febrile neutropenia and were successfully treated with broad-spectrum antibiotics and G-CSF support. One (2%) patient experienced grade 4 fatigue and discontinued treatment. Other grade 3/4 adverse events included diarrhea (3 cases, 2 of whom required hospitalization), alopecia (5 cases), asthenia (2 cases) and allergy (2 cases). Eight (16%) patients required a dose reduction. There were no treatment-related deaths. CONCLUSION: The combination of irinotecan and gemcitabine, administered every two weeks, demonstrated rather modest activity in advanced NSCLC patients who had previously been treated with cisplatin-based chemotherapy. It was well tolerated with mild toxicity and was associated with significant 1-year survival rate and symptomatic benefit response.