Distant metastases in colorectal carcinoma: A proposal for a new M1 subclassification.

INTRODUCTION: In 2010, the seventh Tumour-Node-Metastasis (TNM) cancer staging system of the International Union for Cancer Control (UICC) and the American Joint Committee of Cancer (AJCC) introduced a subdivision of M1 in the TNM classification of colorectal carcinomas. For the eighth TNM edition which will be released in the autumn of 2016 and will become effective in January 2017 new proposals are appreciated. The aim of our study was to define a new and better proposal for M1 subclassification. METHODS: In a total of 814 patients with stage IV colorectal carcinoma treated between 1995 and 2013 prognostic factors were analysed in univariate and multivariate analyses. RESULTS: Advanced age, treatment in the earlier period 1995-2003, involvement of multiple metastatic sites, and non-curative resection were found to be independent prognostic factors. In patients with only one metastatic site, survival was good in patients with liver or lung metastasis, moderate in patients with metastasis of the peritoneum or non-regional lymph nodes and poor in patients with other rarely metastatic involved organs. The new proposal defines M1a, Metastasis confined to one organ: liver or lung (2-year survival 51.6%); M1b, Metastasis confined to one organ: peritoneum or non-regional lymph nodes, or Metastasis confined to liver plus lung (2-year survival 39.4%); and M1c, Metastasis confined to one organ: all other sites, or Metastasis in more than one organ, except liver plus lung (2-year survival 21.6%). CONCLUSION: The new proposal can identify three prognostic groups in stage IV colorectal carcinomas with significant differences in survival.

Comorbidities and personal burden of urgency urinary incontinence: a systematic review.

AIMS: Studies on the burden and comorbidities associated with urgency urinary incontinence (UUI) are difficult to compare, partly because of the evolution of definitions for lower urinary tract symptoms and the various instruments used to assess health-related quality of life (HRQL). This article summarises published evidence on comorbidities and the personal burden associated specifically with UUI to provide clinicians with a clear perspective on the impact of UUI on patients. METHODS: A PubMed search was conducted using the terms: (urgency urinary incontinence OR urge incontinence OR mixed incontinence OR overactive bladder) AND (burden OR quality of life OR well-being OR depression OR mental health OR sexual health OR comorbid), with limits for English-language articles published between 1991 and 2011. RESULTS: Of 1364 identified articles, data from 70 retained articles indicate that UUI is a bothersome condition that has a marked negative impact on HRQL, with the severity of UUI a predictor of HRQL. UUI is significantly associated with falls in elderly individuals, depression, urinary tract infections, increased body mass index, diabetes and deaths. The burden of UUI appears to be greater than that of stress urinary incontinence or overactive bladder symptoms without UUI. UUI adversely impacts physical and mental health, sexual function and work productivity. CONCLUSIONS: UUI is associated with numerous comorbid conditions and inflicts a substantial personal burden on many aspects of patients' lives. Healthcare providers should discuss UUI with patients and be aware of the impact of UUI and its associated comorbidities on patients' lives.

Nocturia: current concepts and future perspectives.

Nocturia is a prevalent highly bothersome urinary symptom that may significantly detriment the health and well-being of sufferers. It is characterized by waking at night to void, each void preceded and followed by sleep, hence leading to fragmentation of sleep and day-time tiredness. This may result in reduced productivity in the workplace, which contributes to the significant burden to the wider society that nocturia incurs. Nocturia was traditionally viewed as one of the many urinary tract symptoms that occur due to lower urinary tract dysfunction. However, recently it has been recognized that due to its multi-factorial aetio-pathogenesis, nocturia should be viewed as distinct clinical condition in its own right. Careful assessment of the nocturic patient is essential so that treatment strategies are guided by the likely causes. Much research is currently being undertaken into the underlying causes and the optimal management approaches. This review will explore the contemporary status of research on nocturia with a focus on the current and newly available pharmacotherapies.

Neurological patients need evidence-based urological care.

AIMS: To report the conclusion of the Think Thank on Neurourology discussions during the first ICI-RS meeting in 2009. METHODS: During a 3-day meeting a group of specialists discussed evidence-based medicine in neurourology and made suggestions for future research. RESULTS: In the vast majority of patients with neurological disease bladder dysfunction occurs. The actual rules of diagnosis and treatment lack a study related evidence base. From a long list of possible research subjects, prevalence, detrusor pressure, imaging, catheterization and surgery have been first discussed. CONCLUSION: In each of these subjects, research items are suggested which can help to improve the care in this patient group.

Neurologic urinary incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic urinary incontinence. METHODS: Through in debt literature review all aspects of neurological urinary incontinence were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment and surgical treatment of neurologic urinary incontinence, levels of evidence and grades of recommendation were made following ICUD criteria. CONCLUSIONS: Though data are available that advice and guide in the management of urinary incontinence in neurologic patients, not many data have a high level of evidence or permit a high grade of recommendation. More and well-structured research is needed.

Neurologic fecal incontinence.

INTRODUCTION: This manuscript summarizes the work of Committee 10 on neurologic bladder and bowel of the International Consultation on Incontinence in 2008-2009. As the data are very large the outcome is presented in different manuscripts. This manuscript deals with neurologic fecal incontinence (FI). METHODS: Through in debt literature review all aspects of neurologic urinary and FI were studied for levels of evidence. Recommendations for diagnosis and treatment, and for future research were made. RESULTS: Pathophysiology was summarized for different levels of lesions. For epidemiology, specific diagnostics, conservative treatment, and surgical treatment of neurologic FI levels of evidence and grades of recommendation were made. CONCLUSIONS: Though data are available that advice and guide in the management of FI in neurologic patients, not many data are with a high level of evidence or high grade of recommendation. More and well-structured research is needed.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Does race affect postoperative outcomes in patients with low-risk prostate cancer who undergo radical prostatectomy?

OBJECTIVES: To assess the magnitude of racial disparities in prostate cancer outcomes following radical prostatectomy for low-risk prostate cancer. METHODS: We retrospectively reviewed our database of 2407 patients who under went radical prostatectomy and isolated 2 cohorts of patients with low-risk prostate cancer. Cohort 1 was defined using liberal criteria, and cohort 2 was isolated using more stringent criteria. We then studied pre- and postoperative parameters to discern any racial differences in these 2 groups. Statistical analyses, including log-rank, chi(2), and Fisher's exact analyses, were used to ascertain the significance of such differences. RESULTS: Preoperatively, no significant differences were found between the white and African-American patients with regard to age at diagnosis, mean prostate-specific antigen, median follow-up, or percentage of involved cores on prostate biopsy. African-American patients in cohort 1 had a greater mean body mass index than did white patients (26.9 vs 27.8, P = .026). The analysis of postoperative data demonstrated no significant difference between white and African-American patients in the risk of biochemical failure, extraprostatic extension, seminal vesicle involvement, positive surgical margins, tumor volume, or risk of disease upgrading. African-American patients in cohort 2 demonstrated greater all-cause mortality compared with their white counterparts (9.4% vs 3.1%, P = .027). CONCLUSIONS: In patients with low-risk prostate cancer treated with radical prostatectomy, there exist no significant differences in surrogate measures of disease control, risk of disease upgrading, estimated tumor volume, or recurrence-free survival between whites and African-Americans.

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer.

BACKGROUND: To compare the efficacy and safety of three different chemotherapy doublets in the treatment of advanced pancreatic cancer (PC). PATIENTS AND METHODS: At total of 190 patients were randomly assigned to receive capecitabine 1000 mg/m(2) twice daily on days 1-14 plus oxaliplatin 130 mg/m(2) on day 1 (CapOx), capecitabine 825 mg/m(2) twice daily on days 1-14 plus gemcitabine 1000 mg/m(2) on days 1 and 8 (CapGem) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus oxaliplatin 130 mg/m(2) on day 8 (mGemOx). Treatment cycles were repeated every three weeks. The primary end point was progression-free survival (PFS) rate at 3 months; secondary end points included objective response rate, carbohydrate antigen 19-9 response, clinical benefit response, overall survival and toxicity. RESULTS: The PFS rate after 3 months was 51% in the CapOx arm, 64% in the CapGem arm and 60% in the mGemOx arm. Median PFS was estimated with 4.2 months, 5.7 months and 3.9 months, respectively (P = 0.67). Corresponding median survival times were: 8.1 months (CapOx), 9.0 months (CapGem) and 6.9 months (mGemOx) (P = 0.56). Grade 3/4 hematological toxicities were more frequent in the two Gem-containing arms; grade 3/4 non-hematological toxicity rates did not exceed 15% in any arm. CONCLUSION: CapOx, CapGem and mGemOx have similar clinical efficacy in advanced PC. Each regimen has a distinct but manageable tolerability profile.

Association of obesity with tumor characteristics and treatment failure of prostate cancer in African-American and European American men.

PURPOSE: The impact of body mass index on tumor characteristics and treatment failure in prostate cancer is not well understood in diverse ethnic groups. We evaluated the effect of body mass index in African-American and European American patients from a radical prostatectomy cohort between 1995 and 2004 with regard to tumor histopathological characteristics and biochemical relapse-free survival. MATERIALS AND METHODS: A total of 924 patients were studied to evaluate whether obese men (body mass index greater than 30) had different preoperative and postoperative tumor characteristics or biochemical relapse-free survival compared to nonobese men. There were 784 European American and 140 African-American patients analyzed using failure time models, adjusted for age, preoperative prostate specific antigen, tumor stage and race. RESULTS: Mean and median followup was 42 and 36 months, respectively. African-American men were significantly more obese than European American men. Mean body mass index was 29.0 in African-American and 28.1 in European American men (p = 0.003). African-American men (OR 2.30, 95% CI 1.04-5.1) were more likely to have higher tumor stage on final pathology. Obesity was a risk factor for biochemical failure in African-American men (adjusted hazard ratio 5.49, 95% CI 2.16-13.9) but not in European American men (HR 1.41, 95% CI 0.96-2.08), and this difference was statistically significant (p value for interaction 0.036). CONCLUSIONS: Obesity is associated with poorer tumor prognostic characteristics and decreased biochemical relapse-free survival, particularly in African-American men. These data suggest that obesity may in part explain the poorer prostate cancer prognosis seen in African-American men compared to other racial and ethnic groups.

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Radiofrequency ablation of small renal cell carcinomas using multitined expandable electrodes: preliminary experience.

PURPOSE: Radiofrequency ablation is a minimally invasive, nephron-sparing option for renal cell carcinoma (RCC) in poor surgical candidates. We report our contemporary experience with RCC radiofrequency ablation using multitined expandable electrodes along with an aggressive treatment strategy to displace adjacent viscera away from probe tines. Involution of the treatment zone was assessed over time. MATERIALS AND METHODS: Over a 36-month period, a quality-assurance database identified 22 patients with 26 sporadic RCC who underwent 43 ablations during 27 radiofrequency ablation sessions. The mean age of the cohort was 71 years (range, 47-89 y). Mean RCC diameter was 2.2 cm (range, 1-4 cm). Twenty-six of radiofrequency ablation sessions were performed using multitined expandable electrodes. All ablations used CT guidance with moderate sedation. Adjunctive techniques used during ablation were recorded, as were instances in which ablation mandated penetration of tines beyond the kidney margin. Post-treatment ablation zones were measured from CT/MR images to evaluate serial involution and treatment response. RESULTS: Technical success in targeting and ablation was 100%. Follow-up periods ranged from 1 to 31 months (mean, 11.2). During this period, one patient presented with marginal local recurrence and underwent repeat radiofrequency ablation. Adjunctive techniques in four patients included water injection for displacement of the tail of the pancreas (n = 1) or descending colon (n = 3). Deliberate penetration of tines beyond the margins of the kidney was performed in 41% of cases; no hemorrhage occurred in these cases. No major complications occurred. Minor complications occurred in 17% of patients, including asymptomatic pneumothorax, perirenal hematomas, subcutaneous hematoma, and subcutaneous abscess. After 6 months, mean involution of the ablation zone was 15% from baseline volume per year. CONCLUSION: Multitined expandable radiofrequency electrodes produce a high rate of local control for small RCCs with a low complication rate, even when tine penetration of the kidney is required for an adequate tumor treatment margin. Adjacent organs can be protected with adjunctive percutaneous maneuvers.

Transitional cell carcinoma of the fossa navicularis in a man with preexisting adenocarcinoma of the prostate.

In this report we present a patient with a history of prostatic adenocarcinoma who was found to have a low-grade/low-stage transitional cell carcinoma of the fossa navicularis. The patient underwent transurethral resection and at approximately 2 years of follow-up he has no evidence of tumor recurrence. Very limited follow-up data exist on which to base management decisions, and this report lends support to the use of transurethral resection alone as a means to treat low-grade/low-stage lesions.

[A case of attenuated familial adenomatous polyposis coli (AFAP)]. / Zufallsbefund einer attenuierten familiären adenomatösen Polyposis (AFAP).

We describe an asymptomatic female patient who was diagnosed with multiple tubular and tubulovillous adenomas in the right-sided colon on routine colonoscopy at the age of 59 years. Genetic testing identified a germline truncating mutation at codon 405 (R405X) of the adenomatous polyposis coli (APC) gene. This mutation is located in the alternatively spliced region of exon 9, a region that is associated with an attenuated phenotype of familial adenomatous polyposis (AFAP). To our knowledge this report describes for the first time the R405X germline mutation in association with AFAP. Our patient had no extracolonic manifestations of AFAP. Treatment consisted of a right hemicolectomy with ileotransversal anastomosis plus complete endoscopic polypectomy in the left-sided colon. AFAP is a poorly defined condition with unknown prevalence and penetrance that requires individual therapy and life-long surveillance. Because of marked intrafamilial phenotypic variance, it is crucial to identify these patients and implement proper endoscopic surveillance at an early age in family members carrying this mutation.

Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer.

An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer. One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62 years, Karnofsky performance 90%, and disease status was comparable for both arms. The objective clinical response rates after 14 weeks treatment (primary end point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI 0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF). The data from this randomised phase II study indicate that ILF provides a better response rate than ELF, and that ILF should be investigated further for the treatment of metastatic gastric cancer.

Neoadjuvant chemotherapy does not increase postoperative complication rate after resection of colorectal liver metastases.

BACKGROUND: This paper discusses, whether neoadjuvant chemotherapy has an impact on the rate of postoperative complications after primary resection of liver metastases from colorectal carcinoma. METHODS: Of 183 patients 64 were studied. The patients were subdivided into two matched groups of 32 patients each-prior neoadjuvant chemotherapy (CT-group) vs. (control-group, primary resection). RESULTS: There were no postoperative complications in 24 patients of the control group (75%) and 26 patients of the CT-group (81%). Following prior chemotherapy, no major complications such as liver failure were observed, even after extended resections. CONCLUSION: Neoadjuvant chemotherapy prior to surgical resection of colorectal liver metastases does not result in an increase of postoperative morbidity and mortality.