Oncologic,Functional, and Complications Outcomes of Robot-assisted Radical Cystectomy with Totally Intracorporeal Neobladder Diversion

Background

Robot-assisted radical cystectomy (RARC) with totally intracorporeal neobladder diversion is a complex procedure that has been reported with good outcomes in small series.

Objective

To present complications and oncologic and functional outcomes of this procedure.

Design, setting, and participants

Between 2003 and 2012 in a tertiary referral center, 70 patients were operated on by two experienced robotic surgeons. Data were collected prospectively and reviewed retrospectively.

Intervention

RARC with totally intracorporeal modified Studer ileal neobladder formation.

Outcome measurements and statistical analysis

The overall outcome of RARC with a totally intracorporeal neobladder was presented by assessing (1) surgical margins, (2) recurrence or cancer-specific death at 24 mo, (3) 30-d and 90-d complications graded according to the modified Clavien-Dindo system, (4) daytime and nighttime continence (no or one pad per day) at 6 and 12 mo, and (5) satisfactory sexual activity or potency at 6 mo and 12 mo. Survival rates were estimated by Kaplan-Meier plots.

Results and limitations

Median follow-up of the cohort was 30.3 mo (interquartile range: 12.7–35.6). We recorded negative margins in 69 of 70 patients (98.6%). Clavien 3–5 complications occurred in 22 of 70 patients (31.4%) at 30 d and 13 of 70 (18.6%) at >30 d. At 90 d, the overall complication rate was 58.5%. Clavien <3 and Clavien ≥3 complications were recorded in 15 of 70 patients (21.4%) and 26 of 70 (37.1%), respectively. Kaplan-Meier estimates for recurrence-free, cancer-specific, and overall survival at 24 mo were 80.7%, 88.9%, and 88.9%, respectively. Daytime continence and satisfactory sexual function or potency at 12 mo ranged between 70% and 90% in both men and women. Limitations of this study include its retrospective design, selection bias due to the learning curve phase, and missing data.

Conclusions

In this expert center for RARC, outcomes after RARC with totally intracorporeal neobladder diversion appear satisfactory and in line with contemporary open series.     

The functional characterization of interleukin-10 receptor expression on human natural killer cells

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.     

Pathways to Colonoscopy in the South: Seeds of Health Disparities

Objectives. We aimed to highlight sociodemographic differences in how patients access colonoscopy.Methods. We invited all eligible patients (n = 2500) from 2 academy-affiliated colonoscopy centers in Alachua County, Florida (1 free standing, 1 hospital based), to participate in a precolonoscopy survey (September 2011–October 2013); patients agreeing to participate (n = 1841, response rate = 73.6%) received a $5.00 gift card.Results. We found sociodemographic differences in referral pathway, costs, and reasons associated with obtaining the procedure. Patients with the ideal pathway (referred by their regular doctor for age-appropriate screening) were more likely to be Black (compared with other minorities), male, high income, employed, and older. Having the colonoscopy because of symptoms was associated with being female, younger, and having lower income. We found significant differences for 1 previously underestimated barrier, having a spouse to accompany the patient to the procedure.Conclusions. Patients’ facilitators and barriers to colonoscopy differed by sociodemographics in our study, which implies that interventions based on a single facilitator will not be effective for all subgroups of a population.Colorectal cancer (CRC), the second leading cause of US cancer deaths in 2013 (50 830),1 is not distributed equally. Nationally, it is estimated that incidence is 25% higher, and mortality from CRC 50% higher, in Black Americans than in Whites.2,3 Most CRC diagnoses follow evaluation by colonoscopy. Although consumers have a range of CRC screening tests, from least invasive (fecal occult blood test, fecal immunochemical test) to most invasive (sigmoidoscopy, colonoscopy),4 if polyps are indicated, a colonoscopy is required as follow-up. Thus, colonoscopy is both an entry point and a pivotal event in the process of preventing, detecting, and treating CRC. CRC can be prevented through the removal of precancerous polyps or detected at an early, easily treatable stage5; findings indicate6 that colonoscopy with polypectomy reduces mortality from CRC by 53%. Although rates of CRC screening have increased,3 there is need for improvement. More than one third of Americans are not in compliance with screening guidelines,7 with rates being lower in the southern United States.8In 2008, Etzioni et al.9 presented a model of patient and provider-level factors that influence decision-making in colon cancer and that can lead to health disparities in disease recurrence and survival. The Etzioni model identifies key points of vulnerability in the treatment process where the potential to achieve high-quality, guideline-recommended care can be lost. The model captures patients after surgery, beginning with the decision to refer patients to a medical oncologist for adjuvant treatment; it is relevant because there is considerable evidence of inequities in who receives adjuvant treatment based on older age,10,11 comorbidities,12,13 low income,7 coverage with Medicaid rather than Medicare,13 Black race,14 female gender,15,16 and being unmarried.9We propose that this model starts too late in the process; health disparities originate prior to colonoscopy and can increase at each decision point along a continuum. In an elaborated model (Figure 1), we suggest that CRC health disparities research should begin with an investigation of entry into the health care system and the subsequent pathways to colonoscopy. Referral patterns, costs, and patient demographics influence patient access to care, colonoscopy compliance, and postcolonoscopy decision-making.Open in a separate windowFIGURE 1—Pathways to colonoscopy, treatment, and outcomes.     

Feasibility of Recruiting Families into a Heart Disease Prevention Program Based on Dietary Patterns

Offspring of parents with a history of cardiovascular disease (CVD) inherit a similar genetic profile and share diet and lifestyle behaviors. This study aimed to evaluate the feasibility of recruiting families at risk of CVD to a dietary prevention program, determine the changes in diet achieved, and program acceptability. Families were recruited into a pilot parallel group randomized controlled trial consisting of a three month evidence-based dietary intervention, based on the Mediterranean and Portfolio diets. Feasibility was assessed by recruitment and retention rates, change in diet by food frequency questionnaire, and program acceptability by qualitative interviews and program evaluation. Twenty one families were enrolled over 16 months, with fourteen families (n = 42 individuals) completing the study. Post-program dietary changes in the intervention group included small daily increases in vegetable serves (0.8 ± 1.3) and reduced usage of full-fat milk (−21%), cheese (−12%) and meat products (−17%). Qualitative interviews highlighted beneficial changes in food purchasing habits. Future studies need more effective methods of recruitment to engage families in the intervention. Once engaged, families made small incremental improvements in their diets. Evaluation indicated that feedback on diet and CVD risk factors, dietetic counselling and the resources provided were appropriate for a program of this type.     

Monosodium urate crystals in the knee joints of patients with asymptomatic nontophaceous gout

We aspirated synovial fluid from the knees of 50 patients with asymptomatic, nontophaceous gout, in whom synovial fluid monosodium urate (MSU) crystals had previously been documented in the knees or other joints. Fifty-eight percent of these asymptomatic patients had MSU crystals in their knee joints. Serum uric acid levels, serum creatinine levels, volume of synovial fluid aspirated, and cell counts of the aspirated fluid did not differentiate the MSU crystal-positive group from the group without MSU crystals. Clinical factors such as alcohol abuse, coronary heart disease, hypertension, duration of gout, duration of the intercritical period, and drug therapy did not differentiate the 2 groups. Nineteen patients consented to aspiration of their other knee. Seven of these patients (37%) had MSU crystals bilaterally, and 6 patients (32%) had them unilaterally. The implications of the persistence of MSU crystals (including those in intracellular locations) in many patients, despite normalization of serum uric acid levels, should be determined. Knee joint aspiration is a sensitive method for the demonstration of MSU crystals in asymptomatic patients. The procedure might also be useful in documenting these crystals in patients who have had attacks of arthritis with features consistent with a diagnosis of gout, but in whom MSU crystals have not been documented.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.