Chronic lymphocytic leukemia: a review of some new aspects of the biology, factors influencing prognosis and therapeutic options.

This review provides some basic information on chronic lymphocytic leukemia (CLL) and attempts to present some of the newer data which have accumulated in recent years including those relating to familial aggregation of CLL and the detection of monoclonal CD5+ lymphocytosis in the general population and families of CLL patients. Novel data on the pathogenesis and concepts of cell origin in CLL are also reviewed stressing the fact that there is biased IgVH gene usage, and the importance of mutational status of the CLL cell, as reported in recent years by different authors. A brief review of the significance of the microenvironmental interactions between stromal cells and other accessory cells, and the leukemic CLL cells is also provided. Other clinical aspects are discussed including diagnostic criteria, clinical staging, and the newer prognostic factors which influence survival and timing of therapy for CLL patients. We also attempt to outline the therapeutic options available and the principles of planning risk and age-adapted treatment, stressing the importance and the necessity for participating in ongoing and future international clinical trials.     

The True Incidence of Gastric GIST—a Study Based on Morbidly Obese Patients Undergoing Sleeve Gastrectomy

Background

Gastrointestinal stromal tumor (GIST) is a rare neoplasm of the alimentary tract. Previous reports described an incidence of 1 per 100,000. Laparoscopic sleeve gastrectomy (LSG) provides pathological specimens of the majority of the stomach. We examined the pathology from LSG and the incidence and location of GIST. The aim of this study was to study the incidence of asymptomatic GISTs found during LSG at our institution.

Methods

A search was conducted in a prospectively maintained bariatric registry. Data collected included the following: gender, age, body mass index (BMI), and concomitant hypertension or diabetes mellitus. Histopathology reports were reviewed for incidental GIST. We compared the patients with incidental GIST to the rest of the cohort.

Results

Pathology reports of 827 patients that underwent LSG between 2007 and 2014 were reviewed. Five patients had GIST in the resected stomach, an incidence of 0.6 %. The group of patients with GIST had lower BMI and older age compared to the remaining 822 patients. All tumors were located close to the lesser curvature.

Conclusions

The incidence of GIST found in this cohort is significantly higher than previously reported. This may be due to an association between these tumors and obesity or because asymptomatic GISTs are underdiagnosed in the general population. These tumors are particularly common in older patients and special attention must be given when performing LSG on this subpopulation. The stomach should be inspected thoroughly before resection. A tumor on the lesser curvature may necessitate changing the surgical plan or aborting the procedure.     

Are they too old? Surgical treatment for metastatic epidural spinal cord compression in patients aged 65 years and older

Abstract

Objectives:

We aimed to assess the efficacy of surgical decompression of metastatic epidural spinal cord compression (MESCC) in patients ≧65 years and review our multidisciplinary surgical decision-making process.

Methods:

We identified all patients operated for MESCC from August 2008 to June 2012. Patients ≧65 years, with a single area of cord compression, back/radicular pain, neurological signs of cord compression, surgery within 48 hours after onset of MESCC-related paraplegia, and follow-up for ≧1 year or until death were included. Files were reviewed retrospectively. The requirement for informed consent was waived. Neurological status was assessed with the American Spinal Injury Association (ASIA) Impairment Scale (AIS). Duration of ambulation and survival were assessed with Kaplan–Meier and Cox regression analysis.

Results:

Twenty-one patients met inclusion criteria (11 women/10 men; mean age 73 years, range 65–87). All presented with debilitating back/neck pain. Ten patients (48%) were not ambulatory before surgery and four suffered urinary incontinence/constipation (19%). Preoperative AIS was E in 5 patients (24%), D in 11 (62%), and C in 5 (24%). Motor symptoms had been present for a mean of 3·8 days (range 1–14). All patients regained ambulation. Overall, mean survival was 320 days (range 19–798) and mean ambulation was 302 days (range 18–747). On 31 March 2013, 7 patients (33%) were alive and ambulatory at a mean of 459 days (range 302–747); 14 patients had died (67%) at a mean of 251 days (range 19–798), with a mean ambulation of 223 days (range 18–730).

Discussion:

With careful patient selection, surgery may achieve long duration of ambulation in patients ≧65 years with MESCC.     

Blood- and tissue-based biomarkers for prediction of outcomes in urothelial carcinoma of the bladder

ObjectivesUrothelial carcinoma of the bladder (UCB) is a highly heterogeneous malignancy that causes significant morbidity and mortality. Standard pathologic features (stage, grade, and nodal status) are insufficient to predict accurately a patient's outcome. Biomarkers could help clinicians provide individualized prognostications and allow risk-stratified clinical decision making regarding surgical and medical treatment. This review summarizes the existing tissue- and blood-based biomarkers in UCB.Material and methodsA PubMed/Medline search was conducted to identify original articles regarding molecular biomarkers and UCB. Searches were limited to papers published in English. Keywords included urothelial carcinoma, bladder cancer, transitional cell, biomarker, marker, staining, cystectomy, recurrence or progression, survival, prediction, and prognosis.ResultsThe articles with the highest level of evidence were selected and reviewed, with the consensus of all the authors of this paper.ConclusionsThere is no doubt that a panel of biomarkers would eventually improve our clinical decision making regarding treatment and follow-up. However, to date, no biomarker panel is yet validated for daily clinical practice.     

Long-term Cancer-specific Outcomes of TaG1 Urothelial Carcinoma of the Bladder

Background

Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB).

Objective

To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC).

Design, setting, and participants

A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n = 11) were excluded.

Intervention

Transurethral resection of the bladder with or without IPIC.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death.

Results and limitations

Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low- and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: ±1). Advancing age (p = 0.04), tumor >3 cm (p = 0.001), multiple tumors (p < 0.001), and recurrent tumors (p < 0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p = 0.001). The actuarial estimate of 5-yr progression-free survival was 95% ± 1. Advancing age (p < 0.001) and multiple tumors (p = 0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% ± 1. Advancing age (p = 0.001) and previous recurrence (p = 0.04) were associated with increased risk, whereas female gender (p = 0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p < 0.01). Limitations include the retrospective design of the study and the lack of a central pathology review.

Conclusions

TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low- and intermediate-risk TaG1 UCB.     

Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.     

Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large single-center Egyptian cohort

Objective

To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients.

Methods

A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan–Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS).

Results

1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20–87) years and median follow-up was 40 months (0–110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p?<?0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p?=?0.003) and ADC (HR 2.17, p?=?0.044) than in UC (HR 1.66, p?=?0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p?=?0.012).

Conclusions

There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.