Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients.

BACKGROUND: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm "Bordier" core needle. We examined the feasibility of using a 2 mm "Jamshidi™" core needle as a more practical and less invasive technique. METHODS: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. RESULTS: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. DISCUSSION: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.

Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma.

Introduction: Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods: In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results: Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions: Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship.

Cutaneous metastasis of renal cell carcinoma masquerading as an infected sebaceous cyst.

Renal cell carcinoma (RCC) is the third most common genitourinary malignancy with an estimated one third of cases with metastatic disease at the time of diagnosis. Though rare, cutaneous metastasis from RCC is more frequent than any other genitourinary malignancy. Metastasis of RCC to skin carries poor prognosis as coexistent visceral spread is the norm. A 38-year-old man presented one year after radical nephrectomy for clear cell carcinoma of the left kidney with a submental lesion that proved to be metastatic. Clinical appearance of cutaneous RCC metastasis is varied and can closely mimic other skin lesions. It is incumbent on general practitioners, dermatologists and urologists to exercise diligence in clinical diagnosis of skin lesions in the background of previous oncological diagnosis.

Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature.

Emphysematous pyelonephritis (EPN) is a rare occurrence in renal allografts. An aggressive approach resulting in transplant nephrectomy is viewed as the standard of care. Over the recent years, treatment with percutaneous drainage (PCD) of the renal and perinephric collections and appropriate antibiotics has been reported with good success in lesser grades of this infection. Only 4 cases of extensive EPN disease with Escherichia coli, treated with conservative management, are reported in the English-language literature. We present a case of severe EPN caused by Klebsiella pneumoniae, successfully managed with early PCD, and propose a step-up strategy aimed toward graft preservation.

Lower urinary tract symptoms and prostatic calculi: A rare presentation of alkaptonuria.

Alkaptonuria is a rare tyrosine metabolic disorder. A deficiency of homogentisic acid oxidase leads to accumulation of homogentisic acid in the body. Dark-colored urine, cutaneous pigmentations and musculoskeletal deformities are characteristic features. Storage and voiding lower urinary tract symptoms due to prostatic calculi is a rare presentation.

Histomorphometric and microarchitectural analyses using the 2 mm bone marrow trephine in metastatic breast cancer patients-preliminary results.

BACKGROUND: Bone-targeted agents are widely used for the treatment of osteoporosis, the prevention of cancer-therapy induced bone loss, and for reducing the risk of skeletal related events in patients with metastatic disease. Despite widespread use, relatively little is known about the in vivo effect of these agents on bone homeostasis, bone quality, and bone architecture in humans. Traditionally bone quality has been assessed using a transiliac bone biopsy with a 7 mm "Bordier" core needle. We examined the possibility of using a 2 mm "Jamshidi" core needle as a more practical and less invasive method to assess bone turnover and potentially other tumor effects. METHODS: A pilot study on the feasibility of assessing bone quality and microarchitecture and tumor invasion using a 2 mm bone marrow trephine was conducted. Patients underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for bone microarchitecture, bone density, and histomorphometry. The study plan was to accrue three patients with advanced breast cancer to assess the feasibility of the study before enrolling more patients. RESULTS: The procedure was well tolerated. The sample quality was excellent to analyze bone trabecular microarchitecture using both microCT and histomorphometry. Intense osteoclastic activity was observed in a patient with extensive tumor burden in bone despite intravenous bisphosphonate therapy. DISCUSSION: Given the success of this study for assessing bone microarchitecture, bone density, and histomorphometry assessment using a 2 mm needle the study will be expanded beyond these initial three patients for longitudinal assessment of bone-targeted therapy.

Maximal androgen blockade for advanced prostate cancer.

Prostate cancer has now become one of the leading types of cancer in urban India. It is now the third most common cancer in Delhi. As we advance in health care with the resultant increase in longevity, we will be seeing more of advanced carcinoma prostate. Since the early 1980.s, there have been many trials on MAB. However, the question remains whether these agents actually make a difference? The role of MAB is probably limited to the prevention of the beta are reaction in patients on LHRH agonists. The non steroidal antiandrogens have a marginal benefit of increased overall survival by approximately 3% to 5% at 5 ve years. There may be a role for MAB in patients with metastatic carcinoma of prostate, low volume metastases, patients with M 1 disease with absence of metastases in the skull, ribs, long bones, and soft tissues excluding lymph nodes.

Prevalence and risk factors for female sexual dysfunction in women attending a medical clinic in south India.

BACKGROUND: Reports from India on the prevalence and determinants of female sexual dysfunction (FSD) are scant. AIMS: To determine the prevalence and risk factors for FSD. SETTINGS AND DESIGN: A cross-sectional survey in a medical outpatient clinic of a tertiary care hospital. MATERIALS AND METHODS: We administered a Tamil version of the Female Sexual Function Index (FSFI) to 149 married women. We evaluated putative risk factors for FSD. We elicited participant's attributions for their sexual difficulties. STATISTICAL ANALYSIS: We estimated the prevalence of possible FSD and sexual difficulties from published FSFI total and domain cut-off scores. We used logistic regression to identify risk factors for possible FSD. RESULTS: FSFI total scores suggested FSD in two-thirds of the 149 women (73.2%; 95% confidence intervals [CI] 65.5% to 79.6%). FSFI domain scores suggested difficulties with desire in 77.2%; arousal in 91.3%; lubrication in 96.6%; orgasm in 86.6%, satisfaction in 81.2%, and pain in 64.4%. Age above 40 years (odds ratios [OR] 11.7; 95% CI 3.4 to 40.1) and fewer years of education (OR 1.2; 95% CI 1.0 to 1.3) were identified by logistic regression as contributory. Women attributed FSD to physical illness in participant or partner, relationship problems, and cultural taboos but none had sought professional help. CONCLUSIONS: Sexual problems suggestive of dysfunction, as suggested by FSFI total and domain scores, are highly prevalent in the clinic setting, particularly among women above 40 and those less educated, but confirmation using locally validated cut-off scores of the FSFI is needed.

Melioidosis presenting as genitourinary infection in two men with diabetes.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It occurs predominantly in tropical regions. The manifestations are protean which include pneumonia, visceral abscesses, septic arthritis, osteomyelitis, acute suppurative and chronic granulomatous lesions with involvement of almost all organ systems. Fulminant sepsis is much more common and is associated with high mortality. Hence prompt recognition and early treatment is warranted. We report unusual presentations of urinary tract melioidosis in two diabetic men.

Occult stress incontinence in women with pelvic organ prolapse.

OBJECTIVES: To study the prevalence of occult stress urinary incontinence (SUI) among Indian women with genitourinary prolapse, and determine the risk of developing SUI after vaginal hysterectomy and pelvic floor repair in Indian women with occult SUI. METHODS: A prospective cohort study of 78 women with significant genitourinary prolapse without symptoms of SUI was conducted at Christian Medical College, Vellore, India. Before the surgical intervention, the prolapse was repositioned using a pessary and a Pyridium (Parke Davis, Morris Plains, NJ, USA) pad test was performed to detect occult SUI. The primary outcome studied was the risk of developing postoperative urinary incontinence. RESULTS: Preoperatively, 67.9% of women were found to have occult SUI. The prevalence of SUI was 43.6% postoperatively, and 64.2% of the women with a positive result to the preoperative Pyridium pad test after pessary insertion were found to have urinary incontinence postoperatively. Postmenopausal women had twice the risk of developing occult SUI. CONCLUSION: Preoperative testing is useful to identify women with genitourinary prolapse who have occult SUI. Women with a positive result may need a systematic clinical evaluation and urodynamic studies to characterize the incontinence. They can be then counseled preoperatively regarding concomitant anti-incontinence procedures.

Shock wave lithotripsy in solitary functioning kidneys: is prophylactic stenting necessary?

OBJECTIVE: To assess the safety of shock wave lithotripsy (SWL) without prophylactic stents in solitary functioning kidneys. PATIENTS AND METHODS: Sixteen solitary functioning kidneys with 23 renal stones with a size of <15 mm were treated with SWL as the primary modality. All patients were counseled about the possibility of obstruction, and treatment was offered to those who consented. The safety of SWL was assessed by the need for interventions and the posttreatment renal function. RESULTS: In 14 patients lithotripsy was uneventful. The duration of treatment ranged from 5 to 35 days. One patient with a 15-mm pelvic calculus presented with anuria which resolved before intervention. In 1 patient fragmentation failed, and percutaneous nephrolithotomy was performed. CONCLUSIONS: In solitary functioning kidneys, SWL is safe without prophylactic stents in properly selected and closely monitored patients. Avoiding stents decreases costs, duration of treatment, and stent-related morbidity without unduly compromising safety.

Bladder-sparing surgery in locally advanced nonurological pelvic malignancy.

INTRODUCTION: The urinary bladder is commonly involved in pelvic malignancy. The incidence of apparent extension into adjacent organs in locally advanced colorectal malignancy is 5-12%. It is not known with other pelvic malignancy. No guidelines are available for its management. Often a dilemma exists between cystectomy and a bladder-sparing procedure. We studied the validity of bladder-sparing surgery (BSS) in locally advanced nonurological pelvic malignancy. METHODS: Hospital records of patients who underwent BSS along with other surgeries (abdomino-perineal resection, anterior resection, anterior exenteration, debulking surgery and total pelvic exenteration) from January 1992 to May 2003 were reviewed. RESULTS: BSS was done in 15 patients. 10 had locally advanced colorectal malignancy, 3 with soft tissue masses of the lateral pelvic wall, 1 had ovarian malignancy and the other had residual mass following radiotherapy and chemotherapy of cancer cervix. In those with locally advanced colorectal malignancy, symptoms suggestive of lower urinary tract involvement were present in 8 (80%). Urine examination and ultrasonography was not helpful in suggesting bladder involvement, unlike CT scan of abdomen and pelvis. Preoperative cystoscopy showed endoscopic evidence of bladder involvement in 7 (87.5%). Bladder was involved supratrigonally in 7. Partial cystectomy was done in 9 patients. The left ureter was involved in 6 patients, and they required ureteric reimplantation. Palliative transurethral resection was done in 1 patient with tumor infiltration at the bladder neck and prostate. 50% patients had bothersome lower urinary tract symptoms at 1 year. One patient died in the immediate postoperative period due to a nonurological cause. Overall 3-year survival rate was 40%. CONCLUSION: Unlike primary bladder cancers these lesions are not multifocal and hence en block conservative bladder-sparing surgery can be offered. Preoperative CT scan or MRI can predict lower urinary tract involvement and help in decision-making by both surgeon and patient. The ultimate decision for bladder sparing is based on intraoperative findings. Sparing the bladder might provide better quality of life by avoiding urinary diversion without altering survival.

Tubercular ureteric strictures.

OBJECTIVE: To review the presentation of tubercular ureteric strictures and assesses the role of balloon dilatation and open surgical repair in their management. METHODS: This was a retrospective review of tubercular ureteric strictures managed between January 1993 and December 2002. The records were analyzed to assess clinical presentation and compare the results of balloon dilatation with open surgical repair. Success was defined as adequate drainage on imaging, no worsening of renal function, no recurrence of symptoms and no requirement of intervention on further follow up. The long term success rates were compared using the t-test for proportion. RESULTS: Of 73 strictures, 88% had lower urinary tract symptoms. Genital abnormalities suggestive of tuberculosis was observed in 40% male patients. Urine examination yielded aseptic pyuria in 85%, positive AFB smears in 36% and positive AFB cultures in 32%. A small capacity bladder and non-functioning renal units were the only consistent findings on intravenous urogram. Nephrectomy was performed in 37% cases due to non salvageable kidneys at presentation. The success rate of stenting fell from 93% on immediate follow up to 59% on a follow-up of 12 months. At 90% success rates on a follow-up of 7 months open surgical repair was superior (p 0.03). Long term success following balloon dilatation in renal units with good function was 78% compared to 25% for poorly functioning units. (p= 0.01) CONCLUSION: Open surgical repair is superior to balloon dilatation in the management of tubercular ureteric strictures. Renal function may predict the success of balloon dilatation.

Isolated tuberculous epididymitis: a review of forty cases.

BACKGROUND: Tuberculous epididymitis is one of the causes of chronic epididymal lesions. It is difficult to diagnose in the absence of renal involvement. AIM: To profile isolated tuberculous epididymitis and to assess our approach in the evaluation of this group of patients. SETTING AND DESIGN: Retrospective study done at Christian Medical College, Vellore, South India. METHODS AND MATERIALS: Between 1992 and 2002, 156 fine needle aspiration cytology specimens and 108 epididymal biopsies were carried out in 187 men for evaluation of chronic epididymal nodules. Isolated epididymal tuberculosis was defined as "tuberculous infection affecting the epididymis without evidence of renal involvement as documented by the absence of acid fast bacilli in the urine sample and on imaging". The age, laterality, mode of presentation and method of histological diagnosis were studied with the objective of profiling isolated tuberculous epididymitis. RESULTS: Fifty-four of the 187 men (median age 32 years; interquartile range: 21-37 years) had tuberculous epididymitis. Fourteen were excluded from the analysis (10 had associated urinary tract tuberculosis and 4 were lost to follow-up). None of the 40 men with isolated tuberculous epididymitis had urinary symptoms. Bilateral involvement was seen in five (12.5%) cases. The salient presenting features included painful swelling (16 subjects, 40%), scrotal sinus (4, 20%) and acute epididymitis (2, 10%). Past history or concomitant presence of tuberculosis was noted in three subjects each. Anti TB treatment resulted in a complete response in 10 and partial response in 18. Five subjects underwent epididymectomy. Tuberculous epididymitis was found incidentally in 5 (10%) cases on high orchiectomy specimen done for suspected testicular tumour. CONCLUSIONS: Tuberculous epididymitis can be the sole presentation of genitourinary tuberculosis.

Pancratistatin: a natural anti-cancer compound that targets mitochondria specifically in cancer cells to induce apoptosis.

The major hurdle in the fight against cancer is the non-specific nature of current treatments. The search for specific drugs that are non-cytotoxic to normal cells and can effectively target cancer cells has lead some researchers to investigate the potential anti-cancer activity of natural compounds. Some natural compounds, such as Taxol, have been shown to possess some anti-cancer potential. Pancratistatin (PST) is a natural compound that was isolated from the spider lily Pancratium littorale and shown to exhibit antineoplastic activity. The specificity of PST to cancer cells and the mechanism of PST's action remain unknown. This study provides a detailed look at the effect of PST treatment on cancerous and normal cells. Our results indicate that PST induced apoptosis selectively in cancer cells and that the mitochondria may be the site of action of PST in cancer cells. A biochemical target available specifically in cancer cells may lead to the development of new and more effective cancer fighting agents.

Does failure to visualize the ureter distal to an impacted calculus constitute an impediment to successful lithotripsy?

BACKGROUND: A severe degree of ureteral obstruction is viewed as a predictor of poor outcome in shockwave lithotripsy (SWL). Impacted stones are often considered a contraindication to in-situ SWL. PATIENTS AND METHODS: Impaction in our study was defined as failure to visualize the ureter distal to the calculus with proximal hold-up of contrast for as long as 3 hours on an intravenous urogram (IVU). We evaluated 30 patients with impacted ureteral calculi, who were compared with a second unimpacted group matched for stone size and stone location. The calculi were reorganized into < or =10-mm and >10-mm groups. The results were compared in terms of clearance rates, number of shockwaves, number of sessions, and number of days between the start of SWL and clearance. RESULTS: Between January 1998 and December 2001, 30 impacted stones were treated with lithotripsy. Complete clearance rates in the impacted as well as the non-impacted group were 76.7%. There was no statistical difference in the number of shockwaves, sessions, or time to clearance. The results were poorer in lower-ureteral than upper-ureteral calculi, but this difference did not reach statistical significance. However, the differences between the < or =10-mm and >10-mm stones were statistically significant. CONCLUSION: Impaction on an IVU does not affect the results of lithotripsy.

Paediatric renal transplantation--a 15 year experience.

OBJECTIVE: To review the outcome of paediatric renal transplantation over a period of 15 years in a developing country. METHODS: This is a retrospective study of 63 children, less than 15 years of age, who underwent living-related renal transplantation in Christian Medical College and Hospital Vellore between 1984 and 1996. RESULTS: The records of 12 patients were not adequate for detailed analysis. Parents were the donors for these children in 84.3% of cases. The most common known cause of end-stage renal disease in these children was reflux nephropathy. Combinations of cyclosporine, azathioprine and prednisolone were used as immunosuppressive drugs. Complications occurred in 16 patients. During the follow-up period, eight patients died and two returned to receiving haemodialysis. Patient survival was 92% at the end of 1 year and 90% at the end of 3 years. Graft survival was 88% and 86% at 1 and 3 years, respectively. CONCLUSION: Our study validates the concept of renal transplantation as optimal therapy with adequate medical, social and functional rehabilitation for children with end-stage renal disease. Our study also indicates that vesicoureteric reflux appears to be underdiagnosed and should be actively pursued to prevent complications.