Development of New Donor-Specific and Human Leukocyte Antigen Antibodies After Transfusion in Adult Lung Transplantation.

OBJECTIVES: The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. DESIGN: A retrospective observational study. SETTING: At a single academic tertiary center. PARTICIPANTS: Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). CONCLUSIONS: Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation.

Case Report Of A Rare Incidentaloma Of The Adrenal Gland-Schwannoma.

The Schwannoma is a benign growth of the nerve sheath cells most commonly seen in the vestibulocochlear nerve. Its prevalence in the adrenal gland is 1-3%. Here we discuss a case that presented as an incidentaloma of the right adrenal gland in a young male patient who had vague abdominal symptoms and a normal hormonal profile. He underwent an excisional biopsy of the right adrenal gland due to the large size of the lesion (more than 4cm). The histopathology report helped to establish the diagnosis of Schwannoma. Incidentaloma is defined as a lesion of the adrenal gland encountered on any radiological investigation carried out for symptoms that are not associated with adrenal pathologies. After discovering such lesions, it is imperative to perform radiological and hormonal investigations in an organised manner to plan further management of such cases.

A clinical study and treatment results of adrenocortical carcinoma patients presented in Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore.

Adrenocortical carcinoma is a rare and aggressive malignancy with an incidence of 0.5-2 per million per year and its overall prognosis is very poor. This study was aimed to point out the factors associated with tumour recurrence and patient's survival after complete surgical resection of this aggressive malignancy. Patients admitted from January 2011 till December 2015 were retrospectively reviewed using case notes. In these five years 29 patients were admitted with adrenal tumour out of which 13 had adrenocortical carcinoma. On five year follow up, six (46.2%) patients developed recurrence. MEAN disease free survival was 31.0 ± 23.92 (2-63) months 53.8% while MEAN overall survival was 46.69 ± 22.81 (14-80) months 92.3%. Results concluded that hormonally active tumour on clinical presentation, positive surgical resection margins, positive nodal status and poorly differentiated tumour on histopathology are the factors associated with tumour recurrence and patient's survival.

Assessing the Efficacy and Long-Term Outcomes of Surgical Intervention Versus Radiotherapy: A Comprehensive Systematic Review and Meta-Analysis of Prostate Cancer Treatment Modalities.

There is controversy regarding the most effective primary treatment of choice for prostate cancer (PCa) in terms of patient outcomes, such as surgery or radiotherapy (RT). This study evaluated the comparative efficacy and long-term outcomes of radical prostatectomy (RP) and RT for PCa treatment. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies published from 2019 onwards. The inclusion criteria included randomized controlled trials (RCTs) and other observational studies comparing survival outcomes in patients treated with surgery and RT. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to provide an overview of the data. We selected 19 studies based on the inclusion criteria. Of the total 19 studies, 12 advocated RP as the preferred treatment to improve survival outcomes in patients with PCa. The results of our synthesis showed that prostate cancer-specific mortality (PCSM) was lower in patients treated with RT. The total effect size for the analysis was calculated as Z=1.19 (p-value=0.23). The heterogeneity in the studies was as follows: Tau2=0.09, Chi2=20.25, df=4, I2=80%. Moreover, overall survival (OS) was shown to be higher in patients who underwent prostatectomy. The combined effect for the analysis was found to be: HR=0.97 (0.93, 1.01). The total effect was calculated as Z=1.33 (p-value= 0.18). The heterogeneity was found to be Tau2=0.00, Chi2=1.33, df=2, and I2=0%. However, overall mortality (OM) was shown to be independent of the treatment modality. RT is the preferred strategy for PCa treatment, as it balances efficacy and long-term outcomes. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine the treatment guidelines.

Comparative Outcomes of Radical Cystectomy in Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

Muscle-invasive bladder cancer poses a significant clinical challenge that necessitates effective therapeutic interventions. Radical cystectomy is a primary treatment option, but a comprehensive understanding of its outcomes is crucial for informed clinical decision-making. This systematic review and meta-analysis aimed to investigate and summarize the outcomes associated with radical cystectomy as a primary treatment for muscle-invasive bladder cancer with a focus on survival rates, complications, and quality of life. A systematic search across databases-PubMed, Google Scholar, and others-covered studies from 2017 onwards. Included were studies reporting survival rates, complications, and quality of life post-radical cystectomy in muscle-invasive bladder cancer patients, including randomized controlled trials, cohort, and observational studies. Multidimensional analysis revealed promising findings regarding the efficacy of radical cystectomy in muscle-invasive bladder cancer. Survival outcomes, including overall survival and disease-specific mortality, have demonstrated significant improvements, particularly in recent randomized controlled trials and cohort studies. Complications associated with the surgical procedure, such as positive surgical margins and lymph node yields, were generally acceptable. Quality of life outcomes post-radical cystectomy exhibited positive trends, although variations were noted in the emotional and social domains. This review underscores radical cystectomy's role in enhancing overall survival and reducing disease-specific mortality in muscle-invasive bladder cancer. Despite reported complications, recent studies support its acceptable risk profile. Detailed examination of various factors contributes to a comprehensive understanding of the procedure. These findings emphasize the importance of individualized treatment approaches in the management of muscle-invasive bladder cancer, considering both oncological efficacy and perioperative outcomes. Radical cystectomy remains fundamental in urological oncology, with ongoing advancements refining its significance.

Outcomes of Uretero-ileal Anastomosis in Bladder Cancer Cystectomies: Bricker vs. Wallace 1.

Background The two commonly used methods for uretero-ileal anastomosis (UIA) during radical cystectomy for muscle-invasive bladder cancer (MIBC) are the Bricker and Wallace 1 techniques. Published data on the incidence of strictures at anastomotic sites is limited. This study compares both anastomotic techniques in terms of uretero-ileal stricture (UIS) rates and the factors that govern it in the patient group. Material and methods Records of all patients presenting with bladder cancer who underwent radical cystectomy at the department of uro-oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) Lahore, Pakistan, from January 1, 2009, to December 31, 2018, were reviewed retrospectively, and all adult patients aged >18 years out of them were selected for the study. Results With a total of 116 patients, the mean age was 54.37 ± 11.16 and a male majority (83.6%). Urinary diversion using ileal conduit was performed in 70 (60.3%) patients and the rest of them i.e. 46 (39.7%) had neobladder formation. Amongst them, uretero-ileal anastomosis was constructed via Bricker and Wallace 1 in 73 (62.9%) patients and 43 (37.1%) patients respectively. Pelvic radiotherapy was received by 13 (11.2%) patients. Anastomotic stricture developed in 19 (16.4%) cases. A relatively similar proportion of stricture rate was found in Bricker and Wallace 1 technique (10% vs 13%). Body mass index (BMI) was found to be significantly higher in patients who developed UIS. Incidence of stricture formation was more on the left than right side i.e. 12 (63.2%) vs five (26.3%) while two (10.5%) patients developed bilateral strictures. Conclusion No significant difference in stricture formation was noted between Bricker and Wallace 1 technique. High BMI and anastomotic leaks were the contributory factors for this complication during our experience.

Oncological Outcomes of Non-Urothelial Bladder Cancers in a Specialized Cancer Hospital of a Developing Country.

Background Non-urothelial bladder cancers (NUBCs) constitute only 5% of all bladder cancers. Because of the scarcity of data, no standardized treatment can be offered to these patients. Surgical treatment can be offered to patients with localized disease; however, generally, the prognosis is unfavorable. Methodology Patients with histology-proven NUBC presenting to the Department of Uro-oncology, Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan, from January 2002 to July 2017 were identified and assessed retrospectively. Results A total of 20 patients with a median presenting age of 52 years (range: 34-87 years) were identified. Clinically, T3 was the commonest stage of presentation, i.e., in 11 (55%), whereas 1 (7.1%) patient had metastatic disease. Four types of NUBCs were identified: adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and inflammatory myofibroblastic tumor. Most of the patients with adenocarcinoma were offered surgical treatment in the form of either partial (64.3%) or radical (28.6%) cystectomy. Two patients with small cell carcinoma and two of the three patients with SCC could only be offered palliative chemotherapy. During a median follow-up of 40 months, 14 (70%) patients developed disease progression or recurrence. All these patients succumbed to their disease during a median period of 37.5 months (range: 5-84 months). Furthermore, three- and five-year disease-free survival was 60% and 51%, respectively, and overall survival was 65% and 31%, respectively. Conclusions NUBC is a rare but aggressive disease that presents at an advanced stage in many cases. Treatment protocols are not uniform; therefore, further collaborative research is needed to improve survival outcomes.

Comparison of Outcomes Between Radical Radiotherapy and Radical Cystectomy in Muscle Invasive Bladder Cancer in a Cancer Specialized Unit of a Developing Country.

Introduction Radical cystectomy (RC) is the current standard of care for treating muscle-invasive bladder cancer (MIBC), however bladder preservation by offering radical radiotherapy (RT) is gaining interest for improving the quality of life while maintaining a reasonable oncological outcome. In this study, we have compared outcomes of the two treatment options. Materials and methods This is a 10-year retrospective cohort study that included all patients who were treated for histologically proven muscle-invasive bladder cancer in the department of uro-oncology at Shaukat Khanum Memorial Cancer Hospital and Research Centre from January 2005 to January 2015. Data was analysed using Statistical Product and Service Solutions (SPSS), version 21 (IBM Corp., Armonk, NY). The primary end point of our study was to calculate the three- and five-year disease-free survival (DFS) and overall survival (OS). Results A total of 230 patients were included in the study with male gender predominating (88%). The mean and standard deviation for age was 58.32+11.128. Radical cystectomy was performed in 119 patients while 111 received RT. Clinically, 34% had stage 2 disease, while 66 % had stage 3 cancer. The median follow-up duration was 41 months (range: 2-155). During follow-up 57.4% of patients showed no recurrence. Local recurrence was found in 9.6% patients and distant metastasis in 32.2%. The three-year DFS of RC was 63% and that of RT was 57% while the five-year DFS for RC and RT were 60% and 49%, respectively (p=0.196). The three-year OS of RC was 64% and that for RT was 58%. On further analysis the five-year OS of RC was 53% and that for RT was 50% (p=0.98). Upon stage-based comparisons, we found no statistically significant difference between the three- and five-year DFS and OS of stage 2 and stage 3 when treated with either modality. Conclusion Most studies favor RC and consider it as the gold standard treatment for muscle-invasive bladder tumor treatment. The current study reveals that bladder preservation approach by chemo radiotherapy is a viable treatment option, having comparable oncological outcomes with patients receiving radical cystectomy, and can be offered to patients having muscle-invasive urothelial bladder cancer.

Survival And Progression After Radical Nephrectomy In A Cohort Of Non-Metastatic Renal Cell Carcinoma Treated With Curative Intent.

BACKGROUND: Radical nephrectomy (RN) is a standard treatment of cure for non-metastatic renal cell carcinoma (NMRCC). Long-term outcome data are limited for Pakistani population. Our aim was to assess the long-term outcomes of RCC treated with curative intent with radical nephrectomy (RN) and to study the 5 & 10years survival outcomes in patients with NMRCC who underwent radical nephrectomy. METHODS: This is a retrospective review and analysis of the data between December 2006 and February 2017. We included all the adult patients (age ≥18 years) with NMRCC from both genders irrespective of their histologic subtypes who underwent radical nephrectomy (RN) with a curative intent. The data was analysed for overall survival and recurrence rates at 5- and 10-years using Kaplan-Meier survival analysis. Multivariate analysis was performed using Cox-regression to identify risk factors associated with poor overall outcome in terms of recurrence and mortality. RESULTS: Three hundred and forty-four patients with 195 (55.5%) males and 149 (44.2%) females with a mean age of 53.5±14.1 years were monitored for a mean follow-up of 31.1±26.77 months (range: 3-132 months). Overall there were 46 (13.4%) deaths. Forty-nine 14.2%) cases had disease recurrence with 33 (9.5%) deaths from disease progression. The 5-year progression-free survival was 37% (95% CI: 49.04-72.76) with the median time to recurrence of 33 months (95% CI: 27.6-38.4) and the median overall survival was 103.7 months (95% CI: 95.7-111.7). The 5-year overall survival was 76.1% (95% CI: 75.2-77) while 10-year survival was 70.8%. There was a significant median survival difference for cases with and without recurrence (log-rank χ2: 117.5, p<0.001), T stage, Fuhrman's grade, and early postoperative recurrence. CONCLUSIONS: Radical nephrectomy offers the best survival for nonmetastatic renal cell carcinoma patients with excellent postoperative survival and progression-free profile. Although renal cell cancer presents in younger age group but the long-term survival after radical nephrectomy in Pakistani population is similar to the rest of the world.

Outcomes of Nephron Sparing in a Specialist Cancer Hospital of a Developing Country.

Introduction Nephron-sparing surgery in the form of partial nephrectomy (PN) is currently considered the standard treatment for relatively small localized renal cell tumors. Objectives This study aimed to determine outcomes of PN regarding complications, recurrence, and survival rates at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Methods We assessed the data of patients older than 18 years undergoing PN from January 2010 to June 2017 who met our inclusion criteria. Data were analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY). Results A total of 35 patients were studied, with a male to female ratio of 2.5:1 with median age of 50 years. The median hospital stay was four days (range: 3-7), and the median RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior location relative to polar lines) Score was five (range: 4-10). The most common pathological tumor stage was T1 (94%), and the median size was 3.5 cm. On histopathology, clear-cell carcinoma was the most common tumor (incidence, 71%). The median Fuhrman's grade was two. On final histopathology, four patients had positive margins. Among them, two patients showed a progressive deterioration in renal functions and were found to have residual disease six months later. Only one patient developed metastasis in the lung. Wound infection was observed in one patient while another had wound dehiscence. Urine leakage was noted in two patients. The median follow-up duration was 18 months (range: 3-84). Mean cancer-free survival was 78.6 months, and overall survival was 79.2 months. The projected three-year and five-year disease-free and overall survival was 96% and 94%, respectively. Conclusion PN is a viable option with excellent outcomes regarding the complication profile, recurrence-free, and overall survival in patients with relatively small localized renal tumors.

Diethylstilbestrol in the Treatment of Castration-resistant Prostate Cancer: A Lower-middle-income Country Experience.

INTRODUCTION:  Prostate cancer is the second most common cancer and the fifth leading cause of death worldwide. Its metastatic stage is associated with considerable morbidity and may lead to death. In Pakistan, given the high levels of economic constraint, patients with castration-resistant metastatic prostate cancer can be treated with cost-effective medications like diethylstilbestrol (DES). OBJECTIVES:  The goal of this study was to assess the efficacy and adverse effects of DES when used in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS:  From January 2011 to December 2016, all medical records of patients with a diagnosis of prostate cancer resistant to the effects of castration presenting at Shaukat Khanum Cancer Hospital and Research Centre, Lahore, were reviewed. All patients were treated with DES (2.5 mg) initially, but the dose was increased for some patients to 5 mg in combination with aspirin (75 mg). The patients were followed clinically with prostate-specific antigen (PSA) value assessment. The PSA response to treatment, time to disease progression, and adverse events were recorded and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY). RESULTS: A total of 91 patients were included in the study, and the mean patient age was 66 ± 8 years. The median baseline PSA was 150 ng/mL (range: 56-626 ng/mL), and the median Gleason's score was eight. A total of 90.1% of patients had metastatic disease at the time of diagnosis. Hormonal ablation was provided with bilateral orchiectomy for 71 patients (78.0%), and luteinizing hormone-releasing hormone (LHRH) analog was provided for 20 patients (22.0%). With this treatment, the median time to PSA progression was 597 days. After DES treatment was started, 78 patients (87.7%) showed a PSA response, and median time to progression was 212 days. In 24 patients (26.4%), the PSA response was maintained for more than a year. The PSA response was quantified as a good response (i.e., ≥50% PSA drop) or as a partial response (i.e., <50% PSA drop). The good PSA response was observed in 56 patients (61.5%) with a median time to progression of 273 days, and 22 patients (24.2%) had a partial response maintained for 109 days. Thirteen patients (14.3%) did not respond to DES treatment. The median percent change in PSA was -55.52% (range: -99.9 to +422). Thromboembolic complication was observed in eight patients (8.7%) patients while two patients suffered from liver toxicity. CONCLUSION:  DES is an effective, economical, and relatively safe drug in patients with CRPC.