Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Arsenic in the Food Chain in Pakistan: Assessing Risks to Human Health and Ensuring Food Security Through Comprehensive Contamination Mitigation Strategies.

Arsenic is a natural element found in the earth's crust and is extensively present in various environmental components. Anthropogenic activities and a few natural events have generated contaminants that have led to massive environmental pollution, one form of which is arsenic contamination. Arsenic enters the human food chain via contaminated crops, water, seafood, and dairy products. In Pakistan, the increasing concentration of arsenic in the water is causing major health problems. Due to the serious health risks posed by arsenic, it is crucial to design and implement strategies for reducing and preventing the bioaccumulation of arsenic and its entry into the human food chain. There is a need for an institutional framework for arsenic mitigation, accountability, and systemic checks and balances. Targeted short- and long-term policies are required for effective and sustainable management.

Use of Novel Open-Source Deep Learning Platform for Quantification of Ki-67 in Neuroendocrine Tumors - Analytical Validation.

Background: Neuroendocrine tumors (NETs) represent a diverse group of neoplasms that arise from neuroendocrine cells, with Ki-67 immunostaining serving as a crucial biomarker for assessing tumor proliferation and prognosis. Accurate and reliable quantification of Ki-67 labeling index is essential for effective clinical management. Methods: We aimed to evaluate the performance of open-source/open-access deep learning cloud-native platform, DeepLIIF (https://deepliif.org), for the quantification of Ki-67 expression in gastrointestinal neuroendocrine tumors and compare it with the manual quantification method. Results: Our results demonstrate that the DeepLIIF quantification of Ki-67 in NETs achieves a high degree of accuracy with an intraclass correlation coefficient (ICC) = 0.885 with 95% CI (0.848-0.916) which indicates good reliability when compared to manual assessments by experienced pathologists. DeepLIIF exhibits excellent intra- and inter-observer agreement and ensures consistency in Ki-67 scoring. Additionally, DeepLIIF significantly reduces analysis time, making it a valuable tool for high-throughput clinical settings. Conclusion: This study showcases the potential of open-source/open-access user-friendly deep learning platforms, such as DeepLIIF, for the quantification of Ki-67 in neuroendocrine tumors. The analytical validation presented here establishes the reliability and robustness of this innovative method, paving the way for its integration into routine clinical practice. Accurate and efficient Ki-67 assessment is paramount for risk stratification and treatment decisions in NETs and AI offers a promising solution for enhancing diagnostic accuracy and patient care in the field of neuroendocrine oncology.

Cerebellar Liponeurocytoma: Publication Trends, Scientometrics Analysis, and Critical Review.

BACKGROUND: The literature on cerebellar liponeurocytoma (CL) has never been systematically assessed using bibliometric analytic methodologies. We quantitatively analyzed the major trends and scientific output regarding CL, highlighting potential avenues for research. METHODS: Elsevier's Scopus database was used to collect all published studies relevant to cerebellar liponeurocytoma from 1978 to 2021. The specific bibliometric parameters were extracted and analyzed with R v4.1.2. RESULTS: Our search yielded 108 documents published in 67 sources from 1978 to 2021. The annual growth rate of publications regarding CL has been 7.47% per year since 1978. Journals with the most publications on CL include Clinical Neuropathology and Neurology India (n = 5), followed by Acta Neuropathologica and Journal of Neuro-oncology (n = 4). A total of 529 authors have published on CL and they have been cited 598 times. The 10 most influential authors in the field were determined using their total number of citations and the local H-index. Kleihues P has the highest number of citations (n = 177) with a local H index of 3, followed by Chimelli L with 167 citations and a local H index of 4. Davis DG has 149 citations and a local H index of 3. China had the most single country publications followed by India, Italy, and the USA. France and Austria have the most multiple country publications followed by China, Tunisia, Brazil, United Kingdom, Egypt, and Israel. CONCLUSIONS: Our study is the first bibliometric analysis evaluating the present literature and publication trends in CL. Generally, the current literature has a few studies regarding CL relative to other neuro-oncological pathologies. This can be due to the low incidence of the disease and highlights a need for high volume database studies that can offer high quality evidence on the subject.

Primary squamous cell carcinoma of liver. First case report from Pakistan and South Asia.

INTRODUCTION AND IMPORTANCE: Primary squamous cell carcinoma (PSCC) of liver is quite rare and very few cases reported in literature. It has high metastatic rate with poor prognosis. The pathogenesis is unclear, but is generally considered to be correlated with the long-term inflammation or metaplasia of biliary epithelial cells or congenital cyst of the liver. We report here a case of PSCC of liver which mimicked a complex hydatid cyst. CASE PRESENTATION: A 25 years male admitted with right hypochondrium pain associated with fever and yellowish discoloration of eyes for 20 days. He was jaundiced with epigastric tenderness and deranged liver function tests. When thoroughly investigated with ultrasound, CT abdomen and MRI liver, he was found to have a large cystic lesion in right lobe of the liver. He underwent right hepatectomy, peri-cystectomy of the cyst and T-tube placement in common bile duct. Histopathology of the resected sample showed primary squamous cell carcinoma of liver. Patient was discharged after 7 days and died after 6 months due to acute liver failure. CLINICAL DISCUSSION: Because of a very low incidence of hepatic SCC, there is not a single definite therapeutic regime and various different methods of management include surgical resection, generalized chemotherapy, radiotherapy, Hepatic Arterial ChemoEmbolization (HACE) and the combinations of these therapies. CONCLUSION: PSCC is a rare condition of the liver and is associated with other benign liver conditions such as non-parasitic and epidermoid cysts. Histopathology with radiological investigations are needed to diagnose and treat this aggressive tumor before it metastasizes.

Hegemonic masculinity: representation of women surgeons in leadership positions in Pakistan.

PURPOSE: Surgery is predominantly a masculine profession worldwide and has largely excluded women in leadership positions. This paper aims to examine the representation of women surgeons in leadership positions in Pakistan. DESIGN/METHODOLOGY/APPROACH: Data were drawn from larger qualitative research examining the experiences of women surgeons in Pakistani hospitals. The data comprises in-depth interviews with ten doctors working in the Rawalpindi and Islamabad cities. The participants were selected by using the purposive sampling method and data were analyzed using thematic analysis. FINDINGS: This study included participants from diverse surgical specialties from different stages of their career with two having leadership experience. Based on participants' perspectives several factors are responsible for this exclusion of women in leadership positions. The most prominent among these were long working hours for surgical leaders, greater responsibilities assigned to leadership positions, gender stereotypes and work-family conflict. Due to masculine hegemony, women were considered less capable and they were expected to have masculine traits to work as successful leaders. Interestingly, some participants had internalized such stereotypes and showed a lack of interest and lack of capabilities for surgical leadership as evident from their narratives. RESEARCH LIMITATIONS/IMPLICATIONS: The findings of this paper are drawn from the perspectives of ten women surgeons working in Islamabad and Rawalpindi cities of Pakistan who were selected using a convenient sampling method. Hence, the results cannot be generalized to the larger population of women surgeons working in other cities of the country. Nevertheless, this study is unique in the sense that it provides useful insight into the experiences of the women surgeons and their perspectives on surgical leadership in Pakistani hospitals. Academically, it contributes to the global debates on surgical leadership by providing empirical evidence from Pakistan. ORIGINALITY/VALUE: This paper contributes to the larger debates on the under-representation of women in leadership positions in surgery by unveiling the experiences of female surgeons from Pakistan. It calls for the need for structural changes in health management and policy to accommodate women surgeons. Organizational efforts could minimize some hurdles and encourage more women to take on more formal leadership roles. The authors also call for an increasing number of women in surgery to pave the way for creating new leadership opportunities.

Brunner's gland hyperplasia: A rare cause of gastrointestinal bleeding.

Brunner's gland hyperplasia (BGH) is an unusual entity that presents with large duodenal polyp or mass and rarely causes gastrointestinal bleeding. It is usually asymptomatic and often an incidental finding during the esophagoduodenoscopy (EGD). However, most of the cases are benign. We encounter a 40 years old man who presented in Emergency Room with melena. EGD revealed solitary, large duodenal polyp in second part of duodenum and later histopathological findings were consistent with BGH.

Impact of Graphic Warning Labels on Cigarette Packs in Changing Smokers' Views and Habits: An Opinion Survey.

BACKGROUND: Smoking has become a major issue worldwide. With the advancement in technology, more vulnerable populations, such as teenagers, are also being harmed. One deterrent is the presence of graphic labels on cigarette packs. With this rationale in mind, the objective of our study is to assess the impact of these warning labels on the habits and opinions of smokers. METHODS: A cross-sectional study was conducted by distributing a validated paper-based questionnaire. The sample size was calculated to be 200 using statistical software. The study targeted students of Islamabad, Pakistan, who were studying in twelfth grade and were smokers. The sampling method used was 'snowball sampling'. FINDINGS: 128 (64%) males and 72 (36%) females participated in the study. The mean age of the participants was 17.59 ± 0.51 years. 40 participants reported choosing local brands for cigarettes due to cigarette 'freshness', regardless of presence or absence of a graphic label, which was a new concept. 94% of participants believed that presence of a visual label helped with understanding the harm and 78% believed that the side effects were accurately portrayed. Participants who were more than 17 years of age believed that the graphic label provided a clear description of the consequences of smoking. Similar results were seen in the female participants of the study. CONCLUSION: There is a general consensus on graphic labels altering the opinions of smokers. The presence of these labels is, however, targeting only a specific type of audience and hence, should be expanded for a larger audience.

ERG oncoprotein expression in prostatic acinar adenocarcinoma; clinicopathologic significance.

OBJECTIVES: T/E fusion results in constitutive expression of ERG oncoprotein resulting in enhanced proliferation and invasive potential of prostatic cancer cells. In the present study we aimed to evaluate the ERG overexpression in 78 cases prostate acinar adenocarcinoma and its association with other prognostic parameters. RESULTS: ERG protein expression was noted in 39.7% (31 cases), out of which 3 cases (3.8%) showed low ERG expression, 10 cases (12.8%) showed intermediate expression and 18 cases (23.1%) revealed high ERG expression. Significant association of ERG expression was noted with gleason score (p = 0.009), WHO grade group (p = 0.008) and perineural invasion (p = 0.043). We found a significant proportion of our patients of prostatic acinar adenocarcinoma to over-express ERG protein which can help in devising therapeutic protocols. Significant association of ERG protein expression with gleason score and perineural invasion signifies its prognostic significance in prostatic carcinoma. Moreover, we also suggest that molecular studies should be performed in patients with prostatic carcinoma to look for T/E fusion gene and its correlation with ERG protein expression.

Staged dental extraction and three interim prostheses for implants based rehabilitation in a periodontally compromised subject.

Studies have shown that the presence of advanced periodontal disease lowers the success of dental implants. The recommended approach for such cases is the delayed placement and delayed loading of implants. The present paper reports a case of a subject who presented with severe periodontally compromised dentition. Placement and early loading of 12 implants was done using a staged approach. Three different sets of fixed-type dental prostheses were employed in the interim period. The final prostheses were cement retained metallo-ceramic fixed bridge. Use of staged extraction and using three sets of interim prostheses helped the patient to maintain his aesthetics and function during the entire treatment period. This approach can be a predictable management option in cases of advanced periodontitis. The key is proper planning and execution of the implant surgery and prosthetics.

Clinicopathologic features of colorectal carcinoma: features predicting higher T-stage and nodal metastasis.

OBJECTIVES: A rising frequency of colorectal carcinoma has been noted in recent years in Pakistan. In the present study, we aimed to evaluate clinicopathologic features of colorectal carcinoma in our population so that protocols could be developed to stratify patients that may require further biomarker/molecular testing. Furthermore, histological features which predict higher T and N stage were also evaluated. RESULTS: Median age at diagnosis was 54.5 (19-85) years. 79% cases were of conventional adenocarcinoma while 13% cases were of mucinous carcinoma. Most of the cases were at T3 stage (81%), while 27 and 68% of cases revealed lymphovascular invasion and nodal metastasis respectively. Mucinous and signet ring tumors were associated with a higher N stage. Pre-existing polyp was associated with lower T and N stage. We found a high proportion of our cases to present at advanced T-stage. Tumor grade and lymphovascular invasion were found to be associated with higher N-stage while tumor infiltrating lymphocytes was associated with lower T and N-stage. Moreover, a high frequency of mucinous differentiation may be linked to microsatellite instability in our cases of colorectal carcinoma; therefore, we suggest that microsatellite instability testing in colorectal carcinoma should be evaluated in our setup.

Mismatch repair deficiency screening in colorectal carcinoma by a four-antibody immunohistochemical panel in Pakistani population and its correlation with histopathological parameters.

BACKGROUND: Microsatellite instability (MSI) operates as the second major pathway in the colorectal carcinogenesis. Although genetic testing remains the gold standard for the detection of MSI, the College of American Pathologists (CAP) recommends an initial immunohistochemical workup with a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) to screen for a defective mismatch repair system. An increased trend towards young age colorectal carcinoma (CRC) has been noticed in our population over recent years; however, neither screening for MSI by immunohistochemistry (IHC)/genetic testing was done nor were its morphological features studied. We aimed to determine the frequency of mismatch repair deficiency (dMMR) by loss of IHC expression of the aforementioned enzymes in CRC patients and its correlatation with clinicopathologic parameters. METHODS: This was a retrospective study conducted at Liaquat National Hospital, Karachi, between 2012 and 2015. A total of 100 cases of CRC were included in the study that underwent surgical resection. IHC stains using antibodies MLH1, PMS2, MSH2, and MSH6 were performed by DAKO EnVision method on representative tissue blocks. The results were interpreted by senior histopathologists and correlated with clinico-pathological parameters. RESULTS: A total of 100 cases of CRC were studied that included 51 males and 49 females. Thirty-four percent (n = 34) of the patients showed loss of IHC staining for MMR markers. Combined loss of expression for MLH1/PMS2 were observed in 16% (n = 16) of the cases. Loss of MSH2/MSH6 were seen in 6% (n = 6) of the cases. Loss of expression for all markers were noted in 7% (n = 7) of the cases. There were 5% (n = 5) of the cases that showed isolated loss of MLH1 only. The tumors with dMMR status were significantly associated with right-sided location (p = 0.013), exhibited intra-tumoral lymphocytosis (p = 0.007), and lymphovascular invasion (p = 0.043). No significant association was seen with gender, age, tumor stage, grade, or other morphological features. CONCLUSION: The frequency of mismatch repair deficiency in CRC patients was found to be 34% in Pakistani population which warrants further genetic testing to exclude Lynch syndrome. Moreover, right-sided location and intra-tumoral lymphocyte count may be used to identify patients who may need further workup.

A single center's experience with pacemaker implantation after the Cox maze procedure for atrial fibrillation.

OBJECTIVE: The Cox maze procedure (CM) is safe and effective for all atrial fibrillation (AF) types. A recent randomized trial found alarming rates of pacemaker implantation (PMI) during hospitalization after CM. The purpose of this study was to assess the rate of PMI and its impact on outcomes after CM. METHODS: Incidence of PMI was captured for all CM patients (2005-2015; N = 739). Data were collected prospectively. Multivariable logistic regression was conducted to determine risk factors for PMI. Propensity score matching was conducted between concomitant CM patients and patients without surgical ablation since 2011. RESULTS: Fifty-two patients (7.0%) had in-hospital PMI after CM. Most common primary indication for PMI was sick sinus syndrome (67%), followed by complete heart block (23%) and sinus bradycardia (10%). The only risk factor for in-hospital PMI was type of procedure (P = .020). Patients with multiple valve procedures were at greatest risk (P = .004-.035). STS-defined perioperative outcomes were similar for patients with and without in-hospital PMI. Sinus rhythm off antiarrhythmic drugs were similar by PMI. After propensity score matching (n = 180 per group), in-hospital PMI was similar in CM patients and those without surgical ablation (5% vs 4%, P = .609). CONCLUSIONS: This study demonstrated lower incidence of PMI after CM procedures than recently reported. When indicated, PMI was not associated with increased short- or long-term morbidity or inferior freedom from atrial arrhythmia. Efforts to increase surgeon training with the CM procedure and postoperative management awareness are warranted to improve rhythm outcome and minimize adverse events and PMI.

A 6-year Evaluation of 223 Tapered Dental Implants and associated prosthesis in 92 patients at a University Hospital.

The aim of the retrospective study was to assess the clinical and radiographic outcome of the dental implant surgery and prosthetics. It was conducted at the Aga Khan University Hospital, Karachi, and comprised of medical charts and radiographic records of patients visiting between 2010 and 2015. Variables such as implant dimensions, final prosthesis, method of retention, loading protocol and patient factors were analysed. A total of 223 implants (143(64.1%) in maxilla and 80(35.9%) in mandible) were placed in 92 subjects (50(54.3%) males and 42(45.7%) females). All implants were Zimmer tapered screw-vent. Length of 108(48.4%) implants was 11.5mm and diameter of 84(37.7%) implants was 4.7mm. Besides, 6(2.7%) implants failed to osseointegrate, whereas 1(0.4%) implant failed at 12 months of loading. Among the 216(96.9%) successful implants, 140(64.8%) served as bridge abutments, 72(33.3%) were single crown abutments and 4(1.9%) were overdenture abutments. Also, 37(17.1%) implants were immediately loaded. The six-year survival rate of implants was 96.9%.

Role of peritoneal washing cytology in ovarian malignancies: correlation with histopathological parameters.

BACKGROUND: Peritoneal dissemination of ovarian tumors is a major prognostic parameter in ovarian malignancies. Analysis of peritoneal washing cytology serves as a useful predictor of ovarian surface involvement and peritoneal metastasis even in the absence of clinical omental spread. The aim of the current study is to correlate peritoneal cytology with various histologic features of ovarian cancers in our setup. METHODS: A total of 60 cases of ovarian tumors were included in the study that underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and omental and lymph node sampling during 2009 till 2014 at the Liaquat National Hospital, Karachi. Any free abdominal fluid was aspirated at the time of surgery. In the absence of free fluid, peritoneal washing was done with 50-100 ml of normal saline. Four cytospin preparations were done along with a cell block preparation. Correlation of peritoneal cytology with various histologic parameters was performed. RESULTS: Out of the 60 cases of ovarian tumors involved in the study, 56 were surface epithelial tumors, 2 germ cell tumors, and 2 metastatic carcinomas. The mean tumor size was 9.6 cm. Capsular invasion was seen in 61 % of the cases, and omental metastasis in 51 % of the cases. Serous carcinoma was found to have a significantly higher frequency of positive peritoneal cytology (76.9 %) compared to endometrioid and mucinous carcinomas (44 and 25 %, respectively). A significant positive correlation was seen between positive peritoneal cytology and capsular invasion and omental metastasis with a p value of <0.001. CONCLUSIONS: Positive peritoneal washing cytology has been implemented in ovarian cancer guidelines because of its prognostic significance in ovarian tumors. In addition to being an indicator of peritoneal metastasis, positive cytology also correlates with capsular invasion and histologic type in ovarian tumors. Therefore, it should always be used as an adjunctive tool in the surgical management of ovarian tumors.

Clinicopathologic patterns of adult renal tumors in Pakistan.

BACKGROUND: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. MATERIALS AND METHODS: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. RESULTS: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. CONCLUSIONS: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.

Effects of socio-economic and demographic factors in delayed reporting and late-stage presentation among patients with breast cancer in a major cancer hospital in South India.

OBJECTIVE: We analyzed the distribution of socio-economic and demographic (SEDs) factors among breast cancer patients and assessed their impact on the stage at diagnosis of the disease and symptom duration. METHODS: Data for the year 2006 was collected from the Hospital Based Cancer Registry, Regional Cancer Centre (RCC), Trivandrum, Kerala, India. Patients (n=522) were included if they were from native Kerala state or adjoining Tamil Nadu. SEDS factors included age, residing district, religion, marital status, income, education and occupation. Other study variables were menopausal status, parity, listed symptoms with duration and stage at diagnosis. Association between SEDs factors by stage at diagnosis and duration of symptoms was tested using chi-square statistics, with odds ratios (OR) estimated through logistic regression modeling. RESULTS: Forty-five percent were reported at early stages and 53% at late stages. Elevated risks for late stage reporting among breast cancer patients were observed for women who were unmarried (OR=3.31; 95%CI: 1.10-9.96), widowed/divorced (OR=1.46; 95%CI: 0.89-2.37), with lower education (OR=2.72; 95%CI: 1.06-7.03 for illiterate women and OR=2.32; 95%CI: 1.05-5.13 for women with primary school education and OR=2.07; 95%CI: 1.02-4.21 for women with middle school education) and post-menopausal women (OR=1.45; 95%CI: 0.97-2.19). CONCLUSIONS: This analysis helped to identify the target population group for receiving health education for early detection of breast cancer.