Browsing by Author "Ullah, Asad"
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Item Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances(MDPI, 2023-06-27) Khan, Jaffar; Ullah, Asad; Goodbee, Mya; Lee, Kue Tylor; Yasinzai, Abdul Qahar Khan; Lewis, James S., Jr.; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineBackground: Acinic cell carcinoma (AciCC) comprises 6-7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC. Methods: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival. Results: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2-4 cm in 47%, and >4 cm in 11%. Low-grade tumors had 5-year survival > 90%, whereas high-grade tumors had survival < 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1-91.9), and disease-specific survival was 94.6% (95%CI 93.3-95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age > 50 (HR = 3.5) and tumor size > 4 cm (HR = 2.5). Conclusions: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.Item Clinicopathological and Treatment Patterns of Combined Small-Cell Lung Carcinoma with Future Insight to Treatment: A Population-Based Study(MDPI, 2023-01-28) Ullah, Asad; Saeed, Omer; Karki, Nabin Raj; Goodbee, Mya; Yasinzai, Abdul Qahar Khan; Waheed, Abdul; Heneidi, Saleh; Thomas, Anish; Karim, Nagla Abdel; Johnson, Joyce; Del Rivero, Jaydira; Khan, Jaffar; Pathology and Laboratory Medicine, School of MedicineBackground: Primary lung cancer is the most common cause of cancer-related mortality in the United States (US). Approximately 90% of lung cancers are associated with smoking and the use of other tobacco products. Based on histology, lung cancers are divided into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs). Most SCLCs are of the pure subtype, while the rare combined SCLCs contain elements of both small-cell and non-small-cell morphologies. This study sought to evaluate the demographics, clinical factors, molecular abnormalities, treatment approaches, and survival outcomes with combined SCLC and NSCLCs. Materials and methods: Data on 2126 combined SCLC patients was extracted from the Surveillance Epidemiology and End Result (SEER) database from 2000 to 2018. Data extracted for analyses included age, sex, race, tumor size, tumor location, metastasis status, stage at diagnosis, treatment received, and treatment outcomes. Multivariate analysis was performed using Statistical Product and Service Solutions (SPSS) software. Results: The patients had a median age of 68 years; 43.9% of the patients were female and 56.1% were male; 84.5% were White and 11.7% were African Americans. The majority of patients had a poorly differentiated disease at 29.6%; 17% were undifferentiated, 3.2% were moderately differentiated, and 0.8% were well differentiated. Chemotherapy was the most common treatment modality (45.3%); 17% underwent surgery only, 10.3% underwent surgery followed by adjuvant chemotherapy, and 10% underwent radiation after surgery. Five-year cancer-specific survival was 15.2% with surgery alone, and combined surgery and chemotherapy provided the highest percentages (38.3% and 34.7%, respectively). Females had significantly higher 1- and 5-year cancer-specific survival rates compared to males (59.3% and 29.9% vs. 48.0% and 23.7, respectively; p < 0.001). Well-differentiated tumors had significantly higher survival compared to other gradings (p < 0.001). Survival decreased as tumor staging moved distally from localized to regional to distant (p < 0.001). Metastasis to bone, liver, brain, and lung significantly decreased survival in comparison to patients who did not have any metastasis (p < 0.001). Females had significantly shorter survival compared to their counterparts when metastasis was to the bone, brain, or liver (p < 0.001). Multivariate analysis identified male sex (Hazard Ratio (HR) = 1.2), undifferentiated grade (HR = 1.9), regional extent of disease (HR = 1.7), distant extent of disease (HR = 3.7), and metastasis to liver (HR = 3.5) as variables associated with worse survival. Conclusion: Combined SCLC is overall very rare. However, the frequency of presentation with combined SCLC is on the rise, in part due to improvements in diagnostic techniques. Despite advances in therapies, treating combined SCLC is challenging, and novel therapies are not utilized, owing to low rates of targetable mutations. Combined SCLC has higher survival rates if well differentiated.Item Colorectal Cancer Screening Challenges in the Recent Afghan Refugee Population: A Comprehensive Review Article(Cureus, 2022-02-20) Waheed, Abdul; McCloskey, Audrey; Kennedy, Frank; Seraj, Siamak M.; Khan, Jaffar; Nama, Noor; Johnson, Omari; Lo, Peter; Magee, Harres; Akbar, Wazir; Ullah, Asad; Cason, Frederick D.; Pathology and Laboratory Medicine, School of MedicineColorectal cancer (CRC) is more prevalent in south-central Asian countries, particularly the Afghan population. Screening for CRC in the Afghan population has always been challenging, primarily due to the tribal and social cultures, lack of facilities, and lack of education. The United States (US) will soon face a significantly massive influx of Afghan refugees. It becomes imperative to initiate and implement effective measures regarding CRC screening in these refugee populations. The current review article aims to identify the most likely challenges faced for CRC screening in this Afghan refugee population in the US and address the possible measures to overcome these challenges.Item Comparative Survival Benefits of Surgery and Adjuvant Chemotherapy in Neuroendocrine Carcinoma of the Gallbladder: A Population-Based Study with Insight into Future Personalized Therapeutic Approach(MDPI, 2023-06-18) Khan, Jaffar; Ullah, Asad; Yasinzai, Abdul Qahar Khan; Waheed, Abdul; Ballur, Kalyani; Dickerson, Thomas E.; Ullah, Kaleem; Mejias, Christopher D.; Saeed, Omer; Pathology and Laboratory Medicine, School of MedicineBackground: Neuroendocrine carcinomas of the gallbladder (NECs-GB) are rare tumors, accounting for <0.2% of all neuroendocrine carcinomas of the gastrointestinal tract. They originate from the neuroendocrine cells of the gallbladder epithelium with associated intestinal or gastric metaplasia. The current study is the largest study from the SEER database on NECs-GB that aims to elucidate the demographic, clinical, and pathologic factors influencing the prognosis and comparative survival analysis of different treatment modalities. Methods: The data from 176 patients with NECs-GB was abstracted from the Surveillance Epidemiology and End Result (SEER) database (2000–2018). Multivariate analysis, non-parametric survival analysis, and a chi-square test were used to analyze the data. Results: NECs-GB had a higher incidence amongst females (72.7%) and Caucasians (72.7%). Most patients had surgery only (N = 52, 29.5%), (N = 40) 22.7% had chemotherapy only, and (N = 23) 13.1% had chemotherapy with surgery. Only (N = 17) 9.7% had trimodaltiy (surgery, chemotherapy, and radiation therapy), and for (N = 41) 23.3% the status of chemotherapy was unknown, and these cases had neither radiation nor surgery. Conclusion: NECs-GB more frequently affects Caucasian females after the 6th decade of life. The combination of surgery, radiation, and adjuvant chemotherapy was associated with better long-term (5 years) outcomes, while surgery alone was associated with better short-term (<2 years) outcome survival.Item Current Understanding of “Mixed Corticomedullary Adrenal Tumor” and an Insight into Genomic Profiling(MDPI, 2022-11-11) Ullah, Asad; Mohamed, Farah Ayman Elsaid; Khan, Jaffar; Tracy, Katharine; Khan, Muhabat; Mohsen, Samiha; Yasinzai, Abdul Qahar Khan; Badini, Kaleemullah; Sobash, Philip T.; Heneidi, Saleh; Karim, Nagla Abdel; Pathology and Laboratory Medicine, School of MedicineBackground: Malignant mixed corticomedullary adrenal tumors (MCMTs) are extremely rare, with limited cases reported in the literature. The pathophysiology of malignant MCMTs is not well understood; the most prevailing theories are that it is a composite tumor of embryologically derived mesodermal (adrenal cortex) and neural crest (medulla) origin, perpetuating as two distinct cell lines forming a singular mass. Clinical features and laboratory diagnosis are associated with hypersecretions of the adrenal cortex and medulla. Surgical resection is curative in an isolated tumor. We reviewed and compared cases in the literature highlighting the pathogenesis and genetics of benign and malignant MCMT. Methods: Comprehensive literature analysis was conducted on PubMed and all the cases of mixed corticomedullary adrenal tumor published in English were included. Results: Most patients were female (73.1%) with a median age of 49 in women and 50 in men. Surgery was performed in all patients, and in four patients with malignant disease, chemotherapy was used as well. Clinically, most patients presented with hypertension (69%) followed by Cushing syndrome (42%) and diabetes (19%). Tumors often produced cortisol (74%), catecholamines (50%), and adrenocorticotrophic hormone (ACTH) (38%), with lower incidence of aldosterone- (7%) or dopamine (4%)-producing tumors. Immunohistochemical staining of 96% of cases showed Chromogranin-A (73%) and Synaptophysin (62%), followed by Inhibin-α (50%), Melan-A (31%), and S-100 (23%). Of the reported four cases with malignant disease, three showed a Ki-67 index of 40-50% with one showing less than 5%. Conclusion: Mixed corticomedullary adrenal tumors rarely present as a malignant disease requiring chemotherapy. Most MCMTs confer a good prognosis and respond well to surgical resection, though their pathogenesis is largely up to speculation because of limited data. Current theories regarding MCMT pathogenesis should be investigated further with genetic testing. Future research on MCMT may provide ways to guide physician diagnosis and subsequent treatment for refractory cases.Item Demographics and Clinicopathologic Profile of Pulmonary Sarcomatoid Carcinoma with Survival Analysis and Genomic Landscape(MDPI, 2023-04-26) Ullah, Asad; Ahmed, Asim; Yasinzai, Abdul Qahar Khan; Lee, Kue Tylor; Khan, Israr; Asif, Bina; Khan, Imran; Tareen, Bisma; Kakar, Kaleemullah; Andam, Gul; Heneidi, Saleh; Khan, Jaffar; Khan, Hina; Karki, Nabin R.; Del Rivero, Jaydira; Karim, Nagla Abdel; Pathology and Laboratory Medicine, School of MedicineBackground: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4-16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3-21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7-22.2); surgery, 41.7% (95% CI = 38.9-44.6); radiation, 19.1% (95% CI = 15.1-23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6-32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes.Item Frequency of Celiac Disease in Patients With Chronic Diarrhea(Cureus, 2021-12-17) Panezai, Muhammad S.; Ullah, Asad; Ballur, Kalyani; Gilstrap, Lauren; Khan, Jaffar; Tareen, Bisma; Kakar, Mirwais; Khan, Javeria; Rasheed, Amna; Waheed, Abdul; Ghleilib, Intisar; White, Joseph; Cason, Frederick D.; Pathology and Laboratory Medicine, School of MedicineIntroduction: Celiac disease (CD) is an immune-mediated disease caused by ingesting gluten-containing foods and is characterized mainly by malabsorptive diarrhea. Furthermore, distinguishing between mild disease and asymptomatic individuals is critical and necessitates a high level of clinical suspicion. Short stature, delayed puberty, bone abnormalities, neurological problems, and intestinal cancer can all be consequences of a delayed diagnosis. This study aimed to determine the prevalence of celiac disease among our community's recurrent diarrhea patients. Methods: This was a cross-sectional study aimed at determining the frequency of celiac disease in patients with chronic diarrhea. One hundred eighty-eight patients between the ages of 18 and 60 years who had chronic diarrhea lasting greater than three months were enrolled in this study. Stratification was utilized to control for modifiers. A p-value of ≤ 0.05 was considered significant. Results: A total of 74.5% of patients (n=140) were male, while 25.5% (n=48) were female with a mean age of 38.48±10.85 years. The average duration of celiac disease symptoms was 8.17± 3.75 months. Celiac disease was found in 12.2% (n=23) of the individuals. Also, 21% of individuals with a positive family history of CD devolved CD, compared to those without prior CD family history (p=0.01). Conclusions: In individuals with chronic diarrhea for more than three months, the prevalence of celiac disease was determined to be 12.2% (n=23). There was a statistically significant difference between those with a positive family history of CD and those who did not have the condition.Item Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy(MDPI, 2022-07-28) Khan, Jaffar; Ullah, Asad; Waheed, Abdul; Karki, Nabin Raj; Adhikari, Nawaraj; Vemavarapu, Lakshmi; Belakhlef, Sami; Bendjemil, Samy Malik; Seraj, Siamak Mehdizadeh; Sidhwa, Feroze; Ghleilib, Intisar; Foroutan, Shahin; Blakely, Andrew M.; Del Rivero, Jaydira; Karim, Nagla Abdel; Vail, Eric; Heneidi, Saleh; Mesa, Hector; Pathology and Laboratory Medicine, School of MedicineIntroduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000−2018. Statistical analysis was performed with IBM SPSS® v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan−Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60−74 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6−10 cm: 36% and they were treated by surgical intervention: 82% and/or chemotherapy/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6−74.7), and the 5-year cause-specific survival 82% (95% CI = 80.7−82.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4−87.3), chemotherapy/targeted therapy with or without surgery at 77% (95% CI = 75.7−78.9), and radiation at 75% (95% CI = 74.5−80). On multivariable analysis tumor size > 5 cm, poorly and undifferentiated grade, age > 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1−2% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually >5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors.Item Incidence, Survival Analysis and Future Perspective of Primary Peritoneal Mesothelioma (PPM): A Population-Based Study from SEER Database(MDPI, 2022-02) Ullah, Asad; Waheed, Abdul; Khan, Jaffar; Mishra, Ankita; Tareen, Bisma; Nama, Noor; Karki, Nabin Raj; Panezai, Muhammad Saleem; Zarate, Luis Velasquez; White, Joseph; Cason, Frederick D.; Matolo, Nathaniel; Misra, Subhasis; Karim, Nagla Abdel; Pathology and Laboratory Medicine, School of MedicineBackground: Primary peritoneal mesothelioma (PPM) is a rare and aggressive tumor arising from the visceral and parietal peritoneum. The diagnosis and treatment of PPM are often delayed because of non-specific clinical presentation, and the prognosis is worse. The current study investigated the demographic, clinical, and pathological factors affecting patient prognosis and survival in PPM. Methods: Demographic and clinical data of 1998 patients with PPM were extracted from the Surveillance Epidemiology and End Results (SEER) database (1975–2016). The chi-square test, paired t-test, and multivariate analysis were used to analyze the data. Results: The majority of PPM patients were male (56.2%, p < 0.005) and Caucasian (90.4%, p < 0.005, with a mean age of diagnosis was 69 ± 13 years. The grading, histological, and tumor size information were classified as “Unknown” in most of the cases, but when available, poorly differentiated tumors (8.7%), malignant mesothelioma, not otherwise specified (63.4%) and tumors > 4 cm in size (8%), respectively, were most common, p < 0.005. Chemotherapy was administered to 50.6% of patients, followed by resection (29.2%) and radiation (1.5%), p < 0.001. The cohort of PPM had a five-year overall survival of 20.3% (±1.1), compared to 43.5% (±5.9), 25.9% (± 8.4), and 18.7% (±1.6) for those with surgery, radiation, or chemotherapy alone, respectively. Poor differentiation (OR = 4.2, CI = 3.3–4.9), tumor size > 4 cm (OR = 3.9, CI = 3.2–4.5), Caucasian race (OR = 2.9, CI = 2.6–4.4), and distant SEER stage (OR = 2.5, CI = 1.1–3.2) were all linked with increased mortality (p < 0.001). Conclusion: An extremely rare and aggressive peritoneal tumor, PPM may be difficult to identify at the time of diagnosis. Radiation therapy likely to have a limited function in the treatment of this condition, with surgery and chemotherapy being the primary choices. All PPM patients should be enrolled in a nationwide registry to improve our understanding of the pathogenesis and identify factors affecting survival.Item Klatskin Tumor in the Light of ICD-O-3: A Population-Based Clinical Outcome Study Involving 1,144 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (2001-2012)(Cureus, 2021-10-21) Khan, Jaffar; Ullah, Asad; Matolo, Nathaniel; Waheed, Abdul; Nama, Noor; Khan, Tahir; Tareen, Bisma; Khan, Zarmina; Singh, Sohni G.; Cason, Frederick D.; Pathology and Laboratory Medicine, School of MedicineIntroduction: Klatskin tumors (KTs) occur at the confluence of the right and left extrahepatic ducts and are classified based on their anatomical and histological codes in the International Classification of Diseases for Oncology (ICD-O). The second edition of the ICD-O (ICD-O-2) allocated a distinctive histological code to KT, which also included intrahepatic cholangiocarcinoma (CC). This unclear coding may result in ambiguous reporting of the demographic and clinical features of KT. The current study aimed to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of KT in the light of the updated third edition of ICD-O, Ninth Revision (ICD-O-3). Methods: Data of 1,144 patients with KT from the Surveillance, Epidemiology, and End Result (SEER) database (2001-2012) were extracted. Patients with KT were analyzed for age, sex, race, stage, treatment, and long-term survival. The data were analyzed using chi-square tests, t-tests, and univariate and multivariate analyses. The Kaplan-Meier analysis was used to compare long-term survival between KT and subgroups of all biliary CCs. Results: Of all biliary CCs, KT comprised 9.35%, with a mean age of diagnosis of 73±13 years, and was more common in men (54.8%) and Caucasian patients (69.5%). Histologically, moderately differentiated tumors were the most common (38.9%) followed by poorly differentiated (35.7%), well-differentiated (23.3%), and undifferentiated tumors (2.2%) (p<0.001). Most tumors in the KT group were 2-4 cm in size (41.5%), while fewer were >4 cm (29.7%) and <2 cm (28.8%) (p<0.001). ICD-O-3 defined most KTs in extrahepatic location (53.5%), while the remainder were in other biliary locations (46.5%) (p<0.001). Most KT patients received no treatment (73%), and for those who were treated, the most frequent modality was radiation (52.7%), followed by surgery (28.1%), and both surgery and radiation (19.2%) (p<0.001). Mean survival time for KT patients treated with surgery was inferior to all CCs of the biliary tree (1.72±2.61 vs. 1.87±2.18 years) (p=0.047). Multivariate analysis identified regional metastasis (OR=2.8; 95% CI=2.6-3.0), distant metastasis (OR=2.1; 95% CI=1.9-2.4), lymph node positivity (OR=1.6; 95% CI=1.4-1.8), Caucasian race (OR=2.0; 95% CI=1.8-2.2), and male sex (OR=1.2; 95% CI=1.1-1.3) were independently associated with increased mortality for KT (p<0.001). Conclusion: The ICD-O-3 has permitted a greater understanding of KT. KT is a rare and lethal biliary malignancy that presents most often in Caucasian men in their seventh decade of life with moderately differentiated histology. Surgical resection does not provide any survival advantage compared to similarly treated biliary CCs. In addition, the combination of surgery and radiation appeared to provide no added survival benefits compared to other treatment modalities for KT.