Journal of the College of Physicians and Surgeons--Pakistan : JCPSP最新文献

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Objective: To evaluate the distribution of cancers across different age groups among residents of Balochistan from 2021 to 2024 and compare these patterns with those observed in other provinces of Pakistan.

Study design: An observational study. Place and Duration of the Study: Pathology-based cancer registry at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan, and Department of Pathology, Aria Institute of Medical Sciences, Quetta, Pakistan, from January 2021 to December 2024.

Methodology: Newly diagnosed, biopsy-confirmed malignant cases received from Quetta and other cities of Balochistan through the Aga Khan University Hospital laboratory network and the collaborating Institute over four years from the cancer registry and one year from the other institute were analysed. Patients were grouped by age and gender into children (0-14 years), adolescents (15-19 years), and adults (≥20 years). Duplicate records were removed through systematic verification. Categorical variables were evaluated using frequencies and percentages.

Results: Out of 16,342 biopsy specimens, 5,145 (31.5%) were malignant. There were 52% (n = 2,659) male and 48% (n = 2,486) female cases. Adults accounted for 93% of cases, while children and adolescents accounted for 7%. Among a total of 2,438 adult males, oesophageal cancer was most frequent (425, 17.4%), followed by stomach (351, 14.4%) and colorectal cancers (225, 9.2%). Out of the total 2,351 adult females, breast cancer was the leading malignancy (526, 22.4%), followed by oesophageal (434, 18.5%) and colorectal cancers (133, 5.7%). In younger groups, brain tumours and lymphomas predominated.

Conclusion: Marked predominance of oesophageal cancer in both genders highlights substantial regional variation. Overall, the predominance of gastrointestinal cancers suggests the presence of region-specific environmental risk factors.

Key words: Cancer registry, Balochistan, Oesophageal cancer, Colorectal cancer.

Objective: To determine the frequency, nature, and severity of drug-induced liver injury (DILI) among patients receiving azole antifungal agents for superficial fungal skin infections.

Study design: A descriptive study. Place and Duration of the Study: Department of National Institute of Liver and Gastrointestinal Diseases, Dow University Hospital, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan, from July 2024 to January 2025.

Methodology: A total of 116 patients were enrolled, and baseline liver function tests (LFTs) were performed at the start of treatment and repeated at 4 and 6 weeks. Those who developed deranged LFTs were referred to the hepatology clinic. Additional investigations were done for those who developed deranged LFTs. DILI was defined according to international criteria and classified using the R-value. The Wilcoxon signed-rank and Friedman tests were used for statistical analysis.

Results: Among 116 patients with tinea corporis/cruris, 102 (87.9%) received itraconazole and 14 (12.1%) voriconazole. Liver function derangement occurred in 65 (56%) patients, of whom only 10 (8.6%) patients developed DILI, predominantly a cholestatic pattern. Six out of 10 DILI cases occurred among itraconazole-treated patients. A short-term (4-week) course showed significant increases in alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels (p = 0.012), whereas 6-week treatment led to marked increases in alanine aminotransferase (ALT), ALP, and AST levels (p <0.001).

Conclusion: This study strengthens the association of azole antifungals with mild biochemical liver abnormalities and infrequent DILI. A short- term course of azoles causes a rise in ALP and AST, while longer courses cause a more comprehensive rise in LFTs. Thus, this highlights a time-dependent effect and necessitates regular monitoring of LFTs during and after treatment.

Key words: Drug-induced liver injury, Liver function tests, Azoles, Dermatophytosis, Tinea corporis/cruri, R-value, Cholestasis.

Human immunodeficiency virus drug resistance (HIVDR) creates a threat to the extended success of antiretroviral therapy (ART) while making it harder to control the HIV epidemic. In this study, a meta-analysis was conducted to analyse Pakistani studies from 2015 to 2025 that documented HIVDR prevalence and resistance-associated mutations (RAMs). The review included studies that analysed ART-experienced and ART- naive participants with available sequencing data. A random-effects meta-analysis was performed to estimate the pooled prevalence of HIV drug resistance, and subgroup analyses were conducted to evaluate resistance patterns according to treatment region and antiretroviral regimen. Sensitivity tests were performed to verify the stability of the results. Fifty-one studies were included, which analysed more than 1,500 participants. ART-experienced patients developed HIVDR at a rate of 35% (95% CI: 30-40%). In the reverse transcriptase and protease regions, the most prevalent non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations were M184V, K103N, L90M, and M46I. The time-trend analysis indicated that NNRTI resistance has increased over the past decade. The analysis relied on simulated effect sizes due to the unavailability of raw data from the included studies. The spread of HIVDR in Pakistan remains a significant challenge because of restricted access to viral load and resistance testing, inadequate treatment options, and poor patient adherence. The National AIDS Control Program (NACP) should implement baseline and routine resistance testing while adopting dolutegravir-based treatment regimens and improving patient adherence programmes. Key Words: HIV drug resistance, Antiretroviral therapy, Resistance-associated mutations.

Typhoid fever (TF) and paratyphoid fever (PTF), collectively known as enteric fever (EF), are acute febrile illnesses that are common and cause significant morbidity and mortality. EF is responsible for about 26.9 million cases of mortality and morbidity worldwide, with Asian nations accounting for over 90% of all EF deaths. There is not enough data to determine the burden of TF in Pakistan, where it is thought to be endemic. Multidrug-resistant H58 clade Salmonella enterica serovar Typhi has expanded far beyond Asia and Africa. The development of multidrug resistance is expected to significantly increase the difficulty and cost of diagnosing and treating EF, particularly in rural areas where resources are scarce.  Hospitalisation costs, prescription drugs, diagnostic testing, and other medical services are included in out-of-pocket expenses (OOPE) for patients with EF in rural areas. The fact that the majority of these patients take antibiotics without consulting a doctor is a serious concern. This needs the implementation of antibiotic stewardship in rural areas of Pakistan and an increase in diagnostic facilities.  Key Words: Multidrug-resistant, Paratyphoid fever, Typhoid fever.

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Pakistan faces an escalating cancer burden, with approximately 185,748 new cases and 118,631 deaths annually. According to GLOBOCAN data, breast cancer (16.5%), lip/oral cavity cancer (8.6%), and lung cancer (5.1%) are the most prevalent, with breast cancer alone accounting for 31.3% of female cases. The country's limited healthcare resources, including severe shortages of oncologists and radiotherapy facilities, exacerbate this crisis, requiring urgent intervention. The delta Mortality-to-Incidence Ratio (dMIR) metric identifies cancers with the largest outcome gaps between Pakistan and top-performing countries, highlighting where improvements could yield the greatest impact. For instance, stomach cancer (dMIR = 0.60), Kaposi sarcoma (0.58), and oral cavity cancer (0.49) represent critical priorities. By focusing resources on high-dMIR cancers through early detection, treatment access, and prevention programs, Pakistan can significantly reduce preventable mortality. To address these challenges, Pakistan must implement a comprehensive National Cancer Control Plan. Key steps include expanding screening programs for breast, cervical, and oral cancers; training healthcare workers; upgrading radiotherapy infrastructure; and launching public awareness campaigns targeting tobacco use and lifestyle risks. Strategic investments in these areas, coupled with policy reforms and public-private partnerships, could transform cancer outcomes in Pakistan. Key Words: Pakistan, Cancer burden, Delta mortality-to-incidence ratio, Cancer disparities, Low- and middle-income countries.

This cross-sectional study aimed to compare serum Retinol-Binding Protein 4 (RBP4) levels in hypertensive and normotensive non-obese individuals. A total of 41 hypertensive and 41 normotensive subjects aged ≥40 years were enrolled. Hypertension was defined as a blood pressure (BP) of ≥140/90 mmHg, whereas normotension was defined as a BP of <120/80 mmHg in the absence of antihypertensive medication (JNC 8 criteria). Five millilitres of venous blood were collected aseptically, and serum RBP4 was measured using a Human RBP4 ELISA kit. Data were analysed using SPSS version 26 with an independent sample t-test; p ≤0.05 was considered statistically significant. Forty-six per cent of participants were male, with a mean age of 53.69 ± 9.86 years in the hypertensive and 52.41 ± 6.30 years in the normotensive group. The mean serum RBP4 was significantly higher in the hypertensive group (62.17 ± 28.22 ng/mL) than in the normotensive group (14.70 ± 5.59 ng/mL), suggesting its potential as a biomarker. Key Words: Hypertension, Normotensive, Serum Retinol-binding Protein-4, Cardiovascular diseases.

Objective: To quantify the proportion of cribriform pattern in Gleason score (GS) 7 prostate cancer (PCa) and evaluate its association with established pathological parameters.

Study design: An analytical study. Place and Duration of the Study: Department of Histopathology, Liaquat National Hospital and Medical College, Karachi, Pakistan, from January 2023 to July 2025.

Methodology: The study included 44 cases of prostatic adenocarcinoma (Grade Groups 2 and 3 [GG2 and GG3]). All histological slides were independently reviewed by two expert histopathologists. The percentage of Gleason pattern 4 (GP4) in GG2 and GG3 tumours and the presence of cribriform architecture were recorded. Cribriform pattern was categorised as absent, <20%, or ≥20%. Associations with GG, intraductal carcinoma, tertiary pattern 5, perineural invasion (PNI), lymphovascular invasion, and tumour volume were analysed using Fisher's exact test.

Results: The mean age of patients was 68.4 ± 10.8 years. Cribriform architecture was identified in 23 (52.2%) cases, with ≥20% cribriform pattern in 8 (18.2%) cases. A significant association was observed between a cribriform pattern ≥20% and PNI (p = 0.047), higher GG (GG3) (p = 0.032), and an increasing GP4 burden in both GG2 and GG3 tumours (p = 0.041 and p = 0.038, respectively). No significant associations were found with other parameters. Subgroup analyses within individual GGs did not show statistically significant associations.

Conclusion: Cribriform GP4 is frequent in GS 7 PCa. It correlates with adverse pathological features. Routine reporting of cribriform architecture may refine risk stratification and provide more personalised management of patients with intermediate-risk PCa.

Key words: Cribriform pattern, Gleason score, Histopathology, Prostate cancer.

Objective: To develop and evaluate a deep learning approach for the automated segmentation of impacted third molars on cone-beam computed tomography (CBCT) images and the classification of each tooth's root apex as open or closed.

Study design: An observational study. Place and Duration of the Study: Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Marmara University, Istanbul, Turkiye, from December 2022 to December 2024.

Methodology: Three hundred CBCT scans containing impacted third molars were retrospectively collected. Experts categorised teeth as having an open apex (incomplete root development) or closed apex (fully formed roots). A 3D nnU-Net convolutional neural network was trained using manual segmentations of the molars (270 scans for training and 30 for testing), with the network output distinguishing between teeth with open and closed apices. Model performance was evaluated on the independent test set using segmentation overlap metrics (Dice similarity coefficient and Jaccard index) and classification metrics derived from confusion matrix components [accuracy, sensitivity, precision, and area under the ROC curve (AUC)]. All performance metrics were automatically computed within the nnU-Net v2 framework and further verified using Python.

Results: The model demonstrated high performance in segmenting closed-apex molars, achieving a Dice similarity coefficient of 0.85, a Jaccard index of 0.78, sensitivity of 0.90, precision of 0.85, and an AUC of 0.95. However, for open-apex molars, performance was substantially lower (Dice: 0.37; Jaccard: 0.30; sensitivity: 0.31; precision: 0.71; AUC: 0.65), primarily attributable to severe class imbalance in the training dataset.

Conclusion: This study demonstrates the feasibility of a deep learning approach for automatically evaluating impacted third molars on CBCT, including tooth segmentation and root maturity assessment. The model's strong performance suggests that such AI tools could assist clinicians in assessing impactions and planning extractions.

Key words: Impacted third molar, Cone-beam computed tomography, Deep learning, Tooth segmentation, Root apex closure, nnU-Net.