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Pancreatic Neuroendocrine Tumors (PNETs) are indolent malignancies that often have a prolonged clinical course. This study assesses disparities in outcomes between PNET patients who live in urban (UA) and rural areas (RA). A retrospective cohort study was performed using the US Neuroendocrine Tumor Study Group database. PNET patients with a home zip code recorded were included and categorized as RA or UA according to the Federal Office of Rural Health Policy. Overall survival (OS) was analyzed by Kaplan-Meier method, log-rank test, and logistical regression. Of the 1176 PNET patients in the database, 1126 (96%) had zip code recorded. While 837 (74%) lived in UA, 289 (26%) lived in RA. RA patients had significantly shorter median OS following primary PNET resection (122 vs 149 months, p ​= ​0.01). After controlling for income, local healthcare access, distance from treatment center, ASA class, BMI, and T/N/M stage, living in a RA remained significantly associated with worse OS (HR 1.60, 95%CI 1.08–2.39, p ​= ​0.02). Rural patients have significantly shorter OS following PNET resection compared to their urban counterparts. •PNETs are rare, needing complex care.•Rural patients have shorter PNET survival.•Better access may aid rural patients.

Erb‐b2 receptor tyrosine kinase 2 (ERBB2; also known as HER2) expression is observed in 25–40% of head and neck squamous cell carcinomas (HNSCC), yet there are no anti‐HER2 therapies under evaluation for HNSCC, as conventional cytostatic anti‐HER2 antibodies have had limited effectiveness and levels of HER2 overexpression are lower in HNSCC tumors compared to breast cancer. Trastuzumab‐deruxtecan (T‐DXd; Enhertu) is a HER2‐targeting antibody‐drug conjugate (ADC) comprising an anti‐HER2 monoclonal antibody, a cleavable linker, and a potent topoisomerase I inhibitor payload, and has shown promising results in very low HER2‐expressing tumors. We compare the efficacy of T‐DXd, trastuzumab‐emtansine (ADC comprising an anti‐HER2 antibody and microtubule inhibitor, T‐DM1; Kadcyla) and trastuzumab (Herceptin) therapy in HNSCC with low and absent HER2 expression in vitro and in vivo. In vitro treatment of a low HER2‐expressing human HNSCC cell line (FaDu) with T‐DXd resulted in dose‐dependent cell death (IC50 values of 9856 ng·mL−1). T‐DXd treatment of FaDu and UMSCC‐47 (low HER2‐expressing cell line) mouse xenografts displayed antitumor activity (P = 0.0001 and 0.015 respectively). When comparing T‐DXd to other approved anti‐HER2 therapies, only FaDu mice treated with T‐DXd showed a reduction in tumor growth (P = 0.0012). In UMSCC‐1 cells (absent HER2 expression), the drug failed to accumulate in tumors and showed no measurable antitumor effect, in contrast to FaDu xenografts, where drug accumulation in the tumor correlated with a therapeutic response. T‐DXd treatment yielded antitumor activity in FaDu and UMSCC‐47 tumors, highlighting the potential for T‐DXd efficacy in low HER2‐expressing tumors. Trastuzumab‐deruxtecan, a HER2‐targeting antibody‐drug conjugate, shows promising antitumor activity in head and neck squamous cell carcinoma with low HER2 expression. In vitro and in vivo studies demonstrated dose‐dependent cell death and tumor growth reduction in low HER2‐expressing cell lines, which correlated with drug accumulation measured using a fluorescent antibody‐drug conjugate.

Metastatic colorectal cancer (mCRC), particularly microsatellite stable (MSS) cases, often exhibits limited responsiveness to immunotherapy, leaving chemotherapy as the primary treatment option. While chemotherapy effectively targets tumor cells, its impact on the broader mutational landscape, including passenger mutations in large genes such as Titin (TTN), remains poorly understood. Passenger mutations, traditionally deemed biologically inert, may reflect tumor mutational burden (TMB) and influence treatment outcomes. In our study involving whole exome sequencing of paired primary and metastatic tumor samples from 22 mCRC patients, recurrent driver mutations in APC, KRAS, and TP53 were consistently observed. However, passenger mutations in large genes, particularly TTN, were notably enriched in chemonaïve specimens and associated with higher TMB. Chemotherapy‐treated samples exhibited a significant reduction in these mutations, suggesting selective depletion of hypermutated subclones. Our findings demonstrate that chemotherapy may selectively reduce passenger mutations in mCRC, potentially influencing the persistence of hypermutated subclones. This highlights the potential role of passenger mutation patterns and TMB as biomarkers for treatment response and raises the hypothesis that they could help guide immunotherapy considerations for patients with MSS mCRC.

Purpose The primary objective of our study is twofold. First, we assessed nontechnical skills (NTSs), such as the cognitive, social, and personal skills of postgraduate residents (PGRs), from paediatric caregivers’ perspectives in a paediatric emergency department (PED) of a tertiary care hospital. Second, we evaluated the reliability and validity of the ‘Parents’ Assessment of Residents Enacting Non-Technical Skills’ (PARENTS) instrument in its Urdu-translated version, ensuring its applicability and accuracy in the Pakistani context. Materials and methods This mixed-method study used an instrument translation and validation design. We translated an existing instrument, PARENTS, into Urdu, the national language of Pakistan, and administered it to paediatric caregivers in the PED of a tertiary care hospital. We collected data from 471 paediatric caregivers and coded them for analysis in AMOS and SPSS. Results The Urdu-translated version of the PARENTS demonstrated reliability and internal validity in our study. The findings from the assessment revealed that paediatric caregivers expressed satisfaction with the knowledge and skill of residents. However, there was comparatively lower satisfaction regarding the residents’ display of patience or empathy towards the children under their care. Conclusion The study findings support the validity and reliability of the PARENTS as an effective instrument for assessing the NTS of PGRs from the perspective of paediatric caregivers. With its demonstrated efficacy, medical educators can utilize PARENTS to pinpoint specific areas that require attention regarding the NTS of PGRs, thus facilitating targeted interventions for enhanced patient care outcomes.

Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability. A total of 717 patients with CRLM who underwent hepatic resection +/- RFA at two tertiary institutions between 09/01/2000-12/01/2015 were eligible for inclusion in this study. Among patients with <4 lesions (n=568), OS in the resection + RFA group (n=48) was significantly worse than in the resection alone group (n=520) (5-year OS: 34.4 % versus 58.9%, p=0.007). Conversely, in patients with ≥4 lesions, OS in the resection + RFA (n=68) and resection alone(n=81) groups were not significantly different (5-year OS: 31.9% versus 34.1%, p=0.48). In patients with <4 lesions, carcinoembryonic antigen (CEA) ≥30 ng/ml, extrahepatic metastasis, preoperative chemotherapy and resection + RFA were independently associated with poor prognosis. Interestingly, in patients with ≥4 lesions, positive primary lymph nodes, KRAS mutation, CEA ≥30 ng/ml and extrahepatic metastasis were independent predictors of poor prognosis; however, the combination of hepatic resection with RFA was not associated with worse survival (p=0.93). Although surgeons should always strive for R0 resection when feasible, combined resection and RFA may be a viable alternative for CRLM patients with a large number of tumors.

BackgroundEsophageal replacement is a challenge to the therapeutic skills of surgeons and a technically demanding operation in the pediatric age group. Various conduits and routes have been described in the literature, each with their specific advantages and disadvantages. We carried out this retrospective study to share our experience of esophageal replacement.MethodologyThis study was conducted at the department of pediatric surgery The Children’s Hospital and The Institute of Child Health, Lahore. The records of patients treated for esophageal replacement were reviewed. The patients under follow-up were called for clinical evaluation and assessed of long terms complications if any.ResultsA total of 93 patients with esophageal replacement were included in the study. Esophageal replacement was done with gastric transposition in 84 cases (90%), colon interposition in 7 cases (7.5%) including one case of redo colonic interposition, and jejunal interposition in 2 cases (2%). Routes of esophageal replacement were trans-hiatal in 71 (76%), retrosternal in 13 (14%), and trans-hiatal with thoracotomy in 9 (10%) patients. Postoperatively, all of the conduits maintained viability. Wound infection was seen in 10 (11%), wound dehiscence in 5 (5%), anastomotic leak in 9 (10%), anastomotic stenosis in 12 (13%), fistula formation in 4 (4%), aortic injury 1 (1%), dumping syndrome 8 (9%), reflux 18 (19%), dysphagia 15 (16%) and death occurred in 12 patients (13%).ConclusionThere are problems with esophageal replacement in developing countries. In this context, gastric conduit appeared as the best conduit for esophageal replacement, using the trans-hiatal route for replacement, in the authors’ experience.

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A comprehensive review of the extant literature on ISO Management System (IMS) standards certified companies conceded into major business performance improvement factors and elements. The worldwide activities of ISO Development of International Standards Total as of the end of December 2023 are 25111 International Standards and standards-type documents. ISO population data files for the years 2018, 2019, 2020, and 2021) show the standards used for certification in Pakistan besides world ISO population data. In 2023, a total of 1,465 International Standards and standards-type documents were published. Due to space limitations in the research paper, only one data file is attached to this paper. The most popular and populous standard among all is the ISO 9000 Quality Management System (QMS) standards adopted in Pakistan. The identified factors and elements /items were reviewed and converted into criteria set and framework. The analysis of this secondary experiential data shows that IMS standards certification improves the businesses’ performance. A survey questionnaire was designed on these business performance improvement factors and elements and pilot-tested to establish its ‘Reliability and Validity’. This questionnaire was used to collect national primary empirical data from both IMS standards-certified and non-certified businesses in all chambers of commerce and industry in Pakistan, including women’s chambers. The analysis of this national primary empirical data also shows an impact of IMS standards certification on businesses’ performance. Hence, it supports the results of secondary ISO experiential data analysis. Also, in comparative performance analysis, the IMS standards certified businesses outperformed the non-certified businesses. The IMS standards certification contributes to the prosperity, sustainability, technical, managerial, financial, Operational, communication, social, and environmental improvement, etc. of the businesses, thus increasing the national GDP. This improvement trend ultimately helps in attaining SDG goals set by the UN for all nations.

Background Alimentary tract duplications are rare anomalies and any delay in the diagnosis may develop various complications. Infection, hemorrhage, or perforation of the duplication cyst may lead to an acute presentation. Occasionally, it may lead to a diagnostic and management dilemma. Herein, we report an unusual complication of gastric duplication cyst. Case presentation A 2.5-year-old girl presented with recurrent abdominal distension, fever, and abdominal pain. The imaging workup revealed a huge intraperitoneal collection. Intraoperatively, a huge pseudocyst was encountered communicating with the gastric duplication cyst. The gastric duplication cyst was sharing a common wall with the greater curvature of the stomach but was not communicating with the gastric lumen. Pseudocyst along with gastric duplication cyst was completely excised. The resultant seromuscular defect of the stomach was also closed. The postoperative period was uneventful. Conclusion Perforation of the gastric duplication cyst should be kept in differentials of intraperitoneal collection not amenable to multiple aspirations. Huge intraperitoneal collection secondary to perforation of gastric duplication is exceedingly rare and scarcely reported in the literature.

The energy sector is a crucial pillar of the economic development of every nation. In developing countries, renewable energy deployment is scarce; consequently, the government and private sectors are exploring efficient energy resources. This research aims to scrutinize the linkages among value orientation, utilitarian benefits, collectivism, the reason for adoption, attitude toward renewable energy (RE), and adoption intention in the renewable energy context. The study analyzes survey data from 359 Pakistani consumers using solar panels for households. An approach called structural equation modeling is applied to evaluate hypotheses. Empirical findings suggest that value orientation positively and significantly influences the reason for the adoption of RE and attitude toward RE. Similarly, the utilitarian benefit positively and substantially affects attitude toward RE. Moreover, collectivism and reason for adoption are substantially and favorably related to attitude toward RE. The study’s findings also show that customer intentions to use renewable energy are favorably and substantially influenced by RE attitudes. The research has contributed to the enhancement of future avenues for scholars and professionals are provided by the literature on renewable practice.