Purpose: Laparoscopic approach to colonic tumor requires skill set and resources to be established as routine standard of care in most centers around the world. It presents particular challenge in country like Pakistan due to economic constrain and lack of teaching and training opportunities available for surgeons to be trained to deliver such service. The aim of this study is to look into changing practice of our institution from conventional approach of open to laparoscopic surgery for right colon cancer. Methods: Consecutive patients between January 2010 to December 2018 who presented to Shaukat Khanum Memorial Cancer Hospital and Research Centre with diagnosis of right colon (cecum, ascending and transverse colon) adenocarcinoma and underwent surgical resections were included in this study. Results: A total of 230 patients with adenocarcinoma of the right colon underwent curative resections during the study period. Of these, 141 patients (61.3%) underwent laparoscopic surgery while open resection was performed in 89 patients (38.7%). Five-year disease-free survival (DFS) of patients with American Joint Committee on Cancer (AJCC) stage III (80.9% vs. 54.8%, P = 0.021) was significantly better if these patients underwent laparoscopic surgery while a trend toward better DFS (96.7% vs. 84.1%, P = 0.111) was also observed in AJCC stage II patients, although this difference was not significant. Conclusion This study demonstrates the adoption of a laparoscopic approach for right colon cancer over 10 years. With a standardized approach and using the principle of oncological surgery, we incorporated this in our minimally invasive surgery practice at our institution.

Objective: To enhance the pharmaceutical potential and oral bioavailability of quercetin contents of Allium cepa peel extract by novel nanosuspension technology. Methods: Nanoprecipitation approach was successfully used for the formulation of nanosuspension. To obtain pharmaceutical-grade nanosuspension with minimum particle size and polydispersity index, sodium lauryl sulphate was selected as a stabilizer. Important formulation parameters were statistically optimized by the response surface methodology approach. The optimized nanosuspension was subjected to stability and in vitro dissolution testing and characterized by scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and zeta sizer. To evaluate the preeminence of nanosuspension over coarse suspension, comparative bioavailability studies were carried out in male albino rats. The pharmaceutical potential of developed nanosuspension was evaluated by antioxidant, antimicrobial, and toxicity studies. Results: The optimized nanosuspension showed an average particle size of 275.5 nm with a polydispersity index and zeta potential value of 0.415 and -48.8 mV, respectively. Atomic force microscopy revealed that the average particle size of nanosuspension was below 100 nm. The formulated nanosuspension showed better stability under refrigerated conditions. Nanosuspension showed an improved dissolution rate and a 2.14-fold greater plasma concentration of quercetin than coarse suspension. Moreover, the formulated nanosuspension exhibited enhanced antioxidant and antimicrobial potential and was non-toxic. Conclusions: Optimization of nanosuspension effectively improves the pharmaceutical potential and oral bioavailability of Allium cepa extract.

PURPOSE: Partner and localizer of BRCA2 (PALB2) is a breast cancer susceptibility gene that plays an important role in DNA repair. This is the first study assessing the prevalence of PALB2 mutations in early-onset and familial breast/ovarian cancer patients from Pakistan. MATERIALS AND METHODS: PALB2 mutation screening was performed in 370 Pakistani patients with early-onset and familial breast/ovarian cancer, who were negative for BRCA1, BRCA2, TP53, CHEK2, and RAD51C mutations, using denaturing high-performance liquid chromatography analysis. Mutations were confirmed by DNA sequencing. Novel PALB2 alterations were analyzed for their potential effect on protein function or splicing using various in silico prediction tools. Three-hundred and seventy-two healthy controls were screened for the presence of the identified (potentially) functional mutations. RESULTS: A novel nonsense mutation, p.Y743*, was identified in one familial breast cancer patient (1/127, 0.8%). Besides, four in silico-predicted potentially functional mutations including three missense mutations and one 5' untranslated region mutation were identified: p.D498Y, novel p.G644R, novel p.E744K, and novel c.-134_-133delTCinsGGGT. The mutations p.Y743* and p.D498Y were identified in two familial patients diagnosed with unilateral or synchronous bilateral breast cancer at the ages of 29 and 39, respectively. The other mutations were identified in an early-onset (≤ 30 years of age) breast cancer patient each. All five mutations were absent in 372 healthy controls suggesting that they are disease associated. CONCLUSION: Our findings show that PALB2 mutations account for a small proportion of early-onset and hereditary breast/ovarian cancer cases in Pakistan.
5' Untranslated Regions ; Breast Neoplasms ; Chromatography, Liquid ; Codon, Nonsense ; Computer Simulation ; DNA Repair ; Germ-Line Mutation ; Humans ; Mass Screening ; Mutation, Missense ; Pakistan ; Prevalence ; Sequence Analysis, DNA

Hibiscus sabdariffa Linn. or also known as roselle which is rich in polyphenols, has been demonstrated to cause loweringof blood pressure in animal and clinical settings. However its exact mechanism of action particularly from polyphenoliccompounds is not clearly understood. Therefore, we aimed to determine the effects of H. sabdariffa polyphenol extract(HPE) towards vascular reactivity and its mechanism of action. The HPE was studied on isolated thoracic aortic ringsfrom normal Sprague-Dawley rats, suspended in a 15-ml organ chambers containing Krebs-Henseleit solution. Thechanges in tension were recorded by isometric transducer connected to data acquisition. HPE relaxed the contractioninduced by phenylephrine (PE, 1 μM) in similar pattern for both endothelium-intact and endothelium denuded aorticrings in dose-dependent manner 0.1 ~ 0.9 mg/ml. The pretreatment with atropine (1 μM), a competitive muscarinicantagonist, and propranolol (1 μM), a non-selective beta- blocker did not alter HPE vasorelaxation response. In addition,HPE did not inhibit the contraction induced by extracellular Ca2+ precontracted by PE (1 μM) or KCl (60 mM), in Ca2+-free solution, suggesting that the relaxation effect of HPE was not via inhibition of calcium channels. In conclusion,HPE demonstrated vasorelaxation effects on rat thoracic aorta although the underlying mechanism is still unknown.The vasorelaxation effect could be via angiotensin type 1 receptor inhibition in the vascular smooth muscle cells or theactivation of hyperpolarizing K+ chan