Central versus distal pancreatectomy for low-grade and benign pancreatic neck-body tumours.

PURPOSE: Central pancreatectomy (CP) offers parenchymal preservation compared to conventional distal pancreato-splenectomy for pancreatic neck and body tumours. However, it is associated with more morbidity. This study is aimed at evaluating the peri-operative and long-term functional outcomes, comparing central and distal pancreatectomies (DPs). METHODS: Retrospective analysis of patients undergoing pancreatic resections for low-grade malignant or benign tumours in pancreatic neck and body was performed (from January 2007 to December 2022). Preoperative imaging was reviewed for all cases, and only patients with uninvolved pancreatic tail, whereby a CP was feasible, were included. Peri-operative outcomes and long-term functional outcomes were compared between CP and DP. RESULTS: One hundred twenty-two (5.2%) patients, amongst the total of 2304 pancreatic resections, underwent central or distal pancreatectomy for low-grade malignant or benign tumours. CP was feasible in 55 cases, of which 23 (42%) actually underwent CP and the remaining 32 (58%) underwent DP. CP group had a significantly longer operative time [370 min (IQR 300-480) versus 300 min (IQR 240-360); p = 0.002]; however, the major morbidity (43.5% versus 37.5%; p = 0.655) and median hospital stay (10 versus 11 days; p = 0.312) were comparable. The long-term endocrine functional outcome was favourable for the CP group [endocrine insufficiency rate was 13.6% in central versus 42.8% in distal (p = 0.046)]. CONCLUSION: Central pancreatectomy offers better long-term endocrine function without any increased morbidity in low malignant potential or benign pancreatic tumours of neck and body region.

MRI of Recurrent Fistula-in-Ano: Is it Different from Treatment-Naïve Fistula-in-Ano and How Does it Correlate with Anal Sphincter Morphology?

Objectives The main aim of this study was to compare magnetic resonance imaging (MRI) findings of recurrent and treatment-naïve fistula-in-ano and to correlate imaging findings with anal sphincter morphology in recurrent fistula-in-ano. Methods This is a retrospective study of adult patients who underwent MRI for suspected fistula-in-ano in 2018. After excluding patients with alternative diagnosis, patients were stratified into recurrent ( n = 103) and treatment-naïve ( n = 106) fistula-in-ano groups. Two blinded radiologists reread MRI scans in consensus for fistula characteristics and anal sphincter morphology. We compared imaging features of recurrent and treatment-naïve fistula-in-ano, assessed the incidence of anal sphincter scarring among patients with recurrent fistula-in-ano, and studied its association with fistula features. Results Two-hundred nine patients (187 males) with mean age of 40.6 (standard deviation: 12.2) years were included. Trans-sphincteric, inter-sphincteric, extra-sphincteric, and supra-sphincteric fistula-in-ano were seen in 63.6, 33, 2.9, and 0.5%, respectively. There were secondary tracts, supralevator extension, and secondary cause for fistula in 49.3, 12.9, and 14.8%, respectively. There was no difference between the fistula features of recurrent and treatment-naïve fistula-in-ano, except for significantly fewer external openings among recurrent fistula-in-ano ( p = 0.005). Among patients with recurrent fistula-in-ano, MRI detected anal sphincter defect/scarring was seen in 53.4% ( n = 55) and was significantly associated with posterior fistula-in-ano ( p = 0.031), collections and/or supralevator extension ( p = 0.010), and secondary tracts ( p = 0.015). Conclusion Fistula features of recurrent and treatment-naïve patients were mostly similar. There was high incidence (53.4%) of MRI-identified anal sphincter scarring/defect among recurrent fistula-in-ano, which was significantly associated with posterior fistula, collections, supra or translevator extension, and secondary tracts. Key Points MRI-identified anal sphincter scarring is very common among patients with recurrent fistula-in-ano and seen in more than half of them.There was significantly higher incidence of sphincter scarring among patients who had posterior fistula, collections, supralevator/translevator extension, and secondary tracts.

Simultaneous resection of synchronous colorectal liver metastasis: Feasibility and development of a prediction model.

Backgrounds/Aims: Timing of resection for synchronous colorectal liver metastasis (CRLM) has been debated for decades. The aim of the present study was to assess the feasibility of simultaneous resection of CRLM in terms of major complications and develop a prediction model for safe resections. Methods: A retrospective single-center study of synchronous, resectable CRLM, operated between 2013 and 2021 was conducted. Upper limit of 95% confidence interval (CI) of major complications (≥ grade IIIA) was set at 40% as the safety threshold. Logistic regression was used to determine predictors of morbidity. Prediction model was internally validated by bootstrap estimates, Harrell's C-index, and correlation of predicted and observed estimates. Results: Ninety-two patients were operated. Of them, 41.3% had rectal cancers. Major hepatectomy (≥ 4 segments) was performed for 25 patients (27.2%). Major complications occurred in 20 patients (21.7%, 95% CI: 13.8%-31.5%). Predictors of complications were the presence of comorbidities and major hepatectomy (area under the ROC curve: 0.692). Unacceptable level of morbidity (≥ 40%) was encountered in patients with comorbidities who underwent major hepatectomy. Conclusions: Simultaneous bowel and CRLM resection appear to be safe. However, caution should be exercised when combining major liver resections with bowel resection in patients with comorbid conditions.

Node positivity in T1b gallbladder cancer: A high volume centre experience.

INTRODUCTION: Identification of early stage gallbladder cancer (GBC) is difficult with simple cholecystectomy being considered curative for T1a GBC but T1b requires radical cholecystectomy due to chances of lymph node metastasis. However there is no consensus regarding the optimal treatment strategy for T1b disease. METHODOLOGY: A retrospective review of a prospectively maintained database of GBC patients operated at our institute from March 2010 to March 2021 was conducted. Only patients with proven gallbladder adenocarcinoma on final histopathology report were included. RESULTS: A total of 1245 patients of suspected GBC who underwent surgery during this period with 76 patients of T1b stage were analysed. We divided the group into a node positive cohort (n = 16, 9 received neoadjuvant treatment due to uptake in periportal nodes and 7 patients were pN1) and a node negative cohort (n = 60). The median nodal harvest was 8 nodes (2-24 nodes). Considering the radiological and pathological parameters, the rate of lymph node positivity was 21% (16/76). The overall major morbidity was 5.2% and there was no mortality. After a median follow up of 47.5 months, 3-year OS and DFS of the node negative and positive cohort was 96.7%, 91.7% and 75% and 62.5% (p = 0.058). The node positive cohort had 43% recurrences whereas the node negative cohort had 8.3% with all recurrences limited to periportal lymph nodes, distant nodes or liver metastasis. CONCLUSION: Nodal positivity for T1b gall bladder cancer ranges around 21% and radical surgery with complete peri -portal lymphadenectomy should be considered as standard of care.

Exploration of statistical experimental design to improve entrapment efficiency of acyclovir in poly (d, l) lactide nanoparticles.

OBJECTIVE: In current exploration, systematic attempts have been made to improve the entrapment efficiency of a model hydrophilic drug substance, i.e. acyclovir, in poly (d, l) lactide (PLA) nanoparticles (NPs) using a modified nanoprecipitation technique. METHODS: Formulation parameters such as drug to polymer ratio, antisolvent selection, electrolyte (NaCl) addition, pH alteration and temperature were screened to improve the entrapment efficiency of acyclovir in PLA NPs. The temperature of the system (0-5 °C), phase volume ratio (1:2), stirring speed (2000 rpm), sonication time (5 min), etc. were kept constant during the preparation of NPs. Drug to polymer ratio and electrolyte addition emerged as critical formulation parameters affecting particle size as well as entrapment efficiency. Hence, in the present investigation a 3(2) full factorial design was used to investigate the combined influence of two factors, i.e. drug to polymer ratio (X1) and the amount of electrolyte, i.e. NaCl (X2) on particle size (Y1) and entrapment efficiency (Y2). The NPs were also evaluated for drug-excipient compatibility study by employing DSC and FT-IR analysis, whereas in vitro drug release studies were performed using dialysis bag technique in phosphate buffer pH 7.4. RESULTS: Statistically significant models were evolved to predict entrapment efficiency and particle size. The effect of factors X1, X2 and [Formula: see text] was found to be statistically significant in nature. Response variables, i.e. entrapment efficiency and particle size, were simultaneously optimized using desirability function using Design Expert software. This process allowed the selection of most suitable level of factors to achieve desired level of particle size and entrapment efficiency. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 250 nm) and entrapment efficiency (more than 17%), the NPs should be prepared using 1:3 drug to polymer ratio and 0.04 M NaCl. Acyclovir was found to be compatible with PLA as indicated by DSC and FT-IR studies. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The drug release from the optimized formulation exhibited biphasic pattern and the drug release kinetics was best explained by Weibull model. CONCLUSION: In conclusion, results of the present study demonstrated that PLA NPs with expected particle size and entrapment efficiency can be obtained by adopting the concept of quality by design.

Development and characterization of glutathione-conjugated albumin nanoparticles for improved brain delivery of hydrophilic fluorescent marker.

The glutathione-conjugated bovine serum albumin (BSA) nanoparticles were constructed in the present exploration as a novel biodegradable carrier for brain-specific drug delivery with evaluation of its in vitro and in vivo delivery properties. BSA nanocarriers were activated and conjugated to the distal amine functions of the glutathione via carbodiimide chemistry using EDAC as a mediator. These nanoparticles were characterized for particle shape, average size, SPAN value, drug entrapment and in vitro drug release. Further, presence of glutathione on the surface of BSA nanoparticles was confirmed by Ellman's assay, which has suggested that approximately 750 units of glutathione were conjugated per BSA nanoparticle. To evaluate the brain delivery properties of the glutathione-conjugated BSA nanoparticles fluorescein sodium was used as a model hydrophilic compound. Permeability and neuronal uptake properties of developed formulations were evaluated against the MDCK-MDR1 endothelial and neuro-glial cells, respectively. The permeability of glutathione-conjugated BSA nanoparticles across the monolayer of MDCK-MDR1 endothelial tight junction was shown significantly higher than that of unconjugated nanoparticles and fluorescein sodium solution. Similarly, glutathione-conjugated nanoparticles exhibited considerably higher uptake by neuro-glial cells which was inferred by high fluorescence intensity under microscope in comparison to unconjugated nanoparticles and fluorescein sodium solution. Following an intravenous administration, nearly three folds higher fluorescein sodium was carried to the rat brain by glutathione-conjugated nanoparticles as compared to unconjugated nanoparticles. The significant in vitro and in vivo results suggest that glutathione-conjugated BSA nanoparticles is a promising brain drug delivery system with low toxicity.