Pulsatillic acid as a potential inhibitor of protein kinase C-alpha in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a global health concern with a significant impact on morbidity and mortality. Small molecule inhibitors targeting genetic mutations like EGFR and ALK have shown promise in NSCLC treatment. This study focuses on Protein Kinase C-alpha (PKCα), implicated in NSCLC pathogenesis. Overexpression of PKCα correlates with advanced disease stages. Preclinical studies suggest its inhibition can suppress NSCLC cell growth. The research employs molecular docking to identify Pulsatillic acid (PA) as a potential PKCα inhibitor. ADMET predictions support PA's candidacy and PASS analysis and Swiss Target Prediction reveal its biological properties. Fluorescence-based binding assays demonstrate PA's inhibitory potency on PKCα, aligning with molecular docking findings. Cytotoxicity assays show PA's minimal impact on HEK-293 cell viability, with an IC50 of 21.03 µM in A549 cells. mRNA expression analysis in A549 cells indicates PA's potential inhibitory effect on PKCα. In conclusion, this study highlights that PA may emerge as a promising therapeutic candidate for NSCLC, emphasizing the need for further research, validation, and exploration of its translational potential. The study contributes valuable insights into NSCLC treatment strategies, emphasizing the significance of targeting PKCα.

Leflunomide-induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κb signaling interplay.

Leflunomide (LFND) is an immunosuppressive and immunomodulatory disease-modifying antirheumatic drug (DMARD) that was approved for treating rheumatoid arthritis. LFND-induced cardiotoxicity was not fully investigated since its approval. We investigated the cardiac injury in male mice and identified the role of nuclear factor erythroid 2-related factor 2/nuclear factor-κ B (Nrf2/NF-κB) signaling. Male albino mice were assigned into five groups as control, vehicle, and LFND (2.5, 5, and 10 mg/kg). We investigated cardiac enzymes, histopathology, and the mRNA expression of Nrf2, NF-κB, BAX, and tumor necrosis factor-α (TNF-α). The bioinformatic study identified the interaction between LFND and Nrf2/NF-κB signaling; this was confirmed by amelioration in mRNA expression (0.5- to 0.34-fold decrease in Nrf2 and 2.6- to 4.61-fold increases in NF-κB genes) and increased (1.76- and 2.625-fold) serum creatine kinase (CK) and 1.38- and 2.33-fold increases in creatine kinase-MB (CK-MB). Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear, and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration and highlights, for the first time, dysregulation in Nrf2/NF-κB signaling.

Phenotype and Genotype of Saudi Pediatric Patients With Neurofibromatosis Type 1: A Seven-Year Multicenter Experience From Saudi Arabia.

Background Neurofibromatosis type 1 (NF1) is a complex disorder. Genetics and environment might be attributed as the leading cause of NF1, which is characterized by multisystemic involvement. We aim to elaborate on Saudi children's NF1 phenotypes and genotypes. Methods This study was conducted in the Ministry of National Guard Health Affairs (MNGHA), Saudi Arabia including three tertiary hospitals, using a retrospective cohort method. Electronic charts were reviewed to extract the variables. All Saudi pediatric patients aged less than 18 with NF1 were included. Consecutive sampling was used due to the limited number of patients. Results The study included 160 patients (81 males) with an average age of 8.08 years. Also, 33 (20.6%) patients had cutaneous neurofibroma while 31 (19.4%) patients had plexiform neurofibromas. Iris lisch nodules were seen in 33.75%. Optic pathway glioma was seen in 29 (18%) cases while non-optic pathway glioma was seen in 27 (17%) cases. Skeletal abnormalities were seen in 27 (17%) of cases. A first-degree relative with NF1 was seen in 83 (52%) of cases. Epilepsy was the presenting feature of 27 (17%) cases. Cognitive impairment was found in 15 (9.4%) patients. Genetic mutation was seen in 82/100 cases, the rest were negative. The types of mutations were as follows: nonsense 30 (36.6%); missense 20 (24.4%); splicing site mutation 12 (14.6%); frameshift 10 (12.2%); microdeletion 7 (8.5%); and whole gene deletion 3 (3.75%) patients. No phenotype-genotype correlation was seen. Conclusion In this cohort of Saudi pediatric patients with NF1, optic pathway glioma and other brain tumors were prevalent. The most common mutation is the nonsense mutation.

Anticipation of Relapse and Acute Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation: The Fundamental Role of Antigen-Presenting (Dendritic) Cells.

Background: Dendritic cells (DCs) are antigen-presenting cells. In humans two distinct lineages of DCs exist: DC1 and DC2. Efforts to explore the role of DCs in acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem-cell transplantation (PBSCT) are gaining traction. However, further research is needed to identify particular lineages and their values in terms of developing an evidence-based aGVHD- or relapse-prevention strategy. We monitored DC counts and subsets in PBSC grafts while harvesting stem cells in recipients to elucidate their value in anticipating disease relapse or aGVHD. Methods: We enrolled 29 participants. Using fluorescence-activated cell sorting, total counts/kg of CD34+, DCs, and DC subsets were analyzed in 29 PBSC-graft components using CMRF44, CD11c, and CD4 monoclonal antibodies (MoAbs). Results: In the 29 grafts, we detected a significant positive correlation (P<0.01) between DCs and both DC1 and DC2. Significantly higher counts (P<0.01) of DCs and DC1 in those who had developed aGVHD (nine cases) were also observed. Relapsed cases (two) were also associated with higher counts of DCs and DC2. A significant positive correlation (P<0.05), was recorded between DCs and DC1 counts and the day of myeloid engraftment, while this was not detected on the day of platelet engraftment. Myeloid engraftment transpired earlier in patients without aGVHD. Increased DC-graft numbers, particularly DC1 measured by CD11c Moabs, were associated with aGVHD. Recipients of higher numbers of CD4bright DCs had an increased risk of relapse after allogeneic PBSCT. Conclusion: This study analyzed DCs in PBSC grafts, using novel specific MoAbs and flow cytometry. Our data showed that higher donor DC1 counts were linked to the incidence of aGVHD and DC2 with relapse. We propose a fundamental role for DC-graft monitoring in anticipating aGVHD and disease relapse.

The Prediction of Malignancy Risk in Thyroid Nodules Classified as Bethesda System Category III (AUS/FLUS) and the Role of Ultrasound Finding for Prediction of Malignancy Risk.

Objective To predict the risk of malignancy in category III of the Bethesda System for Reporting Thyroid Cytopathology "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)" at King Abdulaziz Medical City, Riyadh, Saudi Arabia. It also intends to determine other possible contributing predictors of malignancy in thyroid nodules such as age, sex, and ultrasound (US) findings. Method This retrospectively designed study included 187 patients (mean age, 43.9 ± 14.1 years) with thyroid nodules, which were diagnosed as AUS/FLUS and all patients included had total thyroidectomy or lobectomy between January 2013 and December 2018 at King Abdulaziz Medical City in Riyadh, Saudi Arabia. The electronic medical records, US images, and final cytopathology and histopathology reports were reviewed and analyzed. Result The overall incidence of AUS/FLUS was (46.5%). Multivariate analysis of US features revealed that malignancy was significantly associated with nodules with irregular margins, microcalcification, multiple numbers (P < 0.001), and hypoechogenicity (P 0.04). Conclusion Despite the high rate of malignancy of nodules AUS/FLUS, it is still consistent with previously reported studies. The highly suspicious ultrasound features (irregular margins, microcalcification, multiple nodules, and hypoechogenicity) could be helpful in the diagnosis of thyroid cancer.

Percutaneous endoscopic gastrostomy in children: A single center experience in Saudi Arabia.

OBJECTIVES: To evaluate the demographic data and complications in children who had undergone percutaneous endoscopic gastrostomy (PEG) over 9 years period. METHODS: The demographic data, complications, length of hospital admission related to PEG insertion and follow-up findings of 39 patients who had undergone percutaneous endoscopic gastrostomy using the standard pull-through technique between 2011 and 2020 were examined. The study took place at the Gastroenterology Division, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia RESULTS: The most common indications of feeding with a gastrostomy tube include neurological diseases (n=30, 76.9%), followed by metabolic disorders (n=3, 7.69%), chronic diarrhea (n=2, 5.1%), chronic kidney diseases (n=2, 5.1%), cystic fibrosis (n=1, 2.56%), feeding aversion fibrosis (n=1, 2.56%). Out of the 39 patients, 20 (51%) did not have any complications. However, minor complication are expected. Most common complications included local infection (n=14, 35.89%) followed by granulation tissue (n=6, 15.38%), "buried bumper syndrome" developed in one. CONCLUSION: Percutaneous endoscopic gastrostomy tube is the desirable method for patients who are unable to feed orally, feeding is not adequate for demands, has special feeding requirements, or swallowing dysfunction. The technique has become more widespread because of its simplicity, safety, and low cost. Major complications are rare. The procedure is safe and effective and could be carried out by pediatric gastroenterologists after training.

Risk factors of colorectal cancer among Saudi Population: Case-control study.

BACKGROUND: Colorectal cancer (CRC) incidence and related mortalities have been steadily increasing in KSA over the past 20 years. CRC in the Kingdom of Saudi Arabia (KSA) population presents in younger ages and in more advanced disease states as compared to other countries. This study was aimed to determine factors (demographic, habitual, environmental, nutritional, and genetic) associated with CRC in Riyadh, KSA. MATERIALS AND METHODS: A matched case-control study conducted in the major hospitals in Riyadh (King Khalid university Hospital, King Faisal Specialist Hospital, Riyadh Military Hospital, Security Force Hospital, King Fahd Medical City). Here most of CRC cases are managed. The cases (n = 121) group included all recently diagnosed and pathologically confirmed Saudi cases of CRC identified during the period 1st of January 2017 till 31st of December 2018 who agreed to participate and fulfilled the inclusion criteria. A similar number of controls attending the study settings were selected consecutively from the clinics where cases were managed and matched on a 1:1 basis with cases based on age (+/-3 years) and gender. Data were collected using a structured questionnaire. Conditional logistic regression models were fitted to determine factors associated with risk of CRC. RESULT: This study included similar number of males and females in both groups: males 69 (57%) and females 52 (43%) in each group (Chi-square test P = 1.0). The mean (S.D) age in the cases group was 53.6 (S.D = 12.9) and 53.3 (S.D = 12.9) in the controls group (Student test P = 0.86). In the final multivariate conditional logistic regression model, variables independently associated with risk of colorectal cancer were body mass index (OR = 0.93; 95% CI 0.87-0.98; P = 0.011) employment status (inverse relation: OR = 0.33; 95% CI 0.14-0.77; P = 0.010), colon polyps (OR = 4.09; 95% CI 1.06-15.82; P = 0.041), and constipation (OR = 4.98; 95% CI 1.91-15.99; P = 0.001). CONCLUSION: Factors associated with CRC in the major referral hospitals in KSA were colon polyps, chronic constipation, and unemployment. These factors should be considered when screening for patients at risk for CRC.

Molecular Mechanisms Contributing Bacterial Infections to the Incidence of Various Types of Cancer.

Cancer causes a major health concern worldwide due to high incidence and mortality rates. To accomplish this purpose, the Scopus, PubMed, and Web of Science databases were searched using the keywords bacteria and cancer. Most of published research addressed several different factors that induced cancer, such as toxins, medications, smoking, and obesity. Nonetheless, few studies are dealing with cancer induction via bacterial infection. In addition, mechanisms of cancer induction via bacterial infections are not well understood. Therefore, in this review, we will shed light on different bacteria that induced cancer via different molecular mechanisms. Among the bacterial infection that induced cancer, Helicobacter pylori was the first recognized bacteria which caused gastric cancer and might be also linked to extragastric cancer in humans. H. pylori has been associated with adenocarcinoma in the distal stomach by its ability to cause severe inflammations. It has been found that inflammations induced cancer via different mechanisms including induction of cell proliferation and production of high levels of free radicals. Recently, free radicals were found to induce and cause various types of cancer. Salmonella typhi has been found to be associated with gallbladder carcinoma (GBC). Also, intercellular infection of lungs with Chlamydia pneumoniae was found to contribute as one of the ethological factors of lung cancer. Moreover, infection of the urinary tract with Staphylococcus aureus, Klebsiella spp., and Proteus mirabilis has been found to cause bladder cancer. These microorganisms produce a high level of N-nitrosamines which are metabolically activated leading to the generation of alkylating agents that damage DNA and other macromolecules. It is concluded that a certain bacterium is linked with induction of a specific type of cancer via different molecular and biochemical mechanisms as discussed in the text in details. This infection could potentially affect human health in different ways. In addition, it is important to know the possible factors involved in cancer induction for better treatment of cancer patients.

Burnout Syndrome among Emergency Physicians and Nurses in Abha and Khamis Mushait Cities, Aseer Region, Southwestern Saudi Arabia.

OBJECTIVES: To explore the magnitude and determinants of burnout among emergency physicians and nurses working at emergency departments of hospitals in Abha and Khamis Mushait cities. SUBJECTS AND METHODS: A cross-sectional hospital-based study was conducted in emergency departments of hospitals in Abha and Khamis Mushait cities belonging to Ministry of Health. All physicians (n=95) and nurses (n=187) currently working at these sites were invited to participate in the study by filling a validated self-administered questionnaire including two main sections: personal and professional characteristics of physicians and nurses as well as Maslach burnout inventory (MBI) to assess the three components of the burnout syndrome: emotional exhaustion, depersonalization, and reduced personal accomplishment. RESULTS: The study included 282 physicians and nurses. The age of more than half of them (54.3%) ranged between 31 and 35 years. Most of them (70.9%) were females. About two-thirds of the respondents (66.3%) were nurses while the remaining 33.7% were physicians. Majority of the emergency healthcare professionals (88.7%) had high emotional exhaustion. The prevalence of high depersonalization (cynicism) was 20.6% whereas that of low personal accomplishment was 41.1% among emergency healthcare professionals. The overall prevalence of burnout among healthcare professionals was 16.3%. Multivariate logistic regression analysis revealed that male healthcare professionals were at almost higher three-folded risk for developing burnout compared to females (aOR=2.76; 95% confidence interval (CI): 1.21-6.28, p=0.017)). Smokers were at higher significant risk for burnout compared to nonsmokers (aOR=15.37; 95% CI: 7.06-33.45, p<0.001). Healthcare professionals who reported a history of taking medications for sleep disorders expressed higher risk for burnout opposed to those with no history of sleep disorder medication (aOR=6.59; 95% CI: 2.08-20.81, p=0.001). CONCLUSION: A considerable proportion of physicians and nurses working at emergency departments of hospitals in Abha and Khamis Mushait cities had burnout syndrome, particularly high emotional exhaustion and low personal accomplishment.

Discovery of novel drug sensitivities in T-PLL by high-throughput ex vivo drug testing and mutation profiling.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells with an urgent need for rationally designed therapies to address its notoriously chemo-refractory behavior. The median survival of T-PLL patients is <2 years and clinical trials are difficult to execute. Here we systematically explored the diversity of drug responses in T-PLL patient samples using an ex vivo drug sensitivity and resistance testing platform and correlated the findings with somatic mutations and gene expression profiles. Intriguingly, all T-PLL samples were sensitive to the cyclin-dependent kinase inhibitor SNS-032, which overcame stromal-cell-mediated protection and elicited robust p53-activation and apoptosis. Across all patients, the most effective classes of compounds were histone deacetylase, phosphoinositide-3 kinase/AKT/mammalian target of rapamycin, heat-shock protein 90 and BH3-family protein inhibitors as well as p53 activators, indicating previously unexplored, novel targeted approaches for treating T-PLL. Although Janus-activated kinase-signal transducer and activator of transcription factor (JAK-STAT) pathway mutations were common in T-PLL (71% of patients), JAK-STAT inhibitor responses were not directly linked to those or other T-PLL-specific lesions. Overall, we found that genetic markers do not readily translate into novel effective therapeutic vulnerabilities. In conclusion, novel classes of compounds with high efficacy in T-PLL were discovered with the comprehensive ex vivo drug screening platform warranting further studies of synergisms and clinical testing.

Antioxidant activity of milk protein hydrolysate in alloxan-induced diabetic rats.

We investigated the effects of milk protein concentrate (MPC) and milk protein concentrate hydrolysate (MPCH) as antioxidant agents in rats. Six groups of healthy (non-diabetic) and type-II diabetic rats were used: (1) healthy rats (control), (2) alloxan-induced rats (diabetic control group), (3) healthy rats treated orally with MPC, (4) diabetic rats treated orally with MPC, (5) healthy rats treated orally with MPCH, and (6) diabetic rats treated orally with MPCH. We concluded that treatment with MPC or MPCH reduced the level of thiobarbituric acid reactive substances in healthy and diabetic rats. Treatment with MPC or MPCH improved activities of antioxidant enzymes (catalase, superoxide dismutase, reduced glutathione, glutathione-S-transferase, and glutathione peroxidase) in healthy and diabetic rats. From the present data, we concluded that both MPC and MPCH contain potent antioxidants and could improve the health of rats or other animals with diabetes mellitus.

PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer.

PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233).

Guidelines for Perioperative Care in Bariatric Surgery: Enhanced Recovery After Surgery (ERAS) Society Recommendations.

BACKGROUND: During the last two decades, an increasing number of bariatric surgical procedures have been performed worldwide. There is no consensus regarding optimal perioperative care in bariatric surgery. This review aims to present such a consensus and to provide graded recommendations for elements in an evidence-based "enhanced" perioperative protocol. METHODS: The English-language literature between January 1966 and January 2015 was searched, with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohort studies. Selected studies were examined, reviewed and graded. After critical appraisal of these studies, the group of authors reached a consensus recommendation. RESULTS: Although for some elements, recommendations are extrapolated from non-bariatric settings (mainly colorectal), most recommendations are based on good-quality trials or meta-analyses of good-quality trials. CONCLUSIONS: A comprehensive evidence-based consensus was reached and is presented in this review by the enhanced recovery after surgery (ERAS) Society. The guidelines were endorsed by the International Association for Surgical Metabolism and Nutrition (IASMEN) and based on the evidence available in the literature for each of the elements of the multimodal perioperative care pathway for patients undergoing bariatric surgery.

Obesity-related insulin resistance: implications for the surgical patient.

In healthy surgical patients, preoperative fasting and major surgery induce development of insulin resistance (IR). IR can be present in up to 41% of obese patients without diabetes and this can rise in the postoperative period, leading to an increased risk of postoperative complications. Inflammation is implicated in the aetiology of IR. This review examines obesity-associated IR and its implications for the surgical patient. Searches of the Medline and Science Citation Index databases were performed using various key words in combinations with the Boolean operators AND, OR and NOT. Key journals, nutrition and metabolism textbooks and the reference lists of key articles were also hand searched. Adipose tissue has been identified as an active endocrine organ and the chemokines secreted as a result of macrophage infiltration have a role in the pathogenesis of IR. Visceral adipose tissue appears to be the most metabolically active, although results across studies are not consistent. Results from animal and human studies often provide conflicting results, which has rendered the pursuit of a common mechanistic pathway challenging. Obesity-associated IR appears, in part, to be related to inflammatory changes associated with increased adiposity. Postoperatively, the surgical patient is in a proinflammatory state, so this finding has important implications for the obese surgical patient.

Tissue near infra red spectroscopy change is not correlated with patients' outcome in elective cardiac surgery.

BACKGROUND: Microcirculatory disturbances following cardiac surgery with cardiopulmonary bypass (CPB) are thought to be at the origin of organ dysfunction, although few studies have correlated microvascular alterations with outcome. We aimed to assess the microcirculation with near infrared spectroscopy (NIRS) and correlate NIRS parameters with intensive care length of stay and organ dysfunction. METHODS: Forty patients at increased risk of postoperative systemic inflammatory response syndrome after an elective cardiac surgery with CPB were included in this prospective observational study. Microcirculation of the thenar eminence was analysed by NIRS technology, through the tissue oxygen saturation (StO2 ) and the recovery slope after an ischaemic challenge. Organ dysfunction was assessed with the Sequential Organ Failure Assessment (SOFA) score. Microcirculation parameters were recorded at baseline, at different time points during the surgery and the first 48 postoperative hours. RESULTS: StO2 at baseline was 82% and decreased significantly until 77% at 2 h after CPB. Recovery slope values were 4.3% per second at baseline and decreased to 2.5% per second during CPB (P < 0.05). From 12 h after CPB time point, both parameters were not statistically different from baseline anymore. We found no correlation between microcirculatory parameters and mean arterial pressure, cardiac index, intensive care unit (ICU) length of stay or SOFA score. CONCLUSION: This study confirms, through a non-invasive technology, a significant but transient alteration of the microcirculation during elective cardiac surgery. However, as these microvascular alterations were not correlated with patient's outcome, NIRS-derived parameters seem to be of limited interest in the cardiac surgery setting.

New population of amelanotic spindle cells are clearly demonstrated in vitiliginous skin after ultraviolet radiation.

BACKGROUND: Phototherapy is a well-known method to treat vitiligo and is able to repopulate the skin with new melanocytes. Examination of the pathological changes in vitiligo after ultraviolet therapy revealed the presence of unusual cells. AIM OF STUDY: This study intended to investigate and confirm the repopulation of epidermis with new spindle cells, possibly as precursors for melanocytes after UV therapy. METHODS: Retrospective study was carried out on paraffin sections of biopsies obtained from 30 vitiligo patients treated successfully with ultraviolet therapy. Routine, special and immune staining were utilized to examine these biopsies. RESULTS: Amelanotic spindle cells with slightly eosinophilic cytoplasm and dark flattened nuclei were characteristically demonstrated in all examined sections after ultraviolet therapy. These cells were abundant near infundibular portion of hair follicles. They subsequently developed dendrites and became melanized. CONCLUSIONS: Melanocyte precursors can be demonstrated pathologically and immunologically on tissue samples after ultraviolet therapy. They are capable of proliferation and migration into depigmented epidermis to repopulate it with new generations of melanocytes.

Use of a Pfannenstiel incision in minimally invasive colorectal cancer surgery is associated with a lower risk of wound complications.

BACKGROUND: The Pfannenstiel incision, widely used in gynecological surgery, has been reported to be associated with lower rates of wound complications than midline incisions in open surgery. However, its effect on wound complications in minimally invasive surgery (MIS) is not well understood. We hypothesize that use of a Pfannenstiel incision in MIS colorectal cancer resections would be associated with fewer short-term wound complication rates. METHODS: A retrospective cohort study was performed on 171 patients who had undergone MIS colorectal cancer surgery requiring a specimen extraction/hand-access site, divided into a Pfannenstiel and a midline group depending on the type of incision used. Wound complications compared included disruption, infection, dehiscence, evisceration, and fistula formation. The Mann-Whitney U and Fisher's exact tests were used to analyze differences in risk factors between the groups. Logistic regression was performed to determine factors associated with prevention of wound complications. RESULTS: Patients in the Pfannenstiel group had significantly lower rates of wound disruption (0 vs. 13%, p = 0.02), superficial surgical site infection (7 vs. 22%, p = 0.03), and overall wound complications (13 vs. 30%, p = 0.04). Using multivariate logistic regression, Pfannenstiel incisions and colon rather than rectal resections were significant predictors of prevention of wound complications. CONCLUSIONS: The use of a Pfannenstiel incision in MIS colorectal cancer resections is associated with a decreased risk of short-term wound complications.

Mucins and CD56 as markers of tumour invasion and prognosis in periampullary cancer.

BACKGROUND: This study investigated the association of mucins and cluster of differentiation (CD) 56 with vascular and perineural invasion and survival in patients with periampullary cancer. METHODS: Immunohistochemical staining was performed on formalin-fixed pancreatic tissue microarrays (cancer, chronic pancreatitis and normal pancreatic tissue) constructed from 126 pancreatic resections (cancer, 104; chronic pancreatitis, 22). Mucin (MUC) 1, MUC4 and MUC5AC expression was quantified using the immunohistochemical score (range 0-300), MUC3 expression was described as membranous or cytoplasmic, and expression of CD56, MUC2 and MUC6 as present or absent. RESULTS: In cancers, vascular invasion correlated with overexpression (immunohistochemical score of 100 or more) of MUC1 (P = 0.003) and presence of MUC6 (P = 0.024), and perineural invasion correlated with overexpression of MUC5AC (P = 0.015). Reduced survival was observed with overexpression of MUC4 (P = 0.032) and MUC5AC (P = 0.048), membranous expression of MUC3 (P = 0.048), and presence of CD56 (P = 0.041). Perineural invasion also correlated with CD56 expression (P = 0.001). Overexpression of MUC4 and MUC5AC correlated with tumour recurrence (P = 0.001 and P = 0.034 respectively). Multivariable analysis identified membranous expression of MUC3 (P = 0.023), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.004) as independent predictors of poor survival. CONCLUSION: Mucins and CD56 may be markers of prognosis in patients with periampullary cancer.

Computation of a tetrahedral mesh for striated muscle deformation simulation.

Competing concepts exist regarding surgery for instance of the cleft lip and palate to date. Morphology-based simulations at histological scale may one day be used to help the surgeon predict the possible outcome of a variety of approaches. It however can be a challenge to generate volume meshes that are applicable to the mathematical modelling of three-dimensional spatial modifications. Computation of surface meshes may be considered less delicate. The aim of this study is to design and evaluate a novel algorithm that supports finite element methods. Images of histological serial sections of a striated muscle were segmented. Results of the three-dimensional reconstruction of multiple layers of the polygonal segmentation data characterized the hull of the muscle. The corresponding surface mesh was then converted into a tetrahedral mesh to generate volume. This was achieved by mapping multiple template types onto neighbouring intersection polygons. Muscle contraction was subsequently simulated by mesh deformation. The technique successfully generated volumes and was able to provide data on contraction directions. The mesh supported a novel approach to simulate representations of contraction. However, several drawbacks were evident. Mathematical modelling of scenarios with more than one striated muscle will require considerable modification of the currently presented approach. Future studies need to then evaluate the applicability of volume meshes to represent arrays of three-dimensional biological objects. Surface mesh based mathematical modelling of cleft lip and palate surgery and its results are therefore not yet in reach.