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1.
J Am Chem Soc ; 146(28): 19499-19508, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38959009

ABSTRACT

The design of small molecules with unique geometric profiles or molecular connectivity represents an intriguing yet neglected challenge in modern organic synthesis. This challenge is compounded when emphasis is placed on the preparation of new chemotypes that have distinct and practical functions. To expand the structural diversity of boron-containing heterocycles, we report herein the preparation of novel monocyclic hemiboronic acids, diazaborines. These compounds have enabled the study of a pseudoaromatic boranol-containing (B-OH) ring free of influence from an appended aromatic system. Synthetic and spectroscopic studies have provided insight into the aromatic character, Lewis acidic nature, chemical reactivity, and unique ability of the exocyclic B-OH unit to participate in hydroxy exchange, suggesting their use in organocatalysis and as reversible covalent inhibitors. Moreover, density functional theory and nucleus-independent chemical shift calculations reveal that the aromatic character of the boroheterocyclic ring is increased significantly in comparison to known bicyclic benzodiazaborines (naphthoid congeners), consequently leading to attenuated Lewis acidity. Direct structural comparison to a well-established biaryl isostere, 2-phenylphenol, through X-ray crystallographic analysis reveals that N-aryl derivatives are strikingly similar in size and conformation, with attenuated logP values underscoring the value of the polar BNN unit. Their potential application as low-molecular-weight scaffolds in drug discovery is demonstrated through orthogonal diversification and preliminary antifungal evaluation (Candida albicans), which unveiled analogs with low micromolar inhibitory concentration.

2.
J Laryngol Otol ; : 1-7, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602176

ABSTRACT

BACKGROUND: Rhinological procedures demand a high degree of technical expertise and anatomical knowledge. Because of limited surgical opportunities, ethical considerations and the complexity of these procedures, simulation-based training has become increasingly important. This review aimed to evaluate the effectiveness of simulation models used in rhinology training. METHODS: Searches were conducted on PubMed, Embase, Cochrane and Google Scholar for studies conducted between July 2012 and July 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis ('PRISMA') protocol defined a final list of articles. Each validated study was assigned a level of evidence and a level of recommendation based on the Oxford Centre of Evidence-Based Medicine classification. RESULTS: Following exclusions, 42 articles were identified which encompassed six types of simulation models and 26 studies evaluated validity. The rhinological skills assessed included endoscopic sinus surgery (n = 28), skull base/cerebrospinal fluid leak repair (n = 14), management of epistaxis and/or sphenopalatine artery ligation (n = 8), and septoplasty and septorhinoplasty (n = 6). All studies reported the beneficial impact of their simulation models on trainee development. CONCLUSION: Simulation training in rhinology is a valuable adjunct to traditional surgical education. Although evidence is of moderate quality, the findings highlight the importance of simulation-based training in rhinology training.

3.
Hernia ; 28(3): 839-846, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38366238

ABSTRACT

INTRODUCTION: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines. Given the limited literature and lack of consensus or guidelines for dealing with these hernias, we planned for a Delphi consensus to aid in decision making to repair subcostal hernias. METHODS: We adopted a modified Delphi technique to establish consensus regarding the definition, characteristics, and surgical aspects of managing subcostal hernias (SCH). It was a four-phase Delphi study reflecting the widely accepted model, consisting of: 1. Creating a query. 2. Building an expert panel. 3. Executing the Delphi rounds. 4. Analysing, presenting, and reporting the Delphi results. More than 70% of agreement was defined as a consensus statement. RESULTS: The 22 experts who agreed to participate in this Delphi process for Subcostal Hernias (SCH) comprised 7 UK surgeons, 6 mainland European surgeons, 4 Indians, 3 from the USA, and 2 from Southeast Asia. This Delphi study on subcostal hernias achieved consensus on the following areas-use of mesh in elective cases; the retromuscular position with strong discouragement for onlay mesh; use of macroporous medium-weight polypropylene mesh; use of the subcostal incision over midline incision if there is no previous midline incision; TAR over ACST; defect closure where MAS is used; transverse suturing over vertical suturing for closure of circular defects; and use of peritoneal flap when necessary. CONCLUSION: This Delphi consensus defines subcostal hernias and gives insight into the consensus for incision, dissection plane, mesh placement, mesh type, and mesh fixation for these hernias.


Subject(s)
Consensus , Delphi Technique , Herniorrhaphy , Surgical Mesh , Humans , Herniorrhaphy/methods
4.
J Craniofac Surg ; 33(3): 875-881, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35050560

ABSTRACT

OBJECTIVES: Information about the endonasal endoscopic approach (EEA) for the management of posttraumatic tension pneumocephalus (PTTP) remains scarce. Concomitant rhinoliquorrhea and posttraumatic hydrocephalus (PTH) can complicate the clinical course. METHODS: The authors systematically reviewed pertinent articles published between 1961 and December 2020 and identified 6 patients with PTTP treated by EEA in 5 reports. Additionally, the authors share their institutional experience including a seventh patient, where an EEA resolved a recurrent PTTP without rhinoliquorrhea. RESULTS: Seven PTTP cases in which EEA was used as part of the treatment regime were included in this review. All cases presented with a defect in the anterior skull base, and 3 of them had concomitant rhinoliquorrhea. A transcranial approach was performed in 6/7 cases before EEA was considered to treat PTTP. In 4/7 cases, the PTTP resolved after the first intent; in 2/ 7 cases a second repair was necessary because of recurrent PTTP, 1 with and 1 without rhinoliquorrhea, and 1/7 case because of recurrent rhinoliquorrhea only. Overall, PTTP treated by EEA resolved with a mean radiological resolution time of 69 days (range 23-150 days), with no late recurrences. Only 1 patient developed a cerebrospinal fluid diversion infection probably related to a first incomplete EEA skull base defects repair. A permanent cerebrospinal fluid diversion was necessary in 3/7 cases. CONCLUSIONS: Endonasal endoscopic approach repair of air conduits is a safe and efficacious second-line approach after failed transcranial approaches for symptomatic PTTP. However, the strength of recommendation for EEA remains low until further evidence is presented.


Subject(s)
Pneumocephalus , Endoscopy/adverse effects , Humans , Nose , Pneumocephalus/diagnostic imaging , Pneumocephalus/etiology , Pneumocephalus/surgery , Postoperative Complications/etiology , Retrospective Studies , Skull Base/diagnostic imaging , Skull Base/surgery
5.
BJS Open ; 5(5)2021 09 06.
Article in English | MEDLINE | ID: mdl-34568888

ABSTRACT

BACKGROUND: The incidence of incisional hernia after major abdominal surgery via a midline laparotomy is 20-41 per cent with short-term follow-up, and over 50 per cent in those surviving an abdominal catastrophe. Abdominal wall reconstruction (AWR) requires complex operations, often involving mesh resection, management of scarred skin, fistula takedown, component separation or flap reconstruction. Patients tend to have more complex conditions, with multiple co-morbidities predisposing them to a vicious cycle of complications and, subsequently, hernia recurrence. Currently there appears to be variance in perioperative practice and minimal guidance globally. The aim of this Delphi consensus was to provide a clear benchmark of care for the preoperative assessment and perioperative optimization of patients undergoing AWR. METHODS: The Delphi method was used to achieve consensus from invited experts in the field of AWR. Thirty-two hernia surgeons from recognized hernia societies globally took part. The process included two rounds of anonymous web-based voting with response analysis and formal feedback, concluding with a live round of voting followed by discussion at an international conference. Consensus for a strong recommendation was achieved with 80 per cent agreement, and a weak recommendation with 75 per cent agreement. RESULTS: Consensus was obtained on 52 statements including surgical assessment, preoperative assessment, perioperative optimization, multidisciplinary team and decision-making, and quality-of-life assessment. Forty-six achieved over 80 per cent agreement; 14 statements achieved over 95 per cent agreement. CONCLUSION: Clear consensus recommendations from a global group of experts in the AWR field are presented in this study. These should be used as a baseline for surgeons and centres managing abdominal wall hernias and performing complex AWR.


Subject(s)
Hernia, Abdominal , Incisional Hernia , Consensus , Delphi Technique , Humans , Surgical Flaps
6.
Tech Coloproctol ; 25(9): 1027-1036, 2021 09.
Article in English | MEDLINE | ID: mdl-34117969

ABSTRACT

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an uncommon cancer associated with human immunodeficiency virus (HIV) infection. There has been increasing interest in providing organ-sparing treatment in small node-negative ASCC's, however, there is a paucity of evidence about the use of local excision alone in people living with HIV (PLWH). The aim of this study was to evaluate the efficacy of local excision alone in this patient population. METHODS: We present a case series of stage 1 and stage 2 ASCC in PLWH and HIV negative patients. Data were extracted from a 20-year retrospective cohort study analysing the treatment and outcomes of patients with primary ASCC in a cohort with a high prevalence of HIV. RESULTS: Ninety-four patients were included in the analysis. Fifty-seven (61%) were PLWH. Thirty-five (37%) patients received local excision alone as treatment for ASCC, they were more likely to be younger (p = 0.037, ANOVA) and have either foci of malignancy or well-differentiated tumours on histology (p = 0.002, Fisher's exact test). There was no statistically significant difference in 5-year disease-free survival and recurrence between treatment groups, however, patients who had local excision alone and PLWH were both more likely to recur later compared to patients who received other treatments for ASCC. (72.3 months vs 27.3 months, p = 0.06, ANOVA, and 72.3 months vs 31.8 months, p = 0.035, ANOVA, respectively). CONCLUSIONS: We recommend that local excision be considered the sole treatment for stage 1 node-negative tumours that have clear margins and advantageous histology regardless of HIV status. However, PLWH who have local excision alone must have access to an expert long-term surveillance programme after treatment to identify late recurrences.


Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , HIV Infections , Anus Neoplasms/epidemiology , Anus Neoplasms/surgery , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/surgery , HIV Infections/complications , HIV Infections/epidemiology , Humans , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Retrospective Studies
7.
BJS Open ; 5(3)2021 05 07.
Article in English | MEDLINE | ID: mdl-34013317

ABSTRACT

BACKGROUND: Colorectal multidisciplinary teams (CR MDTs) were introduced to enhance the cancer care pathway and allow for early investigation and treatment of cancer. However, there are no 'gold standards' set for this process. The aim of this study was to review the literature systematically and provide a qualitative analysis on the principles, organization, structure and output of CR MDTs internationally. METHODS: Literature on the role of CR MDTs published between January 1999 and March 2020 in the UK, USA and continental Europe was evaluated. Historical background, structure, core members, education, frequency, patient-selection criteria, quality assurance, clinical output and outcomes were extracted from data from the UK, USA and continental Europe. RESULTS: Forty-eight studies were identified that specifically met the inclusion criteria. The majority of hospitals held CR MDTs at least fortnightly in the UK and Europe by 2002 and 2005 respectively. In the USA, monthly MDTs became a mandatory element of cancer programmes by 2013. In the UK, USA and in several European countries, the lead of the MDT meeting is a surgeon and core members include the oncologist, specialist nurse, histopathologist, radiologist and gastroenterologist. There were differences observed in patient-selection criteria, in the use of information technology, MDT databases and quality assurance internationally. CONCLUSION: CR MDTs are essential in improving the patient care pathway and should express clear recommendations for each patient. However, a form of quality assurance should be implemented across all MDTs.


Subject(s)
Colorectal Neoplasms , Patient Care Team , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Europe , Humans
8.
J Orthop Res ; 39(11): 2455-2464, 2021 11.
Article in English | MEDLINE | ID: mdl-33470467

ABSTRACT

Antibiotic-loaded chitosan pastes have shown advantages in the treatment and coverage of complex musculoskeletal defects. We added mannitol, previously shown to increase antibiotic susceptibility of biofilm, to an injectable chitosan/polyethylene glycol paste for delivery of antibiotics. Ground sponges (0.85% acetic acid solution, 1% chitosan, 0% or 2% mannitol, 1% polyethylene glycol) were hydrated using phosphate-buffered saline with 10 mg/ml amikacin and 10 mg/ml vancomycin added to form pastes. We inoculated rabbit radial defects with 105 colony-forming units of Staphylococcus aureus (UAMS-1) and inserted titanium pins into the cortical bone. Groups compared included mannitol blend pastes, non-mannitol blends, antibiotic-loaded bone cement, vancomycin powder, and no treatment controls. We harvested tissue samples and retrieved the pins retrieved at 3 weeks. All antibiotic-loaded groups lowered bacterial growth and colony-forming unit counts in soft and bone tissue and on titanium pins in in vivo studies. The results indicate this biomaterial is capable of eluting active antibiotics at concentrations that reduce bacterial growth on biomaterials and tissue, which, in turn, may prevent biofilm formation. Blends of chitosan and mannitol may be useful in prevention and treatment of osteomyelitis and implant-associated infections.


Subject(s)
Chitosan , Osteomyelitis , Staphylococcal Infections , Animals , Anti-Bacterial Agents/therapeutic use , Biocompatible Materials , Mannitol , Osteomyelitis/drug therapy , Osteomyelitis/microbiology , Osteomyelitis/prevention & control , Polyethylene Glycols , Rabbits , Staphylococcal Infections/drug therapy , Staphylococcal Infections/prevention & control , Titanium , Vancomycin
9.
Hernia ; 25(2): 491-500, 2021 04.
Article in English | MEDLINE | ID: mdl-32415651

ABSTRACT

INTRODUCTION: Abdominal wall herniation (AWH) is an increasing problem for patients, surgeons, and healthcare providers. Surgical-site specific outcomes, such as infection, recurrence, and mesh explantation, are improving; however, successful repair still exposes the patient to what is often a complex major operation aimed at improving quality of life. Quality-of-life (QOL) outcomes, such as aesthetics, pain, and physical and emotional functioning, are less often and less well reported. We reviewed QOL tools currently available to evaluate their suitability. METHODS: A systematic review of the literature in compliance with PRISMA guidelines was performed between 1st January 1990 and 1st May 2019. English language studies using validated quality-of-life assessment tool, whereby outcomes using this tool could be assessed were included. RESULTS: Heterogeneity in the QOL tool used for reporting outcome was evident throughout the articles reviewed. AWH disease-specific tools, hernia-specific tools, and generic tools were used throughout the literature with no obviously preferred or dominant method identified. CONCLUSION: Despite increasing acknowledgement of the need to evaluate QOL in patients with AWH, no tool has become dominant in this field. Assessment, therefore, of the impact of certain interventions or techniques on quality of life remains difficult and will continue to do so until an adequate standardised outcome measurement tool is available.


Subject(s)
Abdominal Wall , Hernia, Ventral , Abdominal Wall/surgery , Hernia, Ventral/surgery , Herniorrhaphy , Humans , Quality of Life , Recurrence , Surgical Mesh
10.
Hernia ; 24(6): 1361-1370, 2020 12.
Article in English | MEDLINE | ID: mdl-32300901

ABSTRACT

BACKGROUND: There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes. METHODS: A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data. RESULTS: 201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation. CONCLUSION: There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined.


Subject(s)
Abdominal Wall/surgery , Digestive System Surgical Procedures/methods , Herniorrhaphy/methods , Sarcopenia/therapy , Female , Humans , Male , Middle Aged , Prognosis
11.
Colorectal Dis ; 22(10): 1231-1244, 2020 10.
Article in English | MEDLINE | ID: mdl-31999888

ABSTRACT

AIM: The aim was to assess the benefit of adjuvant chemotherapy in high-risk Stage II colorectal cancer. METHOD: A systematic literature review and meta-analysis was performed comparing survival in patients with resected Stage II colorectal cancer and high-risk features having postoperative chemotherapy vs no chemotherapy. RESULTS: Of 1031 articles screened, 29 were included, reporting on 183 749 participants. Adjuvant chemotherapy significantly improved overall survival [hazard ratio (HR) 0.61, P < 0.0001], disease-specific survival (HR = 0.73, P = 0.05) and disease-free survival (HR = 0.59, P < 0.0001) compared to no chemotherapy. Adjuvant chemotherapy significantly increased 5-year overall survival (OR = 0.53, P = 0.0008) and 5-year disease-free survival (OR = 0.50, P = 0.001). Overall survival and disease-free survival remained significantly prolonged during subgroup analysis of studies published from 2015 onwards (HR = 0.60, P < 0.0001; HR = 0.65, P = 0.0001; respectively), in patients with two or more high-risk features (HR = 0.59, P = 0.0001; HR = 0.70, P = 0.03; respectively) and in colon cancer (HR = 0.61, P < 0.0001; HR = 0.51, P = 0.0001; respectively). Overall survival, disease-specific survival and disease-free survival during subgroup analysis of individual high-risk features were T4 tumour (HR = 0.58, P < 0.0001; HR = 0.50, P = 0.003; HR = 0.75, P = 0.05), < 12 lymph nodes harvested (HR = 0.67, P = 0.0002; HR = 0.80, P = 0.17; HR = 0.72, P = 0.02), poor differentiation (HR = 0.84, P = 0.35; HR = 0.85, P = 0.23; HR = 0.61, P = 0.41), lymphovascular or perineural invasion (HR = 0.55, P = 0.05; HR = 0.59, P = 0.11; HR = 0.76, P = 0.05) and emergency surgery (HR = 0.60, P = 0.02; HR = 0.68, P = 0.19). CONCLUSION: Adjuvant chemotherapy in high-risk Stage II colorectal cancer results in a modest survival improvement and should be considered on an individual patient basis. Due to potential heterogeneity and selection bias of the included studies, and lack of separate rectal cancer data, further large randomized trials with predefined inclusion criteria and standardized chemotherapy regimens are required.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Chemotherapy, Adjuvant , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Disease-Free Survival , Humans , Rectal Neoplasms/drug therapy
12.
Mar Drugs ; 17(9)2019 Sep 02.
Article in English | MEDLINE | ID: mdl-31480687

ABSTRACT

Mannitol, a polyalcohol bacterial metabolite, has been shown to activate dormant persister cells within bacterial biofilm. This study sought to evaluate an injectable blend of mannitol, chitosan, and polyethylene glycol for delivery of antibiotics and mannitol for eradication of Staphylococcal biofilm. Mannitol blends were injectable and had decreased dissociation and degradation in the enzyme lysozyme compared to blends without mannitol. Vancomycin and amikacin eluted in a burst response, with active concentrations extended to seven days compared to five days for blends without mannitol. Mannitol eluted from the paste in a burst the first day and continued through Day 4. Eluates from the mannitol pastes with and without antibiotics decreased viability of established S. aureus biofilm by up to 95.5% compared to blends without mannitol, which only decreased biofilm when loaded with antibiotics. Cytocompatibility tests indicated no adverse effects on viability of fibroblasts. In vivo evaluation of inflammatory response revealed mannitol blends scored within the 2-4 range at Week 1 (2.6 ± 1.1) and at Week 4 (3.0 ± 0.8), indicative of moderate inflammation and comparable to non-mannitol pastes (p = 0.065). Clinically, this paste could be loaded with clinician-selected antibiotics and used as an adjunctive therapy for musculoskeletal infection prevention and treatment.


Subject(s)
Anti-Bacterial Agents/chemistry , Chitosan/chemistry , Mannitol/chemistry , Amikacin/chemistry , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Drug Carriers/chemistry , Drug Delivery Systems/methods , Inflammation/drug therapy , Microbial Sensitivity Tests/methods , Polyethylene Glycols/chemistry , Staphylococcus aureus/drug effects , Vancomycin/chemistry , Vancomycin/pharmacology
14.
Int J Biol Macromol ; 133: 372-381, 2019 Jul 15.
Article in English | MEDLINE | ID: mdl-30986460

ABSTRACT

Advanced local delivery systems are needed as adjunctive treatments for severe injuries with high infection rates, such as open fractures. Chitosan systems have been investigated as antimicrobial local delivery systems for orthopaedic infection but possess mismatches between elution and degradation properties. Derivatives of chitosan were chosen that have enhanced swelling ratios or tailorable degradation properties. A combination of trimethyl chitosan and poly(ethylene glycol) diacrylate chitosan was developed as an injectable local delivery system. Research objectives were elution of antimicrobials for 7 days, degradation as open fractures heal, and cytocompatibility. The derivative combination eluted increased active concentrations of vancomycin and amikacin compared to the non-derivatized chitosan paste, 6 vs. 5 days and 5 vs. 4 days, respectively. The derivative combination degraded slower than non-derivatized paste in an enzymatic degradation study, 14 vs. 3 days, which increased antimicrobial delivery duration. Cytocompatibility of the combination with fibroblast and pre-osteoblast cells exceeds the cell viability standard set in ISO 10993-5. Combination paste requires an increased ejection force of 9.40 N (vs. 0.64 N), but this force was within an acceptable injection force threshold, 80 N. These preliminary results indicate combination paste should be further developed into a clinically useful adjunctive local delivery system for infection prevention.


Subject(s)
Anti-Bacterial Agents/chemistry , Chitosan/chemistry , Chitosan/metabolism , Drug Carriers/chemistry , Drug Carriers/metabolism , Polyethylene Glycols/chemistry , Amikacin/chemistry , Amikacin/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Chitosan/toxicity , Drug Carriers/toxicity , Injections , Materials Testing , Mice , Muramidase/metabolism , NIH 3T3 Cells , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Vancomycin/chemistry , Vancomycin/pharmacology , Viscosity
16.
J Magn Reson Imaging ; 49(3): 894-903, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30230107

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) can involve prostate and seminal vesicles but the potential interrelationship of these findings and associations with PKD gene mutation locus and type is unknown. PURPOSE: To determine the interrelationship of seminal megavesicles (seminal vesicles with lumen diameter > 10mm) and prostatic cysts in ADPKD and to determine whether there are associations with PKD gene mutations. STUDY TYPE: Retrospective, case control. POPULATION: Male ADPKD subjects (n = 92) with mutations in PKD1 (n = 71; 77%) or PKD2 (n = 21; 23%), and age/gender-matched controls without ADPKD (n = 92). FIELD STRENGTH/SEQUENCE: 1.5T, axial/coronal T2 -weighted MR images. ASSESSMENT: Reviewers blinded to genotype independently measured seminal vesicle lumen diameter and prevalence of cysts in prostate, kidney, and liver. STATISTICAL TESTS: Nonparametric tests for group comparisons and univariate and multivariable logistic regression analyses to identify associations of megavesicles and prostate median cysts with mutations and renal/hepatic cyst burden. RESULTS: Seminal megavesicles were found in 23 of 92 ADPKD (25%) subjects with PKD1 (22/71, 31%) or PKD2 (n = 1/21, 5%) mutations, but in only two control subjects (P < 0.0001). Prostate median cysts were found in 17/92 (18%) ADPKD subjects, compared with only 6/92 (7%) controls (P = 0.01), and were correlated with seminal vesicle diameters (ρ = 0.24, P = 0.02). Nonmedian prostate cyst prevalence was identical between ADPKD and controls (7/92, 8%). After adjusting for age, estimated glomerular filtration rate, and height-adjusted total kidney volume, ADPKD subjects with megavesicles were 10 times more likely to have a PKD1 than a PKD2 mutation. Among PKD1 subjects, seminal megavesicles occurred more frequently with nontruncating mutations with less severe kidney involvement. DATA CONCLUSION: ADPKD is associated with prostate median cysts near ejaculatory ducts. These cysts correlate with seminal megavesicles (dilated to >10 mm) which predict a 10-fold greater likelihood of PKD1 vs. PKD2 mutation. Cysts elsewhere in the prostate are not related to ADPKD. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:894-903.


Subject(s)
Cysts/diagnostic imaging , Cysts/genetics , Polycystic Kidney, Autosomal Dominant/diagnostic imaging , Polycystic Kidney, Autosomal Dominant/genetics , Prostate/diagnostic imaging , Seminal Vesicles/diagnostic imaging , Adult , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Glomerular Filtration Rate , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Retrospective Studies , TRPP Cation Channels/genetics
17.
BJS Open ; 2(6): 433-451, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30511044

ABSTRACT

A comparison between NCCN, ESMO and JSCCR Guidelines is presented, concerning the treatment of rectal cancer, with an analysis and discussion of their discrepancies. Differences indicate areas for research.

19.
J Am Soc Nephrol ; 29(8): 2139-2156, 2018 08.
Article in English | MEDLINE | ID: mdl-30042192

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy caused by mutations in PKD1 and PKD2 that is characterized by renal tubular epithelial cell proliferation and progressive CKD. Although the molecular mechanisms involved in cystogenesis are not established, concurrent inactivating constitutional and somatic mutations in ADPKD genes in cyst epithelium have been proposed as a cellular recessive mechanism. METHODS: We characterized, by whole-exome sequencing (WES) and long-range PCR techniques, the somatic mutations in PKD1 and PKD2 genes in renal epithelial cells from 83 kidney cysts obtained from nine patients with ADPKD, for whom a constitutional mutation in PKD1 or PKD2 was identified. RESULTS: Complete sequencing data by long-range PCR and WES was available for 63 and 65 cysts, respectively. Private somatic mutations of PKD1 or PKD2 were identified in all patients and in 90% of the cysts analyzed; 90% of these mutations were truncating, splice site, or in-frame variations predicted to be pathogenic mutations. No trans-heterozygous mutations of PKD1 or PKD2 genes were identified. Copy number changes of PKD1 ranging from 151 bp to 28 kb were observed in 12% of the cysts. WES also identified significant mutations in 53 non-PKD1/2 genes, including other ciliopathy genes and cancer-related genes. CONCLUSIONS: These findings support a cellular recessive mechanism for cyst formation in ADPKD caused primarily by inactivating constitutional and somatic mutations of PKD1 or PKD2 in kidney cyst epithelium. The potential interactions of these genes with other ciliopathy- and cancer-related genes to influence ADPKD severity merits further evaluation.


Subject(s)
Epithelial Cells/metabolism , Kidney Transplantation/methods , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/surgery , TRPP Cation Channels/genetics , Adult , Cell Proliferation/genetics , Cells, Cultured , Cohort Studies , Female , Humans , Male , Mutation/genetics , Podocytes/metabolism , Polycystic Kidney, Autosomal Dominant/physiopathology , Preoperative Care , Prognosis , Prospective Studies , Real-Time Polymerase Chain Reaction , Exome Sequencing
20.
Acta Chir Belg ; 118(5): 273-277, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29911510

ABSTRACT

Mixed adenoneuroendocrine carcinoma (MANEC) are rare cancers of the gastrointestinal (GI) and pancreatobiliary tract. They are characterized by the presence of a combination of epithelial and neuroendocrine elements, where each component represents at least 30% of the tumour. Review of literature and consolidation of clinicopathological data. Sixty-one cases of colorectal MANEC have been reported in literature and one seen in this centre. The median age of the patients affected was 61.9 ± 12.4 years (20-94 years). Male to female ratio is 1.0:1.2. Presentations were similar to other colorectal malignancies. 58.0% of colorectal MANECs were found in the right colon, 8.1% cases in the transverse, 16.1% in the left colon, 16.1% in the rectum. These tumours appeared invasiveness 79.1% were T3-T4. Over 90% of cases were presented with metastatic disease. The majority of patient underwent surgical resection of the primary cancer (96.6%). Of these, 10 operations (17.9%) were emergency operations due to obstruction, perforation, or bleeding. Three patients received first line palliative care. In eight cases (13.8%), patients underwent adjuvant chemotherapy. The median overall survival after diagnosis was 10 ± 2.4 months (95% CI: 5.37-14.64 months). MANECs are rare but aggressive colorectal cancers. Surgical resection of localized disease with adjuvant chemotherapy appears to significantly improve survival in small case series. Further understanding through the sharing of experiences is required.


Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Adult , Aged , Colectomy/methods , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/surgery , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Prognosis , Rare Diseases , Risk Assessment , Survival Analysis , Treatment Outcome
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