Interventions that Facilitate Shared Decision-Making in Cancers with Active Surveillance as Treatment Option: a Systematic Review of Literature.

PURPOSE OF REVIEW: Medical decisions concerning active surveillance are complex, especially when evidence on superiority of one of the treatments is lacking. Decision aids have been developed to facilitate shared decision-making on whether to pursue an active surveillance strategy. However, it is unclear how these decision aids are designed and which outcomes are considered relevant. The purpose of this study is to systematically review all decision aids in the field of oncological active surveillance strategies and outcomes used by authors to assess their efficacy. RECENT FINDINGS: A search was performed in Embase, Medline, Web of Science, Cochrane, PsycINFO Ovid and Google Scholar until June 2019. Eligible studies concerned interventions aiming to facilitate shared decision-making for patients confronted with several treatment alternatives, with active surveillance being one of the treatment alternatives. Twenty-three eligible articles were included. Twenty-one articles included patients with prostate cancer, one with thyroid cancer and one with ovarian cancer. Interventions mostly consisted of an interactive web-based decision aid format. After categorization of outcomes, seven main groups were identified: knowledge, involvement in decision-making, decisional conflict, treatment preference, decision regret, anxiety and health-related outcomes. Although active surveillance has been implemented for several malignancies, interventions that facilitate shared decision-making between active surveillance and other equally effective treatment alternatives are scarce. Future research should focus on developing interventions for malignancies like rectal cancer and oesophageal cancer as well. The efficacy of interventions is mostly assessed using short-term outcomes.

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative.

BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. MATERIAL AND METHODS: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. RESULTS: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. CONCLUSION: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting.

Omics-based identification of the combined effects of idiosyncratic drugs and inflammatory cytokines on the development of drug-induced liver injury.

The mechanisms of idiosyncratic drug-induced hepatotoxicity remain largely unclear. It has demonstrated that the drug idiosyncrasy is potentiated in the context of inflammation and intracellular ceramides may play a role in this process. To study the mechanisms, HepG2 cells were co-treated with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, with (I+ and N+) or without (I- and N-) a cytokine mix. Microarray, lipidomics and flow cytometry were performed to investigate the genome-wide expression patterns, the intracellular ceramide levels and the induction of apoptosis. We found that all I+ treatments significantly influenced the immune response- and response to stimulus-associated gene ontology (GO) terms, but the induction of apoptotic pathways, which was confirmed by flow cytometry, only appeared to be induced after the high-dose treatment. The ceramide signaling-, ER stress-, NF-kB activation- and mitochondrial activity-related pathways were biologically involved in apoptosis induced by the high-dose I+. Additionally, genes participating in ceramide metabolism were significantly altered resulting in a measurable increase in ceramide levels. The increases in ceramide concentrations may induce ER stress and activate the JNK pathway by affecting the expression of the related genes, and eventually trigger the mitochondria-independent apoptosis in hepatocytes. Overall, our study provides a potential mechanism to explain the role of inflammation in idiosyncratic drug reactions.

[Correlation between ICIQ-UI-SF score and personality testing results over a urinary incontinent population]. / Corrélation entre le score de l'ICIQ-UI-SF et les résultats d'un test psychométrique de personnalité d'une population ayant une incontinence urinaire.

OBJECTIVE: We found out the personality pattern of an incontinent population and proceeded to a correlation between the personality inventory and the ICIQ-UI-SF (International Consultation Incontinence Questionnaire Urinary Incontinence Short Form) to demonstrate reliability and sincerity of the answers and to establish that a personality disturbance may impact the physiopathology of micturition. MATERIALS AND METHODS: We performed an observational prospective study. It included patient's answers to a computed questionnaire combining a double ICIQ-UI-SF questionnaire and the 71 questions of the Minimult questionnaire. Forty-seven patients were asked to participate. RESULTS: Over 37 patients included, Wilcoxon-Mann-Whitney non parametric test confirmed agreement of the two ICIQ-UI-SF questionnaires with P=0.1792. Twenty-three patients were validated to the Minimult inventory with F scale<70. We analysed variability of the two global ICIQ-UI-SF score in regard with the validity scale using ROC analysis. We observed an AUC of 0.559 with sensitivity 78.6% and specificity 43.5%. No L score was above 70 demonstrating absence of lie. No personality disturbance was found in 9 cases. We observed six cases with a high hypochondric value, five with a high depressive value, and four with a high hysteric value. This neurotic triad was found in two cases. We noticed five cases with psychopathic deviance relative to antisocial behaviour while values of paranoia and hypomania were high in one case without any association of these personality aspects, which demonstrated absence of behavioural problem. Psychotic profile associating schizophrenia, paranoia, depression and hypomania was not found. We outlined in half of the valid population a significant high psycho-asthenic pattern. CONCLUSION: We conclude that a correlation between the personality inventory and the ICIQ-UI-SF is feasible. The comparative study demonstrate reliability of answers. Sincerity is established by the Minimult L scale. We confirm and precise literature information over clinical personality pattern of this population and observe relevant elements concerning the psycho-asthenic pattern which depicts an anxious personality with an important feeling of the problem. These elements permit to suspect that a personality disturbance may impact the physiopathology of the micturition. LEVEL OF EVIDENCE: 4.

Meta-analysis of glue versus sutured mesh fixation for Lichtenstein inguinal hernia repair.

BACKGROUND: Chronic pain remains a frequent complication after Lichtenstein inguinal hernia repair. As a consequence, mesh fixation using glue instead of sutures has become popular. This meta-analysis aimed to clarify which fixation technique is to be preferred for elective Lichtenstein inguinal hernia repair. METHODS: A meta-analysis was conducted according to the PRISMA guidelines. Articles published between January 1990 and April 2012 were searched for in MEDLINE, Embase and the Cochrane Library. Randomized controlled trials (RCTs) comparing glue and sutured mesh fixation in elective Lichtenstein repair for unilateral inguinal hernia were included. The quality of the RCTs and the potential risk of bias were assessed using the Cochrane risk of bias tool. RESULTS: Of 254 papers found in the initial search, a meta-analysis was conducted of seven RCTs comprising 1185 patients. With the use of glue mesh fixation, the duration of operation was shorter (mean difference -2·57 (95 per cent confidence interval (c.i.) -4·88 to -0·26) min; P = 0·03), patients had lower visual analogue scores for postoperative pain (mean difference -0·75 (-1·18 to -0·33); P = 0·001), early chronic pain occurred less often (risk ratio 0·52, 95 per cent c.i. 0·31 to 0·87; P = 0·01), and time to return to daily activities was shorter (mean difference -1·17 (-2·30 to -0·03) days; P = 0·04). The hernia recurrence rate did not differ significantly. CONCLUSION: Elective Lichtenstein repair for inguinal hernia using glue mesh fixation compared with sutures is faster and less painful, with comparable hernia recurrence rates.

The principles of abdominal wound closure.

BACKGROUND: Incisional hernia (IH) is a common complication of abdominal surgery. Its incidence has been reported as high as 39.9%. Many factors influence IH rates. Of these, surgical technique is the only factor directly controlled by the surgeon. There is much evidence in the literature on the optimal midline laparotomy closure technique. Despite the high level of evidence, this optimal closure technique has not met wide acceptance in the surgical community. In preparation of a clinical trial, the PRINCIPLES trial, a literature review was conducted to find the best evidence based technique for abdominal wall closure after midline laparotomy. METHODS: An Embase search was performed. Articles describing closure of the fascia after midline laparotomy by different suture techniques and/or suture materials were selected. RESULTS: Fifteen studies were identified, including five meta-analyses. Analysis of the literature showed significant lower IH rates with single layer closure, using a continuous technique with slowly absorbable suture material. No significant difference in IH incidence was found comparing slowly absorbable and non absorbable sutures. Furthermore, a suture length to wound length ratio of four or more and short stitch length significantly decreased IH rates. CONCLUSIONS: Careful analysis of the literature indicates that an evidenced based optimal midline laparotomy closure technique can be identified. This technique involves single layer closure with a running suture, using a slowly absorbable suture with a suture length to wound length ratio of four or more and a short stitch length. We adopt this technique as the PRINCIPLES technique.

Prevention of incisional hernia after midline laparotomy with prophylactic mesh reinforcement: a meta-analysis and trial sequential analysis.

BACKGROUND: Incisional hernia is a frequent complication after abdominal surgery. The aim of this study was to assess the efficacy of prophylactic mesh reinforcement (PMR) after midline laparotomy in reducing the incidence of incisional hernia. METHODS: A meta-analysis was conducted following PRISMA guidelines. The primary outcome was the incidence of incisional hernia after follow-up of at least 12 months. Secondary outcomes were postoperative complications. Only RCTs were included. A random-effects model was used for the meta-analysis, and trial sequential analysis was conducted. RESULTS: Twelve RCTs were included, comprising 1815 patients. The incidence of incisional hernia was significantly lower after PMR compared with sutured closure (risk ratio (RR) 0·35, 95 per cent c.i. 0·21 to 0·57; P < 0·001). Both onlay (RR 0·26, 0·11 to 0·67; P = 0·005) and retromuscular (RR 0·28, 0·10 to 0·82; P = 0·02) PMR led to a significant reduction in the rate of incisional hernia. The occurrence of seroma was higher in patients who had onlay PMR (RR 2·23, 1·10 to 4·52; P = 0·03). PMR did not result in an increased rate of surgical-site infection. CONCLUSION: PMR of a midline laparotomy using an onlay or retromuscular technique leads to a significant reduction in the rate of incisional hernia in high-risk patients. Individual risk factors should be taken into account to select patients who will benefit most. [Correction added on 19 February 2020, after first online publication: J. García Alamino has been amended to J. M. Garcia-Alamino].

ANTECEDENTES: La eventración (hernia incisional) es una complicación frecuente de la cirugía abdominal. El objetivo es evaluar la eficacia de la inserción de una malla profiláctica de refuerzo (prophylactic mesh reinforcement, PMR) después de la laparotomía media para reducir la incidencia de eventración. MÉTODOS: Se realizó un metaanálisis siguiendo las recomendaciones PRISMA. La variable principal fue la incidencia de eventración después de un seguimiento mínimo de 12 meses. Las variables secundarias fueron las complicaciones postoperatorias. Solo se incluyeron ensayos controlados aleatorizados. Se utilizó un modelo de efectos aleatorios para el metaanálisis y se realizó un análisis secuencial de los ensayos. RESULTADOS: Se incluyeron 12 ensayos aleatorizados y controlados con 1.815 pacientes. La incidencia de eventración fue significativamente menor después de la PMR en comparación con el cierre simple (riesgo relativo, RR 0,35; i.c. del 95%: 0,21-0,57, P < 0,0001). Hubo una reducción significativa de la tasa de eventración tanto si la PMR se colocó en posición supra-aponeurótica (RR 0,26; i.c. del 95% 0,11-0,67, P = 0,005) como retromuscular (RR 0,28; i.c. del 95% 0,0-0,82, P = 0,02). La aparición de seromas fue mayor en los pacientes con RPM supra-aponeurótica (RR 2,23; i.c. del 95% 1,10-4,52, P = 0,03). La PMR no conllevó una mayor tasa de infecciones de la herida quirúrgica. CONCLUSIÓN: Una PMR en una laparotomía de la línea media, tanto en posición supra-aponeurótica como retromuscular, reduce de forma significativa el desarrollo de eventraciones en pacientes de alto riesgo. Se deben considerar los factores de riesgo individuales para seleccionar a los pacientes que más puedan beneficiarse.

Treatment of extra-articular proximal and middle phalangeal fractures of the hand: a systematic review.

The aim of the study was to systematically review the patient reported and functional outcomes of treatment for extra-articular proximal or middle phalangeal fractures of the hand in order to determine the best treatment options. The review methodology was registered with PROSPERO. A systematic literature search was conducted in electronic bibliographic databases. Two independent reviewers performed screening and data extraction. The evaluation of quality of the included studies was performed using the Structured Effectiveness Quality Evaluation scale. The initial search yielded 2354 studies. The full text manuscripts of 79 studies were evaluated of which 16 studies met the inclusion criteria. In total, 513 extra-articular proximal and middle phalangeal fractures of the hand were included of which 118 (23%) were treated non-operatively, 188 (37%) were treated by closed reduction internal fixation (CRIF) and 207 (40%) by open reduction internal fixation. It can be recommended that closed displaced extra-articular phalangeal fractures can be treated non-operatively, even fractures with an oblique or complex pattern, provided that closed reduction is possible and maintained. Conservative treatment is preferably performed with a cast/brace allowing free mobilization of the wrist. No definite conclusion could be drawn upon whether closed reduction with extra-articular K-wire pinning or transarticular pinning is superior; however, it might be suggested that extra-articular K-wire pinning is favoured. When open reduction is necessary for oblique or spiral extra-articular fractures, lag screw fixation is preferable to plate and screw fixation. But, similar recovery and functional results are achieved with transversally inserted K-wires compared to lag screw fixation. TYPE OF STUDY/LEVEL OF EVIDENCE: therapeutic III.

The idiosyncratic drug-induced gene expression changes in HepG2 cells.

The inflammatory stress has been associated with an increase in susceptibility to idiosyncratic drug-induced liver injury (DILI). However, the molecular mechanisms of this inflammation-associated idiosyncratic drug hepatotoxicity remain unknown. We exposed HepG2 cells with high and low doses of three idiosyncratic (I) and three non-idiosyncratic (N) compounds, in the presence (I+ and N+) or absence (I- and N-) of a cytokine mix for 6, 12 and 24 h. To investigate the genome-wide expression patterns, microarray was performed using the Agilent 4×44K Whole Human Genome chips. The data presented in this DIB include the expression of genes participating in the ceramide metabolism, ER stress, apoptosis and cell survival pathways. The functions of these genes were illustrated in our associated article (Jiang et al., 2017) [1]. Raw and normalized gene expression data are available through NCBI GEO (accession number GSE102006).

The impact of mandibular advancement on articulation, resonance and voice characteristics in Flemish speaking adults: a pilot study.

Bilateral saggital split osteotomy (BSSO) of the mandible is a frequently performed mandibular orthognathic procedure, used to resolve mandibular disharmonies. Literature review showed contradictory findings regarding the effect of the orthognathic surgery on speech characteristics. The purpose of the present study was to determine a detailed analysis of the articulation, resonance and voice characteristics after BSSO with mandibular advancement for the treatment of Class II malocclusions using objective and subjective assessment techniques (perceptual evaluations, Dysphonia Severity Index, nasalance scores) in eight subjects. The findings of the present study indicate that before and after BSSO with mandibular advancement three types of articulation disorders may predominate in the Flemish language: the incorrect production of the trill sound /r/ and the /s/ sound and devoicing of the /z/. After orthognathic surgery most patients showed an identical articulation pattern (normal or disturbed pattern) as in the presurgical condition. In this study the BSSO with mandibular advancement had no significant impact on the nasality characteristics and the nasalance values probably due to the competent velopharyngeal valving in the presurgical condition. And, as expected the vocal quality revealed no significant difference. The maxillofacial surgeon and the speech language pathologist must be aware of the persistency of these preoperative articulation errors in the postsurgical condition.

A systematic review of the surgical treatment of large incisional hernia.

PURPOSE: Incisional hernia (IH) is one of the most frequent postoperative complications. Of all patients undergoing IH repair, a vast amount have a hernia which can be defined as a large incisional hernia (LIH). The aim of this study is to identify the preferred technique for LIH repair. METHODS: A systematic review of the literature was performed and studies describing patients with IH with a diameter of 10 cm or a surface of 100 cm2 or more were included. Recurrence hazards per year were calculated for all techniques using a generalized linear model. RESULTS: Fifty-five articles were included, containing 3,945 LIH repairs. Mesh reinforced techniques displayed better recurrence rates and hazards than techniques without mesh reinforcement. Of all the mesh techniques, sublay repair, sandwich technique with sublay mesh and aponeuroplasty with intraperitoneal mesh displayed the best results (recurrence rates of <3.6%, recurrence hazard <0.5% per year). Wound complications were frequent and most often seen after complex LIH repair. CONCLUSIONS: The use of mesh during LIH repair displayed the best recurrence rates and hazards. If possible mesh in sublay position should be used in cases of LIH repair.

Origin of primordial germ cells, as characterized by the presence of nuage, in embryos of the teleost fish Barbus conchonius.

The presence, location and morphology of cells containing nuage, an ultrastructural characteristic of primordial germ cells (PGCs), is described from the moment of first morphological recognition of PGC (around 100% epiboly) in embryos of the teleost fish Barbus conchonius. Thus characterized cells were studied in relation to their cellular contacts with somatic germ layer cells, possibly involved in the determination of PGCs. The results show that from the very moment that cells, likely to be PGCs, can be light microscopically identified with morphological and positional criteria (from 10 h post fertilization (p.f.) onwards), they contain nuage near the nuclear envelope, which is a strong indication of their PGC-identity. During the studied period (9-12 h and 24 h p.f.) nuage-containing cells seem to translocate from the mesoderm towards the yolk syncytial layer (YSL). These PGCs usually appear not to be directly connected with the YSL but to remain separated from the YSL by one or more endodermal extensions, at least up to 12 h p.f. Also at 24 h p.f. somatic cells separate the PGCs from the YSL.

Recognition of surface antigens on spermatozoa of the common carp (Cyprinus carpio L., Teleostei) using monoclonal antibodies and scanning electron microscopy.

The distribution of antigenic determinants, recognized by seven anti-carp spermatozoa monoclonal antibodies (MAbs) and two anti-carp spermatogonia MAbs were studied using fresh, unfixed carp spermatozoa. The location of the antigenic determinants was analysed in light- and in scanning electron microscopy, in the latter with the backscattered imaging mode. With all seven anti-carp spermatozoa MAbs a similar regular distribution of the immuno-gold labeling was present on heads, midpieces and tails of carp spermatozoa, whereas with the anti-carp spermatogonia MAbs only low or no labeling was observed. The regular distribution of antigenic determinants, as observed with the anti-spermatozoa MAbs in carp, is in agreement with data on agglutination of spermatozoa by autoantibodies in Salmo gairdneri and data on distribution of antigenic sites on spermatozoa in Xenopus laevis. It differs from data in mammals in which the presence of specialized domains on spermatozoa was shown. These results are discussed.

Precocious onset of spermatogenesis in juvenile carp (Cyprinus carpio L., Teleostei) following treatment with low doses of L-thyroxine.

Two strains of carp (Cyprinus carpio L.), a heterogenic and an all male isogeneic, were used as experimental models to assess the effects of low doses of L-thyroxine (T4) on testicular development in juvenile fish. In four experiments (two with each strain) precocious onset of spermatogenesis was induced following exposure to 15 micrograms T4 l-1, but not to 8 micrograms or 30 micrograms T4 l-1. No significant increase in body weight and testis diameter (week 16 excepted) or numbers of primary spermatogonia was observed. Total T4, measured in the isogeneic strain, increased significantly in the serum of experimental specimens within two weeks after the onset of exposure, evidencing a readily absorption of the exogeneous T4. The contents of free T4 and total triiodothyronine (T3) in the serum were measured too, showing different levels in the two experiments, as also was observed with total T4. The content of free T3, which is formed in the cells of peripheral tissues by deiodination of T4 and which supposedly exerted the observed effect on spermatogenesis, could not be determined by the used standard Amerlite assays. It is hypothesized that T3 enhances in males the activity of gonadotropic hormones, which in turn will stimulate steroid production, similar to findings in females.

[Actinomycosis of the abdominal wall. Report of a case]. / Actinomycose de la paroi abdominale. Rapport d'un cas.

We report a primary case of Actinomycosis of the abdominal wall. The diagnosis is obtained on the basis of the CT-scan and the pathological examination. The treatment is a surgical excision and a long term administration of antibiotics.

[Appendicular mucocele. Report of 2 cases]. / Le mucocèle appendiculaire. Rapport de deux cas.

We report two cases of mucocele of the appendix produced by a cystadenocarcinoma, with pseudomyxoma peritonei in one. The treatment consisted in appendectomy with partial resection of the caecum, for the first patient. It consisted in wide resection and in local chemotherapy for the second.

[Association of an appendicovesical fistula and an appendiceal adenoma. Case report]. / Association d'une fistule appendico-vésicale et d'un adénome de l'appendice. Rapport d'un cas.

A new case of appendicovesical fistula is reported. A hundred cases of such fistula are described in the literature. Usually the origin is appendicitis. Cecal diverticulitis, cystadenocarcinoma or carcinoid tumours of appendix are other less common causes. In one case, association with neuroma of appendix is found. We report a case of appendicovesical fistula caused by papillo-villous adenoma of appendix. In this case, echography and cystoscopy were helpful in management of diagnosis and planning for the therapeutic approach. Only two other cases of benign tumour of appendix forming fistula are reported in the literature.

Simulation of appendicitis by tumor-like lesion of cecum.

Four cases are presented in which an initial diagnosis of appendicitis was made. At laparotomy, a cecal lesion simulating a tumour was found. Pathological examination showed inflammatory granulomatous tumour against foreign body, non specific ulcer, diverticulitis and acute solitary diverticulitis. When malignancy is excluded, hemicolectomy is not necessarily the best treatment and we propose conservative management for these patients.

[A simple functional diagnostic test. The isotope nephrogram]. / Un test de dépistage fonctionnel simple. Le néphrogramme isotopique.

Developed daily in our urological consultation the conventional O.I.H. renogram assesses the vascular, tubular and interstitial renal function and the outflow of the kidneys and ureters cavities. The dose of irradiation is extremely low. Ecological advantages associated to a very low cost price and keen informations put this functional test to a first place in the urological technical screen.