Irreversible electroporation to bring initially unresectable locally advanced pancreatic adenocarcinoma to surgery: the IRECAP phase II study.

OBJECTIVES: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). MATERIALS AND METHODS: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). RESULTS: Six men and 11 women were included (median age 61 years, range 37-77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4-undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4-25) for the 11 patients without resection or R2 resection (logrank p = 0.044). CONCLUSION: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. CLINICAL RELEVANCE STATEMENT: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. KEY POINTS: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3-4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4-undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4-25) for the patients without resection or R2 resection (logrank p = 0.044).

Development and validation of a performance assessment checklist for insertion of an intra-uterine device (IUD).

OBJECTIVES: The World Health Organization (WHO) supports increasing the availability and acceptability of long-acting reversible contraception including intra-uterine device (IUD), but its insertion includes certain risks (uterine perforation). The objective was to develop and validate an IUD insertion performance assessment checklist. MATERIAL AND METHODS: This prospective study took place in hospitals and simulation center of the Poitou-Charentes region, France. The checklist content reached consensus among 10 experts solicited by a Delphi method. A modified gynecologic mannequin Zoe (Gaumard®) was used for simulations. Psychometric testing included 30 multi-professional participants for internal consistency and reliability between two independent observers, and 27 residents for assessment of score evolution over time and reliability. Cronbach alpha (CA) and intraclass coefficient (ICC) were used. Progression of performance was carried out using ANOVA for repeated measures. The data collected were used to plot receiver operating characteristic (ROC) curves for the score values and the area under the curve (AUC) was determined. RESULTS: The checklist included 27 items (2 sections, total score = 27). Psychometric testing showed CA = 0.79, ICC = 0.99, and good clinical relevance. The checklist is discriminative, showing a significant increase in performance scores when the simulations were repeated (F = 77.6, p < 0.0001). ROC curve [AUC: 0.792 (95% CI: 0.71-0.89); p < 0.0001] revealed the best score cutoff predictive of 100% sensitivity, i.e., true positive rate or success rate. Performance score was highly correlated to success rate. The cut-off score guaranteeing successful IUD insertion was 22/27. CONCLUSIONS: This coherent and reproducible checklist for IUD insertion provide an objective assessment of the procedure during SBT, with the aim of obtaining a score ≥ 22/27.

Should we recommend occipital plate fixation using bicortical screws or inverted occipital hooks to optimize occipito-cervical junction fusion? A biomechanical study combining an experimental and analytical approach.

BACKGROUND: Occipito-cervical fusion can be necessary in case of cranio-cervical junction instability. Proximal stabilisation is usually ensured by bi-cortical occipital screws implanted through one median or two lateral occipital plate(s). Bone thickness variability as well as the proximity of vasculo-nervous elements can induce substantial morbidity. The choice of site and implant type remains difficult for surgeons and is often empirically based. Given this challenge, implants with smaller pitch to increase bone interfacing are being developed, as is a surgical technique consisting in inverted occipital hook clamps, a potential alternative to plate/screws association. We present here a biomechanical comparison of the different occipito-cervical fusion devices. METHODS: We have developed a 3D mark tracking technique to measure experimental mechanical data on implants and occipital bone. Biomechanical tests were performed to study the mechanical stiffness of the occipito-cervical instrumentation on human skulls. Four occipital implant systems were analysed: lateral plates+large pitch screws, lateral plates+hooks, lateral plates+small pitch screws and median plate+small pitch screws. Mechanical responses were analysed using 3D displacement field measurements from optical methods and compared with an analytical model. FINDINGS: Paradoxical mechanical responses were observed among the four types of fixations. Lateral plates+small pitch screws appear to show the best accordance of displacement field between bone/implant/system interface providing higher stiffness and an average maximum moment around 50 N.m before fracture. INTERPRETATION: Stability of occipito-cervical fixation depends not only on the site of screws implantation and occipital bone thickness but is also directly influenced by the type of occipital implant.

Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed.

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs. Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers. Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ. Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes. An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.

Impact of a simulation-based training in hand hygiene with alcohol-based hand rub in emergency departments.

BACKGROUND: Hand hygiene is the primary measure for reducing nosocomial infections based on 7 steps recommended by the WHO. The aim of this study was to assess the duration and the quality of hand hygiene before and after simulation-based training (SBT). METHODS: The study took place in a University Hospital Pediatric Department among its residents and nurses. In assessment A, 10 hand-rubbing procedures per participant during a work day were scored by observers using a validated, anatomically based assessment scale. Two weeks later, all participants received a didactic course and SBT, followed 1 month later by assessment B, observation of 10 hand-rubbing procedures. Assessments were performed by 2 independent observers. Before-and-after testing was used to evaluate the demonstration of theoretical knowledge. RESULTS: In total, 22 participants were included, for whom 438 hand hygiene procedures were assessed: 218 for assessment A and 220 for assessment B. The duration of hand rubbing increased from 31.16 seconds in assessment A to 35.75 seconds in assessment B (P=.04). In assessment A, participants averaged 6.33 steps, and in assessment B, participants averaged 6.03 steps (difference not significant). Significant improvement in scores was observed between assessments A and B, except for the dorsal side of the right hand. The wrist and interdigital areas were the least-cleaned zones. A difference between assessments A and B was observed for nail varnish (P=.003) but not for long nails or jewelry. Theoretical scores increased from 2.83 to 4.29 (scale of 0-5; P<.001). CONCLUSION: This study revealed that an optimal number of steps were performed during hand-rubbing procedures and that SBT improved the duration and quality of hand hygiene, except for the dorsal right side. Emphasis should be placed on the specific hand areas that remained unclean after regular hand-rubbing procedures.

Design and validation of an anatomically based assessment scale for handwashing with alcohol-based hand rub.

An anatomically based assessment scale of handwashing quality with alcohol-based hand rub was designed. Contents of the scale divided each hand into 40 zones. Psychometric measurements were studied in 30 participants (120 hand sides). The scale was both valid (Cronbach α: 0·83 dorsal side and 0·73 palmar side) and reproducible (linear regression R2, 0·91; intraclass correlation coefficient, 0·99).

Predictive factors of endocrine and exocrine insufficiency after resection of a benign tumour of the pancreas.

BACKGROUND: The aim of the present study is to evaluate the risk factors of endocrine and exocrine insufficiency occurring few years after pancreatic resections in a consecutive series of patients who underwent pancreatoduodenectomy (PD), left pancreatectomy (LP) or enucleation for benign neoplasms at a referral centre. METHODS: Pancreatic exocrine insufficiency (PEI) was defined by the onset of steatorrhea associated with weight loss, and endocrine insufficiency was determinate by fasting plasma glucose. Association between pancreatic insufficiency and clinical, pathological, and perioperative features was studied using univariate and multivariate Cox regression analysis. RESULTS: A prospective cohort of 92 patients underwent PD (48%), LP (44%) or enucleation (8%) for benign tumours, from 2005 to 2016 in the University Hospital in Poitiers (France). The median follow-up was 68.6±42.4months. During the following, 54 patients developed exocrine insufficiency whereas 32 patients presented endocrine insufficiency. In the Cox model, a BMI>28kg/m2, being a man and presenting a metabolic syndrome were significantly associated with a higher risk to develop postoperative diabetes. The risks factors for the occurrence of PEI were preoperative chronic pancreatitis, a BMI<18.5kg/m2, tumours located in the pancreatic head, biological markers of chronic obstruction and fibrotic pancreas. Undergoing LP or enucleation were protective factors of PEI. Histological categories such as neuroendocrine tumours and cystadenomas were also associated with a decreased incidence of PEI. CONCLUSION: Men with metabolic syndrome and obesity should be closely followed-up for diabetes, and patients with obstructive tumours, pancreatic fibrosis or chronic pancreatitis require a vigilant follow up on their pancreatic exocrine function.

Irreversible Electroporation for Locally Advanced Pancreatic Cancer: Where Do We Stand in 2017?

Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are considered as unresectable because of involvement of celiac and/or mesenteric vessels. Irreversible electroporation has recently been introduced to induce permanent cell death by apoptosis. Irreversible electroporation is a nonthermal cell-destruction technique that was claimed to allow destruction of cancerous cells with less damage to surrounding supporting connective tissues with collagenic structure (such as nearby blood vessels, biliary ducts, and nerves) than other types of treatment. Applications on pancreatic adenocarcinoma seem promising, and this article is an up-to-date review of the first results.

Colonoscopy uptake for high-risk individuals with a family history of colorectal neoplasia: A multicenter, randomized trial of tailored counseling versus standard information.

BACKGROUND: Colonoscopic screening is recommended for first-degree relatives of patients diagnosed with colorectal cancer (CRC) or colorectal adenomatous polyps (CAP) before the age of 60 years. This has the potential to reduce CRC-related morbidity and mortality, but uptake is currently inadequate. METHODS: The aim of the study was to compare the effectiveness of standard information versus a nurse-led tailored intervention designed to promote uptake of colonoscopy screening by siblings of CRC or CAP patients. A randomized controlled trial was conducted. Digestive surgeons and gastroenterologists recruited index patients who developed CRC or CAP before the age of 60 years. All index patients received standard screening information for their siblings, in keeping with current guidelines. Centrally computerized randomization of index patients resulted in allocating all their siblings to the same group, intervention or control. The tailored intervention targeted the index patient first, to help them convey information to their siblings. The nurse then provided the siblings with tailored information based on their answers to a self-questionnaire which explored health behaviors, derived from psychosocial models of prevention. Then the siblings were given a personalized information leaflet to hand to their regular physician. The primary endpoint was the rate of documented colonoscopy performed in siblings within 1 year after diagnosis of the index patient. The intent-to-treat analysis included siblings who refused to participate in the study. Statistical analysis was adjusted for intrafamilial correlation. RESULTS: A total of 304 siblings of 125 index patients were included: 160 in the intervention group and 144 in the control group. The rate of colonoscopy uptake among siblings was 56.3% in the intervention group and 35.4% in the control group (P = 0.0027). The respective rates after exclusion of refusals were 69.2% and 37.0% (P < 0.0001). More lesions were detected in the intervention group (1 invasive cancer and 11 advanced adenomas vs 5 advanced adenomas; P = 0.022). CONCLUSIONS: This study demonstrates the effectiveness of a nurse-led tailored intervention designed to promote colonoscopy screening uptake by siblings of patients diagnosed with CRC or CAP before age 60 years. Such tailored interventions that also involve physicians should help to reduce CRC-related mortality.

What is the pelvic lymph node normal size? Determination from normal MRI examinations.

PURPOSE: There are few previous reports on maximal pelvic lymph node sizes and no data on normal mesorectal nodes. Therefore, the aim of the study was to estimate the normal size of pelvic lymph nodes and to determine the upper limits of the normal range. MATERIALS AND METHODS: Pelvic magnetic resonance imaging (MRI) examinations were prospectively carried out using a Intera 1.5 T magnet (Philips, the Netherlands), on 36 healthy volunteers (22 females, 14 males, mean age 25 years). A balanced fast field echo (b-FFE) sequence was used with the following parameters: 3-mm-thick contiguous slice, matrix 512 × 512. Short axis diameters of pelvic and inguinal lymph nodes were measured in each anatomic territory (internal iliac, external iliac, common iliac, mesorectum and inguinal). After normalization of the measurements, the influences of age, gender, laterality and territory were evaluated. Upper limits (95th percentile) were then calculated. RESULTS: A total of 1147 lymph nodes were measured. Age, gender and side (right/left) had no significant influence on size. The upper limits of the normal range were, respectively, 5.3, 4.4, 6.3 and 3.9 mm for the external and common iliac, internal iliac, inguinal and mesorectum nodes. CONCLUSION: This work presents maximal normal values for each pelvic area, and the values for mesorectum nodes are reported for the first time. ADVANCES IN KNOWLEDGE: The mesorectum nodes should be considered as abnormal when they are over 4 mm in short diameter. For the other node areas, the upper limits of the normal range were, respectively, 6, 6, 5, 7 mm for the external and common iliac, internal, iliac and inguinal nodes for the short axis.

Reliability and validity of a new measurement of lumbar foraminal volume using a computed tomography.

PURPOSE: Measuring foraminal stenosis is generally determined by an area calculation. It is difficult to know exactly where it is most appropriate to measure. No precise data are available on a method for calculating the foraminal volume using a CT. To develop a new method for measuring lumbar foraminal volume, we analyzed repeatability and reliability for measuring methods for foraminal volume using CT. METHODS: The measurements were performed using a CT scan from ten healthy patients, with a mean age of 26.3 years. L3-L4, L4-L5 and L5-S1 foramen were studied, to obtain 60 foraminal measurements. Inter- and intra-observer reproducibility was calculated. Each series was analyzed using the VitreaCore® reconstruction software for volume calculation. RESULTS: Average volume measurements of 60 foramina and 20 L4-L5 foramina were, respectively, 1.17 and 1.25 mm(3) for observer 1 and 1.21 and 1.29 for observer 2. The intra-observer correlation coefficients for observer 1 when measuring all foramina and L4-L5 foramina were 0.98 and 0.99, respectively. For observer 2, coefficients were 0.90 and 0.92, respectively. The inter-observer correlation coefficients for observer 1 when measuring all foramina and L4-L5 foramina were 0.78 and 0.83, respectively. For observer 2, coefficients were 0.77 and 0.8, respectively. The average differences in intra- and inter-observer measurements regardless of the evaluator group were less than 0.2 mm(3). CONCLUSIONS: This is the first study measuring lumbar foraminal volume using CT. The excellent reproducibility of this simple measure can supplement a range of foramen measurement tools.

Development of the right colon and the peritoneal surface during the human fetal period: human ontogeny of the right colon.

BACKGROUND: Development of the digestive tract during the human fetal period has been the subject of many studies, but there are no works that study the ontogeny of both the right colon and the peritoneum. METHODS: Based on the dissections of adult male cadavers and human fetuses, the aim of this anatomical study was to demonstrate the rules of the morpho-functional group, consisting of the right colon and its peritoneum surface, in human ontogeny. RESULTS: The morphology of the right colon results from a rotational motion, inducting the migration of the cecum in the right iliac fossa and formation of the hepatic flexure. This intestinal migration is based on the axis of rotation of the spreading area of the colon at the ventral side of the lower pole of the right kidney, which becomes visible after the 17th week. CONCLUSION: Our different observations plead in favor of the peritoneal fusion theory. A few variations of this fusion can explain all the disorders in the position of the cecum-appendix that are encountered in current surgery, as well as the possibility of internal hernias.

Normal ultrasound anatomy of the triangular fibrocartilage of the wrist: a study on cadavers and on healthy subjects.

PURPOSE: To report the normal sonographic anatomy of the triangular fibrocartilage (TFC) of the wrist in cadavers and volunteers. METHOD: Five hands from cadavers were examined sonographically before and after wrist dissection, during which the TFC was marked with surgical wires. Twenty volunteers without wrist limitation or pain, and without any history of wrist disease or inflammatory arthritis (mean age, 26 years (range,19-45 years) were also examined. RESULTS: Sonograms showed that the meniscus and the TFC were clearly separated. The meniscus appeared as a triangular structure that was homogeneous and slightly hyperechoic. Compared with the meniscus, the TFC appeared hypoechoic. The same patterns were observed for cadavers and volunteers. In 3 volunteers (15%), the TFC was not visualized. CONCLUSIONS: Using high-resolution ultrasound systems, the TFC can be separated from meniscus. However, visualization of the TFC remains limited due to its deep location and the presence of acoustic shadowing from bony structures.

Comparison of conventional and laparoscopic Hartmann's procedure reversal.

PURPOSE: This study compares open Hartmann's procedure reversal (OHPR) and laparoscopic Hartmann's procedure reversal (LHPR) in patients first treated for peritonitis (Henchey III or IV). METHODS: Fourteen patients who underwent LHPR during a 2-year period were compared with 20 patients who had previously undergone an open procedure at the same institution. RESULTS: Conversion rate was 14.28%. Operating time was shorter for the laparoscopic group [143 (90 to 240) vs. 180 (90 to 350) min, P<0.05]. Hospital length of stay was shorter for the laparoscopic group [9.5 (4 to 18) vs. 11 (6 to 39)]. Use of patient-controlled analgesia was not significantly shorter in the laparoscopic group [3 (0 to 4) vs. 3.5 (0 to 8)]. Morbidities observed in the LHPR group include a parietal abscess and an anastomotic stenosis without surgical treatment. The OHPR group had 6 complications: 1 anastomotic leak and 5 incisional hernias. CONCLUSIONS: LHPR with a conversion rate of 14.28% seems to be a method with shorter operating time and less morbidity compared with OHPR.

Influence of warm ischemia time on peripheral-type benzodiazepine receptor: a new aspect of the role of mitochondria.

The peripheral benzodiazepine receptor (PBR) is located mainly in the outer mitochondrial membrane and many functions are associated directly or indirectly with the PBR. We have studied the influence of different durations of warm ischemia (WI) on renal function, tissue damage and PBR expression in a Large Whitepig model. After a midline incision, the renal pedicle was clamped for 10 (WI10), 30 (WI30), 45 (WI45), 60 (WI60) or 90 min (WI90), and blood and renal tissue samples were collected between 1 day and 2 weeks after reperfusion for assessment of renal function. Metabolite excretion associated with renal ischemia reperfusion injury such as trimethylamine-N-oxide (TMAO) was quantified in blood by magnetic resonance spectroscopy. PBR mRNA and protein expression were determined in renal tissue. TMAO levels rose progressively and significantly with increasing duration of WI. PBR mRNA expression was upregulated between 3 h and 1 day after reperfusion in WI30, WI45 and WI60. Its upregulation was noted 3 days after reperfusion in WI90. At day 14, PBR transcript expression was not different from basal level in any group. PBR protein followed the same pattern. These findings suggest a new role for PBR which could be a major target in the regeneration process during ischemia reperfusion.

[How is an abdominal hernia formed?]. / Comment se forme une hernie abdominale?

Abdomen can be compared in broad outline with an irregular cylinder, limited at the top by the diaphragm and below by the pond. The walls of this cylinder are musculo-aponevrotic and present "zones of weakness" seats of the hernias of the abdominal wall. We propose a topographic anatomical approach of abdominal hernias.