Suprapubic versus transurethral catheterization for bladder drainage in male rectal cancer surgery (GRECCAR10), a randomized clinical trial.

BACKGROUND: Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain. METHODS: This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer. Patients were followed at postoperative days 4, 30, and 180. RESULTS: In 208 patients (median age 66 years [IQR 58-71]) randomized to TUC (n = 99) or SPC (n = 109), the rate of urinary infection at POD4 was not significantly different whatever the type of drainage (11/99 (11.1%) vs. 8/109 (7.3%), 95% CI, - 4.2% to 11.7%; p = 0.35). There was significantly more pyuria in the TUC group (79/99 (79.0%) vs. (60/109 (60.9%), 95% CI, 5.7-30.0%; p = 0.004). No difference in bacteriuria was observed between the groups. Patients in the TUC group had a shorter duration of catheterization (median 4 [2-5] vs. 4 [3-5] days; p = 0.002). Drainage complications were more frequent in the SPC group at all followup visits. CONCLUSIONS: TUC should be preferred over SPC in male patients undergoing surgery for mid and/or lower rectal cancers, owing to the lower rate of complications and shorter duration of catheterization. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02922647.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.

Early and late morbidity of local excision after chemoradiotherapy for rectal cancer.

BACKGROUND: Local excision (LE) after chemoradiotherapy is a new option in low rectal cancer, but morbidity has never been compared prospectively with total mesorectal excision (TME). Early and late morbidity were compared in patients treated either by LE or TME after neoadjuvant chemoradiotherapy for rectal cancer. METHOD: This was a post-hoc analysis from a randomized trial. Patients with clinical T2/T3 low rectal cancer with good response to the chemoradiotherapy and having either LE, LE with eventual completion TME, or TME were considered. Early (1 month) and late (2 years) morbidities were compared between the three groups. RESULTS: There were no deaths following surgery in any of the three groups. Early surgical morbidity (20 per cent LE versus 36 per cent TME versus 43 per cent completion TME, P = 0.025) and late surgical morbidity (4 per cent versus 33 per cent versus 57 per cent, P < 0.001) were significantly lower in the LE group than in the TME or the completion TME group. of LE, was associated with the lowest rate of early (10 versus 18 versus 21 per cent, P = 0.217) and late medical morbidities (0 versus 7 versus 7 per cent, P = 0.154), although this did not represent a significant difference between the groups. The severity of overall morbidity was significantly lower at 2 years after LE compared with TME or completion TME (4 versus 28 versus 43 per cent grade 3-5, P < 0.001). CONCLUSION: The rate of surgical complications after neoadjuvant chemoradiotherapy in the LE group was half that of TME group at 1 month and 10 times lower at 2 years. LE is a safe approach for organ preservation and should be considered as an alternative to watch-and-wait in complete clinical responders and to TME in subcomplete responders.

The value of 18F-FDG positron emission tomography to differentiate benign from malignant intraductal papillary mucinous neoplasms: A prospective multicenter study.

OBJECTIVE: To assess the value of 18F-FDG PET/CT in differentiating between benign and malignant intraductal papillary mucinous neoplasms (IPMN) of the pancreas. SUMMARY BACKGROUND DATA: Malignant or high-risk IPMN require surgical resection but surgery should be avoided in patients with IPMN carrying a low risk of malignancy. 18F-FDG PET has been studied mostly in small, single center, retrospective series. METHODS: Prospective, non-comparative, multicenter French study. The primary endpoint was the specificity of PET/CT for identifying malignant IPMN (in situ or invasive carcinoma). Final diagnosis was obtained from pathological examination of the resected specimen. RESULTS: Among 120 patients analyzed, 99 had confirmed IPMN, including 24 with malignant lesions, namely 9 with carcinoma in situ and 15 with invasive carcinoma. The 18F-FDG PET/CT was positive in 44 and 31 patients in the overall and IPMN populations respectively. In the 99 IPMN patients, PET/CT showed 13 true positive, 18 false positive, 57 true negative and 11 false negative results. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of malignancy were 54.2%, 76.0%, 83.8% and 41.9% respectively, versus 64.9%, 75.9%, 82.9% and 54.5% in the overall population. We could not identify a cut-off value for SUVmax to distinguish benign from malignant lesions. Conventional imaging included computed tomography, magnetic resonance cholangiopancreatography and endoscopic ultrasound. In IPMN patients who underwent the 3 techniques, sensitivity, specificity, NPV and PPV were 66.7%, 84.4%, 84.4% and 66.7% respectively. CONCLUSIONS: In this study, 18F-FDG PET/CT did not perform better than conventional imaging to differentiate malignant from benign IPMN.

[Ocular syphilis, a re-emergent pathology: Series of 12 patients in one Hospital, 2017]. / La syphilis oculaire, une pathologie ré-émergente : série de 12 patients au CHU de Marseille en 2017.

INTRODUCTION: Syphilis is a sexually transmitted disease. All organs might be affected, but ocular syphilis only occurs in 0.6 percent of patients. We collected all cases of ocular syphilis requiring hospitalization at the University Hospital Center (UHC) in Marseille in 2017. PATIENTS AND METHODS: This was a retrospective monocentric study. The diagnosis of ocular syphilis was based on the combination of ocular inflammation with a positive syphilitic serology. For each patient, sex, age, HIV status, ocular and extraocular symptoms, initial visual acuity, syphilis serology, cerebrospinal fluid (CSF) analysis if done, treatment and clinical response were collected. RESULTS: Ten men and two women, aged 28 to 86 years, were hospitalized. Two patients were HIV-positive. Ophtalmological lesions were heterogeneous the posterior structures were most affected. Anterior uveitis was isolated in one patient. Five patients had extraocular signs with cutaneous and/or mucosal involvement. No patient had neurological symptoms. Diagnosis of neurosyphilis through CSF analysis was definite for one patient, probable for 5 patients and ruled out for 2 patients. Six patients received treatment with penicillin G and six with ceftriaxone. Visual acuity improved in all cases. DISCUSSION: Ophtalmic cases of syphilis have become more frequent over the past few years in France. The diagnosis should be suspected in cases of eye inflammation even in the absence of favourable clinical presentation or anamnesis. Search for HIV co-infection should be systematic. Our study shows that ceftriaxone remains an effective alternative to penicillin G.

Impact of prior interventional treatment on the complications after Frey procedure for chronic pancreatitis.

PURPOSE: Chronic pancreatitis is an inflammatory disease responsible for pain partially explained by pancreatic duct dilatation. Early surgery has become the treatment of choice for hypertrophic pancreatic head with main pancreatic duct dilatation. Frey procedure (FP), combining both surgical resection and decompression, is one of the standard surgical procedures. However, a "step-up approach" with endoscopic or limited surgical procedures is still frequently proposed before referring to expert pancreatic centres. The aim of the study was to evaluate the impact of a prior treatment on post-operative complications of FP. METHODS: All 61 consecutive patients who underwent FP between 2006 and 2017 were included. Perioperative data and outcomes were analyzed and compared according to the presence of a prior treatment. RESULTS: Twenty-four patients did not receive any prior treatment and thirty-seven patients had a prior endoscopic or limited surgical treatment. Preoperative data and outcomes were similar between the 2 groups. The rate of biliary derivation during FP was significantly higher in the group without prior endoscopic procedure. A prior treatment was not a risk factor for major morbidity (Clavien grade ≥ III). CONCLUSIONS: A first attempt of endoscopic or limited surgical procedures before FP may not influence post-operative complications. Even if not recommended, a "step-up approach" proposing a first less invasive treatment could still be proposed to the patients who want to delay a morbid surgical procedure.

Survival Benefit of the Surgical Management of Retroperitoneal Sarcoma in a Reference Center: A Nationwide Study of the French Sarcoma Group from the NetSarc Database.

BACKGROUND: Guidelines recommend that retroperitoneal sarcoma (RPS) be managed in a reference sarcoma center (RSC), but the benefit remains to be demonstrated. This study investigated the impact of initial surgery performed within the NetSarc network on overall survival (OS). METHODS: NetSarc is a network of 26 RSCs with specialized multidisciplinary tumor boards (MDTs) that is funded by the French NCI. Since 2010, presentation to an MDT and second pathological review are mandatory for sarcoma patients, and data have been collected in a nationwide database. We extracted data for all patients who received surgery in or outside the network and who presented at a NetSarc center (NSC) for primary nonmetastatic RPS between 2010 and 2017. RESULTS: A total of 2945 patients were included: 1078 (36.6%) underwent the first surgery in an NSC, and 1867 (63.4%) in an out-of-network center. The median number of operations at an NSC during the study period was 23 (range: 3-209), and the corresponding median was 1 (range: 1-2) at out-of-network centers. The diagnostic procedures followed significantly more clinical practice guidelines within NetSarc, where there were significantly more first R0 resections [452 (41.9%) vs. 230 (12.3%)]. The OS was significantly superior for patients treated within NetSarc, with a 2-year OS of 87% vs. 70% (p < 0.001). In the multivariate analysis, surgery within an NSC was an independent predictor of OS, with a twofold lower odds ratio of death. CONCLUSIONS: In this national study, surgery for primary RPS within an NSC was associated with a better OS.

Thoracotomy and esophageal surgery: Key points to preserve the possibilities of flaps.

Anastomotic leakage frequently complicates esophagectomy and can trigger a rare life- threatening complication, a tracheoesophageal fistula. No guideline has yet addressed this complication. Plastic surgeons play a crucial role for salvage surgery. When a re-operation is chosen the possibilities of flap interposition depend on how the thoracotomy was initially performed. This study tried to identify key techniques in order help thoracic or general surgeons to preserve all the local flaps available for TEF if it occurs. These techniques improve flap conservation, helping plastic surgeons when a later transposition flap is required.

[What is the best management for a spermatic cord sarcoma in 2018?] / Quelle prise en charge optimale pour un sarcome du cordon spermatique en 2018 ?

Spermatic cord sarcomas are rare tumors for which the most important is the initial diagnostic procedure. They are frequently misdiagnosed after surgery for inguinal hernia, inguinal lymphadenectomy or testicular malignancy. Any clinical suspicion has to lead to perform imaging with MRI and a core needle biopsy in order to obtain an accurate preoperative diagnosis. Liposarcoma and leiomyosarcoma are the most common histological subtypes in elderly adults, rhabdomyosarcoma in children or in young adults. A CT scan will precede the treatment in order to look for distant metastasis and abdominal involvement. The therapeutic strategy as well as the surgical planning are then adapted to the histological, morphological and prognostic factors. Surgery is the cornerstone for the treatment of spermatic cord sarcoma. The minimum requirements for the surgical procedure are a wide excision of the tumor en bloc with radical orchidectomy, excision of the ipsilateral scrotum and high spermatic cord ligation. It could be enlarged to the anterior abdominal wall and adjacent organs some required a soft tissue flap. Spermatic cord sarcoma and trunk wall sarcoma have the same prognosis for which local recurrence could significantly decrease survival. Consequently, surgeon in charge with these tumors has to be familiar with soft tissue sarcoma and the management of these patients must be carried out under the supervision of a multidisciplinary team within the Netsarc network.

Multicentre study of neoadjuvant chemotherapy for stage I and II oesophageal cancer.

BACKGROUND: The benefit of neoadjuvant chemotherapy (NCT) for early-stage oesophageal cancer is unknown. The aim of this study was to assess whether NCT improves the outcome of patients with stage I or II disease. METHODS: Data were collected from 30 European centres from 2000 to 2010. Patients who received NCT for stage I or II oesophageal cancer were compared with patients who underwent primary surgery with regard to postoperative morbidity, mortality, and overall and disease-free survival. Propensity score matching was used to adjust for differences in baseline characteristics. RESULTS: Of 1173 patients recruited (181 NCT, 992 primary surgery), 651 (55·5 per cent) had clinical stage I disease and 522 (44·5 per cent) had stage II disease. Comparisons of the NCT and primary surgery groups in the matched population (181 patients in each group) revealed in-hospital mortality rates of 4·4 and 5·5 per cent respectively (P = 0·660), R0 resection rates of 91·7 and 86·7 per cent (P = 0·338), 5-year overall survival rates of 47·7 and 38·6 per cent (hazard ratio (HR) 0·68, 95 per cent c.i. 0·49 to 0·93; P = 0·016), and 5-year disease-free survival rates of 44·9 and 36·1 per cent (HR 0·68, 0·50 to 0·93; P = 0·017). CONCLUSION: NCT was associated with better overall and disease-free survival in patients with stage I or II oesophageal cancer, without increasing postoperative morbidity.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

French intensive training course in laparoscopic surgery (HUGOFirst) on live porcine models: Validation of a performance assessment scale and residents' satisfaction in a prospective study.

INTRODUCTION: Simulation as a method for practical teaching of surgical residents requires objective evaluation in order to measure the student's acquisition of knowledge and skills. The objectives of this article are to publish our evaluation and validation grids and also the measure of student satisfaction. METHOD: A teaching platform based on practical exercises with a porcine model was created in 2009 at seven French University Hospitals. Three times a year, 31 Diplôme d'Études Spécialisées Complémentaires (DESC) surgical residents underwent timed assessment of the performance of five surgical tasks: trocar insertion (trocars) testing the convergence of instruments (convergence), intra-corporeal knot tying (knots), running of the small intestine to find a lesion (exploration), and performance of a running suture closure of the peritoneum (closure). Two experts evaluated performances prospectively on grid score sheets specifically designed and validated for these exercises. We measured time, scores on a rating scale, and the interest and satisfaction of the residents. RESULTS: Data for 31 residents between May 2011 and March 2012 were analyzed. Rating scales were statistically validated and correlated (Kappa correlation coefficient K>0.69) for each task. The performance times of the most experienced residents decreased significantly for all tasks except for small bowel exploration (P=0.2). After four sessions, times were significantly improved with better quality (fewer errors and higher average scores [>88%]), regardless of the residents' experience. Of the participants, 92% were satisfied, 86% thought that the sessions improved their technical skills and 74% thought it had a favorable impact on their clinical practice. CONCLUSION: This study shows that the performance of surgical techniques can be improved through simulation, that HUFEG grids are valid, and that this teaching program is popular with surgical residents.

Leiomyosarcoma of the inferior vena cava.

BACKGROUND: Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare tumor with poor prognosis. Optimal treatment includes complete resection of the malignant lesion. METHODS: From 1997 to 2013, eight patients underwent surgery in our department for IVC LMS. LMS was considered to arise from the IVC if the tumor presented intraluminal development or if complete resection (R0) required removal of part of the IVC with an extraluminal mass. RESULTS: There were two grade 1 tumors (25%), four grade 2 (50%) and two grade 3 (25%). The median length of stay was 16 days and there were no peri-operative deaths. Median of follow-up was 56 months and mean overall survival was 120 months. Mean 3-year survival rate was 87.5%. Six patients (75%) developed a local recurrence. Four patients died from disease progression. Two patients underwent to surgery for recurrence. CONCLUSION: IVC LMS have a poor prognosis if surgical resection cannot be achieved. Long-term survival is related to an extensive surgery, in the event of recurrence, surgery should again be proposed and may be effective for controlling disease progression, possibly improving survival.

Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent.

OBJECTIVES: To analyse the effect of biological agents (BAs) in terms of achieving inactive disease (ID) or clinical remission (CR) in patients with systemic juvenile idiopathic arthritis (SJIA), to describe effects of switching or discontinuing a BA and to assess the proportion of patients able to maintain ID or CR off steroids and after withdrawing BA therapy. METHODS: Retrospective study in a French paediatric rheumatology reference centre using the CEMARA (CEntre des MAladies RAres) register. RESULTS: Seventy-seven patients were included with a cumulative follow-up of 245.5 patient-years (median 1.1, range 0.5-8.0). On a first BA, ID was achieved in 37 patients, including 1 patient out of 12 patients on etanercept, 26 patients out of 51 on anakinra and 7 out of 10 on canakinumab. One patient on abatacept and two patients on tocilizumab also achieved ID. Switching of BA was common. The switch to a second (n=34), third (n=18) or fourth (n=4) BA resulted in ID in a further 13 patients, either on canakinumab (n=6) or tocilizumab (n=7). At last follow-up, 40 patients were in CR (27 patients off steroids, 5 patients having never received steroid treatment), either on (n=29) or off (n=11) BA. CONCLUSIONS: In this series of patients with SJIA, interleukin-1 inhibitors were associated with a higher proportion of ID than tumour necrosis factor inhibitors when used as first BA. Switching allowed some patients to achieve ID when treated with canakinumab or tocilizumab. CR was eventually achieved in more than half of the patients.

Additive methane-mitigating effect between linseed oil and nitrate fed to cattle.

The objective of this study was to test the effect of linseed oil and nitrate fed alone or in combination on methane (CH4) emissions and diet digestibility in cows. The experiment was conducted as a 2 × 2 factorial design using 4 multiparous nonlactating Holstein cows (initial BW 656 ± 31 kg). Each experimental period lasted 5 wk, with measures performed in the final 3 wk (wk 3 to 5). Diets given on a DM basis were 1) control (CON; 50% natural grassland hay and 50% concentrate), 2) CON with 4% linseed oil (LIN), 3) CON with 3% calcium nitrate (NIT), and 4) CON with 4% linseed oil plus 3% calcium nitrate (LIN+NIT). Diets were offered twice daily and were formulated to deliver similar amounts (DM basis) of CP (12.2%), starch (25.5%), and NDF (39.5%). Feed offer was restricted to 90% of voluntary intake (12.4 kg DMI/d). Total tract digestibility and N balance were determined from total feces and urine collected separately for 6 d during wk 4. Daily CH4 emissions were quantified using open chambers for 4 d during wk 5. Rumen fermentation and microbial parameters were analyzed from samples taken before and 3 h after the morning feeding. Rumen concentrations of dissolved hydrogen (H2) were measured continuously up to 6 h after feeding using a H2 sensor. Compared with the CON diet linseed oil and nitrate decreased (P < 0.01) CH4 emissions (g/kg DMI) by 17 and 22%, respectively, when fed alone and by 32% when combined. The LIN diet reduced CH4 production throughout the day, increased (P = 0.02) propionate proportion, and decreased (P = 0.03) ruminal protozoa concentration compared with CON diet. The NIT diet strongly reduced CH4 production 3 h after feeding, with a simultaneous increase in rumen dissolved H2 concentration, suggesting that nitrate does not act only as an electron acceptor. As a combined effect, linseed plus nitrate also increased H2 concentrations in the rumen. Diets had no effect (P > 0.05) on total tract digestibility of nutrients, except linseed oil, which tended to reduce (P < 0.10) fiber digestibility. Nitrogen balance (% of N intake) was positive for all diets but retention was less (P = 0.03) with linseed oil. This study demonstrates an additive effect between nitrate and linseed oil for reducing methanogenesis in cows without altering diet digestibility.

[Intra-cystic renal calcium milk]. / Le cas clinique du mois. Lait calcique intra-kystique renal.

Intra-cystic renal calcium milk is a rare entity. The authors report a clinical case, and describe the radiographic and tomodensitometric appearances. This 50 year old patient has been followed up for more than ten years for urinary lithiasis with recurrent pain.

Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment.

PURPOSE: To evaluate the downstaging efficacy of yttrium-90 radioembolization (Ytt-90)-associated with chemotherapy and the results of surgery for initially unresectable huge intrahepatic cholangiocarcinoma (ICC). METHODS: Between January 2008 and October 2013, unresectable ICC were treated with chemotherapy and Ytt-90. Patients with unique tumors localized to noncirrhotic livers and without extrahepatic metastasis were considered to be potentially resectable and were evaluated every 2 months for possible secondary resection. RESULTS: Forty-five patients were treated for unresectable ICCs; ten had potentially resectable tumors, and eight underwent surgery. Initial unresectability was due to the involvement of the hepatic veins or portal vein of the future liver remnant in seven and one cases, respectively. Preoperative treatment induced significant decreases in tumor volume (295 vs. 168 ml, p = 0.02) and allowed for R0 resection in all cases. Three patients (37.5 %) had Clavien-Dindo grade three or higher complications, including two postoperative deaths. The median follow-ups were 15.6 [range 4-40.7] months after medical treatment initiation and 7.2 [0.13-36.4] months after surgery. At the end of the study period, five patients were still alive, with one patient still alive 40 months after medical treatment initiation (36.4 months after surgery); two patients experienced recurrences. CONCLUSIONS: For initially unresectable huge ICCs, chemotherapy with Ytt-90 radioembolization is an effective downstaging method that allows for secondary resectability.

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

OBJECTIVE: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. METHODS: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. RESULTS: 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. CONCLUSIONS: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.