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Background: to date, long-term outcomes of R1 vascular (R1vasc) and R1 parenchymal (R1par) resections in the setting of intrahepatic cholangiocarcinoma (iCCA) have been examined in only one study which did not find significant difference. Patients and Methods: we analyzed consecutive patients who underwent iCCA resection between 2000 and 2019 in two tertiary French medical centers. We report overall survival (OS) and disease-free-survival (DFS). Univariate and multivariate analyses were performed to determine associated factors. Results: 195 patients were analyzed. The number of R0, R1par and R1vasc patients was 128 (65.7%), 57 (29.2%) and 10 (5.1%), respectively. The 1- and 2-year OS rates in the R0, R1par and R1vasc groups were 83%, 87%, 57% and 69%, 75%, 45%, respectively (p = 0.30). The 1- and 2-year DFS rates in the R0, R1par and R1vasc groups were 58%, 50%, 30% and 43%, 28%, 10%, respectively (p = 0.019). Resection classification (HR 1.56; p = 0.003) was one of the independent predictors of DFS in multivariate analysis. Conclusions: the survival outcomes after R1par resection are intermediate to those after R0 or R1vasc resection. R1vasc resection should be avoided in patients with iCCA as it does not provide satisfactory oncological outcomes.

International audience; BACKGROUND: Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post-liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre-liver resection criteria. METHODS: This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test). RESULTS: Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score

To evaluate the comparative outcomes of three-dimensional (3D) versus two-dimensional (2D) imaging during laparoscopic cholecystectomy. We conducted a systematic search of electronic information sources and bibliographic reference lists and applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits. Procedure time, Calot’s triangle dissection time, gallbladder removal time, gallbladder perforation, intraoperative bleeding, postoperative complications, conversion to open and intraoperative errors were the evaluated outcome parameters. We identified 6 randomised controlled trials (RCT) reporting a total of 577 patients who underwent laparoscopic cholecystectomy using 3D (n = 282) or 2D (n = 295) imaging. The 3D imaging was associated with significantly shorter procedure time (MD − 4.23, 95% CI − 8.14 to − 0.32, p = 0.03), Calot’s triangle dissection time (MD − 4.19, 95% CI − 6.52 to − 1.86, p = 0.0004) and significantly lower risk of gallbladder perforation (RR 0.50, 95% CI 0.28–0.88, p = 0.02) compared to the 2D approach. No significant difference was found in gallbladder removal time (MD − 0.79, 95% CI − 2.24 to 0.66, p = 0.28), intraoperative bleeding (RR 1.14, 95% CI 0.68–1.90, p = 0.61), postoperative complications (RD − 0.01, 95% CI − 0.06 to 0.05, p = 0.85), conversion to open (RD 0.00, 95% CI − 0.02 to 0.03, p = 0.70) or intraoperative errors (RR 0.96, 95% CI 0.79–1.17, p = 0.70) between the two groups. Although our findings suggest that the use of 3D imaging during laparoscopic cholecystectomy may be associated with significantly shorter procedure time, Calot’s triangle dissection time and gallbladder injury compared to the 2D imaging, the differences seem to be clinically insignificant. Moreover, both approaches carry s similar risk of postoperative morbidities. The impact of the surgeon’s level of experience and difficulty of the procedure on the outcomes of each imaging modality remains unknown.

Patient selection for combined liver-kidney transplantation (CLKT) is a current issue on the background of organ shortage. This study aimed to compare outcomes and post-transplant renal function for patients receiving CLKT and liver transplantation alone (LTA) based on native renal function using estimated glomerular filtration rate (eGFR) stratification. Using the UK National transplant database (NHSBT) 6035 patients receiving a LTA (N = 5912; 98%) or CLKT (N = 123; 2%) [2001-2013] were analysed, and stratified by KDIGO stages of eGFR at transplant (eGFR group-strata). There was no difference in patient/graft survival between LTA and CLKT in eGFR group-strata (P > 0.05). Of 377 patients undergoing renal replacement therapy (RRT) at time of transplantation, 305 (81%) and 72 (19%) patients received LTA and CLKT respectively. A significantly greater proportion of CLKT patients had severe end-stage renal disease (eGFR < 30 ml/min/1.73 m2 ) at 1 year post-transplant compared to LTA (9.5% vs. 5.7%, P = 0.001). Patient and graft survival benefit for patients on RRT at transplantation was favouring CLKT versus LTA (P = 0.038 and P = 0.018, respectively) but the renal function of the long-term survivors was not superior following CLKT. The data does not support CLKT approach based on eGFR alone, and the advantage of CLKT appear to benefit only those who are on established RRT at the time of transplant.

International audience; BACKGROUND: HCC are known to have satellite nodules and microvascular invasions requiring sufficient margins. An alpha-fetoprotein (AFP) level >100 ng/mL is associated with worse pathological features in HCC. In practice, large resection margins, particularly >1~cm, are infrequently retrieved on the specimens. METHODS: 397 patients from 5 centres were included from 2012 to 2017. The primary endpoint was time-to-recurrence in relation to AFP level (> or or

This research aims to reveal the current situation in the field of occupational exposure to microbes By measuring the microbial load of airborne microbes In some Jizan region hospitals, the hospitals in which the study was conducted are: King Fahd Central Hospital, Prince Muhammad bin Nasser Hospital, Damad General Hospital, Sabya General Hospital and Al- Umais Hospital (private). The maximum bacterial load was 1900cfu/m3, emergency room in King Fahd Central Hospital, and the minimum bacterial load was 60cfu/m3 in lab department in Alemies hospital. The maximum fungal load value was 90cfu/m3 in emergency room, Prince Mohammed Hospital, and the minimum fungal load was 7cfu/m3 in lab department inside Damad General Hospital. Correlation coefficient between bacteria and fungi in King Fahd Hospital, Prince Muhammad, Al- Umais, Damad and Saba. There is a very strong direct correlation with statistical significance (0,04) between bacteria in King Fahd Hospital and fungi in Prince Muhammad Hospital. The correlation coefficient was equal to (0.998), there is a direct correlation Very strong and statistically significant (0,02) between bacteria in King Fahd Hospital and bacteria in Saba Hospital, and the correlation coefficient was equal to (0.999),and there is also a complete statistically significant correlation (0,02) between fungi in Prince Muhammad Hospital and bacteria in Saba Hospital, and the correlation coefficient was equal to (1)

This research aims to identify the level of awareness (knowledge, behavior and practices) of workers in the field of health care towards the occupational hazards surrounding them in hospitals in the Jazan region in the Kingdom of Saudi Arabia, a study to measure awareness of the use of (KAP), and also aims to know the impact of training at the level of awareness. The descriptive analytical survey method and the quazi experimental approach were used through the pre and post exam for its suitability for this research. The study was conducted on a sample size of 326 participants’categories are (doctors, nursing, and laboratory specialists) and the experimental group to conduct the training was on Damad and Al-Umais Hospitals The results of the study showed that the level of knowledge was good before the training program and the axes of attitude, practices and training were not satisfactory in the total group before the program. After the training program, the levels of all axes increased with arithmetic averages, some of which reached 100%, which confirms the need to intensify training programs for workers and this is what The researcher recommended it in addition to the need to have a department responsible for monitoring and developing measures to protect against occupational exposures and raise awareness among workers.

Pancreatic cancer is characterised by desmoplasia, driven by activated pancreatic stellate cells (PSCs). Over-expression of FGFs and their receptors is a feature of pancreatic cancer and correlates with poor prognosis, but whether their expression impacts on PSCs is unclear. At the invasive front of human pancreatic cancer, FGF2 and FGFR1 localise to the nucleus in activated PSCs but not cancer cells. In vitro, inhibiting FGFR1 and FGF2 in PSCs, using RNAi or chemical inhibition, resulted in significantly reduced cell proliferation, which was not seen in cancer cells. In physiomimetic organotypic co-cultures, FGFR inhibition prevented PSC as well as cancer cell invasion. FGFR inhibition resulted in cytoplasmic localisation of FGFR1 and FGF2, in contrast to vehicle-treated conditions where PSCs with nuclear FGFR1 and FGF2 led cancer cells to invade the underlying extra-cellular matrix. Strikingly, abrogation of nuclear FGFR1 and FGF2 in PSCs abolished cancer cell invasion. These findings suggest a novel therapeutic approach, where preventing nuclear FGF/FGFR mediated proliferation and invasion in PSCs leads to disruption of the tumour microenvironment, preventing pancreatic cancer cell invasion.

Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and β-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.

Aim The study investigated whether experience gained during a UK laparoscopic colorectal fellowship enabled the fellow subsequently to train consultant colleagues in laparoscopic surgery. Method In one unit a newly appointed post-laparoscopic fellowship consultant (PFC) mentored his other two colleagues. Prospectively collected data regarding surgical outcome were compared with those of the year preceding the PFC appointment. Results In the preceding year 18.5% of 260 resections were attempted laparoscopically. This increased to 92.6% (of 270) in the year after (P

Background: Histone deacetylase inhibitors (HDACi) have been shown as a potential therapeutic agent for pancreatic cancer in vitro and in vivo (Donadelli et al. 2003; Fritsche et al. 2009; von Burstin et al. 2009; Schuler et al. 2010). However, recent clinical trials using HDACi have been far from promising. Until now, the effect of HDACi on pancreatic cancer stroma has not been well studied. Recently, we published work demonstrating that administration of all-trans-retenoic acid (ATRA) reverses the myofibroblast/activated phenotype of pancreatic stellate cells (PSC) to a quiescent one (Froeling et al. 2011). In addition, functional genetic screens have revealed that retinoic acid signaling is a target of HDACi (Epping et al. 2007). Consequently, the tumor-stroma cross-talk may be a vital target for HDACi, which has been ignored in studies thus far. Aim: To investigate the effect of HDACi on the tumor-stroma cross talk using the 3-D organotypic collagen/matrigel culture model. Methods: Vorinostat (suberoylanilide hydroxamic acid, SAHA), valproic acid (VPA), and trichostatin acid (TsA) were used to treat PSC, Capan1, and AsPc1 cell lines. Treatment was done on cells plated both in 2-D (on plastic) and in 3-D using collagen/matrigel organotypic culture models. Results: Using HDACi on the cells in 2-D cell culture showed that PSC were more susceptible to treatment especially with low physiologic doses of HDACi. This was shown by MTS and PI DNA content FACS analysis. There was increase in sub-G1 fraction with corresponding decreased viability on MTS data, suggesting apoptosis. A corresponding dose related increase in acetylated histone 3 was shown on Western blots (a marker for effectiveness of HDACi). Similar effect was shown on cancer cells but only using higher nonphysiologic doses. In the 3-D culture model, SAHA was used to treat cancer cells co-cultured with PSC daily for 7 days. There was a dose related reduction in the number of cancer cells, and decreased invasion into the gels. This was accompanied by reduction in Ki-67 staining and increase caspase-3. There is also a corresponding dose related increased acetylated histone-3. Interestingly this effect was not as significant when cancer cells were used on their own despite similar effect on acetylated histone 3. Conclusion: Our data so far show the PSC to be a more appropriate target for HDACi than the cancer cells using physiologic doses, which can be used in-vivo. It is now established that PSC play a key role in promoting cancer cell growth and invasion. When co-cultured together in 3-D, HDACi is reversing the proliferative and metastatic effect of the PSC on the Capan1. HDACi have shown to be an interesting drug for targeting tumor-stroma cross-talk in pancreatic cancer. The machinery of the effect is currently being studied with gene expression microarray and FACS of cells isolated from the 3-D gels. Citation Format: Mohammed Ayman Ghallab, Rosignoli Guglielmo, Irene Sangrador Escrig, Ian R. Hart, Satya Bhattacharya, Hemant M. Kocher. Targeting pancreatic cancer stroma with histone deacetylase inhibitors. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B80.

Duodenal-jejunal intussusception is an extremely rare occurrence and has never been reported in the context of a gastrointestinal stromal tumour (GIST). We present the case of a duodenal GIST which presented with major intestinal haemorrhage in addition to duodenal-jejunal intussusception.

This study aimed to investigate the possible protective role of curcumin against renal damage caused by administration of cyclosporine A (CsA) in adult male rats. For this purpose, 27 adult male albino rats were used and divided into three equal groups. Group I (control group) and group II (CsA-treated group) received a daily subcutaneous injection of CsA at a dose of 20 mg/kg b.w. Group III (prophylactic group) received a daily oral curcumin at a dose of 15 mg/kg b.w. simultaneously with CsA. After 21 days, all the animals were anaesthetized and the kidneys were rapidly removed and processed to prepare paraffin sections stained with H&E, PAS and Masson's trichrome. In addition, the glutathione S-transferase (GST) enzyme was detected immunohistochemically. The optical density and the area (in %) of positive GST immunoreactions were measured in the cytoplasm of renal tubules and glomeruli and the data were statistically analyzed. Examination of sections from CsA-treated group showed renal tubules with vacuolated cytoplasm and others with darkly stained pyknotic nuclei. Apical brush borders of proximal tubules were undefined and PAS positive granules were noticed in their cytoplasm. The renal corpuscles contained shrunken glomeruli with widening of their Bowman's spaces. Inflammatory cellular infiltrate and increase in the collagen fibers were observed between the renal tubules. In prophylactic group, the structure of renal tubules and corpuscles were preserved except few tubular darkly stained pyknotic nuclei. Numerous blood vessels, few cellular infiltration and thin collagen fibers were observed between the renal tubules. Statistical analysis of morphometric data showed significant increase in the optical density of GST immunoreactivity in the cells of renal tubules and glomeruli of CsA-treated group when compared with the control or prophylactic groups. However, a significant decrease in the area of GST immunoreactivity in sections from prophylactic group was observed when compared with control or CsA-treated groups. In conclusion, protective effect of curcumin against cyclosporine-induced nephrotoxicity in rats was proven based on the study of histological changes and GST immunoexpression. This study supposes the possible therapeutic applications of curcumin in CsA-treated patients.

Pancreatic cancer carries a terrible prognosis, as the fourth most common cause of cancer death in the Western world. There is clearly a need for new therapies to treat this disease. One of the reasons no effective treatment has been developed in the past decade may in part, be explained by the diverse influences exerted by the tumour microenvironment. The tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response rate. Thus, appropriate preclinical in vitro models which can bridge simple 2D in vitro cell based assays and complex in vivo models are required to understand the biology of pancreatic cancer. Here we discuss the evolution of 3D organotypic models, which recapitulare the morphological and functional features of pancreatic ductal adenocarcinoma (PDAC). Organotypic cultures are a valid high throughput preclinical in vitro model that maybe a useful tool to help establish new therapies for PDAC. A huge advantage of the organotypic model system is that any component of the model can be easily modulated in a short time-frame. This allows new therapies that can target the cancer, the stromal compartment or both to be tested in a model that mirrors the in vivo situation. A major challenge for the future is to expand the cellular composition of the organotypic model to further develop a system that mimics the PDAC environment more precisely. We discuss how this challenge is being met to increase our understanding of this terrible disease and develop novel therapies that can improve the prognosis for patients.

Background: It is now appreciated that, in pancreatic cancer, transformed cells interact with stromal cells, extracellular matrix proteins, and neighboring normal epithelial cells to exploit feedback mechanisms and facilitate tumour progression. Studies have shown that overexpression of FGF2 in pancreatic cancer correlates with poor patient survival and nuclear FGF2 has been observed in pancreatic cancer patient tissue but not in normal patient samples (Yamanka et al 1993). A number of mechanisms have been proposed for the nuclear accumulation of FGFR1 and its ligand; however, the role of intracrine FGF2 signalling in tumour invasion remains poorly understood. We investigated whether nuclear translocation of FGFR1 with FGF2 plays a role in pancreatc stellate cell (PSC) behaviour. Design: FGF2 and FGFR1 RNAi, together with an FGFR inhibitor (PD173074) were used on pancreatic cancer cell lines PSCs and in organotypic cultures to assess their effect on cell behaviour and to assess the effects of blocking FGF signalling on cancer cell behaviour and invasion. Nuclear FGFR1 and FGF2 expression were also studied in vivo. Results: FGF2 and FGFR1 localised to the nucleus in stromal fibroblasts at the invasive front of human pancreatic cancer tissue. In vitro, FGFR1 and FGF2 co-localised to the nucleus in PSCs but not in cancer or normal ductal epithelial cell lines. PSCs but not cancer cells secrete both HMW and LMW FGF2 isoforms. Abolishing nuclear FGFR1 and FGF2 in PSCs using either RNAi or FGFR inhibitor resulted in a significant reduction in cell proliferation which correlated with a G1 cell-cycle block and reduction in the G1 cyclin, cyclin D1. In an organotypic model, nuclear FGFR1 and FGF2 were significantly greater in PSCs invading into the matrix. When treated with FGFR inhibitor, PSCs were unable to invade into the extra-cellular matrix and FGFR1 and FGF2 remained cytoplasmic. Effective blockade of nuclear FGFR1 signalling in PSCs abolished cancer cell invasion. Conclusion: These studies show for the first time that nuclear FGFR1 and FGF2 plays a role in driving pancreatic stellate cell proliferation. Preventing nuclear FGF/FGFR mediated proliferation in PSCs leads to disruption of the tumour microenvironment, thus preventing pancreatic cancer cell invasion.

s / Pancreatology 13 (2013) e1–e20 e4 postoperative bleeding between the resection groups. There was no difference in resection margin status (R0 in 85 PDVR (37%) and 397 PD (48%) p1⁄40.09). Conclusion: This study demonstrates no significant difference in perioperative mortality in the three groups. It also demonstrates a similar overall survival in the PD and PDVR groups, significantly better compared to SB. The group also comprises C Coldham, A Saleh, A Al-Hilli, G Spoletini, S Aroori, J Hammond, G Bond-Smith, Q Jalal, J Terrace, Y Puri and G Preziosi. Take-home message: Portal vein resection in locally advanced pancreatic cancer confers a survival benefit over surgical bypass, has a comparable survival to standard resection and is a safe procedure when performed in specialist HPB units. Abstract previously presented? yes (European Society of Surgical Oncology 2012) Any disclosures? no ()