Publications by authors named "Serge Rohr"

34 Publications

CDX2 controls genes involved in the metabolism of 5-fluorouracil and is associated with reduced efficacy of chemotherapy in colorectal cancer.

Biomed Pharmacother 2022 Mar 17;147:112630. Epub 2022 Jan 17.

Strasbourg University, INSERM, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, 3 avenue Molière, 67200 Strasbourg, France. Electronic address:

Most patients affected with colorectal cancers (CRC) are treated with 5-fluorouracil (5-FU)-based chemotherapy but its efficacy is often hampered by resistance mechanisms linked to tumor heterogeneity. A better understanding of the molecular determinants involved in chemoresistance is critical for precision medicine and therapeutic progress. Caudal type homeobox 2 (CDX2) is a master regulator of intestinal identity and acts as tumor suppressor in the colon. Here, using a translational approach, we examined the role of CDX2 in CRC chemoresistance. Unexpectedly, we discovered that the prognosis value of CDX2 for disease-free survival of patients affected with CRC is lost upon chemotherapy and that CDX2 expression enhances resistance of colon cancer cells towards 5-FU. At the molecular level, we found that CDX2 expression correlates with higher levels of genes regulating the bioavailability of 5-FU through efflux (ABCC11) and catabolism (DPYD) in patients affected with CRC and CRC cell lines. We further showed that CDX2 directly regulates the expression of ABCC11 and that the inhibition of ABCC11 improves 5-FU-sensitivity of CDX2-expressing colon cancer cells. Thus, this study illustrates how biological functions are hijacked in CRC cells and reveals the therapeutic interest of CDX2/ABCC11/DPYD to improve systemic chemotherapy in CRC.
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http://dx.doi.org/10.1016/j.biopha.2022.112630DOI Listing
March 2022

Is Lanreotide Really Useful in High Output Stoma? Comparison between Lanreotide to Conventional Antidiarrheal Treatment Alone.

J Invest Surg 2021 Dec 4;34(12):1312-1316. Epub 2020 Aug 4.

Department of Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.

Background: The incidence of high-output stoma (HOS) was reported to be approximately 3 to 16% in the literature, and HOS can cause dehydration. This complication is often severe enough to warrant hospital readmission and may result in renal failure. The aim of this study was to show a decrease of 50% in ileostomy output in the experimental arm using lanreotide treatment.

Methods: Patients with an ileostomy output ≥ 1.5 l/24 hours were included in this prospective, open, multicentre randomized trial. Patients were randomly allocated between treatment arms with either lanreotide (LAN) and antidiarrhoeal treatments (TAD) (LAN-TAD group) or antidiarrhoeal treatments only (TADS group). The primary outcome was ileostomy output after 72 days. The secondary endpoints were ileostomy output during the first 6 days, blood urea and creatinine values, hospital length of stay and serious adverse events.

Results: In the per-protocol analysis, there were nine patients in the control group (TADS) and six patients in the experimental group (TAD-LAN group). The stoma outputs at Day 3 (D3) in the experimental and control groups were 1,900 ± 855.7 mL and 1,728.6 ± 845.5 mL, respectively ( = 0.2). No differences were found concerning stoma output at D6, renal function, or hospital length of stay between the two groups.

Conclusion: The trial was prematurely stopped due to the low number of patients included. The question of the usefulness of somatostatin analogues in HOS persists, especially as the cost of this treatment is high, and there is a lack of evidence of its effectiveness.
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http://dx.doi.org/10.1080/08941939.2020.1800871DOI Listing
December 2021

Evaluating the Surgeon's Experience as a Risk Factor for Post-Esophagectomy Chylothorax on a Four-Year Cohort.

Cureus 2020 Jun 19;12(6):e8696. Epub 2020 Jun 19.

Visceral and Digestive Surgery, Hautepierre University Hospital, Strasbourg, FRA.

Background: Chylothorax (CHT) is a known post-operative complication after esophageal surgery with vaguely defined risk factors.

Methods: This is a retrospective chart review of 70 consecutive patients with operable cancer over a period of four years (January 2013 to December 2016). Ivor Lewis and McKeown interventions were performed. Thoracic duct is identified and ligated routinely. Factors related to the patient, the tumor, and the operating surgeon were analyzed.

Results: Incidence of CHT was 10%. Surgeons with less than five years of esophageal surgery experience had the most CHT, 71% (p=0.001). No association was found between tumor location, type, body mass index (BMI), neoadjuvant therapy, response to neoadjuvant therapy or male sex, and CHT. The odds of developing CHT were 17 times higher in patients operated by a junior surgeon (odds ratio, OR=17.67, confidence interval, CI 2.68-116.34, p=0.003). Four patients (5.7%) had anastomotic leaks, none of them had CHT. Senior surgeons had less operative time and harvested more lymph nodes (p=0.0002 and p=0.1086 respectively).

Conclusion: Surgeon's experience might be considered a major risk factor to develop CHT. This finding needs to be confirmed by a larger multicentric series taking into consideration the human factor.
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http://dx.doi.org/10.7759/cureus.8696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370582PMC
June 2020

How to Prevent Sarcopenia Occurrence during Neoadjuvant Chemotherapy for Oesogastric Adenocarcinoma?

Nutr Cancer 2021 25;73(5):802-808. Epub 2020 May 25.

Department of Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.

The aim of this study was to evaluate the impact of a preoperative feeding jejunostomy (FJ) on the occurrence of sarcopenia before and after preoperative chemotherapy for patients with an oesogastric adenocarcinoma (OGA). Forty-six patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. Sarcopenia was evaluated by measuring muscle surfaces (psoas, paraspinal and abdominal wall muscles) on abdominal CT images at the level of the 3rd lumbar vertebra. A FJ was placed in 31 patients (67.4%) before the neoadjuvant treatment (FJ group), while 15 patients (32.6%) started neoadjuvant treatments without FJ (control group). After preoperative chemotherapy, there were significantly more sarcopenic patients in the control group, compared to the FJ group. In the FJ group, 13% of the patients ( = 4) were sarcopenic before treatment and 22.6% of them ( = 7) became sarcopenic after preoperative chemotherapy ( = 0.3). In the control group, if initially only 6.7% ( = 1) of patients were sarcopenic, the majority of the patients (60%,  = 9) became sarcopenic after chemotherapy ( = 0.012). The FJ was an independent risk factor of sarcopenia after neoadjuvant chemotherapy. FJ with enteral nutritional support during the preoperative management of OGA seemed to efficiently counteract sarcopenia occurrence during preoperative chemotherapy.
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http://dx.doi.org/10.1080/01635581.2020.1770813DOI Listing
August 2021

Prognostic Factors Analysis for Colon Cancer with Lymph Node Negative.

Chirurgia (Bucur) 2018 Jul-Aug;113(4):503-515

Purpose: The analysis of high risk relapse prognosis factors and their importance regarding recurrence risk for stage I and II colon cancer, according to TNM classification 8th edition, 2017.

Material And Method: We performed a retrospective analysis regarding the impact of prognosis factors for patients with high recurrence risk in stages I and II. We studied 99 patients with T2, T3 and T4 tumors who suffered a curative resection and whom may or may not present indication for adjuvant chemotherapy according to histoprognostic factors and molecular biomarkers. We performed a univariate Cox regression which highlighted that male sex is a risk factor for disease relapse (HR=5.53, p 0.05, IC95% = 1.29 to 23.73). Although with a low statistical significance effect, T4 tumors seems to be associated with a poor prognosis regarding disease relapse (HR = 2.56, p = 0.06, IC95% = 0.94 to 6.99) compared to T2 and T3 tumors. Patients with d'MMR (MSI-H) seem to have a more favorable evolution compared to patients with p'MMR (MSS/MSI-L) - HR (d'MMR vs p'MMR) = 0.19, IC95% = 0.02 to 1.61, p = 0.13. We believe that it would be useful for MSS / MSI to be systematically analyzed, our data suggesting a better response of d`MMR patients to adjuvant chemotherapy. The multivariate Cox regression did not identify independent risk factors of relapse.
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http://dx.doi.org/10.21614/chirurgia.113.4.503DOI Listing
June 2019

Biliary pancreatitis in a duplicate gallbladder: a case report and review of literature.

J Surg Case Rep 2018 May 29;2018(5):rjy112. Epub 2018 May 29.

Department of General and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France.

Duplicated gallbladder is a rare congenital anomaly that require special attentions due to its clinical, surgical and diagnostic difficulties. We present a case of a 39-year-old female patient with a duplicated gallbladder who presented with an acute biliary pancreatitis, a case to our knowledge is the first in the literature. A double gallbladder in an abdominal ultrasonography was doubtful, thus a computed tomography scan, a magnetic resonance cholangiopancreatography and an endoscopic retrograde cholangiopancreatography were done that confirmed the double gallbladder. A laparoscopic cholecystectomy with an intraoperative cholangiography was performed safely two months after the acute attack. The histopathological report revealed a Y-shaped type 1 double gallbladder according to the Harlaftis classification.
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http://dx.doi.org/10.1093/jscr/rjy112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007220PMC
May 2018

Surgical management of a De Garengeot's hernia using a biologic mesh: A case report and review of literature.

Int J Surg Case Rep 2017 18;39:273-275. Epub 2017 Aug 18.

Department of Digestive Surgery, Strasbourg University, 1 Avenue Moliere, 67000 Strasbourg, France. Electronic address:

Introduction: A De Garengeot hernia is a rare form of femoral hernia, where the appendix is found in the herniated sac. This feature is important to report, as both the diagnosis and the treatment are quite challenging in this particular condition.

Presentation Of Case: We report the case of a 77-year-old female presenting with a femoral hernia, containing an incarcerated necrotic vermiform appendix (De Garengeot hernia). A laparoscopic appendectomy was performed and the herniated defect was repaired according to Rives technique, using a biological mesh.

Discussion: The De Garengeot hernia is often unexpected and diagnosed intra-operatively. A pre-operative diagnosis is quite difficult, as it often presents clinically as a strangled femoral hernia. In patients without peritoneal signs, a contrast-enhanced Computed Tomography (CT) of the abdomen is useful for the diagnosis. Many surgical techniques have been discussed in literature, but there is no consensus. We show the feasibility and safety of the hernia repair according to Rives technique, through an inguinotomy with a biologic mesh. A laparoscopic approach was used to remove the necrotic appendix.

Conclusion: The De Garengeot hernia is an uncommon differential diagnosis for patients presenting with clinical signs of strangled femoral hernia. Although hernia repairs with a synthetic mesh in the presence of appendicitis have been reported, we describe a case of femoral hernia repair using a biologic mesh, in a patient with a De Garengot hernia.
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http://dx.doi.org/10.1016/j.ijscr.2017.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587892PMC
August 2017

Could a Feeding Jejunostomy be Integrated into a Standardized Preoperative Management of Oeso-gastric Junction Adenocarcinoma?

Ann Surg Oncol 2017 Oct 26;24(11):3324-3330. Epub 2017 Jun 26.

Department of Digestive Surgery, Strasbourg University Hospital, 1 Avenue Moliere, 67000, Strasbourg, France.

Purpose: To evaluate the impact of a feeding jejunostomy (FJ) on the preoperative management of patients with an oesogastric adenocarcinoma (OGA).

Methods: From January 2007 to December 2014, patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. FJ was performed before starting perioperative treatments in patients presenting with dysphagia or with a nutritional risk index (NRI) <97.5. The patients who did not require a FJ served as a control group.

Results: Among the 114 patients with OGA consecutively admitted in our surgical department, 88 (77.2%) were enrolled for neoadjuvant treatment. A FJ was placed in 50 patients (56.8%) before the neoadjuvant treatment (FJ group), whereas 38 patients (43.2%) started neoadjuvant treatments without FJ (control group). Ninety-six percent of patients (n = 48) in the FJ group successfully completed the neoadjuvant treatment but only 81.6% of patients without FJ (n = 31; p = 0.004). The FJ group was divided between responders: 37 patients with a weight response (74%), and nonresponders: 13 patients without weight response (26%). In the FJ group, the nutritional response during preoperative chemotherapy was a significant predictive factor for the achievement of second stage oesogastric resection (p = 0.002).

Conclusions: FJ with enteral nutritional support during the preoperative management of OGA is a safe and effective support for the completion of the preoperative chemotherapy. The weight response to the enteral support is a predictor factor for a completion of the preoperative chemotherapy and could identify a group of patients who would have a better chance of reaching radical surgery.
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http://dx.doi.org/10.1245/s10434-017-5945-9DOI Listing
October 2017

Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin.

Oncology 2017 2;93(3):183-190. Epub 2017 Jun 2.

Service de chirurgie générale et digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France.

Background: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT.

Methods: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively).

Results: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis.

Conclusion: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.
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http://dx.doi.org/10.1159/000475758DOI Listing
December 2017

Management of rectal squamous cell carcinoma.

Clin Res Hepatol Gastroenterol 2017 10 5;41(5):e71-e73. Epub 2017 May 5.

Service de chirurgie générale et digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, 2, avenue Molière, 67200 Strasbourg, France.

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http://dx.doi.org/10.1016/j.clinre.2017.03.012DOI Listing
October 2017

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

Eur J Cardiothorac Surg 2017 02;51(2):255-262

Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.

Objectives: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status.

Methods: We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known.

Results: A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001].

Conclusion: Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.
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http://dx.doi.org/10.1093/ejcts/ezw304DOI Listing
February 2017

Small Bowel Carcinoid: The "Dancing Bowel Sign" on 18F-FDOPA PET/CT.

Clin Nucl Med 2016 Dec;41(12):944-945

From the Departments of *Biophysics and Nuclear Medicine, †Digestive and General Surgery, and ‡Internal Medicine, Hautepierre Hospital, University Hospitals of Strasbourg; and §ICube, UMR 7357 CNRS/University of Strasbourg and Fédération de Médecine Translationelle de Strasbourg (FMTS), Faculty of Medicine, Strasbourg, France.

The localization of small bowel (SB) neuroendocrine tumors (NETs) remains a diagnostic challenge in clinical practice. In about a third of cases, SB-NETs are multiple at diagnosis. However, the sensitivity of conventional presurgical diagnostic investigations is not exhaustive. F-FDOPA (6-L-F-fluorodihydroxyphenylalanine) PET seems to be a valuable diagnostic technique for the detection of midgut NETs. According to our experience, a delayed PET/CT acquisition centered on abdominopelvic region and performed after oral hydration may improve the detection of primary tumor and the identification of patients with multifocal SB-NETs who could benefit from a more accurate intraoperative palpation of the entire SB.
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http://dx.doi.org/10.1097/RLU.0000000000001402DOI Listing
December 2016

Treatment that follows guidelines closely dramatically improves overall survival of patients with anal canal and margin cancers.

Crit Rev Oncol Hematol 2016 May 4;101:131-8. Epub 2016 Mar 4.

Radiotherapy Department, Centre Paul Strauss, 3, Rue de la Porte de l'Hôpital, 67065 Strasbourg Cedex, France; Radiobiology Lab., EA3430, Strasbourg University, France. Electronic address:

Background: To assess relevance of ESMO-ESSO-ESTRO treatment guidelines in a retrospective analysis of patients with anal canal or anal margin cancers.

Material And Methods: 155 patients were separated into standard treatment group (STG), treated according to or closely the guidelines, and an altered treatment group (ATG).

Results: The median follow-up time was 50.7 months. In the STG, the 5- and 10-year LR-DFS rates were 75.2% and 72.7%; in the ATG, they were 66.8% and 61.2%, respectively. In the STG, the 5- and 10-year OS rates were 81.8% and 68%; in the ATG, they were 63.3% and 49.5%, respectively (p=0.037). In the multivariate analysis, favorable prognostic factors for OS included the standard treatment, age <60, tumor 50.4Gy.

Conclusion: This study identifies the superiority of treatment according to standard guidelines compared to altered treatment. Our results corroborate the guidelines.
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http://dx.doi.org/10.1016/j.critrevonc.2016.03.001DOI Listing
May 2016

Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study.

Surg Obes Relat Dis 2016 Mar-Apr;12(3):613-621. Epub 2015 Sep 19.

Faculty of Pharmacy, UMR CNRS 7213, University of Strasbourg, Strasbourg, France.

Background: The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking.

Objectives: The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs).

Setting: University hospital.

Methods: A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2×4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA.

Results: A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution.

Conclusions: This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs. (Surg Obes Relat Dis 2015;0:000-000.) © 2015 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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http://dx.doi.org/10.1016/j.soard.2015.08.505DOI Listing
October 2017

Peritoneal carcinomatosis with synchronous liver metastases from colorectal cancer: Who will benefit from complete cytoreductive surgery?

Int J Surg 2016 Jan 1;25:98-105. Epub 2015 Dec 1.

Department of General and Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.

Purpose: Selection of patients for resection of synchronous liver metastases (LM) and peritoneal carcinomatosis (PC) of colorectal cancer (CRC) remains a debated issue since morbidity of this surgery is not negligible. We aimed to define overall survival (OS) prognostic criteria in patients undergoing PC surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and LM resection.

Methods: This monocentric and comparative study included all consecutive patients operated for LM (LM group, n = 77), PC (HIPEC group, n = 18) and PC + LM (LM + HIPEC group, n = 9) from January 2007 to May 2011. Characteristics of the 3 groups were prospectively collected and retrospectively compared.

Results: Median follow-up was 56,5 months. Major morbidity and mortality were respectively 14% and 3%. Two-year disease free and overall survival rates were respectively 23% and 76%. There were significantly more Dindo grade III-IV complications in LM + HIPEC group. In multivariate analysis, grade II and III preoperative chemotherapy-induced toxicity and size of LM were identified as poor OS prognostic factors whereas response to preoperative chemotherapy significantly increases OS. OS was not different (p = 0.235) between the 3 groups.

Conclusion: Toxicity to preoperative chemotherapy and size of LM were identified as poor prognostic factors in patients undergoing simultaneous PC and LM surgery. These criteria could help in better selecting patients for such extensive surgery.
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http://dx.doi.org/10.1016/j.ijsu.2015.11.025DOI Listing
January 2016

Complex abdominal wall defect reconstruction using a latissimus dorsi free flap with mesh after malignant tumor resection.

Microsurgery 2017 Jan 2;37(1):38-43. Epub 2015 Jun 2.

Department of Plastic Surgery, Strasbourg Academic Hospital, Strasbourg, France.

Purpose: Extended and full-thickness abdominal wall defects are commonly reconstructed using free flaps. Published surgical outcomes involving the latissimus dorsi (LD) free flap procedure are limited and are less numerous than those with free flaps involving the thigh. The aim of this report was to describe the immediate and long-term evaluation of complex abdominal wall reconstruction using a LD free flap with mesh.

Patients And Methods: Between 2005 and 2013, nine patients with extended malignant tumors of the abdominal wall underwent surgeries. After the surgical resection, the mean defect size was 385 cm (range: 190-650 cm ). Full-thickness abdominal wall reconstruction was performed with a combination of LD free flaps and meshes. The immediate and long-term outcomes were assessed regarding the complications, sustainable strength of the abdominal wall and cancer recurrence.

Results: The meshes measured 927 cm in average (range: 500-1036 cm ). Eight Parietex Composite® and 1 Bard Collamend Implant® were used. No donor site complications occurred, and complete LD flap survival was achieved without partial necrosis or thrombosis. One obese patient who received a porcine dermis mesh developed an eventration four days postoperatively and exhibited a limited amount of abdominal skin necrosis around the flap. Two patients died from cancer evolution. After a mean follow-up of 60.4 months (range: 29-94 months), clinical evaluation of the abdomen revealed 2 patients without anomalies, 4 cases of abdominal bulging without functional discomfort and 1 case of major abdominal distension.

Conclusions: Complex abdominal reconstruction with LD free flap and mesh allows extended satisfactory coverage with a low incidence of flap and donor site complications. However, patients should be advised of the significant risk of abdominal bulging. © 2014 Wiley Periodicals, Inc. Microsurgery 37:38-43, 2017.
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http://dx.doi.org/10.1002/micr.22434DOI Listing
January 2017

Posterior perineal reconstructions with "supra-fascial" lotus petal flaps.

J Plast Reconstr Aesthet Surg 2015 Jan 27;68(1):e7-12. Epub 2014 Oct 27.

Department of Plastic Surgery, Strasbourg Academic Hospital, Strasbourg, France.

Background: The lotus petal flap procedure is widely used for vulvovaginal reconstructions after gynecologic resections, but its effectiveness for posterior perineal coverage and filling is not yet well defined.

Methods: We conducted a retrospective evaluation of 10 lotus petal flap procedures performed between 2010 and 2014. Six patients were operated upon with posterior transpositions of unilateral (n = 2) or bilateral (n = 4) supra-fascial flaps. The patient demographics, comorbidities, and previous surgical treatments were surveyed. The postoperative outcomes, including length of stay, time of healing, and complications, were analyzed.

Results: Lotus petal flaps were indicated for filling of the chronic perineal cavity (n = 4) and for skin resurfacing (n = 2). The mean patient age was 61.5 years, and four patients previously underwent radiotherapy. The total operative time was 2.2 h on average. No wound complications or flap necrosis instances occurred during the follow-up consultations, which occurred at a mean of 20.5 months. The hospital stay duration was 11.3 days, and the duration of healing was 35.2 days, on average. Each flap transposition achieved the sustainable perineal reconstruction goal.

Conclusions: The supra-fascial lotus petal flap is an easy and safe procedure for posterior perineal reconstructions. Whether for an immediate or a delayed operation, unilateral or bilateral flap harvestings allow for effective coverage and filling. Furthermore, the donor-site morbidity remained low because the scars were hidden in the gluteal fold.
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http://dx.doi.org/10.1016/j.bjps.2014.10.028DOI Listing
January 2015

Diagnostic markers of postoperative morbidity after laparoscopic Roux-en-Y gastric bypass for obesity.

Langenbecks Arch Surg 2014 Apr 19;399(4):503-8. Epub 2014 Mar 19.

Service de Chirurgie Générale et Digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Avenue Molière, 67098, Strasbourg Cedex, France,

Purpose: The main objective of this study was to detect subacute complications that can arise from laparoscopic Roux-en-Y gastric bypass and take a rational approach to manage these complications.

Methods: A prospective observational study was performed from November 2010 to December 2012. All patients undergoing gastric bypass surgery for morbid obesity were included in this study. Patients with complications before day 5 were excluded from the study. Clinical and laboratory data (C-reactive protein, leukocyte count) at postoperative day 5, 30-day morbidity, were recorded. The diagnostic value of C-reactive protein (CRP) and leukocytes were determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results: One hundred and twenty-six patients were included. The overall incidence of 30-day morbidity was 8.7 %, and anastomotic leakage rate was 3.2 %. C-reactive protein at postoperative day 5 was a good predictor of complications (AUC was 0.862 (95 % CI [0.76; 0.96]; p < 0.001) and anastomotic leakage (AUC was 0.863 (95 % CI [0.66; 1]; p = 0.014). A CRP cutoff level of 136 mg/l at postoperative day 5 yielded a specificity of 95.5 % and a sensitivity of 57.1 % for the detection of postoperative complications. The negative predictive value was 94.6 %. A CRP level of 136 mg/l at day 5 was significantly associated with postoperative morbidity.

Conclusions: C-reactive protein dosage at postoperative day 5 is a relevant predictor of postoperative complications permitting to select patients at risk. Radiological examination and close monitoring could be restricted to patients with CRP level exceeding 136 mg/l.
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http://dx.doi.org/10.1007/s00423-014-1180-zDOI Listing
April 2014

Hypoxia differentially regulated CXCR4 and CXCR7 signaling in colon cancer.

Mol Cancer 2014 Mar 14;13:58. Epub 2014 Mar 14.

Université de Strasbourg (UdS), EA 3430 Progression tumorale et microenvironnement, Approches translationnelles et Epidémiologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Bâtiment U1113, 3 Avenue Molière, 67200 Strasbourg, France.

Background: HIF-1α and CXCR4/CXCL12 have crucial roles in the metastatic process of colorectal cancer. Our aim was to study the significance of targeting HIF-1α and the CXCR4/CXCL12 axis in colorectal cancer to prevent the dissemination process in vitro.

Methods: We investigated CXCR4 and CXCR7 mRNA and protein expression in human colon carcinomas and the modulation of their expression by hypoxia and HIF-1α in colon cancer cell lines. The migration of tumor cells in a Boyden chamber was studied after CXCR4 inhibition with siRNA or the CXCR4/CXCL12 neutraligand, chalcone 4.

Results: Analysis of a cohort of colon polyps and chromosome-unstable carcinomas showed that the expression of CXCR4 and CXCR7 was similar to that of the normal mucosa in the polyps and early-stage carcinomas but significantly increased in late stage carcinomas. Our data demonstrate that hypoxia strongly induced the expression of CXCR4 transcript and protein at the cell membrane, both regulated by HIF-1α, whereas CXCR7 expression was independent of hypoxia. After transient hypoxia, CXCR4 levels remained stable at the cell membrane up to 48 hours. Furthermore, reducing CXCR4 expression impaired CXCL12-induced Akt phosphorylation, whereas Erk activation remained unchanged. In contrast, reducing CXCR7 expression did not affect Akt nor Erk activation. In the presence of CXCR4 or CXCR7 siRNAs, a significant reduction in cell migration occurred (37% and 17%, respectively). Although irinotecan inhibited cell migration by 20% (p <0.001), the irinotecan and chalcone 4 combination further increased inhibition to 40% (p <0.001).

Conclusion: We demonstrated, for the first time, that hypoxia upregulated CXCR4 but not CXCR7 expression in tumor cells and that the CXCR4 receptor protein level remains high at the cell membrane when the tumor cells return to normoxia for up to 48 hours. In addition we showed the interest to inhibit the CXCR4 signaling by inhibiting both the HIF-1α and CXCR4/CXCL12 pathway. CXCR4 seems to be a relevant target because it is continuously expressed and functional both in normoxic and hypoxic conditions in tumor cells.
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http://dx.doi.org/10.1186/1476-4598-13-58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975457PMC
March 2014

In vivo and in vitro evidence of somatostatin receptors expression in a dedifferentiated retroperitoneal liposarcoma.

Clin Nucl Med 2014 Oct;39(10):892-3

From the *Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg; †ICube, University of Strasbourg/CNRS (UMR 7357) and Fédération de Médecine Translationnelle de Strasbourg, Faculty of Medicine, Strasbourg; ‡Departments of Pathology and §General Surgery, Strasbourg University Hospitals, Strasbourg; ¶Molecular Biology Laboratory, Conception University Hospital, Marseille; and ∥Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France.

A 62-year-old patient presented with mildly elevated catecholamines and an abdominal painless mass. Abdominal CT revealed an 18 × 12 cm tumor in the right retroperitoneum with intense contrast enhancement. Somatostatin receptor scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of paraganglioma, the patient was referred to surgery for tumor removal. Surprisingly, the histopathological examination revealed a dedifferentiated liposarcoma. Somatostatin receptors of type 2 were identified and quantified by reverse transcription polymerase chain reaction. The unexpected presentation of our patient draws clinicians' attention when performing diagnostic procedure for retroperitoneal lesions, even though hormone secretion and positive SRS strongly suggest paraganglioma.
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http://dx.doi.org/10.1097/RLU.0000000000000374DOI Listing
October 2014

Does the association of 18F-FDG uptake intensity and lesion topography reveal histological phenotype and tumor differentiation in esophageal cancer?

Hell J Nucl Med 2011 Sep-Dec;14(3):239-42

Service de Biophysique et de Médecine Nucléaire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67098 Strasbourg, France.

In daily clinical practice, the esophageal squamous cell cancer (ESCC) is considered to be more (18)F-FDG avid than adenocarcinoma (EAD). To date, the few studies concerning the existence of a real metabolic difference based on esophageal cancer (EC) histology, show divergent and not definitive results. A retrospective analysis of (18)F-FDG PET/CT of 87 patients with ESCC and EAD was performed to investigate the role played by both histopathological subtype and tumor differentiation in the characterization of glucose metabolic profile of EC. Esophageal squamous cell cancer was well differentiated (WD) in 42 cases and poorly differentiated (PD) in 12 patients. Twenty-one of the 33 patients had WD EAD, while 12 had a PD EAD. The (18)F-FDG maximal standardized uptake value (SUV(max)) was determined for all lesions and used for inter and intra-group comparison. In ESCC, the SUV(max) ranged from 4 to 31 with a mean value of 16±6. In EAD, the SUV(max) ranged from 2 to 25 with a mean value of 10±6. A statistically significant difference (P<0.0001) was found between ESCC and EAD. According to histological classification and tumor differentiation, we obtained the following results: a) the SUV(max) values of WD ESCC and WD EAD were 17±5 (range: 7-31) and 7±3 (range: 2-12) respectively (P<0.00001), b) the SUV(max) values of PD ESCC and PD EAD were 11±4 (range: 4-19) and 17±6 (range: 7-25) respectively (P<0.05). Moreover, a statistically significant difference of SUV(max) values was found between WD and PD ESCC (P<0.005) as well as between WD and PD differentiated EAD (P<0.0001). In order to predict tumor histology (ESCC, EAD) from both SUV(max) and lesion location, a multivariate discriminant analysis was performed on the whole population with a resulting diagnostic accuracy equal to 82% (P<0.00001). In conclusion, we provide additional arguments about (18)F-FDG uptake difference between ESCC and EAD as well as between poorly and well-differentiated forms of both EC histological subtypes.
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April 2016

In vivo topoisomerase I inhibition attenuates the expression of hypoxia-inducible factor 1α target genes and decreases tumor angiogenesis.

Mol Med 2012 Feb 10;18:83-94. Epub 2012 Feb 10.

EA 4438 Physiopathologie et Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.

Topoisomerase I is a privileged target for widely used anticancer agents such as irinotecan. Although these drugs are classically considered to be DNA-damaging agents, increasing evidence suggests that they might also influence the tumor environment. This study evaluates in vivo cellular and molecular modifications induced by irinotecan, a topoisomerase I-directed agent, in patient-derived colon tumors subcutaneously implanted in athymic nude mice. Irinotecan was given intraperitoneally at 40 mg/kg five times every 5 d, and expression profiles were evaluated at d 25 in tumors from treated and untreated animals. Unexpectedly, the in vivo antitumor activity of irinotecan was closely linked to a downregulation of hypoxia-inducible factor-1α (HIF1A) target genes along with an inhibition of HIF1A protein accumulation. The consequence was a decrease in tumor angiogenesis leading to tumor size stabilization. These results highlight the molecular basis for the antitumor activity of a widely used anticancer agent, and the method used opens the way for mechanistic studies of the in vivo activity of other anticancer therapies.
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http://dx.doi.org/10.2119/molmed.2011.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269639PMC
February 2012

Allelotyping identification of genomic alterations in rectal chromosomally unstable tumors without preoperative treatment.

BMC Cancer 2010 Oct 18;10:561. Epub 2010 Oct 18.

Service de Chirurgie Générale et Digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg Cedex, France.

Background: Numerous studies reported genomic alterations in colorectal human tumors but few focused on rectal tumors with the specification of preoperative-treated or untreated tumors. The goals of this study were to list chromosome allelic imbalances and correlate their frequency with tumor progression and to identify potential molecular markers of progression in rectal chromosomally unstable tumors without preoperative treatment.

Methods: Genomic alterations of 57 rectal tumors assessed by allelotyping targeting 33 chromosomal loci, were clusterised and compared to those of 151 left colon tumors.

Results: Clustering separated the rectal tumors without preoperative treatment into three subtypes according to the allelic imbalance frequency and genomic alteration associations. The tumors without preoperative treatment displayed a significantly higher allelic imbalance frequency (54%) than the tumors with preoperative treatment (33%), suggesting that treatment could target highly altered tumor clones. Interestingly, the survival analysis identified three potential prognostic molecular survival markers, D1S197, D5S430, and D14S65, for tumors without preoperative treatment.

Conclusion: Based on the genomic status of 33 chromosomal loci, we observed that rectal tumors without preoperative treatment segregate according to the global allelic imbalance frequency but without correlation to the tumor progression. Moreover, the detailed associations of alterations in rectal tumors are different from those described in colon tumors suggesting that rectal and left tumors should be considered as separate entities. Finally, potential prognostic genomic molecular markers for survival are proposed which status could specify the clinical course of the tumors.
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http://dx.doi.org/10.1186/1471-2407-10-561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973944PMC
October 2010

Adjuvant chemotherapy in elderly patients with colorectal cancer. A retrospective analysis of the implementation of tumor board recommendations in a single institution.

Crit Rev Oncol Hematol 2010 Jun 26;74(3):211-7. Epub 2009 Jun 26.

Pôle d'Hématologie et d'Oncologie, Hôpitaux Universitaires de Strasbourg, 1 Avenue Molière, 67098 Strasbourg, France.

Background: A number of studies have shown that elderly cancer patients were denied optimal anticancer treatment because of age. Colorectal cancer is among the most frequent cancers in Western countries, and adjuvant chemotherapy has proven efficacy and tolerance in this condition. This study was undertaken to explore the current approaches to adjuvant chemotherapy in elderly cancer patients in a single institution.

Patients And Methods: We retrospectively analyzed all patients' files that were discussed in the gastro-intestinal tumor board of the Hôpitaux Universitaires de Strasbourg during 3 years (2004-2006). The recorded variables included sex, age, tumor stage, cancer location colon vs rectum, number of comorbidities, occurrence of an oncogeriatric assessment, type and tolerance of chemotherapy. We investigated the reason to not administer adjuvant therapy in patients whom should have received this treatment if guidelines had to be applied.

Results: A total of 193 consecutive patients' files were extracted from colorectal cancer patients that had been discussed in the gastro-intestinal tumor board. Among these, we isolated patients over 70 years old who were proposed with either adjuvant chemotherapy (group A, n=65) or follow up (group B, n=128). The median age in group A was 75.3 years old. Tumor board recommendations were in accordance with guidelines in 91% of cases. Chemotherapy was delivered in 44 pts (76%) and completed in 42 (95%). The median age in group B was 78.6 years old, and in this group tumor board proposal met the guidelines in 83% of cases. In the logistic regression model, disease stage was the major variable leading to adjuvant treatment recommendation, age and comorbidities being of lesser importance.

Conclusions: In our series, elderly colorectal cancer patients are not undertreated. Efforts should be maintained to educate physicians with regard to feasibility of adjuvant chemotherapy in elderly patients.
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http://dx.doi.org/10.1016/j.critrevonc.2009.05.003DOI Listing
June 2010

Isolated microcytic anemia disclosing a unicentric Castleman disease: The interleukin-6/hepcidin pathway?

Eur J Intern Med 2008 Jul 26;19(5):367-9. Epub 2007 Oct 26.

Service de Médicine interne et de Nutrition, Hôpital Universitaire de Hautepierre, avenue Molière, 67098 Strasbourg Cedex, France.

Castleman disease (CD) is a rare lymphoproliferative disorder of uncertain origin. Anemia is commonly reported and is related to an inflammatory mechanism. Occasionally an autoimmune hemolytic anemia appears as the leading clinical feature. Three histological types have been differentiated, a hyaline-vascular type (HV), a plasma cell type (PC), and a mixed type. Clinically CD is separated into unicentric (localized) or multicentric (generalized) forms. The former is most frequently of HV type (80-90%), affecting a single lymph node. The PC type is encountered in 10-20% of the unicentric CD and in almost all of the multicentric cases. Numerous systemic manifestations have been described usually associated with PC type. An isolated and markedly microcytic anemia revealing a unicentric CD has never been reported in English literature. Recent data concerning iron metabolism, interleukin-6 and hepcidin provide interesting clues to understand the particular microcytic anemia of CD.
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http://dx.doi.org/10.1016/j.ejim.2007.09.006DOI Listing
July 2008

Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study.

Anesthesiology 2007 Sep;107(3):461-8

Department of Anesthesiology and Intensive Care, St. Antoine Hospital, Paris, France.

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.

Conclusions: Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery.
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http://dx.doi.org/10.1097/01.anes.0000278903.91986.19DOI Listing
September 2007

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes.

Int J Cancer 2007 Feb;120(3):524-32

Centre de Chirurgie Viscérale et Transplantation, Hôpital de Hautepierre, Avenue Molière, Strasbourg Cedex, France.

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2-way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN-High, CIN-Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K-Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN-Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.
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http://dx.doi.org/10.1002/ijc.22343DOI Listing
February 2007

A role for chromogranin A (4-16), a vasostatin-derived peptide, on human colonic motility. An in vitro study.

Regul Pept 2004 Sep;121(1-3):31-9

INSERM Unit 575 Pavillon Poincaré 1 place de l'Hôpital Civil 67091 Strasbourg, France.

The hypothesis that CgA-derived peptides may be involved in mechanisms modulating motility was tested. Human colonic smooth muscles were studied using an organ bath technique. Acetic acid (AA) effects were characterized on spontaneous mechanical activities (SMA) and on responses to transmural nerve stimulation (NS). AA induced a significant decrease in tone and abolished SMA; this effect was insensitive to either TTX or L-NAME/apamin. The AA-induced inhibitory effects were significantly reduced in the presence of CgA4-16. This effect was insensitive to TTX or L-NAME/apamin. Furthermore, AA-induced effects were blocked in the presence of BAYK8644 and CgA4-16 together. The inhibitory effect of nifedipine was delayed in the presence of CgA4-16. NS induced a triphasic response. Only the excitatory components were reduced in the presence of AA. This effect was dose-related and remained unchanged in the presence of CgA4-16 alone, but was blocked in the presence of simultaneous administration of CgA4-16 and L-NAME/apamin. AA application induced inhibition of human colon motility in vitro. This effect may be mediated through an action on L-type calcium channels. CgA4-16 may display a protective role, which prevents the inhibition of motility due to AA to occur, by acting on both smooth muscle and afferent terminals.
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http://dx.doi.org/10.1016/j.regpep.2004.04.003DOI Listing
September 2004

[Chronic fever revealing an urachal cyst].

Ann Med Interne (Paris) 2003 Dec;154(8):541-3

Service de Médecine Interne, Diabète et Maladies Métaboliques, Clinique Médicale B, Hôpital de Hautepierre, Strasbourg.

In the adult, the urachus remains as a non-specific fibrous formation extended from the bladder dome to the Retzius space. This urachal remnant is commonly asymptomatic or may be revealed by a cyst. This later may also be asymptomatic or lead to local inflammation or inflammatory pseudo-tumor. We report an original observation of chronic fever revealing an urachal cyst in a 21-Year-old male.
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December 2003
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