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Article ; Online: Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants.

Nagourney, Adam J / Gipoor, Joshua B / Evans, Steven S / D'Amora, Paulo / Duesberg, Max S / Bernard, Paula J / Francisco, Federico / Nagourney, Robert A

Genes

2023 Volume 14, Issue 3

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Female ; Humans ; Cisplatin ; Tumor Suppressor Protein p53/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Ovarian Neoplasms/drug therapy
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Tumor Suppressor Protein p53 ; Antineoplastic Agents ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-03-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030747
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Article: Diagnostic and Prognostic Performance of Metabolic Signatures in Pancreatic Ductal Adenocarcinoma: The Clinical Application of Quantitative NextGen Mass Spectrometry.

D'Amora, Paulo / Silva, Ismael D C G / Evans, Steven S / Nagourney, Adam J / Kirby, Katharine A / Herrmann, Brett / Cavalheiro, Daniela / Francisco, Federico R / Bernard, Paula J / Nagourney, Robert A

Metabolites

2024 Volume 14, Issue 3

Abstract: With 64,050 new diagnoses and 50,550 deaths in the US in 2023, pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all human malignancies. Early detection and improved prognostication remain critical unmet needs. We applied next- ... ...

Abstract	With 64,050 new diagnoses and 50,550 deaths in the US in 2023, pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all human malignancies. Early detection and improved prognostication remain critical unmet needs. We applied next-generation metabolomics, using quantitative tandem mass spectrometry on plasma, to develop biochemical signatures that identify PDAC. We first compared plasma from 10 PDAC patients to 169 samples from healthy controls. Using metabolomic algorithms and machine learning, we identified ratios that incorporate amino acids, biogenic amines, lysophosphatidylcholines, phosphatidylcholines and acylcarnitines that distinguished PDAC from normal controls. A confirmatory analysis then applied the algorithms to 30 PDACs compared with 60 age- and sex-matched controls. Metabolic signatures were then analyzed to compare survival, measured in months, from date of diagnosis to date of death that identified metabolite ratios that stratified PDACs into distinct survival groups. The results suggest that metabolic signatures could provide PDAC diagnoses earlier than tumor markers or radiographic measures and offer insights into disease severity that could allow more judicious use of therapy by stratifying patients into metabolic-risk subgroups.
Language	English
Publishing date	2024-02-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo14030148
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Article ; Online: Therapeutic Targeting of P53: A Comparative Analysis of APR-246 and COTI-2 in Human Tumor Primary Culture 3-D Explants

Nagourney, Adam J. / Gipoor, Joshua B. / Evans, Steven S. / D’Amora, Paulo / Duesberg, Max S. / Bernard, Paula J. / Francisco, Federico / Nagourney, Robert A.

Genes (Basel). 2023 Mar. 19, v. 14, no. 3

2023

Abstract: Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to ... ...

Abstract	Background: TP53 is the most commonly mutated gene in human cancer with loss of function mutations largely concentrated in “hotspots” affecting DNA binding. APR-246 and COTI-2 are small molecules under investigation in P53 mutated cancers. APR binds to P53 cysteine residues, altering conformation, while COTI-2 showed activity in P53 mutant tumors by a computational platform. We compared APR-246 and COTI-2 activity in human tumor explants from 247 surgical specimens. Methods: Ex vivo analyses of programmed cell death measured drug-induced cell death by delayed-loss-of-membrane integrity and ATP content. The LC50s were compared by Z-Score. Synergy was conducted by the method of Chou and Talalay, and correlations were performed by Pearson moment. Results: APR-246 and COTI-2 activity favored hematologic neoplasms, but solid tumor activity varied by diagnosis. COTI-2 and APR-246 activity did not correlate (R = 0.1028) (NS). COTI-2 activity correlated with nitrogen mustard, cisplatin and gemcitabine, doxorubicin and selumetinib, with a trend for APR-246 with doxorubicin. For ovarian cancer, COTI-2 showed synergy with cisplatin at 25%. Conclusions: COTI-2 and APR-246 activity differ by diagnosis. A lack of correlation supports distinct modes of action. Cisplatin synergy is consistent with P53’s role in DNA damage. Different mechanisms of action may underlie disease specificity and offer better disease targeting.
Keywords	DNA ; DNA damage ; cisplatin ; cysteine ; doxorubicin ; genes ; humans ; mutants ; nitrogen ; ovarian neoplasms ; programmed cell death ; therapeutics
Language	English
Dates of publication	2023-0319
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030747
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Article ; Online: Metabolomic Profiling of Peripheral Plasma by GC-MS and Correlation With Size of Uterine Leiomyomas.

Barison, Gustavo Anderman Silva / D'Amora, Paulo / Izidoro, Mário Augusto / Corinti, Mariana / Martins, Luísa Marcella / Bonduki, Claudio Emílio / Castro, Rodrigo de Aquino / Girão, Manoel João Batista Castello / Gomes, Mariano Tamura Vieira

Journal of the Endocrine Society

2022 Volume 6, Issue 7, Page(s) bvac061

Abstract: Background: Uterine leiomyomas are benign monoclonal tumors originating from the myometrium. Little information exists concerning metabolomics and the presence of leiomyomas.: Objective: The present study evaluated circulating metabolites in the ... ...

Abstract	Background: Uterine leiomyomas are benign monoclonal tumors originating from the myometrium. Little information exists concerning metabolomics and the presence of leiomyomas. Objective: The present study evaluated circulating metabolites in the plasma and their correlation with the presence and size of leiomyomas. Study design: Cross-sectional observational study, including women divided into 3 groups: 37 with leiomyomas and uterus >500 cm Results: There was no statistical difference between patients' anthropometric and demographic features and laboratory tests. Statistical differences in uterus volume ( Conclusion: There are different plasma metabolites levels of amino acids, fatty acids, and carbohydrates among patients with leiomyomas, most of them reduced, but some significantly increased in large leiomyomas, compared to leiomyoma-free patients.
Language	English
Publishing date	2022-04-14
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvac061
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Article ; Online: Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Rabelo, Iara B / Chiba, Akemi K / Moritz, Elyse / D'Amora, Paulo / Silva, Ismael Dale C G / Rodrigues, Celso A / Barros, Melca M O / Bordin, José O

British journal of haematology

2022 Volume 201, Issue 1, Page(s) 140–149

Abstract: Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional ... ...

Abstract	Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.
MeSH term(s)	Humans ; Anemia, Hemolytic, Autoimmune/therapy ; Hemolysis ; Cross-Sectional Studies ; Erythrocytes
Language	English
Publishing date	2022-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18584
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Article ; Online: Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture.

Kamergorodsky, Gil / Invitti, Adriana L / D'Amora, Paulo / Parreira, Rafael M / Kopelman, Alexander / Bonetti, Tatiana C S / Girão, Manoel J B C / Schor, Eduardo

Molecular and cellular endocrinology

2020 Volume 505, Page(s) 110743

Abstract: To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in ... ...

Abstract	To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in cultured endometrial cells from women with deep infiltrating endometriosis and healthy controls using real-time quantitative PCR. This study was conducted at a University hospital and included patients with and without deep infiltrating endometriosis (DIE). Primary endometrial stromal cells (ECs) from women with DIE and controls were treated with 17β-estradiol and progesterone prior to microphysiometer measurements and qPCR evaluations. Decreased progesterone responsiveness and decreased total nuclear PR and HSD17B1 mRNA expression were observed in cultured ECs from women with deep infiltrating endometriosis relative to those from control samples before and after hormone treatment. These cells also showed increased 17β-hydroxysteroid dehydrogenases types 2 (HSD17B2) relative to control group and increased expression of aromatase (CYP19) after exposure to progesterone. These physiological and expression patterns observed in ECs cultures from women with DIE reinforces previous findings in the literature supporting the progesterone resistance hypothesis in the pathogenesis of endometriosis.
MeSH term(s)	Acids/metabolism ; Adult ; Cells, Cultured ; Endometriosis/genetics ; Endometriosis/metabolism ; Endometriosis/pathology ; Enzymes/genetics ; Enzymes/metabolism ; Estrogens/metabolism ; Extracellular Space/metabolism ; Female ; Gene Expression Regulation ; Humans ; Progesterone/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Progesterone/metabolism ; Stromal Cells/metabolism
Chemical Substances	Acids ; Enzymes ; Estrogens ; RNA, Messenger ; Receptors, Progesterone ; Progesterone (4G7DS2Q64Y)
Language	English
Publishing date	2020-01-28
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2020.110743
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Article ; Online: Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis.

D'Amora, Paulo / Silva, Ismael Dale C G / Tewari, Krishnansu S / Bristow, Robert E / Cappuccini, Fabio / Evans, Steven S / Salzgeber, Marcia B / Addis-Bernard, Paula J / Palma, Anton M / Marchioni, Dirce M L / Carioca, Antonio A F / Penner, Kristine R / Alldredge, Jill / Longoria, Teresa / Nagourney, Robert A

Gynecologic oncology

2021 Volume 163, Issue 1, Page(s) 162–170

Abstract: Objective: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic ... ...

Abstract	Objective: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers. Methods: In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival. Results: Of 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 μg/ml (range 0.4-3.1). Cisplatin LC50's correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46-1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p < 0.001). Conclusions: Metabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carboplatin/administration & dosage ; Cisplatin/administration & dosage ; Drug Resistance, Neoplasm ; Female ; Humans ; Metabolomics/methods ; Middle Aged ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/mortality ; Paclitaxel/administration & dosage ; Uterine Neoplasms/drug therapy ; Uterine Neoplasms/metabolism ; Uterine Neoplasms/mortality ; Young Adult
Chemical Substances	Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2021-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.08.001
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Article: Progesterone's role in deep infiltrating endometriosis: Progesterone receptor and estrogen metabolism enzymes expression and physiological changes in primary endometrial stromal cell culture

Kamergorodsky, Gil / Invitti, Adriana L / D'Amora, Paulo / Parreira, Rafael M / Kopelman, Alexander / Bonetti, Tatiana C.S / Girão, Manoel J.B.C / Schor, Eduardo

Molecular and cellular endocrinology. 2020 Apr. 05, v. 505

2020

Abstract	To study progesterone signaling activation, we measured changes in extracellular pH as a reflection of Na+/H+ exchange (NHE) using a cytosensor microphysiometer and assessed progesterone receptor (PR) and estrogen metabolism enzymes mRNA expression in cultured endometrial cells from women with deep infiltrating endometriosis and healthy controls using real-time quantitative PCR. This study was conducted at a University hospital and included patients with and without deep infiltrating endometriosis (DIE). Primary endometrial stromal cells (ECs) from women with DIE and controls were treated with 17β-estradiol and progesterone prior to microphysiometer measurements and qPCR evaluations. Decreased progesterone responsiveness and decreased total nuclear PR and HSD17B1 mRNA expression were observed in cultured ECs from women with deep infiltrating endometriosis relative to those from control samples before and after hormone treatment. These cells also showed increased 17β-hydroxysteroid dehydrogenases types 2 (HSD17B2) relative to control group and increased expression of aromatase (CYP19) after exposure to progesterone. These physiological and expression patterns observed in ECs cultures from women with DIE reinforces previous findings in the literature supporting the progesterone resistance hypothesis in the pathogenesis of endometriosis.
Keywords	aromatase ; cell culture ; endometrium ; estradiol ; gene expression ; hospitals ; messenger RNA ; metabolism ; pH ; pathogenesis ; patients ; progesterone ; progesterone receptors ; protons ; quantitative polymerase chain reaction ; sodium ; stromal cells ; women
Language	English
Dates of publication	2020-0405
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2020.110743
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Article ; Online: Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection.

D'Amora, Paulo / Silva, Ismael Dale C G / Budib, Maria Auxiliadora / Ayache, Ricardo / Silva, Rafaela Moraes Siufi / Silva, Fabricio Colacino / Appel, Robson Mateus / Júnior, Saturnino Sarat / Pontes, Henrique Budib Dorsa / Alvarenga, Ana Carolina / Arima, Emilli Carvalho / Martins, Wellington Galhano / Silva, Nakal Laurenço F / Diaz, Ricardo Sobhie / Salzgeber, Marcia B / Palma, Anton M / Evans, Steven S / Nagourney, Robert A

PloS one

2021 Volume 16, Issue 12, Page(s) e0259909

Abstract: This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, ... ...

Abstract	This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.
MeSH term(s)	Adult ; Aged ; Area Under Curve ; COVID-19/mortality ; COVID-19/pathology ; COVID-19/virology ; Carnitine/metabolism ; Citrulline/metabolism ; Female ; Glutamic Acid/metabolism ; Humans ; Kynurenine/metabolism ; Male ; Metabolome ; Metabolomics/methods ; Middle Aged ; Ornithine/metabolism ; ROC Curve ; Risk Factors ; SARS-CoV-2/isolation & purification ; Severity of Illness Index ; Tryptophan/metabolism
Chemical Substances	Citrulline (29VT07BGDA) ; Kynurenine (343-65-7) ; Glutamic Acid (3KX376GY7L) ; Tryptophan (8DUH1N11BX) ; Ornithine (E524N2IXA3) ; Carnitine (S7UI8SM58A)
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0259909
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Article ; Online: Evaluation of pre- and post-operative symptoms in patients submitted to linear stapler nodulectomy due to anterior rectal wall endometriosis.

Kamergorodsky, Gil / Lemos, Nucelio / Rodrigues, Francisco C / Asanuma, Fernando Yassuo / D'Amora, Paulo / Schor, Eduardo / Girão, Manoel J B C

Surgical endoscopy

2015 Volume 29, Issue 8, Page(s) 2389–2393

Abstract: Background: The objective of this study was to evaluate the feasibility and safety of a more versatile rectosigmoid nodulectomy technique using a linear stapler.: Methods: Case series.: Setting: tertiary care (reference center for endometriosis ... ...

Abstract	Background: The objective of this study was to evaluate the feasibility and safety of a more versatile rectosigmoid nodulectomy technique using a linear stapler. Methods: Case series. Setting: tertiary care (reference center for endometriosis surgery). Patients: Sixty-one consecutive patients who were operated on between January 2006 and February 2013. Intervention: anterior rectal wall nodulectomy technique using sequential bites of the linear stapler. Measurements: Perioperative complications were recorded, and a condition-specific bowel dysfunction quality of life questionnaire (Rome III--Constipation) was applied pre-operatively and post-operatively during the first week of April 2013. Design classification: Canadian Task Force III RESULTS: A total of 61 patients were submitted to the intervention. After a mean follow-up period of 1.83 years (.25-7.1 ± 1.97), no post-operative fistula or leakage was observed. In addition, no cases of rectal stenosis or bowel obstruction were recorded, and two patients were excluded for not answering the post-operative questionnaire. According to the Rome III questionnaire, constipation symptoms improved significantly in 12 out of 17 questions. No patient reported worsening of symptoms in question. Conclusions: Linear stapler resection is a safe alternative to segmentar resection for endometriotic nodules on the anterior rectal wall.
MeSH term(s)	Adult ; Constipation/etiology ; Constipation/surgery ; Endometriosis/surgery ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Patient Outcome Assessment ; Quality of Life ; Rectal Diseases/surgery ; Retrospective Studies ; Surgical Stapling
Language	English
Publishing date	2015-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639039-0
ISSN	1432-2218 ; 0930-2794
ISSN (online)	1432-2218
ISSN	0930-2794
DOI	10.1007/s00464-014-3945-4
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