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Surgery in Gynecological Cancer
J. Sehouli
Director of the Department of Gynecology and
Center for Oncological Surgery ESGO Ovarian Cancer Center of Excellence
Charité Comprehensive Cancer Center Charité/ Campus Virchow-Klinikum
University of Berlin
©Sehouli 2018 Charité Berlin
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Modifikationen
Preperation of ureter
Resection of
Lig. sacro-uterinum
Resection of parametry
Vaginal cuff
Adnektomy
Nervesparing
techniques
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early versus advanced
Prognostic factors: stage, stroma
infiltration,V1,L1,(Grading), lymph node,
margins 17th ESO-E
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Plexus hypogastricus
inferior
Plexus pudendus 17th E
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Blasen- und Rectumpfeiler keine einheitlichen Platten...
...eher eigene Bandstrukturen 17th ESO-E
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©Sehouli 2017 Charité Berlin
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©Sehouli 2017 Charité Berlin
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©Sehouli 2017 Charité Berlin
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Compartments of the pelvic floor
1 Posterior C. Anorectal
1
2 Medial C. Uterovaginal
2
3 Anterior C: Vesicourethral
3
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sensitiv resisistent
Deperitonealisierung 43% 51%
©Sehouli 2017 Charité Berlin
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©Sehouli 2017 Charité Berlin
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Surgery
Preoperative management
Intraoperative management
Postoperative management
©Sehouli 2017 Charité Berlin
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What are the drivers in complication?
Surgical Technique and comlication depend on various
factors;
therapy
tumor biology/tumor pattern
health status, comorbidities, comedication, nutrition
status
cervical cancer, endometrial cancer, ovarian previous
therapy (eg radiation, surgery, chemotherapy,
complications)
health status of the patients (prior, during and after
surgery)
infrastructure of the clinic
experience of the surgeon(s) and the whole medical
team
luck
©Sehouli 2018 Charité Berlin
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detailled
exploration of the
abdomen
infragastr. omentectomy
Pelvic / paraaortal
lymph node
dissection
total
hysterectomy,
bilateral salpingo-
oophorectomy
Indication for
bowel resection
Peritonectomy /
Infrared
contactcoag.
Sehouli/ 2006
©Sehouli 2017 Charité Berlin
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V. renalis sinistra
V. cava sinistra
V. cava
dextra
A. renalis dextra
A. mestenterica inf.
V. renalis dextra
A. Iliaca dextra
A. Iliaca sin
V. ovarica sinistra Ureter sin.
Plexus
hypogastricus
Aorta abdominalis
V. ovarica dextra
N. Ilio-inguinalis sin ©Sehouli 2017 Charité Berlin
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Risk factors for venous thromboembolism – multivariate
analysis (Cox regression) in operated patients with
primary ovarian cancer under systemic chemotherapy in
76 out of 2743 patients.
Variable Hazard Ratio ± Std. Err. [95% Conf. Interval] P>|z|
Age (35-81y) /10yrs 1.4 ± 0.2 1.1 – 1.8 0.006
BMI
(vs. < 30 kg/m2) 3.2 ± 0.8 2.0 – 5.2 <0.001
FIGO IIIc or IV
(vs. FIGO <IIIc) 1.0 ± 0.3 0.6 – 1.7 0.959
Chemotherapy*
(yes vs. no) 0.2 ± 0.1 0.1 – 0.7 0.009
Ascites
(yes vs. no) 1.5 ± 0.3 0.9 – 2.3 0.123
Paraaortic
lymphadenectomy*
(yes vs. no)
.5 ± 0.2 0.3 – 1.0 0.059
Pelvic
lymphadenectomy
(yes vs. no)
1.1 ± 0.3 0.6 – 2.0 0.832
*protective Fotopoulou, duBois et
Sehouli
J Clin Oncol. 2008 Jun
1;26(16):2683-9
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Risk factors for mortality – multivariate analysis (Cox
regression) in operated patients with primary ovarian
cancer under systemic chemotherapy.
in 76 out of 2743 patients.
Fotopoulou, duBois et
Sehouli
J Clin Oncol. 2008 Jun
1;26(16):2683-9
Variable Hazard ratio 95% Confidence interval p-value
Age (35-81y) /10yrs 1.17 1.11 – 1.23 < 0.001
FIGO stage IIIc or higher
(vs. FIGO < IIIc) 1.68 1.46 – 1.93 < 0.001
Chemotherapy* (yes vs. no)
0.48 0.27 – 0.88 0.017
Incomplete tumor resection (i.e. tumor
residuals >0mm)
(yes vs. no)
2.76 2.41 – 3.16 < 0.001
Pulmonary embolism
(yes vs. no) 2.86 1.82 – 4.50 < 0.001
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Abstr. 5500: LION – LYMPHADENECTOMY IN
OVARIAN NEOPLASMS.
A prospective randomized AGO Study Group led
Gynecologic Cancer Intergroup trial. AGO OVAR OP3/ENGOT-ov31.
Philipp Harter1, J. Sehouli2, D. Lorusso3, A. Reuss4, I. Vergote5, C. Marth6,
JW Kim7, F. Raspagliesi8, B. Lampe9, F. Landoni10, W. Meier11, D. Cibula12,
A. Mustea13, S. Mahner14, I. Runnebaum15, B. Schmalfeldt16, A. Burges14,
R. Kimmig17, U. Wagner18, A. du Bois1
1 AGO & Essen, Germany, 2 AGO & Berlin, Germany, 3 MITO & Milan, Italy, 4 KKS Marburg, Germany; 5 BGOG &Leuven, Belgium, 6 AGO-Austria & Innsbruck, Austria,7 KGOG & Seoul, South Korea, 8 MITO & Milan, Italy, 9 AGO & Düsseldorf, Germany,10 MaNGO & Milan, Italy, 11 AGO & Düsseldorf, Germany, 12 AGO & Prague, Czech Republic, 13 AGO & Greifswald, Germany, 14 AGO & Hamburg, Germany, 15 AGO & Jena, Germany,16 AGO & München, Germany,
17 AGO & Essen, Germany, 19 AGO & Marburg, Germany
AGO Study Group NCT00712218
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The “LION” Study: Characteristics of surgery
LNE (%) No LNE (%) P-
value
Bilateral Salpingo-
oophorectomy*
319 (98.8) 320 (98.8) 0.99
Hysterectomy* 321 (99.4) 322 (99.4) 0.99
Omentectomy 319 (98.8) 322 (99.4) 0.41
(Partial) peritonectomy •Pelvis
•Paracolic
•Diaphragm
291 (90.1) 276 (85.5)
193 (59.8)
173 (53.6)
291 (89.8) 278 (85.8)
208 (64.2)
196 (60.5)
0.99
Gastrointestinal tract resection Stoma
169 (52.3) 34 (10.5)
167 (51.5) 24 (7.4)
0.84 0.17
Splenectomy 62 (19.2) 56 (17.3) 0.53
Porta hepatis/lesser omentum 61 (18.9) 69 (21.3) 0.44
Partial pancreatectomy
Partial hepatectomy
Pleurectomy
7 (2.1)
27 (8.4)
20 (6.2)
7 (2.1)
28 (8.6)
24 (7.4)
0.99
0.90
0.54
Complete resection 321 (99.4) 322 (99.4) 0.99
* Including earlier performed
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The “LION-Study”: Characteristics of surgery
Presented by: Philipp Harter
AGO & KEM
Essen, Germany
LNE (%) No LNE (%) Difference p-value
Study procedure according to
randomisation
320 (99.1) 313 (96.6)
Resected LN total (median, IQR)
Para-aortic LN
Pelvic LN
57 (45-73)
22 (16-33)
35 (26-43)
Lymph node metastases 180 (55.7)
Duration (median, IQR) [min] 340 (270-
420)
280 (210-
360)
+ 1 hour <0.001
Blood loss (median, IQR) [ml] 650 (400-
1000)
500 (300-
900)
+ 150 ml <0.001
Transfusions Massive transfusions (> 10 RBC/24h)
205 (63.7) 7 (2.2)
181 (56.0) 2 (0.6)
+ 8% 0.005 0.09
Fresh-frozen plasma 117 (36.3) 96 (29.7) + 7% 0.07
Intermediate/Intensive Care
Unit
250 (77.6) 223 (69.4) + 8% 0.01 17th ESO-E
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LION: Post-surgical outcome
Presented by: Philipp Harter
AGO & KEM
Essen, Germany
LNE (%) No LNE (%) p-value
Infections requiring antibiotics
Fever > 38.0o Celsius
Sepsis
83 (25.8)
41 (12.7)
6 (1.9)
60 (18.6)
32 (9.9)
3 (0.9)
0.03
0.21
0.31
Thrombosis 7 (2.2) 5 (1.6) 0.56
Pulmonary embolism 12 (3.7) 15 (4.6) 0.56
Secondary wound healing 31 (9.6) 19 (5.9) 0.12
Prolonged ileus (conservative management) 15 (4.6) 17 (5.3) 0.72
Peripheral sensoric neurologic event 7 (2.2) 7 (2.2) 0.99
Peripheral motoric neurologic event 10 (3.1) 8 (2.5) 0.63
Asymptomatic lymph cysts 14 (4.4) 1 (0.3) <0.001
Symptomatic lymph cysts 10 (3.1) 0 0.001
Fistula 5 (1.6) 7 (2.2) 0.56
Readmission rate 40 (12.4) 27 (8.3) 0.09
Rate of re-laparotomy for complications 40 (12.4) 21 (6.5) 0.01
60 day postoperative mortality 10 (3.1) 3 (0.9) 0.049
Platinum + Taxan i.v. 257 (79.6) 274 (84.6) 0.09 17th E
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More than 20 years „Fast track stories“…but
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Kein Aszites
(n = 56)
Aszites
(<500ml)
(n = 42)
Aszites
(>500ml)
(n = 21)
p Wert
Intraoperative Transfusion
0.001
§
No transfusion, n (%) 33 (58.9) 23 (54.8) 4 (19.0)
Transfusion 1 to 9 units, n (%) 21 (37.5) 15 (35.7) 12 (57.1)
Transfusion more than 10 units, n (%) 2 (3.6) 4 (9.5) 5 (23.8)
Höchste Noradrenaline (NA) Gabe
0.019
§
No NA administration, n (%) 34 (60.7) 20 (47.6) 7 (33.3)
Low Dose NA (<0.2µg/kg/min),n(%) 21 (37.5) 16 (38.1) 12 (57.1)
High Dose NA (0.2-0.5 µg/kg/min),n(%) 1 (1.8) 4 (9.5) 2 (9.5)
Very High NA (>0.5 µg/kg/min), n (%) 0 (0) 2 (4.8) 0 (0)
Episoden Hypotension (syst. Arterieller
Blutdruck (SBP) Abfall für 5 min)
SBP < 100mmHg (number) 5.0(2.0;15.75) 9.5(5.0;20.5) 15.0(4.5;24.0) 0.078 #
SBP < 90mmHg (number) 0 (0; 3) 3(0; 6) 4 (0; 8) 0.066 #
SBP < 80mmHg (number) 0 (0; 0) 0 (0; 0.25) 0 (0; 1.0) b 0.046 #
Feldheiser et al. Int J Gynecol Cancer 2014; 24: 478-487.
Impact of Ascites on the Perioperative
Outcome in Ovarian Cancer
x x
x x
x x
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Different persepctives rgarding volume
management
liberal
Surgical view 17th E
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liberal
Restrictiv
Anesthetic view
Differences in observing
and interpetration
Surgical view 17th E
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Restrictive Volume-Management!!!
Brandstrup, B. et al., Ann Surg, 2003 17th E
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Hemodynamic curves in pts with ovarian cancer
Feldheiser et al. REDAR, 2016 Mar;63(3):149-158. 17th ESO-E
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The „Charité-Experience“ (n=536 pts)
Jumana Almuheimid, Zelal Muallem, Jalid Sehouli et al
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© Charité/Sehouli/2017
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© Charité/Sehouli/2017
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© Charité/Sehouli/2017
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Overall Survival
complete resected
incomplete resected
© Charité/Sehouli/ ESGO 2017
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© Charité/Sehouli/ ESGO 2017
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SURGICAL CHARACTERISTICS IN ALL PATIENTS WITH
ADVANCED OVARIAN CANCERS UNDERGOING PRIMARY
CYTOREDUCTIVE SURGERY
© Charité/Sehouli/ ESGO 2017
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POSTOPERATIVE COMPLICATION AFTER PRIMARY CYTOREDUCTIVE
SURGERY IN PATIENTS WITH ADVANCED OVARIAN CANCERS
© Charité/Sehouli/ ESGO 2017
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PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL IN PATIENTS WITH
ADVANCED OVARIAN CANCER UNDERGOING PRIMARY CYTOREDUCTIVE SURGERY
© Charité/Sehouli/ ESGO 2017
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Abstr. 5501: Randomized controlled phase III study
evaluating the impact of secondary cytoreductive surgery in
recurrent ovarian cancer: the interim analysis of
AGO DESKTOP III / ENGOT ov20
Andreas du Bois1, I. Vergote2, G. Ferron3, A Reuss4, W. Meier1, S. Greggi5,
P. Jensen6, F. Selle3, F. Guyon3, C. Pomel3, F. Lecuru3, R. Zang7,
E. Avall-Lunqvist6, JW Kim8, J. Ponce9, F. Raspagliesi5,
S. Ghaem-Maghami10, A. Reinthaller11, P. Harter (PI)1 , and J. Sehouli1
1 AGO & Essen, Düsseldorf, Essen, Berlin, Germany; 2 BGOG & Leuven, Belgium; 3 GINECO & Toulouse, Paris, Bordeaux, Clermont-Ferrand, Paris France; 4 KKS Marburg, Germany; 5 MITO & Naples, Milan, Italy; 6 NSGO & Odense, Stockholm, Denmark & Sweden; 7 SGOG & Shanghai, China; 8 KGOG & Seoul, Korea; 9 GEICO & Barcelona, Spain; 10 NCRI & London, UK; 11 AGO-Austria & Wien, Austria
AGO Study Group
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AGO DESKTOP III: Surgery arm (AGO–OVAR OP.4; ENGOT-ov20; NCT01166737)
Presented by: Andreas du Bois
AGO & KEM
Essen, Germany
Duration of surgery (minutes; median /
quartiles)
220 (150 – 300)
Bowel resection 33.2%
Stoma diversion temporary / permanent 3.5% / 3.5%
Blood loss (ml; median / quartiles) 250 (50 – 500)
RBC transfusion 20.3%
Fever > 38°C 4.8%
Antibiotic treatment (mainly for urinary tract
infections)
19.0%
Peri-OP thrombosis 1.1%
Re-laparotomy rate 3.2%
Macroscopic complete resection
rate
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Retrospective evaluation of cytoreductive surgery in ovarian
cancer patients older than 70 years. (Fotopoulou, Sehouli et
al., 2009)
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Procedure
performed
Patients
[%]
(n= 101)
Procedure
performed
Patients
[%]
(n= 101)
Hysterectomy 63 [62.4] Colostomy /
Ileostomy
9 [8.9]
Pelvic LND 41 [40.6] Pancreas resection 0 [0]
Para- aortic LND 37 [36.6] Peritonectomy 57 [56.4]
Intestinal Resection 43 [42.6] Splenectomy 2 [1.98]
Partial resection
urinary bladder
with ureter
reimplantation
1 [0.99] Partial Hepatectomy 0 [0]
Diaphragmatic
Resection
1 [0.99] Partial Gastrectomy 1 [0.99]
Organ involved Patients
[%]
(n= 101)
Organ involved Patients
[%]
(n= 101)
Omentum 65 [64.4] Liver capsule 4 [3.9]
Pouch of Douglas 21 [20.8] Serosa of the
Stomach
6 [5.9]
Pelvic wall 29 [28.7] Diaphragma 31 [30.7]
Uterus 63 [62.4] Abdominal wall 2 [1.98]
Serosa of the urinary
bladder
13 [12.9] Small intestine 33 [32.7]
Splenic hilus 7 [6.9] Mesenteruim 38 [37.6]
Omental bursa 18 [17.8] Large intestine 54 [53.5]
Surgical procedures
performed during primary
tumordebulking surgery in
the elderly patients (>70
years old) with epithelial
ovarian cancer and
intraoperative tumor
dissemination pattern
according to the
„Intraoperative Mapping of
Ovarian Cancer“
documentation tool.
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Surgical outcome – tumor residuals
and morbidity
Patients [%]
(total=101)
Postoperative tumor residuals
None
<0.5cm
0.5-1cm
1-2cm
≥2cm
45 [44.6]
10 [9.9]
7 [6.9]
18 [17.8]
16 [15.8]
Postoperative morbidity
-venous thrombosis
- infection/sepsis
- fistula formation
- ileus
- postoperative bleeding
- renal failure
- neurological impairment
- pulmonary edema
- postoperative lymph fistula
- electrolytic imbalance
- multiorgan failure
- relaparotomy due to
complication
- Death
3 [2.97]
7 [6.93]
4 [3.96]
2 [1.98]
3 [2.97]
5 [4.95]
2 [1.98]
2 [1.98]
2 [1.98]
4 [3.96]
3 [2.97]
10 [9.90]
6 [5.94]
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Impact of cytoreductive surgery on
overall survival
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Kaplan Meier Overall survival curve and data for overall
and progression free survival for elderly patients
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intraoperative
Anesthesia
aspiration
Cardiac arrest
trachea injury
pneumothorax
positioning injury
surgical:
„Operability“
Rogan injuries
bleeding (tumor induced/iatrogen)
nerve leasions (positioning)
postoperative
Internistisch:
Thromboembol.
cardiopulmonary morbidity
Infections
SIRS
Liver failure
Takotsubo Cardiomypathy
surgical:
Fistula/ Perforations, (bowel, pancreas, bladder, stomach,
vessels)
secondary wound healing
peritonitis
hemorraghy
Bowel obstruction
Ischemia/Infarct
lymphorroe
compartmentsyndr.
emboly
COMPLICATIONS
MORBIDITY - MORTALITY ©Sehouli 2017 Charité Berlin
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©Sehouli 2017 Charité Berlin
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©Sehouli 2017 Charité Berlin
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2010
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...“drains to prevent
lymphocyst formation
can safely be omitted
following radical
hysterectomy and
pelvic LND“
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„FRAILTY“
Subproject of “BIOCOG”
Prospektive Untersuchung etablierter Tests zur
Risikostratifizierung und Prädiktion von postoperativen
Komplikationen bei Patientinnen mit gynäkologischen
Malignomen
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Frailty Studie
Studiendesign: Prospektive nicht-interventionelle klinische
Kohortenstudie
237 Frauen ≥ 18 Jahre mit elektiven chirurgischen Therapie bei
gynäkologischen onkologischen Erkrankungen
Oktober 2015 -Januar 2017
Primärer Endpunkt: Postoperative Komplikationen nach Clavien-
Dindo (30 Tage postoperative)
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Drop-outs N= 5
9 (3.8%) patients has died
Grade V complication according Clavien-Dindo
41(17.3%) experienced a grade≥3b complication
according Clavien-Dindo
Gynecological cancer patients
n = 237 (Median Age 59 years)
Frailty Ergebnisse
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Pre-Frail
p< 0,009 OR 3,3 95%CI 1,344- 8,103
Frail
P< 0,001 OR 4,1 95%CI 1,736- 9,803
Frailty Ergebnisse
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• ASA, BMI, Albumin, Potassium and Fried Frailty Score are associated with postoperative complications (Clavien- Dindo IIIB - V)
• Hand grip strength is associated with postoperative delirium in
elderly patients
• feasible to conduct during the busy clinical routine
• an evidence-based frailty score could also provide the option for interventions that reduce the amount of vulnerability pre-surgery
Conclusion
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Logistische Regression
Complications (IIIB-V)
Age p=0.34, OR 1.01 (95% CI 0.98-1.03)
Age>70 p=0.25, OR 1.51 (95% CI 0.73-3.11)
Barthel-Index <100 p=0.003, OR 3.62 (95% CI 1.55-8.43)
IADL p=0.03 OR 0.58 (95%CI 0.35-0.956)
ASA p<0.0001, OR 2.98 (95% CI 1.65-5.38)
Charlson Comorbidity P=0.015, OR 2.33 ( 95% CI 1.18-4.61
Polypharmacy p<0.001, OR 3.40 (95% CI 1.63-7.10)
Albumin<3.5 g/dl p<0.009, OR 3.22 (95% CI 1.33-7.79)
Potassium < 3.6 mmol/L p<0.007, OR 5.11 (95% CI 1.55-16.81)
BMI>30 kg/m2 p<0.001, OR 4.99 (95% CI 2.00-12.43)
Nutritional Risk Score >2 P=0.04 OR 1,51 (95%CI 1.01-2.26)
Frailty Results
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Multivariate analysis
Complications (IIIB-V)
Age p=0.49, OR 0.89 ( 95% CI 0.95-1.02),
ASA p=0.01, OR 2.60 (95% CI 1.20-5.60)
Duration of surgery p=0.012, OR 1.26 (95% CI 1.05-1.52)
Albumin<3.5 g/dl p=0.028, OR 3.37 (95% CI 1.14-10.00)
BMI >30kg/m2 p=0.009, OR 3.81 (95% CI 1.40-10.35)
Potassium < 3.6 mmol/L p=0.02, OR 3.69 (95% CI 1.20-11.38)
Charlson Score > 2 p=0.88, OR 1.06 (95% CI 0.42-2.69)
Polypharmacy p=0.65, OR 1.26 (95% CI 0.41-3.98)
Frailty Results
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Logistische Regression
Complications (IIIB-V)
Bioimpedance Phase angle<4.75 p=0.007, OR 3.08 (95% CI 1.35-7.01)
Sport p=0.05, OR 0.82 (95% CI 0.67-1.00)
Climbing Stairs p=0.001, OR 4.15 (95% CI 1.73-9.98)
Weight loss p=0.41 OR 1.5 (95%CI 0,56-4,00)
Distress Thermo >8 p=0.004, OR 3.90 (95% CI 1.55-9.79)
Pain p<0.001, OR 3.45 ( 95% CI 1.66-7.18)
Fatigue p<0.0001, OR 5.05 (95% CI 2.43-10.52)
Nicotine p=0.009, OR 3.22 (95% CI 1.33-7.79)
Time up to go >9s p<0.001, OR 5.93 (95% CI 2.055-17.12)
Hand grip <18 P=0.01 OR 3.43 (95% CI 1.23-9.53)
MMSE 26-18/30-27 p=0.14 OR 3,00 (95%CI 0.06-13.08)
Frailty Results
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Surgical approach in the „elderly
patient and/or fragile patient“
Healthy and fit „elderly patient“:
according to guidelines
Fragile „elderly patient“:
short time of surgery, priorization of
procedures
(starting with resection of main tumor burden,
en-bloc-resections or rather absolutely
necessary procedures, thorough hemostasis,
as little anastomoses as possible, critical
indication for multivisceral operation
techniques and lymphonodectomy)
©Sehouli 2017 Charité Berlin
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Steps during treatment/operation
Discussion of therapeutic options
Definition of therapeutic aim of surgery (Improvement of
symptoms vs. Improvement of PFS)
Definition of therapeutic concept after surgery
Best preoperative organization and preparation (Less may be
more!)
Best intraoperative assistance (Weniger ist mehr)
Evaluation of abdominal situation, preparation of all relevant
(retroperitoneal) structures without damage
Re-Evaluation and if acquired adaption of therapeutic goal and
alternative and/or following therapy
Identification of emergency exit
Priorization of operative procedures (starting with resection of
main tumor burden, preferably en-bloc-resections, restriction to
small amount of anastomoses)
Postoperative: fast-track
Re-Evaluation and if acquired adaption of therapeutic goal and
alternative and/or following therapy
Pre-OP
OP
Post-OP
©Sehouli 2017 Charité Berlin
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What are the main points?
• Infrastructure (surgery team, back-up)
• Prevent damage! (GI, vessels)
• Don‘t get too impressed by the tumor
burden
• Try to interpret pattern of tumor burden
• Define healthy organ structures
• Define realistic ending of surgery
• Take safe routes (extra- and
retroperitoneal)
©Sehouli 2017 Charité Berlin
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Advice and more…
• Step-wise preparation according to
anatomy (each step makes you more
courageous)
• Use your ressources
• Involve everyone of your team
• Accompany your patients before,
during and after the operation
©Sehouli 2017 Charité Berlin
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Important steps of surgical education
Thorough indication
Understanding of absolute and
relative contraindications
Experience complications
Provoke complications
Realize complications
Prevent complications
Master complications
©Sehouli 2017 Charité Berlin
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17th ESO-E
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rclass
Clin
ical O
ncology