55
DISEASES OF THE COLON &RECTUM VOLUME 65: 1 (2022)
Earn Continuing Education (CME) credit online at cme.lww.com. This activity has been approved for AMA PRA Category 1 credit.TM Funding/Support: None reported.
Financial Disclosures: None reported.
Presented at the meeting of Association of Hepato-Biliary Surgery and Liver Transplantation/French Society of Digestive Surgery, Paris, France, November 27 to 29, 2019.
Correspondence: Gilles Manceau, M.D., Ph.D., Université de Paris, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Digestive and Oncologic Surgery, 20, rue Leblanc, 75908 PARIS Cedex 15, France. E-mail: [email protected] Dis Colon Rectum 2022; 65: 55–65
DOI: 10.1097/DCR.0000000000001937
© The ASCRS 2021
What Is the Optimal Elective Colectomy for Splenic Flexure Cancer: End of the Debate? A Multicenter Study From the GRECCAR Group With a Propensity Score Analysis
Gilles Manceau, M.D., Ph.D.
1• Arnaud Alves, M.D., Ph.D.
2• Hélène Meillat, M.D.
3Léonor Benhaïm, M.D., Ph.D.
4• Mehdi Ouaïssi, M.D., Ph.D.
5• Yves H. Panis, M.D., Ph.D.
6Jean-Jacques Tuech, M.D., Ph.D.
7• Bertrand Dousset, M.D., Ph.D.
8Cécile Brigand, M.D., Ph.D.
9• Eddy Cotte, M.D., Ph.D.
10• Zaher Lakkis, M.D., Ph.D.
11Bogdan Badic, M.D., Ph.D.
12• Frédéric Marchal, M.D.
13• Charles Sabbagh, M.D., Ph.D.
14Momar Diouf, Ph.D.
15• Mehdi Karoui, M.D., Ph.D.
11 Université de Paris, Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Digestive and Oncologic Surgery, Paris, France
2 University Hospital of Caen, Department of Digestive Surgery, Caen, France
3 Institut Paoli Calmettes, Department of Digestive Surgical Oncology, Marseille, France 4 Gustave Roussy Cancer Campus, Department of Surgical Oncology, Villejuif, France
5 Trousseau Hospital, Department of Digestive, Oncological, Endocrine, Hepato-Biliary, Pancreatic and Liver Transplant Surgery, Chambray Les Tours, France.
6 Université de Paris, Assistance Publique - Hôpitaux de Paris, Beaujon Hospital, Department of Colorectal Surgery, Clichy, France 7 Charles Nicolle Hospital, Rouen University, Department of Digestive and General Surgery, Rouen, France
8 Université de Paris, Assistance Publique - Hôpitaux de Paris, Cochin Hospital, Department of Digestive, Hepato-Biliary and Endocrine Surgery, Paris, France
9 Strasbourg University Hospital, Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg, France 10 Lyon University Hospital, Center for Digestive and Endocrine Surgery, Lyon Sud Hospital, Lyon, France
11 University Hospital of Besançon, Department of Digestive Surgery, Besançon, France
12 La Cavale Blanche University Hospital, Department of General and Digestive Surgery, Brest, France
13 University of Lorraine, Cancer Institute of Lorraine, Department of Surgery, Vandœuvre-lès-Nancy Cedex, France 14 Amiens University Hospital, Department of Digestive Surgery, Amiens, France
15 Department of Clinical Research and Innovation, Amiens University Hospital, France
BACKGROUND: The optimal elective colectomy in
patients with splenic flexure tumor is debated. OBJECTIVE: This study aimed to compare splenic flexure colectomy, left hemicolectomy, and subtotal colectomy for perioperative, histological, and survival outcomes in this setting.
DESIGN: This is a multicenter retrospective cohort study.
SETTING: Patients diagnosed with nonmetastatic splenic flexure tumor who underwent elective colectomy were included.
PATIENTS: Between 2006 and 2014, 313 consecutive patients were operated on in 15 French Research Group of Rectal Cancer Surgery centers.
INTERVENTIONS: Propensity score weighting was performed to compare short- and long-term outcomes.
MAIN OUTCOME MEASURES: The primary end point was disease-free survival. Secondary end points included overall survival, quality of surgical resection, overall postoperative morbidity, surgical postoperative morbidity, and rate of anastomotic leakage.
ABSTRACT
RESULTS: The most performed surgery was splenic flexure colectomy (59%), followed by subtotal colectomy (23%) and left hemicolectomy (18%). Subtotal colectomy was more often performed by laparotomy compared with splenic flexure colectomy and left hemicolectomy (93% vs 61% vs 56%, p < 0.0001), and was associated with a longer operative time (260 minutes (120–460) vs 180 minutes (68–440) vs 217 minutes (149–480), p < 0.0001). Postoperative morbidity was similar between the 3 groups, but the median length of hospital stay was significantly longer after subtotal colectomy (13 days (5–56) vs 10 (4–175) vs 9 (4–55), p = 0.0007). The median number of harvested lymph nodes was significantly higher after subtotal colectomy compared with splenic flexure colectomy and left hemicolectomy (24 (8–90) vs 15 (1–81) vs 16 (3–52), p < 0.0001). The rate of stage III disease and the number of patients treated by adjuvant chemotherapy were similar between the 3 groups. There was no difference in terms of disease-free survival and overall survival between the 3 procedures.
LIMITATIONS: The study was limited by its retrospective design.
CONCLUSIONS: In the elective setting, splenic flexure colectomy is safe and oncologically adequate for patients with nonmetastatic splenic flexure tumor. However, given the oncological clearance after splenic flexure colectomy, it seems that the debate is not completely closed. See Video Abstract at http://links.lww.com/DCR/B703.
¿CUÁL ES LA COLECTOMÍA ELECTIVA ÓPTIMA PARA EL CÁNCER DE ÁNGULO ESPLÉNICO: FIN DEL DEBATE? UN ESTUDIO MULTICÉNTRICO DEL GRUPO GRECCAR CON UN ANÁLISIS DE PUNTAJE DE PROPENSIÓN
ANTECEDENTES: La colectomía electiva óptima en pacientes con tumores del ángulo esplénico continua en debate.
OBJETIVO: Comparar la colectomía de ángulo esplénico, hemicolectomía izquierda y colectomía subtotal
para los resultados perioperatorios, histológicos y de supervivencia en este escenario.
DISEÑO: Estudio de cohorte retrospectivo multicéntrico.
ESCENARIO: Se incluyeron pacientes diagnosticados de tumores del ángulo esplénico no metastásicos que se sometieron a colectomía electiva.
PACIENTES: Entre 2006 y 2014, 313 pacientes consecutivos fueron intervenidos en 15 centros GRECCAR.
INTERVENCIONES: Se realizó una ponderación del puntaje de propensión para comparar los resultados a corto y largo plazo.
PRINCIPALES MEDIDAS DE RESULTADO: El criterio de valoración principal fue la supervivencia libre de
enfermedad. Los criterios de valoración secundarios incluyeron la supervivencia general, la calidad de la resección quirúrgica, la morbilidad posoperatoria general, la morbilidad posoperatoria quirúrgica y la tasa de fuga anastomótica.
RESULTADOS: La cirugía más realizada fue la colectomía del ángulo esplénico (59%), seguida de la colectomía subtotal (23%) y la hemicolectomía izquierda (18%).
La colectomía subtotal se realizó con mayor frecuencia mediante laparotomía en comparación con la colectomía de ángulo esplénico y la hemicolectomía izquierda (93% frente a 61% frente a 56%, p <0.0001), y se asoció con un tiempo quirúrgico más prolongado (260 min [120-460] frente a 180 min [68-440] frente a 217 min [149-480], p <0.0001). La morbilidad posoperatoria fue similar entre los tres grupos, pero la duración media de la estancia hospitalaria fue significativamente más prolongada después de la colectomía subtotal (13 días [5-56] frente a 10 [4-175] frente a 9 [4-55], p = 0.0007).
La mediana del número de ganglios linfáticos extraídos fue significativamente mayor después de la colectomía subtotal en comparación con la colectomía del ángulo esplénico y la hemicolectomía izquierda (24 [8-90]
frente a 15 [1-81] frente a 16 [3-52], p <0.0001). La tasa de enfermedad en estadio III y el número de pacientes tratados con quimioterapia adyuvante fueron similares entre los 3 grupos. No hubo diferencias en términos de supervivencia libre de enfermedad y supervivencia general entre los 3 procedimientos.
LIMITACIONES: El estudio estuvo limitado por su diseño retrospectivo.
CONCLUSIONES: En un escenario electivo, la colectomía del ángulo esplénico es segura y oncológicamente adecuada para pacientes con tumores del ángulo esplénico no metastásicos. Sin embargo, dado el aclaramiento oncológico tras la colectomía del ángulo esplénico, parece que el debate no está completamente cerrado. Consulte Video Resumen en http://links.lww.
com/DCR/B703. (Traducción—Dr. Jorge Silva Velazco)
KEY WORDS: Colon cancer; Left hemicolectomy; Splenic flexure; Splenic flexure colectomy; Subtotal colectomy;
Surgery.
W
ith more than 1.8 million cases in 2017, colorec- tal cancer is the fourth most common cancer worldwide.1 Representing 3% of all colorectal cancers, splenic flexure tumors (SFTs) are associated with an increased risk of bowel obstruction and a worse prog- nosis than other colonic locations.2–6 The splenic flexure is a watershed region with a dual lymphatic drainage system, and, in the elective setting, there is still a debate regard- ing the optimal colectomy for SFT.7–10 Some authors arguethat an extensive surgical approach, ie, subtotal colectomy (STC) or left hemicolectomy (LHC), allows them to over- come the variations of the vascularization and lymphatic drainage of the splenic flexure,11–13 allows the removal of potential metastatic lymph nodes (LNs) elsewhere than along the left colic artery (LCA),14–16 and decreases the risk of leakage by avoiding a colo-colic anastomosis.17 Even for surgeons who advocate an extended resection, whether the colectomy should favor the superior mesenteric LN dissection with STC, or an inferior mesenteric one with LHC, is unknown.18,19 In contrast, others favor a more con- servative approach, ie, splenic flexure colectomy (SFC).7–10 The rationale for this approach is based on the oncological safety in terms of proximal and distal margins and number of harvested LNs,20,21 and the better long-term functional results with no negative impact on survival.7–10,22–24
No meaningful conclusions can be drawn from series comparing these 3 surgical procedures in patients with SFT, because all were retrospective or monocentric, the study period was long, the studied population was small and heterogeneous including stage IV disease, emergency surgery, or colonic stent, and some have pooled for analy- sis SFC and LHC in a “left colic resection group.”7–10,25 As a result, there is a lack of consensus regarding the surgical management of SFTs, which translates into great varia- tions in practices between countries.26,27
The aim of the present multicenter study from the French Research Group of Rectal Cancer Surgery (GRECCAR) group was to compare elective SFC, LHC, and STC in patients with nonmetastatic SFT with particu- lar focus on postoperative and oncological outcomes.
MATERIALS AND METHODS Study Population
All the 20 surgical center members of the French GRECCAR were invited to participate in this retrospec- tive study. Data from all consecutive patients operated on between January 2006 and December 2014 were retrospec- tively analyzed. The collected data were provided by the surgeons of each center on a voluntary basis and extracted from prospectively maintained databases. Because this work was a retrospective nonintervention study and col- lected anonymous patients’ data, no institutional review board was required.
Inclusion and Exclusion Criteria
Inclusion criteria were as follows: 1) elective surgery for SFT, ie, located between the distal third of the transverse colon and first part of the descending colon3,5,7,8,23,25,28,29; 2) histologically proven adenocarcinoma; 3) no synchronous metastatic disease; and 4) surgery with curative intent.
Exclusion criteria were: 1) complicated tumor requiring emergency surgery, 2) colonic stent insertion or primary
diverting colostomy before elective surgery, 3) synchro- nous colorectal cancer, 4) history of colectomy, and 5) ulcerative colitis or Crohn’s disease.
Operative Procedures
Tumor location was confirmed intraoperatively. The type of colectomy was defined according to the extent of colonic resection: SFC was defined as a resection of a part of the transverse colon, the splenic flexure, and a part of the descending colon, with high ligation of both the left branch of the middle colic artery (MCA) and the LCA;
LHC was defined as a resection from the distal third of the transverse colon to the upper rectum, with high liga- tion of left branch of the MCA and the inferior mesenteric artery; and STC was defined as a resection of the terminal ileum, the right and transverse colon, as well as parts of the descending and sigmoid colon, with high ligation of the ileocolic vessels, right colic vessels, MCA, and LCA.
In case of LHC, additional maneuvers required to achieve a tension-free colorectal anastomosis (retroileal transmes- enteric colorectal anastomosis or Deloyers procedure) were recorded.30,31
Study End Points
The primary end point was to compare STC, LHC, and SFC for 3-year disease-free survival (DFS), defined as the period of time between the date of surgery and the date of the first relapse of the disease (locoregional or distant) or death. All recurrences were confirmed by radiological and/or pathological assessment. Secondary end points included the comparison between the 3 sur- gical procedures for: 1) 5-year overall survival (OS), defined as the period of time between the date of surgery and the date of death, whatever the cause; 2) quality of surgical resection; 3) overall postoperative morbidity; 4) surgical postoperative morbidity; and 5) rate of anasto- motic leakage.
Variables and Outcome Measures
Postoperative mortality and morbidity were defined as any death or complication occurring within 30 postoperative days. Morbidity was graded according to the classification system validated by Clavien and Dindo.32 Anastomotic leakage was defined as a defect of the intestinal wall at the anastomotic site with a communication between the intra- and extraluminal compartments and included any abscess in the proximity of the anastomosis.33 Patients’
follow-up was standardized in all participating centers and done according to the French recommendations.34 It was performed every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter.
During follow-up, patients underwent clinical examina- tion, thoraco-abdomino-pelvic CT scan, and blood sam- ple for tumor markers.
Statistical Analysis
For descriptive analysis, categorical variables are pre- sented as frequencies and percentages and compared with the Pearson χ2 test or Fisher exact test, as appropriate.
Continuous variables are presented as median (range) and compared with the Kruskal-Wallis H test. Propensity score estimation was based on the McCaffrey et al method35 implemented in the “mnps” function from the “twang”
R package. The following variables were included in the propensity score model: invasion of a neighboring organ (“clinically T4” primary tumor), surgical morbidity, anas- tomotic leakage, tumor size, tumor perforation, pT stage, pN stage, vascular invasion, perineural invasion, micro- satellite instability, and adjuvant chemotherapy. After weighting the population for average treatment effect according to McCaffrey et al,35 survival curves were plot- ted according to the Kaplan-Meier method, and differ- ences between survival distributions were assessed using the Wald test with robust standard error estimated from a marginal Generalized Estimating Equation Cox model to account for center effect. After average treatment effect propensity score weighting, balancing in key covariates was assessed by a standardized mean difference below 0.25.36 All tests were 2 sided, with a level of significance set at p < 0.05. Statistical analyses were performed using JMP software (version 14.0.0; SAS Institute, Cary, NC) and R software version 3.6.0 (R Foundation for Statistical Computing, Vienna, Austria; www.r-projet.org) through the RStudio.Inc Interface Version 1.2.5019, © 2009 to 2019.
The article was prepared according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.37
RESULTS
Studied Population and Intraoperative Findings
From 2006 to 2014, 313 consecutive patients with non- metastatic SFT matched the inclusion criteria in 15 GRECCAR surgical centers (participation rate 75%), with a median of 21 patients (2–60) per center (Table 1).
The most performed elective surgical procedure was SFC (n = 183, 59%), followed by STC (n = 73, 23%), and LHC (n = 57, 18%). The type of procedure significantly dif- fered between the surgical centers (p < 0.0001). No differ- ence was observed regarding preoperative characteristics between the 3 groups.
A minimally invasive approach was used in 102 patients (33%), and 21 (21%) were converted to open surgery for the following reasons: technical difficulties (n = 10), unclear identification of tumor location (n = 6), locoregional invasion (n = 4), and obesity (n = 1). Open sur- gery was more frequently performed for STC than for SFC and LHC (93% vs 61% vs 56%, p < 0.0001). When compar- ing the 2 study periods (2006–2010 and 2011–2014), the
rate of laparoscopic colectomy for SFT had increased from 24% to 37% (p = 0,021). Enlarged resection to a neigh- boring organ was required in 41 (13%) patients: jejunum (n = 15), abdominal wall (n = 13), stomach (n = 11), pan- creas (n = 6), spleen (n = 5), diaphragm (n = 3), kidney (n = 1), gonadal vessels (n = 1), and psoas muscle (n = 1).
Intraoperative complications occurred in 22 patients (7%), with no difference between the 3 groups: splenic injury (n = 9), duodenal, intestinal serosal tear (n = 5), refashion- ing the anastomosis (n = 5), gonadal vessels injury (n = 1), and adverse anesthetic event (n = 1). LN dissection was extended to the MCA in 24% of SFC and in 11% of LHC.
A primary anastomosis was performed in 93% of patients, with no statistical difference between the 3 groups. In the LHC group, stapled anastomoses were performed more frequently (<0.0001). In the STC group, the site of anastomosis was the sigmoid and the descending colon in 79% and 21% of patients. Among patients who underwent LHC, 13 (23%) required addi- tional maneuvers to ensure a tension-free colorectal anastomosis: a retroileal transmesenteric colorectal anastomosis in 10 patients (18%) or a Deloyers proce- dure in the remaining 3 (5%). The median operative time for the entire cohort was 210 minutes (68–480).
It was significantly longer in the STC group than in the SFC and LHC groups (260 minutes (120–460) vs 180 min- utes (68–440) vs 217 minutes (149–480), p < 0.0001).
Postoperative Outcomes
There was no statistical difference between the 3 groups for overall postoperative morbidity, severe postopera- tive morbidity, surgical morbidity, anastomotic leak and postoperative mortality rates (Table 2). The reasons for unplanned reoperation were the following: anastomotic leakage (n = 18), wound dehiscence or abscess (n = 5), postoperative ileus (n = 4), intra-abdominal collection (n = 3), and hemoperitoneum (n = 1). The median length of hospital stay for the entire population was 10 days (4–175). It was significantly longer after STC than after SFC and LHC (13 days (5–56) vs 10 days (4–175) vs 9 (4-55), p = 0.0007). After propensity score weighting, no differ- ence was observed between the 3 groups regarding overall postoperative morbidity (34% vs 41% vs 39%, p = 0.33), surgical postoperative morbidity (28% vs 27% vs 26%, p = 0.91), and anastomotic leak rates (9% vs 5% vs 8%, p = 0.34).
Pathological Results
Tumor size tended to be larger in the STC group, although this difference did not reach statistical significance (Table 3). The proportion of patients with a free resec- tion margin of more than 5 cm was significantly higher in the STC group than in the SFC and LHC groups. After propensity score adjustment, this difference remained
significant (95% vs 72% vs 66%, p = 0.001). No patient had an involved longitudinal resection margin. The median number of harvested LNs was significantly higher after STC than after SFC and LHC (24 (8–90) vs 15 (1–81) vs 16 (3–52), p < 0.0001). After propensity score adjustment, the rate of surgical specimen with at least 12 harvested LNs was significantly higher after STC than after SFC and LHC (93% vs 71% vs 74%, p < 0.0001). There was no difference between the 3 procedures for pT and pN (N0/N+) stages.
Oncological Outcomes
The median follow-up was 45.1 months (0.4–162.7) and was not different between the 3 groups (47.1 months (0.4–162.7) for SFC, 48.9 months (1.1–127.8) for LHC, and 36.7 months (0.4–128.8) for STC, p = 0.39). Adjuvant systemic chemotherapy was administrated in 131 patients (42%), with FOLFOX as the preferred regimen (105 patients, 80%). The rate of patients receiving adjuvant chemother- apy was similar between the 3 groups (41% for SFC, 46%
for LHC, and 42% for STC, p = 0.85). During follow-up,
56 recurrences and 54 deaths occurred. No difference was observed between the 3 groups regarding 3-year DFS (72%
vs 82% vs 72%, p = 0.94) and 5-year OS (80% vs 81% vs 78%, p = 0.63). Oncological outcomes were also similar in the 3 groups after stratification on TNM stage (data not shown). After propensity score adjustment, survival dis- tributions were not different between the 3 groups for DFS (for SFC vs STC, p = 0.8580; for LHC vs STC, p = 0.8350;
and for LHC vs SFC, p= 0.9810) and OS (for SFC vs STC, p = 0.5030; for LHC vs STC, p = 0.4510; and for LHC vs SFC, p = 0.9350; Figs. 1 and 2). Three-year DFS was 72%, 80%, and 72% for SFC, LHC, and STC; whereas 5-year OS was 81%, 80%, and 78% for SFC, LHC, and STC.
DISCUSSION
Whether patients with SFT should undergo a SFC or a more extensive resection in an elective setting is still debated. In the present multicenter study comparing SFC, LHC, and STC, we found that: 1) STC was more often
TABLE 1. Baseline characteristics and intraoperative data of 313 patients operated on for splenic flexure tumor in elective setting Characteristics
Overall cohort, n (%) n = 313
Splenic flexure colectomy, n (%) n = 183
Left hemicolectomy, n (%) n = 57
Subtotal colectomy, n (%)
n = 73 p value
Age, ya 68.5 (27.5–96.3) 68.1 (27.5–94.1) 66.9 (40.6–89.5) 70.5 (29.1–96.3) 0.80
Sex 0.50
Male 188 (60) 105 (57) 37 (65) 46 (63)
Female 125 (40) 78 (43) 20 (35) 27 (37)
BMI, kg/m2a 25.2 (13.3–63.1) 25.0 (13.3–46.9) 26.1 (17.4–63.1) 25.1 (16.8–51.3) 0.44
ASA score 0.24
1 23 (10) 12 (10) 6 (12) 5 (9)
2 130 (56) 71 (57) 28 (57) 31 (53)
3 68 (29) 39 (31) 14 (29) 15 (26)
4 11 (5) 3 (2) 1 (2) 7 (12)
History of laparotomy 0.34
Yes 113 (37) 60 (33) 23 (40) 30 (42)
No 195 (63) 120 (67) 34 (60) 41 (58)
Surgical approach <0.0001*
Open surgery 211 (67) 111 (61) 32 (56) 68 (93)
Hand-assisted laparoscopy 9 (3) 5 (3) 2 (4) 2 (3)
Laparoscopy 93 (30) 67 (37) 23 (40) 3 (4)
Extended resection 0.49
Yes 41 (13) 21 (11) 10 (18) 10 (14)
No 272 (87) 162 (89) 47 (82) 63 (86)
Intraoperative complication 0.063
Yes 22 (7) 11 (6) 8 (14) 3 (4)
No 290 (93) 171 (93) 49 (86) 70 (96)
Anastomosis 0.48
Yes 290 (93) 168 (92) 52 (91) 70 (96)
No 23 (7) 15 (8) 5 (9) 3 (4)
Type of anastomosis <0.0001*
Handsewn 213 (73) 132 (79) 19 (37) 62 (89)
Stapled 77 (27) 36 (21) 33 (63) 8 (11)
Study period 0.33
2006–2010 170 (54) 94 (51) 31 (54) 45 (62)
2011–2014 143 (46) 89 (49) 26 (46) 28 (38)
aMedian (range).
*p value significant at the 0.05 level (comparison between the 3 groups).
performed by laparotomy with a longer operative time, and LHC required additional maneuvers in about 25%
of patients to ensure a tension-free anastomosis; 2) STC
was associated with an increased hospital stay, although no difference was reported between the 3 procedures for the other postoperative outcomes; and 3) despite a higher
TABLE 2. Postoperative outcomes of 313 patients operated on electively for a splenic flexure tumor Characteristics
Overall cohort, n (%) n = 313
Splenic flexure colectomy, n (%) n = 183
Left hemicolectomy, n (%) n = 57
Subtotal colectomy, n (%)
n = 73 p value
Postoperative death 0.85
Yes 6 (2) 3 (2) 1 (2) 2 (3)
No 307 (98) 180 (98) 56 (98) 71 (97)
Postoperative complication 0.97
Yes 121 (40) 69 (39) 23 (41) 29 (40)
No 183 (60) 107 (61) 33 (59) 43 (60)
Medical morbidity 75 (25) 38 (22) 15 (27) 22 (31) 0.31
Urinary tract infection 19 (6) 10 (6) 4 (7) 5 (7) 0.85
Pulmonary complication 25 (8) 11 (6) 6 (11) 8 (11) 0.34
Cardiac complication 16 (5) 8 (5) 1 (2) 7 (10) 0.13
DVT/PE 3 (1) 2 (1) 1 (2) 0 0.57
Postoperative delirium 15 (5) 9 (5) 2 (4) 4 (6) 0.94
Othera 20 (7) 10 (6) 5 (9) 5 (7) 0.63
Surgical morbidity 83 (27) 46 (26) 14 (25) 23 (32) 0.64
Anastomotic leak 25 (8) 14 (8) 3 (5) 8 (11) 0.52
Wound complications 29 (10) 16 (9) 4 (7) 9 (12) 0.60
Hemorrhage 7 (2) 5 (3) 1 (2) 1 (1) 0.87
Unplanned reoperation 31 (10) 18 (10) 3 (5) 10 (14) 0.30
Otherb 28 (9) 15 (9) 8 (11) 5 (9) 0.83
Clavien-Dindo ≥3 55 (18) 28 (16) 13 (23) 14 (19) 0.44
DVT = deep venous thrombosis; PE = pulmonary embolism.
aIncluded acute urinary retention, lymphangitis, central catheter infection, acute renal failure, bedsore, pleural effusion requiring drainage, and decompensation of cirrhosis.
bIncluded prolonged postoperative ileus, intra-abdominal collection distant from the anastomosis, and pancreatic complication.
*p value significant at the 0.05 level (comparison between the 3 groups).
TABLE 3. Pathological results of the 313 patients who underwent colectomy for splenic flexure tumor Characteristics
Overall cohort, n (%) n = 313
Splenic flexure colectomy, n (%) n = 183
Left hemicolectomy, n (%) n = 57
Subtotal colectomy, n (%)
n = 73 p value
Size of tumor, cma 4.5 (0.4–23) 4.85 (0.7–23) 3.5 (0.4–11) 5 (1–11) 0.050
Length of resected specimen, cma 30 (5–130) 22 (5–63) 33 (15–99) 69 (37–130) <0.0001*
Free resection margin, cma 7 (1–54) 6.25 (1–34) 5 (1–45) 17 (2–54) <0.0001*
Longitudinal resection margin
< 5 cm
68 (23) 47 (27) 18 (33) 3 (5) 0.0002*
Tumor perforation 18 (6) 9 (5) 2 (4) 7 (10) 0.27
pT stage 0.21
pTis-1 34 (11) 23 (13) 8 (14) 3 (4)
pT2 32 (10) 18 (10) 9 (16) 5 (7)
pT3 187 (61) 106 (59) 30 (53) 51 (70)
pT4 56 (18) 32 (18) 10 (18) 14 (19)
Vascular invasion 76 (27) 50 (31) 10 (19) 16 (24) 0.19
Lymphatic invasion 53 (28) 28 (31) 5 (12) 20 (36) 0.024*
Perineural invasion 45 (17) 29 (20) 5 (10) 11 (17) 0.28
Less than 12 harvested LNs 71 (23) 52 (29) 15 (27) 4 (5) 0.0002*
pN stage 0.23
pN0 213 (69) 117 (65) 41 (72) 55 (75)
pN+ 18 (25) 63 (35) 16 (28) 18 (25)
pTNM stage: 0.021*
Stage 0-I 61 (20) 37 (21) 16 (28) 8 (11)
Stage II 152 (49) 80 (44) 25 (44) 47 (64)
Stage III 97 (31) 63 (35) 16 (28) 18 (25)
Microsatellite instability 26 (21) 12 (19) 3 (14) 11 (27) 0.43
Missing 188 121 35 32
LN = lymph node.
aMedian (range).
*p value significant at the 0.05 level (comparison between the 3 groups).
number of harvested LNs and a longer free resection mar- gin after STC, there was no difference between the 3 pro- cedures for survival.
To our knowledge, only 4 recently published retro- spective studies (Table 4), including 2 with a propensity score analysis, compared the postoperative and oncologi- cal outcomes between SFC, LHC, and STC for SFT.7–10 Three were single-center studies, the study period ranged from 11 to 23 years, one7 included 30.5% of patients requir- ing urgent colectomy or patients treated with preoperative stent insertion, and in the later one10 14.5% of patients had stage IV disease and 5% received neoadjuvant chemo- therapy or underwent a 2-step procedure via temporary ostomy. In our series, to have a homogeneous population, we excluded patients with metastases and those requir- ing urgent surgery. In addition, the study period started in 2006 when adjuvant chemotherapy regimens were well standardized.
In the present study, SFC was the most performed sur- gical procedure (59%), whatever the study period. This is
in line with the recently published French intergroup sur- vey, in which SFC was the procedure of choice for 70% of surgeons interviewed.27 This finding is also consistent with the study by Rega et al,8 in which SFC was performed in 55% of patients. In contrast, LHC was the procedure of choice in the Bademci et al9 study (44%), and in the series reported by Arevalo et al,7 when only elective surgeries were taken into account (46 of 118, 39%). In the study by de’Angelis et al,10 the 3 surgical procedures were per- formed equally, although STC was preferred in patients with a weight loss >10% and presenting with more than 1 comorbidity, and SFC was preferred in those with a his- tory of abdominal surgery.10 In this later study, no expla- nation was given for these significant differences, nor the details of surgical procedures by participating country.
The rate of laparoscopy (33%) in our series was in the lower reported ranges of 16% to 74% in the litera- ture, with STC performed more frequently by open sur- gery.7,10 Our low rate of laparoscopy in patients with SFT might have also been influenced by the high percentage
12 0
SFC LHC STC
Wald-test p value (SFC vs. STC) = 0.8580 1.0
0.8
0.6
Survival probabilit y
0.4
0.2
0.0
24 36 48 60
Months 72 84 96 108 120
Wald-test p value (LHC vs. STC) = 0.8350 Wald-test p value (LHC vs. SFC) = 0.9810
206 275
224 228
168 141 106 81 51 33 18 9 6
184 171 149 110 64 50 23 21 14 7
161 118 98 65 48 36 25 18 18 13
FIGURE 1. Survival analyses for disease-free survival after propensity score adjustment. LHC = left hemicolectomy; SFC = splenic flexure colectomy; STC = subtotal colectomy.
(13%) of locally advanced primary tumors and the rela- tively long period of inclusion with increased use of the laparoscopic approach over time. Although participating centers from the GRECCAR group have high expertise in laparoscopy and colorectal surgery, the conversion rate in our series was 21%, which was higher than the 10%
and 16% reported by de’Angelis et al10 and Bademci et al.9 Technical difficulties, inadequate exposure, or visual- ization due to tumor fixation or invasion were the most frequently reported causes of conversion. In the present study, we found that nearly 25% of patients undergoing LHC required additional maneuvers, such as retroileal transmesenteric or Deloyers procedures to ensure a ten- sion-free colorectal anastomosis, highlighting that LHC for SFT is a major undertaking and requires expertise in colorectal surgery.
In the present study, no difference was observed between STC, LHC, and SFC with respect to postopera- tive mortality, morbidity, and reoperation rate. All but 1 study reported similar results. De’Angelis et al10 showed that the rate of postoperative complications was higher
among patients undergoing STC (58%) compared with the SFC (34%; p<0.001) and LHC groups (44%; p = 0.043), but there were no group differences in terms of severity (p = 0.548). Regarding the rate of anastomotic leakage, segmental colectomy with colo-colonic anastomosis was reported to be associated with a higher risk of dehiscence compared with other types of colectomy.17 However, this assertion was not supported by our results or by others.7–10
The length of hospital stay was significantly longer after STC. This result could be explained by the underuse of laparoscopy or by the higher number of ASA class 4 patients (12%), although the difference was not significant.
Another possible explanation could be the time to bowel recovery. Indeed, in the literature, STC is associated with a risk of postoperative ileus in almost 40% of patients22,38,39 and a delay of recovery of bowel function resulting in an increased of hospital stay.25 However, in the present study, postoperative ileus and time to recovery of bowel function were not available in the database and could not be evalu- ated. Similarly, the quality of life and bowel function, both reported by You et al23 to be better in 321 patients with 12
0
SFC LHC STC
Wald-test p value (SFC vs. STC) = 0.5030 1.0
0.8
0.6
Survival probability
0.4
0.2
0.0
24 36 48 60
Months 72 84 96 108 120
Wald-test p value (LHC vs. STC) = 0.4510 Wald-test p value (LHC vs. SFC) = 0.9350
215 275
224 228
188 170 131 91 56 38 25 12 7
195 179 153 114 76 56 30 26 17 9
173 144 109 74 61 46 31 24 18 13
FIGURE 2. Survival analyses for overall survival after propensity score adjustment. LHC = left hemicolectomy; SFC = splenic flexure colectomy; STC = subtotal colectomy.
TABLE 4. Four published series comparing STC, LHC, and SFC in patients operated on for SFT SeriesCountryType of studyStudy periodnLaparos- copy, %
Extended resection, n (%) Operative time, minMortal- ity, %Morbid- ity, %Leak, %Ileus, %Reinterven- tion, %Hospital stay, daysHarvested LNPositive LN, %OS, %DFS, % Martin Arevalo et al7 (2018)
SpainRetrospective Monocentric1995– 2016170164 (2)622a6NM7.5NM3-y3-y SFC3683%152 (85–330)c14505.5NM14NM17.5 (2–32)c2287.587.5 LHC63193%180 (75–385)c2435NM5NM15 (2–68)c36.595.589 STC71171.5%180 (58–360)c7348.5NM7NM17 (3–60)c389496 Rega et al8 (2019)ItalyRetrospective Monocentric2006– 201610317.511 (11)0.86a3NM5NM SFC5717.514%105.3 ± 49.6b25NMNMNM6.9 ± 3.1b21.5 ± 9.6b33NMNM LHC24218%109 ± 50.8b04NMNMNM8 ± 3.2b23.3 ± 13.9b37.5NMNM STC22144.5%121 ± 58.6b09NMNMNM7.9 ± 3.7b28.9 ± 13b21NMNM Bademci et al9 (2019)SpainRetrospective Monocentric1998– 20181246100.82745.5NMNMDistant recurrenceLocal recurrence SFC2893*128 ± 30.2b02888NM8 ± 3.8b15 ± 7.13b40100 LHC5558147 ± 41.5b0244%4NM9 ± 4.8b17± 7.8b3954 STC4168142 ± 27.6b2%31%27NM8 ± 3.6b21 ± 11.6b2450 De’Angelis et al10 (2020)Europe (11 surgical units/6 countries) Retrospective Multicentric Propensity score analysis
2000– 20183997436 (9)427913.59.5NM5-y5-y SFC125695%204.7 ± 52.6b63495.55.58.6 ± 4.6b*18.1 ± 8.5bNM7670 LHC1317910%225.1 ± 71.9b14411111616.8 ± 20.9b19.9 ± 11.1bNM7483 STC14375.512%232.8 ± 77.5b*758633 *1314.3 ± 13.3b25.1 ± 12.7b*NM6674 GRECCAR (Present study)FranceRetrospective Multicentric Propensity score analysis
2006– 20143133341 (13)210 (68–480)c2408NM1010 (4–175)c5-y3-y SFC1833911%180 (68–440)c2398NM1010 (4–175)c15 (1–81)c358172 LHC574418%217 (149–480)c2415NM59 (4–55)c16 (3–52)c288080 STC737*14%260 (120–460)c*34011NM1413 (5–56)c*24 (8–90)c*257872 DFS = disease-free survival; LHC = left hemicolectomy; LN = lymph nodes; NM = not mentioned; OS = overall survival; SFC = splenic flexure colectomy; SFT = splenic flexure tumor; STC = subtotal colectomy. aDindo grade >2. bMean ± SD. cMedian (ranges). *Statistically significant.
segmental colectomy than in those with extensive resec- tion, could not be assessed in our series.
In our study and in accordance with others,8,23,25,39 STC was associated with a greater number of harvested LNs in the surgical specimen. Despite a more extensive LN dissection with STC, it did not translate into a higher rate of stage III disease (pN+) highlighting that performing a more extensive resection with STC or LHC did not induce a stage migration (Will Rogers phenomenon), with a bet- ter stage II and III classification or a higher rate of adjuvant chemotherapy administration.40 We did not show signifi- cant differences between the surgical techniques for OS and DFS, and this was still true after stratification on TNM stage. Similarly, Arevalo et al,7 using a two-by-two com- parisons with propensity score matching on 170 patients with SFTs, showed no pairwise differences between the surgical techniques for 3-year OS and DFS. In the study by de’Angelis et al,10 the type of surgery was not a significant predictor of 5-year OS or DFS at multivariate analysis.
Splenic flexure colectomy with LN dissection centered on the left branch of the MCA seems adequate for LN staging and curative resection. In a series of 30 patients, Vasey et al41 reported that lymphatic drainage of SFT was preferentially through the LCA and was 9.2 times greater toward this direction in comparison with the left branch of the MCA. In the study by Nakagoe et al,29 the largest LN involvement in SFT occurred mainly along the paracolic arcade and at the origin of the LCA with positive LNs at the left branch of the MCA in a lower proportion. In a pre- vious study, we reported that 10% of patients with meta- static SFT had involved LNs along the right colic artery and could benefit from STC if the metastatic disease was suitable for curative treatment.16
It is important to emphasize, however, that less than 12 retrieved LNs and a longitudinal resection margin of less than 5 cm was reported in 29% and 27% in the SFC group, 2 well recognized histological features affecting oncologi- cal outcomes after surgery for colorectal cancer. Other authors reported these findings with a rate of less than 12 examined LNs up to 45%,23–25 and longitudinal resection margins <5 cm up to 43% after SFC.25 Nevertheless, despite this apparent suboptimal quality of surgical resection, SFC did not miss LN metastases and was not associated with an increased risk of recurrence.
The present study is limited by its retrospective nature, which led to missing data. The occurrence of postoperative ileus, time to recovery of bowel function, and quality of life, especially, were not available in our database. We also know that the choice between the 3 surgical procedures was not randomized but rather determined according to the policy of each participating center and surgeon’s pref- erence; thus, no procedure can be strongly recommended.
The choice of the procedure might have also been influ- enced by the exact location of the primary tumor, prefer- ring LHC for tumors located within the descending colon
and STC for those located within the transverse colon.
However, these limits were counterbalanced by the high number of patients included, the expertise of surgical teams in colorectal surgery, and the use of a propensity score matching for data analysis.
CONCLUSION
In patients with SFT, SFC is safe and feasible and provides results similar to other surgical procedures. Because more aggressive surgical approaches such as STC and LHC do not seem to provide any clinical benefit, SFC should be regarded as an alternative procedure in patients with non- metastatic SFT undergoing elective resection. However, given the quality of surgical resection after SFC in terms of longitudinal resection margins and number of LNs har- vested, it seems that the debate is not completely closed.
ACKNOWLEDGMENTS
The authors thank Drs Roukaya Belhadj Amor, Elisabeth Hain, and Arthus Vauchaussade de Chaumont for their help in data collection.
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