Patients characteristics:
Patient characteristics are presented in Table 1. A total of 166 patients underwent surgery for LRRC in the pelvic region at our department from April 2010 to March 2022. The median age of patients was 62.5 years (IQR, 53.8–71 years), with 113 males (68.1%) and 53 females (31.9%). The median body mass index (BMI) was 22.1 kg/m2 (IQR, 20-24.1 kg/m2), and 4 patients were classified as ASA-PS class III or higher. Of the 132 patients who received preoperative treatment, 33 underwent chemotherapy, 5 underwent radiotherapy (RT), and 94 underwent chemoradiotherapy (CRT). Regarding comorbidity and past history, 31 patients had high blood pressure (HT), 8 had hyperlipemia (HL), 22 had diabetes mellitus (DM), 3 had atrial fibrillation (Af), 3 had inflammatory bowel disease (IBD), 5 had paralysis or stroke, and 1 had a past history of VTE.
Table 1
Clinical characteristics of the patients with locally recurrent rectal cancer in the pelvic region
| n = 166 |
Age (year-old), median (IQR) | 62.5 (53.8–71) |
Sex, [male / female], n (%) | 113 (68.1%)/ 53 (31.9%) |
Body Mass Index, median (IQR) | 22.1 (20-24.1) |
ASA-PS ≧ 3, n (%) | 4 (3.2%) |
Preoperative treatment +/-, n (%) Chemotherapy/RT/CRT | 132 (79.5%)/ 34 (20.5%) 33/ 5/ 94 |
Comorbidity/Past history HT, n HL, n DM, n Af, n IBD, n Paralysis/ Stroke, n VTE, n | 31 8 22 3 3 5 1 |
IQR; Interquartile range, BMI; Body Mass Index, ASA-PS; American Society of Anesthesiologists physical status, RT; Radiotherapy, CRT; Chemoradiotherapy, HT; High blood pressure, HL; Hyperlipemia, DM; Diabetes mellitus, Af; Atrial fibrillation, IBD; Inflammatory bowel disease, VTE; Venous thromboembolism |
Surgical outcomes:
Table 2 presents the short-term outcomes according to surgical procedures. Of the 166 patients, 110 patients underwent open abdominal surgery (66.3%) and 56 underwent laparoscopic surgery (33.7%). Among those who underwent laparoscopic surgery, 3 cases were converted from laparoscopic surgery to open abdominal surgery, and 1 case was performed with robot-assisted endoscopic surgery. Out of the 56 patients who underwent laparoscopic surgery, a total of 21 (37.5%) were treated with an additional laparoscopic transanal or transperineal approach. Of the 166 patients, 120 (72.3%) needed multivisceral resection. In terms of sacral resection, 55 patients (33.1%) required it, with 18 having the resection level located above the lower edge of the S2 vertebra, 23 above the lower edge of the S3 vertebra, 14 above the lower edge of the S4 vertebra .
Table 2
Surgical procedures for treating locally recurrent rectal cancer
| n = 166 |
Approach, n (%) Laparotomy Laparoscopy* | 110 (66.3%) 56 (33.7%) |
Combined with laparoscopic anal/ perineal approach, n (%) | 21 (12.7%) |
Multivisceral resection, n (%) | 120 (72.3%) |
Sacral resection, n (%) S2/ S3/ S4 | 55 (33.1%) 18/ 23/ 14 |
TPE, n (%) | 52 (31.3%) |
LLND, n (%) | 102 (61.4%) |
Blood loss, median, ml (IQR) | 455 (121.3–1470) |
Blood transfusion, n (%) | 61 (36.7%) |
Operating time, median, min (IQR) | 619 (399-766.5) |
Postoperative complication, Clavien Dindo ≧ 3a, n (%) | 53 (31.9%) |
Hospital stay, median, days (range) | 33.5 (22-51.5) |
Pharmacologic Prophylaxis of VTE, n (%) Fondaparinux sodium (FPX)/ Enoxaparin sodium (ENP) | 121 (73.3%) 36/ 85 |
VTE, n (%) | 7 (4.2%) |
TPE; Total pelvic exenteration, LLND; Lateral lymph node dissection, IQR; Interquartile range, VTE; Venous thromboembolism |
*In 3 cases, the procedure was converted from laparoscopy to laparotomy; 1 case was performed with robotic assistance. |
Additionally, 102 patients (61.4%) needed lateral lymph node dissection. The median blood loss volume was 455 ml (IQR, 121.3–1470 ml), and 61 patients (36.7%) needed a blood transfusion. The median operative time was 619 minutes (IQR, 399-766.5 minutes). Postoperative severe complications, graded IIIa or higher according to the Clavien-Dindo classification, occurred in 53 patients (31.9%). The median duration of hospital stay was 33.5 days (IQR, 22-51.5 days). Pharmacologic prophylaxis for the prevention of VTE was administered to 121 patients (73.3%) using Fondaparinux sodium (FPX) and Enoxaparin sodium (ENP). The VTE incidence was 4.2% (7 patients) among patients who underwent surgery for LRRC.
The details of the patient characteristics are shown in Table 3. Patient characteristics revealed no significant difference between the VTE group and the no-VTE group. Short-term outcomes according to surgical procedures are summarized in Table 4. Sacral resection was performed more often in the VTE group than in the no-VTE group (71.4% vs 31.5%, p = 0.041). Operating time was longer in the VTE group than in the no-VTE group (median, 915 minutes vs 606 minutes, p = 0.006) and the hospital stay period was longer in the VTE group than in the no-VTE group (median, 68 days vs 33 days, p = 0.013). The other parameters showed no significant difference between the two groups.
Table 3
Clinical characteristics of the patient with locally recurrent rectal cancer in the pelvic region, comparing the VTE group and no-VTE group
| VTE(+) n = 7 | VTE(-) n = 159 | p value |
Age (year-old), median (IQR) | 51 (46–48) | 63 (54–71) | 0.169 |
Sex, [male/ female], n (%) | 1 (14.3%)/ 6(85.7%) | 52 (32.7%)/ 107(67.3%) | 0.432 |
BMI, median (IQR) | 23.1 (10.4–26.6) | 22.0 (10.0- 24.1) | 0.472 |
ASA-PS ≧ 3, n (%) | 0 (0%) | 4 (3.4%) | 1.000 |
Comorbidity/ Past history, n (%) HT, n (%) HL, n (%) DM, n (%) Af, n (%) IBD, n (%) Paralysis/ Stroke, n (%) VTE, n (%) | 3 (42.9%) 2 (28.6%) 1 (14.3%) 1 (14.3%) 0 (0%) 0 (0%) 1 (14.3%) 0 (0%) | 85 (53.5%) 29 (18.2%) 7 (4.4%) 21 (13.2%) 3 (1.9%) 3 (1.9%) 4 (2.5%) 1 (0.6%) | 0.707 0616 0.297 1.000 1.000 1.000 0.196 1.000 |
Preoperative treatment, n (%) Chemotherapy, n (%) RT, n (%) CRT, n (%) | 5 (71.4%) 1 (14.3%) 1 (14.3%) 3 (42.9%) | 127 (79.9%) 32 (20.1%) 4 (2.5%) 91 (57.2%) | 0.517 0.694 0.183 0.455 |
Preoperative D-dimer, median (IQR) | 0.49 (0.32–1.79) | 0.52 (0.29–1.01) | 0.988 |
IQR; Interquartile range, BMI; Body Mass Index, ASA-PS; American Society of Anesthesiologists physical status, HT; High blood pressure, HL; Hyperlipemia, DM; Diabetes mellitus, Af; Atrial fibrillation, IBD; Inflammatory bowel disease, VTE; Venous thromboembolism RT; Radiotherapy, CRT; Chemoradiotherapy |
Table 4
Surgical procedures for treating locally recurrent rectal cancer, comparing the VTE group and no-VTE group
| VTE(+) n = 7 | VTE(-) n = 159 | p value |
Approach, n (%) Laparoscopy Laparotomy | 3 (42.9%) 4 (57.1%) | 53 (33.3%) 106 (66.7%) | 0.689 |
Combined with laparoscopic anal/perineal approach, n (%) | 0 (0%) | 21 (13.2%) | 0.5973 |
Multivisceral resection, n (%) | 6 (85.7%) | 114 (71.7%) | 0.675 |
Sacral resection, n (%) S2/ S3/ S4 | 5 (71.4%) 2/ 2/ 1 | 50 (31.5%) 16/ 21/ 13 | 0.041 |
TPE, n (%) | 2 (28.6%) | 50 (31.5%) | 1.000 |
LLND, n (%) | 6 (85.7%) | 96 (60.4%) | 0.251 |
Blood loss, median (ml, IQR) | 1200 (530–4820) | 400 (110–1320) | 0.052 |
Blood transfusion, n (%) | 4 (57.1%) | 57 (35.9%) | 0.263 |
Operating time, median (min, IQR) | 915 (804–956) | 606 (390–760) | 0.006 |
Hospital stay (days, IQR) | 68 (48–139) | 33 (22–50) | 0.013 |
Pharmacologic Prophylaxis of VTE, n (%) Fondaparinux sodium (FPX)/ Enoxaparin sodium (ENP) | 5 (71.4%) 3/ 2 | 116 (73.4%) 82/ 34 | 1.000 0.633 |
LLND; Lateral lymph node dissection, IQR; Interquartile range, VTE; Venous thromboembolism |
Postoperative VTE incidence was evaluated for each factor using univariate analysis (Table 5). Univariate analysis showed that VTE incidence was significantly higher in the patients who required sacral resection (OR = 5.45, 95% CI: 1.02–29.06, p = 0.047). In this study, univariate analysis showed statistical significance for only one factor, with other factors not demonstrating significance. Additionally, there was a clear correlation among these factors, suggesting the potential for multicollinearity. Therefore, to avoid the complexities of interpretation associated with multicollinearity, multivariate analysis was not conducted in this study. The cutoff value for age, a known risk factor for VTE, was set at 50 years. Additionally, the cutoff value for BMI, following the standards for obesity in Japan, was set at 25 kg/m2. The cutoff values for blood loss and operating time were determined based on median values.
Table 5
Univariate analysis of clinical characteristics associated with VTE
| Univariate |
Variables | OR | 95%CI | p value |
Age (year-old) [ ≧ 50/ <50] | 0.23 | 0.05–1.07 | 0.061 |
Sex [Female/ Male] | 0.34 | 0.04–2.92 | 0.328 |
BMI [ ≧ 25/ <25] | 1.72 | 0.32–9.30 | 0.529 |
Approach [laparotomy/ laparoscopy] | 1.5 | 0.32–6.95 | 0.604 |
LLND [+/ -] | 3.94 | 0.46–33.49 | 0.210 |
Blood loss (ml) [ ≧ 455/ <455 ] | 6.39 | 0.75–54.29 | 0.089 |
Operating time (min) [ ≧ 619/ <619 ] | 6.39 | 0.75–54.29 | 0.089 |
Postoperative complication [Clavien Dindo ≧ 3a/ <3a] | 2.99 | 0.65–13.88 | 0.161 |
Pharmacologic Prophylaxis of VTE [+/ -] | 0.91 | 0.17–4.84 | 0.907 |
Pharmacologic Prophylaxis of VTE [FPX/ ENP] | 1.61 | 0.26–10.06 | 0.612 |
TPE [+/ -] | 0.87 | 0.16–4.65 | 0.873 |
Sacral resection [+/ -] | 5.45 | 1.02–29.06 | 0.047 |
BMI; Body Mass Index, LLND; Lateral lymph node dissection, VTE; Venous thromboembolism, FPX; Fondaparinux sodium, ENP; Enoxaparin sodium, TPE; Total pelvic exenteration |
Table 6 presents the results regarding postoperative VTE. The appearance of VTE was also evaluated in both groups; sacral resection group and no-sacral resection group. The incidence of VTE was significantly higher in the sacral resection group than in the no-sacral resection group (9.09% vs 1.80%, p = 0.041).
Table 6
The appearance of VTE was also evaluated in both groups; sacral resection group and no-sacral resection group
| Sacral resection(+) n = 55 | Sacral resection(-) n = 111 | p value |
| | | 0.041 |
VTE + | 5 (9.09%) | 2 (1.80%) | |
VTE - | 50 (90.9%) | 109 (98.2%) | |
VTE; Venous thromboembolism |
The details of VTE cases are shown in Table 7. Case 1–5 were the patients with sacral resection, case 6–7 were the patients without sacral resection. Two of these were non-symptomatic VTE cases, and pharmacologic prophylaxis of VTE was not administered in place in two patients. The operative methods were varied; highly invasive operations, such as resection involving multiple organs, were commonly performed. Operating time exceeded 521 minutes, and blood loss volume was often substantial, with transfusions performed in more than half of the patients. The onset of VTE varied in timing, ranging from 1 to 42 days after surgery. In six patients, the C-D classification of VTE was grade II, and they received anticoagulant therapy. In contrast, one patient’s C-D classification of VTE was grade IIIa, and an IVC filter was placed.
Table 7
Case | Sacral resection | Age | Sex | BMI | Details of VTE(symptomatic+/-) | Pharmacologic Prophylaxis | Timing of VTE (POD) | Operative method | Approach | Operating time (min) | Blood loss(ml)/ Blood transfusion+/- | Hospital stay(days) | Postoperative complication | C-D of VTE | Additional information |
1 | + | 41 | M | 26.6 | DVT(-) | FPX | 14 | Tumor resection, Total cystectomy, Phallectomy, Pubic bones excision, Ischiectomy, Sacrectomy, Ileal conduit, Rectus abdominis muscle skin valve | Open | 928 | 4200/+ | 48 | Pelvic abscess, SSI | 2 | Paralysis |
2 | + | 46 | M | 23.6 | DVT(+), PTE(-) | FPX | 29 | TPE, Ileal conduit, Rectus abdominis muscle skin valve, Inguinal lymph nodes dissection, Sacrectomy, LLND | Open | 1280 | 4820/+ | 139 | Ileus, Perforation, Pelvic abscess | 3a | |
3 | + | 51 | M | 20.4 | DVT(+), PTE(-) | ENP | 15 | APR, Left uretectomy, LLND, Sacrectomy, Omentoplasty | Lap | 915 | 1200/+ | 61 | Lymphocyst | 2 | |
4 | + | 62 | M | 22.9 | DVT(+) | ENP | 41 | LAR, Small bowel resection, LLND, Sacrectomy | Lap | 956 | 530/- | 116 | Postoperative hemorrhage, Bradder injury | 2 | |
5 | + | 68 | M | 23.1 | DVT(+) | - | 42 | LAR, LLND, Sacrectomy | Lap | 835 | 630/- | 68 | SSI | 2 | CKD |
6 | - | 47 | F | 15.9 | DVT(+), PTE(-) | - | 1 | TPE, Left external iliac vein resection, para-aortic lymph nodes dissection, Ileal conduit, LLND | Open | 804 | 7560/+ | 147 | Pelvic abscess | 2 | |
7 | - | 72 | M | 27.2 | PTE(-) | ENP | 6 | LLND, Left internal iliac artery/vein resection, Left piriformis muscle・coccyx muscle・levator muscle of anus resection | Lap | 521 | 200/- | 17 | - | 2 | |
BMI; Body Mass Index, VTE; Venous thromboembolism, CD; Clavien-Dindo classification, DVT; Deep vein thrombosis, PTE; pulmonary thromboembolism, FPX; Fondaparinux sodium, ENP; Enoxaparin sodium, TPE; Total pelvic exenteration, LLND; Lateral lymph node dissection, APR; Abdominoperineal resection, LAR; Low anterior resection, SSI; surgical site infection, CKD; Chronic kidney disease |