Abstract
Objectives:
This study aimed to evaluate the safety and long-term outcomes of a one-stage resection and anastomosis approach without preoperative decompression in patients with left-sided incomplete obstructive colorectal cancer.
Methods:
We conducted a retrospective analysis of 571 patients diagnosed with pT3-4NanyM0 left-sided colorectal cancer who underwent radical resection and primary anastomosis without preoperative decompression or a diverting stoma from April 2012 to December 2019. Of these, 97 (17%) patients presented with incomplete obstruction, while 474 (83%) had no obstruction. Incomplete obstruction was characterized by the inability of a small-caliber endoscope to pass through the tumor without necessitating emergency surgery or decompression due to bowel obstruction. We compared perioperative short-term outcomes, as well as the 5-year overall survival rate and the 5-year relapse-free survival rate between the two groups.
Results:
Patients in the incomplete obstruction group experienced significantly longer median intervals between admission and surgery (6 vs. 2 days, P<0.001), higher complication rates (25.8% vs. 15%, P=0.016), and longer median postoperative hospital stays (10 vs. 9 days, P=0.002). However, the rates of anastomotic leakage (2.1% vs. 2.3%, P=1), the 5-year overall survival (91.5% vs. 93.7%, P=0.436), and the 5-year relapse-free survival (80.2% vs. 85.6%, P=0.195) were comparable between the groups.
Conclusions:
The outcomes regarding anastomotic leakage and long-term survival for one-stage resection and anastomosis without preoperative decompression in cases of incomplete obstructive colorectal cancer are promising. This management strategy appears feasible and safe with appropriate preoperative bowel preparation.
Keywords: colorectal cancer, obstruction, incomplete obstruction, anastomosis, outcomes
Introduction
Obstructive colorectal cancer (OCRC) represents 10% of colorectal cancers[1] and is associated with a poor prognosis[2]. Left-sided OCRC often necessitates emergency operations[3] or preoperative decompression procedures[4]. Emergency surgeries can lead to permanent stoma creation and high complication rates[3,5]. Consequently, the use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for OCRC has been developed[6]. The European Society of Gastrointestinal Endoscopy (ESGE) Guidelines strongly recommend discussing stenting as a BTS option with patients diagnosed with potentially curable left-sided OCRC, presenting it as an alternative to emergency resection[7]. Following the approval of SEMS by Japan's national health insurance in 2012, decompression procedures are now indicated based on the ColoRectal Obstruction Scoring System (CROSS) score (Table 1)[8]. SEMS for BTS is appropriately indicated for patients with a CROSS score of 0-1 and is frequently utilized in patients with a CROSS score of 2 OCRC[9]. Although CROSS scores of 3 and 4 are generally not recommended for SEMS placement, SEMSs are sometimes used in these cases for convenience. A prospective, multicenter study by Tomita et al. reported that SEMSs were placed in 20.4% of CROSS 3-4 cases and in 5.2% of asymptomatic patients[10]. SEMS placement, however, carries risks, including stent-related perforation, stent migration, and ongoing debates regarding both long-term and short-term outcomes, particularly concerning stent-related complications[11]. A meta-analysis has shown a higher overall recurrence rate (37.0% vs. 25.9%, p=0.049) and an increased risk of systemic recurrence in a group treated with SEMS compared to an emergency surgery group[12]. Thus, unnecessary placement of SEMS should be avoided.
Table 1.
The ColoRectal Obstruction Scoring System (CROSS).
| Level of oral intake | Score |
|---|---|
| Requiring continuous decompression | 0 |
| No oral intake | 1 |
| Liquid or enteral nutrient intake | 2 |
| Soft solids, low-residue, and full diet with symptoms of stricture* | 3 |
| Soft solids, low-residue, and full diet without symptoms of stricture | 4 |
*Symptoms of stricture include abdominal pain/cramps, abdominal distention, nausea, vomiting, constipation, and diarrhea and are related to gastrointestinal transit
In cases of incomplete obstructive colorectal cancer (IOCRC), where a colonoscope cannot pass through the tumor without accompanying bowel obstruction or obstructive colitis[13], IOCRC mainly corresponds to CROSS scores of 3 and includes some CROSS 4 cases. Placement of SEMS in these situations may be unnecessary. Although IOCRC is commonly encountered in clinical settings, it is less frequently reported than OCRC. To our knowledge, only one study has evaluated the safety and oncological outcomes of one-stage radical resection and anastomosis for IOCRC compared to non-obstructive colorectal cancer (NOCRC)[13]. Additionally, no studies have yet reported on left-sided colorectal cancer specifically. If managing IOCRC without preoperative decompression is feasible, stenting for CROSS 3 and 4 cases should be reconsidered. However, if this approach increases complications or adversely affects prognosis, preoperative decompression should be considered. Consequently, we have retrospectively reviewed cases of primary left-sided colorectal cancer at our hospital, classifying them as IOCRC or NOCRC. This study aims to investigate the safety and long-term outcomes of one-stage resection and anastomosis without preoperative decompression in patients with left-sided IOCRC.
Methods
Study design and patients
This retrospective, observational study analyzed clinicopathological data from the hospital database and was approved by the Institutional Review Board of the Cancer Institute Hospital, Japanese Foundation for Cancer Research. The study adhered to the tenets of the 1964 Declaration of Helsinki and later amendments. Due to the retrospective nature of the study, the need for informed consent was waived. The study also complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
Data were collected for patients diagnosed with pT3-4NanyM0 left-sided CRC who underwent elective curative resection and primary anastomosis without preoperative decompression or a diverting stoma at the Cancer Institute Hospital, Japanese Foundation for Cancer Research, between April 2012 and December 2019. Staging was based on the Union for International Cancer Control (UICC) TNM classification, 8th edition[14]. Left-sided colorectal cancer was defined as cancer located from just distal to the splenic flexure to the upper rectum. Patients were excluded if they had synchronous multiple cancers in other organs, synchronous multicentric cancers, inflammatory bowel disease, or were unable to be followed postoperatively.
The patient data, extracted according to the criteria mentioned, were categorized into two groups: IOCRC and NOCRC. IOCRC was defined as a condition in which a small-caliber colonoscope could not pass through the tumor, but which did not necessitate emergency surgery or decompression due to bowel obstruction or obstructive colitis[13]. NOCRC was identified as a condition where a colonoscope could pass through the tumor. The presence or absence of symptoms did not influence the classification of IOCRC or NOCRC.
Perioperative management for NOCRC and IOCRC
For patients with NOCRC, 50 g hypertonic magnesium citrate and 75 mg sodium pyrosulfate were provided for mechanical bowel preparation 1 day before surgery. Also, kanamycin (1,000 mg) and metronidazole (750 mg) 2 times a day were administrated 1 day before surgery for chemical bowel preparation.
In cases diagnosed with IOCRC during the initial consultation, magnesium oxide was prescribed, and patients were admitted to the hospital as soon as possible. Upon admission, patients were restricted from oral intake and received 50 g of hypertonic magnesium citrate daily for 2-3 days before surgery. Basically, we manage nutrition preoperatively by administering peripheral parenteral nutrition. However, for severely malnourished patients, such as those with an albumin level below 3.5, we address the issue by introducing total parenteral nutrition (TPN). Chemical bowel preparation was administrated as the same manner to NOCRC.
For both NOCRC and IOCRC, prophylactic antibiotics (cefmetazole sodium) were administered at the beginning of surgery, and then every three hours thereafter during the surgery. Postoperatively, the antibiotics were administered once, six hours after the final intraoperative dose.
For IOCRC cases, early postoperative colonoscopy was scheduled because it is difficult to identify multiple cancers located on the oral side of the primary lesion preoperatively.
Outcome measures
Short-term outcomes included incidences of postoperative complications, stoma creation rate, and length of postoperative hospital stay. Long-term outcomes assessed were the 5-year overall survival (OS) and the 5-year relapse-free survival (RFS) rates.
Data collection
Clinicopathological data were sourced from the hospital database. Parameters examined included sex, age, body mass index (BMI), preoperative hemoglobin level, preoperative albumin level, presence of diabetes, tumor location, and pathological findings such as stage, depth of the tumor, lymph node metastasis, lymphatic and vascular invasion, and histological types classified by grades. Histological types were categorized as low grade (well or moderately differentiated, or papillary adenocarcinoma) and high grade (poorly differentiated, mucinous adenocarcinoma, or signet-ring cell carcinoma). The rate of adjuvant chemotherapy was also reviewed. Perioperative outcomes assessed were the interval between admission and surgery, surgical approach (laparoscopy or robot-assisted), rates of open conversion, surgical procedures, anastomosis methods, operation time, blood loss, extent of lymph node dissection, number of lymph nodes harvested, resection margin status, postoperative complications, rates of reoperation, stoma creation at reoperation, mortality, and length of postoperative hospital stay. Perioperative complications were categorized using the Clavien-Dindo classification[15]. Mortality was defined as any death occurring within 30 days post-surgery.
Statistical analysis
Clinicopathological parameters were analyzed using the Mann-Whitney U-test and Fisher's exact test. The risk factors for postoperative complications were assessed through univariate and multivariate analyses using a logistic regression model. Prognostic factors for 5-year OS and RFS were evaluated using both univariate and multivariate analyses with a Cox proportional hazards regression model. Variables that achieved a P-value of <0.05 in the univariate analysis were included as covariates in the multivariate analysis. The 5-year OS and RFS rates were estimated using the Kaplan-Meier method and compared between groups with the log-rank test. All statistical analyses were conducted using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan, version 1.50), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria, version 3.6.3). EZR is essentially a modified version of R Commander (version 2.6-2) that incorporates additional statistical functions frequently utilized in biostatistics[16]. A P-value of <0.05 was considered statistically significant.
Results
Patient characteristics
Of the total 596 patients, exclusions included two patients with synchronous multiple cancers in other organs, two with synchronous multicentric cancers, and 19 who were unable to follow up. Finally, 571 patients who underwent one-stage curative resection and primary anastomosis without preoperative decompression or diverting stoma were included in this analysis (IOCRC; n=97 [17%], NOCRC; n=474 [83%]) (Figure 1).
Figure 1.
Study population and flowchart of patient enrollment.
Table 2 displays the clinicopathological features of the patients with IOCRC and NOCRC. The median follow-up durations were not significantly different between the two groups (67.4 months vs. 63.8 months, P=0.14). The median BMI (22.0 kg/m2 vs. 22.7 kg/m2, P=0.035), the median preoperative hemoglobin level (12.2 g/dL vs. 13 g/dL, P=0.002), and the median preoperative albumin level (3.9 g/dL vs. 4.1 g/dL, P=0.002) were lower in the IOCRC group than in the NOCRC group. Patients in the IOCRC group had fewer cases of rectal cancer (12.4% vs. 32.1%, P<0.001), but more T4 tumors (57.7% vs. 27.2%, P<0.001), and more instances of lymphatic invasion (74.2% vs. 61.4%, P=0.02) compared to the NOCRC group. Other characteristics were similar between the two groups.
Table 2.
Patient Characteristics and Clinicopathological Findings.
| Variables | Total n = 571, n (%) | IOCRC n = 97, n (%) | NOCRC n = 474, n (%) | P value | |
|---|---|---|---|---|---|
| Sex | Male | 280 (49) | 46 (47.4) | 234 (49.4) | 0.739 |
| Female | 291 (51) | 51 (52.6) | 240 (50.6) | ||
| Age (years), median (range) | 62 (24-93) | 64 (32-83) | 62 (24-93) | 0.453 | |
| BMI (kg/m2), median (range) | 22.6 (14-38) | 22.0 (14-33.8) | 22.7 (14.1-38) | 0.035 | |
| Preoperative hemoglobin (g/dL), median (range) | 12.9 (7.4-17.7) | 12.2 (7.4-13.9) | 13 (7.7-17.7) | 0.002 | |
| Preoperative albumin (g/dL), median (range) | 4.1 (2.3-4.9) | 3.9 (2.3-4.8) | 4.1 (2.7-4.9) | 0.002 | |
| Preoperative albumin | < 3.5 g/dL | 47 (8.2) | 14 (14.4) | 33 (7) | 0.024 |
| Diabetes | Present | 79 (13.8) | 12 (12.4) | 67 (14.1) | 0.748 |
| Absent | 492 (86.2) | 85 (87.6) | 407 (85.9) | ||
| Tumor location | Descending colon | 45 (7.9) | 13 (13.4) | 32 (6.7) | < 0.001 |
| Sigmoid colon | 362 (63.4) | 72 (74.2) | 290 (61.2) | ||
| Rectum* | 164 (28.7) | 12 (12.4) | 152 (32.1) | ||
| Pathological stage | II | 293 (51.3) | 43 (44.3) | 250 (52.7) | 0.148 |
| III | 278 (48.7) | 54 (55.7) | 224 (47.3) | ||
| Depth of tumor | T3 | 386 (67.6) | 41 (42.3) | 345 (72.8) | < 0.001 |
| T4 | 185 (32.4) | 56 (57.7) | 129 (27.2) | ||
| Lymph node metastasis | N0 | 294 (51.5) | 43 (44.3) | 251 (52.9) | 0.158 |
| N1 | 204 (35.7) | 43 (44.3) | 161 (34) | ||
| N2 | 73 (12.8) | 11 (11.4) | 62 (13.1) | ||
| Lymphatic invasion | Present | 363 (63.6) | 72 (74.2) | 291 (61.4) | 0.02 |
| Absent | 208 (36.4) | 25 (25.8) | 183 (38.6) | ||
| Vascular invasion | Present | 181 (31.7) | 84 (86.6) | 377 (79.5) | 0.121 |
| Absent | 390 (68.3) | 13 (13.4) | 97 (20.5) | ||
| Histological type | Low grade (tub, pap) | 549 (96.1) | 93 (95.9) | 456 (96.2) | 0.778 |
| High grade (por, sig, muc) | 22 (3.9) | 4 (4.1) | 18 (3.8) | ||
| Adjuvant chemotherapy | Induced | 323 (56.6) | 62 (63.9) | 261 (55.1) | 0.117 |
| Not induced | 248 (43.4) | 35 (36.1) | 213 (44.9) | ||
| Observation period (years), median (range) | 64 (2-139.9) | 67.4 (2-131) | 63.8 (5.5-139.9) | 0.14 | |
IOCRC, incomplete obstructive colorectal cancer; NOCRC, non-obstructive colorectal cancer
*Low rectal cancer was not included.
Perioperative data and short-term outcomes
Table 3 presents the perioperative data and short-term outcomes for each group. The median interval between admission and surgery was significantly longer in the IOCRC group than in the NOCRC group (6 days vs. 2 days, P<0.001). The rate of anterior resection was higher in the NOCRC group compared to the IOCRC group (33.7% vs. 17.5%, P=0.004). The IOCRC group experienced longer operation times (235 min vs. 205 min, P=0.003), more blood loss (15 ml vs. 10 ml, P<0.001), and a higher number of harvested lymph nodes (24 vs. 22, P=0.012). The incidence of all-grade postoperative complications was significantly higher in the IOCRC group (25.8% vs. 15%, P=0.016), although the rates of severe postoperative complications (Clavien-Dindo classification >III) were similar between the two groups (11.3% vs. 6.5%, P=0.132), the rates of anastomotic leakage (2.1% vs. 2.3%, P=1), reoperation (3.1% vs. 2.7%, P=0.742), and stoma creation at reoperation (2.1% vs. 2.1%, P=1) did not differ significantly. A diverting ileostomy was not created during the initial operation but was implemented during reoperations. The median postoperative hospital stay was significantly longer for the IOCRC group than for the NOCRC group (10 days vs. 9 days, P=0.002).
Table 3.
Perioperative Data and Short-Term Outcomes.
| Variables | Total n = 571, n (%) | IOCRC n = 97, n (%) | NOCRC n = 474, n (%) | P value | |
|---|---|---|---|---|---|
| Interval between admission and operation (days), median (range) | 2 (1-25) | 6 (2-25) | 2 (1-15) | < 0.001 | |
| Approach | Laparoscopic | 568 (99.5) | 97 (100) | 471 (99.4) | 1 |
| Robot-assisted | 3 (0.5) | 0 (0) | 3 (0.6) | ||
| Conversion to laparotomy | 6 (1.1) | 2 (2.1) | 4 (0.8) | 0.271 | |
| Surgical procedure | Partial resection | 12 (2.1) | 3 (3.1) | 9 (1.9) | 0.004 |
| Left hemicolectomy | 36 (6.3) | 10 (10.3) | 26 (5.5) | ||
| Sigmoidectomy | 346 (60.6) | 67 (69.1) | 279 (58.9) | ||
| Anterior resection | 177 (31) | 17 (17.5) | 160 (33.7) | ||
| Anastomotic type | DST | 506 (88.6) | 81 (83.5) | 425 (89.7) | 0.228 |
| FEEA | 40 (7) | 11 (11.3) | 29 (6.1) | ||
| TA | 24 (4.2) | 5 (5.2) | 19 (4) | ||
| Overlap (intracorporeal) | 1 (0.2) | 0 (0) | 1 (0.2) | ||
| Operation time (min), median (range) | 208 (95-584) | 235 (123-545) | 205 (95-584) | 0.003 | |
| Blood loss (ml), median (range) | 10 (0-1220) | 15 (0-1220) | 10 (0-800) | < 0.001 | |
| Lymph node dissection | D3 | 547 (95.8) | 92 (94.8) | 455 (96) | 0.581 |
| D2 | 24 (4.2) | 5 (5.2) | 19 (4) | ||
| Harvested lymph nodes (n), median (range) | 22 (9-55) | 24 (12-55) | 22 (9-53) | 0.012 | |
| Harvested lymph nodes | ≥ 12 | 569 (99.6) | 97 (100) | 472 (99.6) | 1 |
| < 12 | 2 (0.4) | 0 (0) | 2 (0.4) | ||
| Resection status of the primary lesion | R0 | 567 (99.3) | 95 (97.9) | 472 (99.6) | 0.136 |
| R1 | 4 (0.7) | 2 (2.1) | 2 (0.2) | ||
| Postoperative complications (Clavien-Dindo) | All (I-V) | 96 (16.8) | 25 (25.8) | 71 (15) | 0.016 |
| Anastomotic leakage | 13 (2.3) | 2 (2.1) | 11 (2.3) | 1 | |
| Surgical site infection | 22 (3.9) | 7 (7.2) | 15 (3.2) | 0.078 | |
| Anastomotic bleeding | 21 (3.7) | 5 (5.2) | 16 (3.4) | 0.378 | |
| Paralytic ileus | 7 (1.2) | 2 (2.1) | 5 (1.1) | 0.339 | |
| Small bowel obstruction | 2 (0.4) | 1 (1) | 1 (0.2) | 0.311 | |
| Intraabdominal abscess | 5 (0.9) | 0 (0) | 5 (1.1) | 0.595 | |
| Urinary dysfunction, urinary tract infection | 7 (1.2) | 3 (3.1) | 4 (0.8) | 0.099 | |
| Pneumonia | 4 (0.7) | 0 (0) | 4 (0.8) | 1 | |
| Intraabdominal bleeding | 1 (0.2) | 1 (1) | 0 (0) | 0.17 | |
| Colon necrosis | 1 (0.2) | 0 (0) | 1 (0.2) | 1 | |
| Others | 13 (2.3) | 3 (3.1) | 10 (2.1) | 0.471 | |
| ≥ III | 42 (7.4) | 11 (11.3) | 31 (6.5) | 0.132 | |
| Reoperation | 16 (2.8) | 3 (3.1) | 13 (2.7) | 0.742 | |
| Stoma creation during reoperation* | 12 (2.1) | 2 (2.1) | 10 (2.1) | 1 | |
| 30 day mortality | 0 (0) | 0 (0) | 0 (0) | - | |
| Postoperative hospital stay (days), median (range) | 9 (5-50) | 10 (7-50) | 9 (5-36) | 0.002 | |
IOCRC, incomplete obstructive colorectal cancer; NOCRC, non-obstructive colorectal cancer; DST, double-stapling technique; FEEA, functional end-to-end anastomosis; TA, triangular anastomosis
*Diverting ireostomy was created in all cases.
Table 4 shows the results of the univariate and multivariate logistic regression analyses of postoperative all-grade complications. In the univariate analysis, male gender, age >70 years, T4 tumor, and IOCRC (odds ratio [OR]: 1.97, 95% confidence interval [CI]: 1.17-3.32, P=0.011) were the explanatory variables. In the multivariate analysis, male gender (OR: 1.72, 95% CI: 1.09-2.7, P=0.02), age >70 years (OR: 1.85, 95% CI: 1.16-2.94, P=0.01), and T4 tumor (OR: 1.85, 95% CI: 1.15-2.96, P=0.011) remained independent risk factors for all-grade complications. IOCRC was not an independent risk factor for complications (OR: 1.63, 95% CI: 0.94-2.83, P=0.081).
Table 4.
Predictors of All-Grade Postoperative Complications.
| Variables | Total n = 571 | Postoperative complications (all grade) | |||||
|---|---|---|---|---|---|---|---|
| n = 96 | Univariate analysis | Multivariate analysis | |||||
| OR (95% CI) | P value | OR (95% CI) | P value | ||||
| Sex | Male | 280 | 57 | 1.65 (1.06-2.58) | 0.027 | 1.72 (1.09-2.7) | 0.02 |
| Female | 291 | 39 | Reference | Reference | |||
| Age | ≥ 70 years | 161 | 38 | 1.87 (1.19-2.96) | 0.007 | 1.85 (1.16-2.94) | 0.01 |
| < 70 years | 410 | 58 | Reference | Reference | |||
| BMI | ≥ 25 kg/m2 | 150 | 30 | 1.34 (0.83-2.17) | 0.225 | ||
| < 25 kg/m2 | 421 | 66 | Reference | ||||
| Preoperatibe albumin | < 3.5 g/dL | 47 | 11 | 1.58 (0.77-3.22) | 0.21 | ||
| ≥ 3.5 g/dL | 524 | 85 | Reference | ||||
| Diabetes | Present | 79 | 9 | 0.599 (0.29-1.24) | 0.169 | ||
| Absent | 492 | 87 | Reference | ||||
| Surgical procedure | Anterior resection | 177 | 30 | 1.01 (0.63-1.63) | 0.953 | ||
| Others | 394 | 66 | Reference | ||||
| Anastomotic type | DST | 506 | 83 | 0.785 (0.41-1.51) | 0.466 | ||
| Others | 65 | 13 | Reference | ||||
| Tumor location | Rectum | 164 | 27 | 0.965 (0.59-1.57) | 0.887 | ||
| D, S | 407 | 69 | Reference | ||||
| Stage | III | 278 | 55 | 1.52 (0.97-2.36) | 0.066 | ||
| II | 293 | 41 | Reference | ||||
| Depth of tumor | T4 | 185 | 44 | 2 (1.28-3.13) | 0.002 | 1.85 (1.15-2.96) | 0.011 |
| T3 | 386 | 52 | Reference | Reference | |||
| Lymph node metastasis | N2 | 73 | 12 | 0.97 (0.5-1.88) | 0.927 | ||
| N0, N1 | 498 | 84 | Reference | ||||
| Statement of obstruction | IOCRC | 97 | 25 | 1.97 (1.17-3.32) | 0.011 | 1.63 (0.94-2.83) | 0.081 |
| NOCRC | 474 | 71 | Reference | Reference | |||
BMI, body mass index; DST, double-stapling technique; D, descending colon; S, sigmoid colon; IOCRC, incomplete obstructive colorectal cancer; NOCRC, non-obstructive colorectal cancer; OR, odds ratio; CI, confidence interval
Long-term outcomes
Figure 2A displays the Kaplan-Meier curves for the 5-year OS in the IOCRC and NOCRC groups across all stages. There were no significant differences in the 5-year OS between the two groups (91.5% vs. 93.7%, P=0.436). Figure 2B illustrates the Kaplan-Meier curves for 5-year OS in the IOCRC and NOCRC groups by disease stage. The 5-year OS was not significantly different between the two groups in either stage II and stage III cases (stage II: 90.6% vs. 97.7%, stage III: 92.2% vs. 89.3%; IOCRC vs. NOCRC, P=0.593). In the univariate and multivariate Cox proportional hazards regression analyses for 5-year OS (Table 5), factors such as age >70 years, stage III, T4 tumor, and N2 lymph node metastasis were considered for the multivariate analysis. IOCRC was not a significant factor (hazard ratio [HR]: 1.365, 95% CI: 0.62-2.99, P=0.438). The multivariate analysis identified that age ≥70 years (HR: 2.259, 95% CI: 1.17-4.38, P=0.016), stage III (HR: 2.329, 95% CI: 1.03-5.26, P=0.042), and T4 tumor (HR: 2.674, 95% CI: 1.35-5.3, P=0.005) were independent prognostic factors for poor OS.
Figure 2.
Kaplan–Meier curves for 5-year overall survival in patients of (A) all stages and (B) according to the disease stage.
Table 5.
Cox Proportional Hazards Regression Analyses for Long-Term Outcomes.
| Variables | Total n = 571 | 5-year overall survival | 5-year relapse-free survival | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | |||||||
| HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |||
| Sex | Male | 280 | 1.04 (0.54-2) | 0.903 | - | 0.89 (0.58-1.35) | 0.572 | |||
| Female | 291 | Reference | Reference | |||||||
| Age | ≥ 70 years | 161 | 2.14 (1.11-4.13) | 0.023 | 2.26 (1.17-4.38) | 0.016 | 1.07 (0.67-1.71) | 0.773 | ||
| < 70 years | 410 | Reference | Reference | Reference | ||||||
| Tumor location | Rectum | 164 | 1.23 (0.62-2.47) | 0.554 | - | 1.02 (0.64-1.62) | 0.94 | |||
| D, S | 407 | Reference | Reference | |||||||
| Stage | III | 278 | 3.17 (1.49-6.74) | 0.003 | 2.33 (1.03-5.26) | 0.042 | 2.19 (1.4-3.42) | < 0.001 | 1.64 (0.89-3.04) | 0.116 |
| II | 293 | Reference | Reference | Reference | ||||||
| Depth of tumor | T4 | 185 | 3.35 (1.71-6.54) | < 0.001 | 2.67 (1.35-5.3) | 0.005 | 2.35 (1.54-3.58) | < 0.001 | 2.01 (1.27-3.16) | 0.003 |
| T3 | 386 | Reference | Reference | Reference | ||||||
| Lymph node metastasis | N2 | 73 | 2.75 (1.32-5.69) | 0.007 | 1.62 (0.74-3.57) | 0.232 | 3.45 (2.17-5.46) | < 0.001 | 2.37 (1.39-4.05) | 0.002 |
| N0, N1 | 498 | Reference | Reference | Reference | ||||||
| Lymphatic invasion | Present | 363 | 2.28 (0.1-5.2) | 0.051 | - | 1.71 (1.05-2.78) | 0.03 | 1.07 (0.63-1.8) | 0.81 | |
| Absent | 208 | Reference | Reference | |||||||
| Vascular invasion | Present | 181 | 0.98 (0.43-2.24) | 0.963 | - | 2.81 (1.3-6.08) | 0.009 | 2.29 (1.05-5) | 0.037 | |
| Absent | 390 | Reference | Reference | |||||||
| Histological type | High grade | 22 | 0.71 (0.1-5.16) | 0.732 | - | 0.58 (0.14-2.34) | 0.442 | |||
| Low grade | 549 | Reference | Reference | |||||||
| Adjuvant chemotherapy | Induced | 323 | 1.51 (0.75-3.01) | 0.247 | - | 1.61 (1.03-2.53) | 0.038 | 0.68 (0.37-1.25) | 0.213 | |
| Not induced | 248 | Reference | Reference | |||||||
| Statement of obstruction | IOCRC | 97 | 1.37 (0.62-2.99) | 0.438 | - | 1.4 (0.84-2.33) | 0.197 | |||
| NOCRC | 474 | Reference | Reference | |||||||
D, descending colon; S, sigmoid colon; IOCRC, incomplete obstructive colorectal cancer; NOCRC, non-obstructive colorectal cancer; HR, hazard ratio; CI, confidence interval
Figure 3A shows the Kaplan-Meier curves for the 5-year RFS in the IOCRC and NOCRC groups across all stages. There were no significant differences in the 5-year RFS between the two groups (80.2% vs. 85.6%, P=0.195). Figure 3B presents the Kaplan-Meier curves for 5-year RFS in the IOCRC and NOCRC groups according to disease stage. The 5-year RFS was not significantly different between the IOCRC and NOCRC groups in either stage II and stage III cases (stage II: 83.3% vs. 91.0%, stage III: 77.8% vs. 91.0%, P=0.311).
Figure 3.
Kaplan–Meier curves for 5-year relapse-free survival in patients of (A) all stages and (B) according to the disease stage.
Table 6 displays the types of recurrence in the IOCRC and NOCRC groups. The overall recurrence rate for all patients was 15.1%. There were no significant differences in total recurrence rates between the two groups (19.6% vs. 14.1%, P=0.211). The rate of distant lymph node recurrence was higher in the IOCRC group compared to the NOCRC group (6.2% vs. 1.7%, P=0.019). Other types of recurrence, including liver (6.2% vs. 5.9%, P=0.818), lung (3.1% vs. 4.6%, P=0.784), local (2.1% vs. 1.1%, P=0.335), and peritoneal dissemination (4.1% vs. 1.9%, P=0.251), were not significantly different between the two groups.
Table 6.
Sites of Recurrence.
| Variables | Total n = 571, n (%) | IOCRC n = 97, n (%) | NOCRC n = 474, n (%) | P value |
|---|---|---|---|---|
| Total recurrence* | 86 (15.1) | 19 (19.6) | 67 (14.1) | 0.211 |
| Liver | 34 (6) | 6 (6.2) | 28 (5.9) | 0.818 |
| Lung | 25 (4.4) | 3 (3.1) | 22 (4.6) | 0.784 |
| Distant lymph nodes | 14 (2.5) | 6 (6.2) | 8 (1.7) | 0.019 |
| Local | 7 (1.2) | 2 (2.1) | 5 (1.1) | 0.335 |
| Peritoneal dissemination | 13 (2.3) | 4 (4.1) | 9 (1.9) | 0.251 |
| Others | 1 (0.2) | 0 (0) | 1 (0.2) | 1 |
IOCRC, incomplete obstructive colorectal cancer; NOCRC, non-obstructive colorectal cancer
* There is some duplication.
Discussion
This study examined the short- and long-term outcomes of one-stage radical resection and anastomosis without preoperative decompression for left-sided IOCRC and NOCRC. The incidences of Clavien-Dindo >III complications, such as anastomotic leakage, reoperation, and stoma creation, did not increase in the IOCRC group despite the higher number of all-grade complications. The median postoperative hospital stay was significantly longer in the IOCRC group, but the difference was only one day (10 days vs. 9 days). Additionally, the long-term outcomes for IOCRC were comparable to those of NOCRC. To our knowledge, only one study has explored short- and long-term outcomes in a similar context[13], and that study included right-sided colon cancer. This study provides valuable data for the perioperative management of left-sided IOCRC.
According to previous research on BTS using SEMSs, the rates of anastomotic leakage and reoperation requiring stoma creation were 3.8% and 0.8%, respectively[10]. These rates were similar to those observed in the IOCRC group of our study. Since IOCRC mainly corresponds to CROSS 3 cases, the results suggest that one-stage radical resection and anastomosis without preoperative decompression or a diverting stoma is acceptable for such cases, as the risk of severe anastomotic complications requiring reoperation or stoma creation did not increase compared to NOCRC and BTS cases. However, a more cautious approach should be considered to ensure safe anastomosis. In our institution, a longer-than-usual interval between admission and surgery was necessary for this disease, involving mild preoperative bowel preparation with magnesium citrate for 2-3 days and no oral intake, which might have contributed to our favorable outcomes.
On the other hand, the all-grade complication rate was increased in the IOCRC group, implying likely impact of the poor preoperative nutritional status. Although the multivariate analysis in this study showed that severe malnutrition with albumin levels below 3.5 g/dL was not an independent risk factor for increased complications, previous reports have indicated that malnutrition is a risk factor for complications[17]. Based on these reports, TPN and administration of lipid emulsions would likely to be considered to improve preoperative nutritional status. Increasing all-grade complications should be mentioned especially in cases of elderly IOCRC patients because increasing complications lead longer hospital stays and worsened activities of daily living. In addition, multivariate analysis in the present study showed that age >70 years was an independent risk factor for postoperative complications. Therefore, applying the same strategy to elderly IOCRC patients should be considered with caution.
Long-term outcomes between the IOCRC and NOCRC groups were comparable. The oncological quality of surgery in the IOCRC group appears to be acceptable, as evidenced by the satisfactory number of harvested lymph nodes. OS and RFS in both stage II and III were not significantly different between the IOCRC and NOCRC groups, even though the IOCRC group had more T4 and lymphatic invasion cases. While the rate of distant lymph node recurrence was higher in the IOCRC group, this increase may be attributed to the higher rate of lymphatic invasion observed within the group. However, rates of other metastatic types did not increase in the IOCRC group. SEMSs raise concerns about the risk of peritoneal dissemination due to the forceful expansion of the tumor[18] and an increased risk of recurrence[12], particularly in cases with stent-related perforation[11]. Given these risks and the potential for negative oncological outcomes, it is crucial that stents are not placed in IOCRC cases unless absolutely necessary.
A previous study reported that IOCRC increased postoperative complications and the risk of poor OS and RFS in both stage II and III[13], even without the use of SEMS. However, this study included right-sided colon cancer, which may have contributed to the negative outcomes due to the biologically poorer prognostic characteristics of right-sided versus left-sided colon cancer[19]. Our study focused solely on left-sided colorectal cancer, aligning with the indications for SEMS according to the European Society of Gastrointestinal Endoscopy (ESGE) guidelines. Nonetheless, a more precise evaluation is required.
This study has several limitations. First, it was a single-center study that included a diverse patient population with a relatively small sample size of IOCRC cases. Selection bias may make the results difficult to interpret. Especially in terms of long-term outcomes, despite that the IOCRC group had more advanced characteristics such as T4 and lymphatic invasion, those of IOCRC and NOCRC were not significantly different. Biases, such as a lower ratio of rectal cancer in the IOCRC group, may influence to these results. Second, the diagnosis of incomplete obstruction was reliant on the skill of the endoscopist. To minimize the impact of varying endoscopist skills, colonoscopies were repeated in all cases. Third, patients who underwent Hartmann's procedure were excluded because one of our main interests in this study was the risk of anastomotic leakage. Generally, patients undergoing Hartmann's procedure often have poor condition, and excluding the patients from the cohort may make some impacts to the outcomes.
In conclusion, this study demonstrated acceptable short- and long-term outcomes for one-stage radical resection and anastomosis without preoperative decompression and diverting stoma for left-sided IOCRC. Our therapeutic strategy, which forgoes preoperative decompression, may be enhanced by careful preoperative bowel preparation management.
Conflicts of Interest
There are no conflicts of interest.
Author Contributions
Conceptualization: Kentaro Sato, Yosuke Fukunaga, Manabu Takamatsu, Tatsuki Noguchi, Takashi Sakamoto, Shimpei Matsui, Toshiki Mukai, Tomohiro Yamaguchi, and Takashi Akiyoshi; Methodology: Kentaro Sato, Yosuke Fukunaga; Formal analysis and investigation: Kentaro Sato; Writing - original draft preparation: Kentaro Sato and Yosuke Fukunaga; Writing - review and editing: Kentaro Sato, Yosuke Fukunaga, Manabu Takamatsu, Tatsuki Noguchi, Takashi Sakamoto, Shimpei Matsui, Toshiki Mukai, Tomohiro Yamaguchi, and Takashi Akiyoshi; Funding acquisition: Not applicable; Resources: Not applicable; Supervision: Yosuke Fukunaga.
Approval by Institutional Review Board (IRB)
This study was approved by the Institutional Review Board of the Cancer Institute Hospital, Japanese Foundation for Cancer Research (Tokyo, Japan; reference no. 2024-GB-034).
Consent to Participate
The need for informed consent to participate in the study was waived due to the retrospective nature of the study.
Consent for Publication
The need for informed consent was waived due to the retrospective nature of the study.
Availability of Data and Material
The data supporting this study's findings are available upon request from the corresponding author.
Acknowledgments
The authors thank Editage (www.editage.jp) for the English language editing.
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