Volume 1(4); Pages: 297-301, 2021 | DOI: 10.21873/cdp.10039
KAZUHIKO YOSHIMATSU, TEPPEI KONO, YOSHITOMO ITO, MASAYA SATAKE, YASUFUMI YAMADA, SACHIYO OKAYAMA, HAJIME YOKOMIZO, SHUNICHI SHIOZAWA
KAZUHIKO YOSHIMATSU1, TEPPEI KONO2, YOSHITOMO ITO2, MASAYA SATAKE3, YASUFUMI YAMADA3, SACHIYO OKAYAMA3, HAJIME YOKOMIZO3 and SHUNICHI SHIOZAWA3
1Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan
2Department of Surgery, Saitamaken Saiseikai Kurihashi Hospital, Kuki, Japan
3Department of Surgery, Tokyo Women’s Medical University, Medical Center East, Tokyo, Japan
Correspondence to: Kazuhiko Yoshimatsu, Department of Digestive Surgery, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama 701-0192, Japan. Tel: +81 864621111 ext. 44202, Fax +81 864621199, e-mail: email@example.com
Received May 3, 2021 | Revised June 2, 2021 | Accepted June 5, 2021
Background: The short- and long-term results from several reports suggest that laparoscopic surgery (LAP) for elderly patients is expected to reduce the risk of complications due to its minimal invasiveness, However, little is known about the effect of LAP on long-term prognosis aside from cancer. Patients and Methods: Eighty-five cases over 80 years old with colorectal cancer whose primary lesions were resected consecutively were enrolled. Risk factors for complications were searched using categorized clinicopathological factors. The factors for death unrelated to cancer were analyzed in patients by excluding cancer-related death. Results: Incidence of all complications, those of Clavien–Dindo grade 2 or more, and surgical site infection were significantly lower in LAP-treated patients (p=0.0343, p=0.0015 and p=0.0015, respectively). By multivariate analysis, LAP (odds ratio=0.19, 95% confidence intervaI=0.05-0.75, p=0.0177) and no pulmonary dysfunction (odds ratio=0.24, 95% confidence intervaI=0.06-0.96, p=0.0441) were significantly associated with reduced risk of complications of Clavien–Dindo grade 2 or more. LAP, no pulmonary dysfunction and Eastern Cooperative Oncology Group performance status of 0 or 1 were also significantly associated with reduced risk for death from non cancer-related causes. Additionally, LAP was significantly associated with improved survival excluding cancer-related death in patients with pulmonary dysfunction (p=0.0020) or with poor performance status (p=0.0412). Conclusion: These results suggest that fewer complications and non cancer-related deaths were achieved in very elderly patients with colorectal cancer when treated by LAP.
Life expectancy has been increasing in Japan. Since life expectancy has recently exceeded 85 years for both men and women (1), the opportunities of surgery for cases with colorectal cancer over 80 years old has also increased. Because life expectancy at the age of 80 is now nearly 10 years (1), longer survival can be expected even in octogenarians if they can be curatively treated for colorectal cancer.
In the past decade, laparoscopic surgery (LAP) for colorectal cancer has globally spread due to its less invasiveness, and even in terms of curativeness, comparable good results to open surgery (OP) have been obtained. LAP is not inferior to OP and results in lesser complications (2-12).
A large inequality exists between actual age and physical age in elderly patients. Patients over 80 years old needing treatment for colorectal cancer are often found to have sarcopenia or be frail (13, 14). However, selecting surgery for elderly patients with colorectal cancer is increasingly feasible for resolving symptoms such as stenosis and melena due to advances in anesthesia and perioperative management. Since elderly patients are considered vulnerable to invasive procedures, LAP is expected to reduce the risk of complications due to its minimal invasiveness (15-18). Therefore, treatment results are expected to improve. However, little is known about the effects of LAP on non cancer-related long-term prognosis.
In this study, we investigated whether LAP contributes to the reduction of complications and survival in a cohort of patients over 80 years old consecutively treated with surgery over the past 7 years.
Patients. Eighty-five patients who were aged 80 years or older with colorectal cancer whose primary lesion was resected were consecutively enrolled from April 2012 to March 2019.
Surgical methods. The approach of the surgical procedure with LAP or open laparotomy was chosen by individual surgeons. In the cases treated with LAP, the ligation of vessels and the mobilization of mesocolon or mesorectum were performed laparoscopically. For reconstruction with double-stapling technique, intracorponeal anastomosis by circular stapler was performed in those with sigmoidal or rectal cancer after extraction of the resected specimen through the umbilical incision. In cases with proximal cancer, the extraction of the specimen and the reconstruction with functional end to end anastomosis using a linear stapler were extracorponeally achieved through umbilical incision.
Study endpoints. Complications were evaluated according to the Clavien–Dindo (CD) classification. Risk factors for complications were searched using categorized clinicopathological factors, including operative approach and preoperative performance status (PS); the presence of comorbidities, including diabetes mellitus, heart disease, cerebrovascular disease, hypertension, renal dysfunction and pulmonary dysfunction; anti-coagulant drug use; and National Nosocomial Infection Surveillance risk index (RI) for surgical site infection (SSI) (19).
Disease-free and overall survival were analyzed in patients with curative resection. To elucidate the factors associated with survival due to surgical intervention, non cancer-related survival was calculated using death caused by other disease as the event.
Statistical analysis. JMP version 13 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis. The correlation between two variables was evaluated using the chi-square test and Student’s t-test. Disease-free and overall survival after surgery were calculated using the Kaplan–Meier method. Significant differences were identified using the log-rank test. p-Values of less than 0.05 were used to denote statistical significance.
The protocol of this study was approved by the Institutional Review Board of Saitamaken Saiseikai Kurihashi Hospital (approved no. 63).
Patient characteristics and operative outcomes. Baseline characteristics and operative outcomes are summarized in Table I. There were no significant differences in baseline characteristics between the LAP and OP groups, except for the prevalence of comorbidity, hypertension and RI. However, the proportion of patients with RI of including 1 or 2 was not significantly different. Significantly more patients with comorbidities or hypertension were observed in the OP group.
Regarding operative details, significantly longer operative time (LAP: 174 min vs. OP: 134 min; p=0.0003) and less bleeding (LAP: 5 vs. OP: 25 ml; p=0.0005) were observed for the LAP group.
Regarding postoperative outcomes, 38 patients had postoperative complications, including 23 of CD grade 2 or more, and 14 patients had SSI. The incidence rates of complications overall, complications of CD grade 2 or more, and SSI were significantly lower in the LAP group (p=0.0343, p=0.0015 and p=0.0015, respectively). No mortality was recorded in this study.
Factors associated with reduced complications. Factors associated with reduced likelihood of CD grade 2 or more complications were LAP (p=0.0015), and PS 0 or 1 (p=0.0282). Moreover, the absence of pulmonary dysfunction (p=0.0742) and RI of −1 or 0 (p=0.0686) tended be associated with reduced frequency of complications of CD grade 2 or more by univariate analysis. Multivariate analysis using these factors was performed and showed that LAP [odds ratio (OR)=0.19, 95% confidence interval (CI)=0.05-0.75; p=0.0177] and the absence of pulmonary dysfunction (OR=0.24, 95% CI=0.06-0.96, p=0.0441) were significantly associated with reduced complications of CD grade 2 or more (Table II).
Prognosis. The 3-year disease-free survival rate after curative resection was 74.2% in the LAP group and 60.1% in the OP group; the difference was insignificant (p=0.1138). The 5-year overall survival rate was significantly better for the LAP group (85.8%) than the OP group (58.3%) (p=0.0031).
Survival in patients, excluding cancer-related death. To elucidate the factors for survival due to surgical intervention, analysis was performed in patients, excluding cancer-related death. LAP, the absence of pulmonary dysfunction, and PS 0 or 1 were factors significantly associated with survival, excluding cancer-related death, in univariate and multivariate analyses (Table III).
Additionally, LAP improved survival in patients with pulmonary dysfunction (p=0.0020) or with poor PS (p=0.0412).
Since its introduction more than 20 years ago, LAP for colorectal cancer has become widespread and is performed as a standard procedure. Several large-scale clinical trials have revealed that short-term outcomes, including the incidence of complications, and long-term prognosis in LAP are almost equivalent to those in OP (2, 4, 5, 9). Additionally, less incidence of complications in LAP was recently reported due to its minimal invasiveness (20, 21). Some recent studies have reported good outcomes of LAP in octogenarians with colorectal cancer (15-18).
Since the opportunities for surgery in cases of elderly patients with cancer are increasing, choosing the treatment procedure for these patients considering curativeness and surgical stress is difficult. However, at 80 years old, the life expectancy of a Japanese patient is approximately 10 years (1); however, patient age should not be a contraindication to surgery for colorectal cancer. Therefore, we investigated the benefits of LAP in patients with colorectal cancer over 80 years old compared with OP during the past 7 years.
Firstly, we found LAP reduced complications of CD grade 2 or higher. Additionally, in the multivariate analysis, pulmonary dysfunction was a risk factor for poorer outcomes. Even though LAP is less invasive, it takes a longer operative time due to technical difficulties. However, the incidence of complications has been decreasing due to advances in anesthesia techniques and perioperative management, the introduction of enhanced recovery after surgery (22), and the standardization of LAP. The incidence of complications following LAP has decreased compared with those in the initial period and at approximately 10 years ago (20, 21). Since LAP is less invasive than OP, complications would be expected to be less frequent.
In studies, the impact of surgical stress on the long-term prognosis has been evaluated using overall survival or cancer-related survival, and these studies have shown that the oncological outcomes of LAP were not inferior to those of OP as a standard treatment for colorectal cancer (11, 12). However, surgical stress in elderly patients may affect short- and long-term survival, even if the disease were judged as completely cured. Thus, non cancer-related survival should be evaluated in elderly patients because surgical stress may affect the physical prognosis. Therefore, whether LAP would affect deaths unrelated to cancer was examined. LAP improved the prognosis concerning non cancer-related death in patients over the age of 80 years. Additionally, LAP can be performed on cases with pulmonary dysfunction or poor PS to improve survival rates. Thus, LAP should be chosen in cases with poor physical conditions if surgery is plausible.
This cohort study has several limitations. Firstly, the choice of operative approach was not randomized. Secondly, a larger-scale cohort is needed because operator bias might exist in this cohort as the patients only came from one institution. However, designing a large-scale trial to prove the benefits of LAP for these small categories of patients may be difficult because more than 70% of surgeries for colorectal cancer are performed via the LAP approach in Japan. Using such big data from a Japanese registry system for recently treated surgical cases, it may be possible to verify the results of this study.
In conclusion, this cohort study revealed that LAP resulted in fewer complications and reduced long-term mortality in patients with colorectal cancer over the age of 80 years.
All Authors have no declaration of conflicts of interest.
All Authors read and approved the final version of the article. K.Y., T.K. and Y.I. mainly designed study, collected data, performed analyses and wrote the article. M.S., Y.Y., S.O. and H.Y. supported the collection of the patient data. S.S. supervised all of this work.