In our analysis, neither nonoperative management with ILA nor nonoperative management without ILA were dominant strategies in the treatment of complicated appendicitis compared with operative management. Base case results demonstrated that nonoperative management without ILA was the most cost-effective and preferred strategy compared with operative management. However, sensitivity analysis showed that nonoperative management without ILA was not a cost-effective strategy among the simulated cases. In contrast, nonoperative management with ILA was the most effective strategy, but also the most costly. Given these findings, we suggest that operative management remains the standard therapeutic strategy, and nonoperative management without ILA and nonoperative management with ILA should not be recommended routinely in the management of complicated appendicitis. To our knowledge, ours is the first study performing an economic analysis comparing the costs of different treatment strategies for complicated appendicitis in the Japanese public health-care system.
Acute appendicitis was complicated by perforation, abscess, or cellulitis in 14.2%–17.8% of cases. [4] [24] However, management of patients diagnosed with complicated appendicitis is still controversial. Immediate surgical treatment of complicated appendicitis is associated with a more than 3-fold increase in morbidity compared with nonoperative management, and may result in unnecessary ileocecal resection or right-sided hemicolectomy, for technical reasons. [4] Laparoscopic appendectomy offers superior benefits to open appendectomy, and laparoscopic appendectomy has been used for various types of appendicitis. [25] [26] [27] However, the controversy between laparoscopic appendectomy and open appendectomy for complicated appendicitis persists. [6] [27] A recent meta-analysis concluded that laparoscopic appendectomy requires significant resources and surgical expertise to reach maximum efficiency. Therefore, if these technical and surgical criteria cannot be met, open appendectomy should be the surgical treatment of choice. [28]
The best procedure for complicated appendicitis has not been conclusively determined. However, because of continued improvements in the quality and accessibility of computed tomography, the efficacy and feasibility of performing nonoperative management, including targeted intra-abdominal drainage, have increased, and recent evidence supports performing nonoperative management in complicated appendicitis. It is important to note that several studies reported higher rates of recurrence after nonsurgical treatment of complicated appendicitis of up to 38% within 1 year. [29] [30] To avoid this high chance of recurrence, reports suggest routine elective interval appendectomy following nonoperative management; however, because of the consistent morbidity, routine interval appendectomy after successful nonoperative management is not justified in every patient. Overall, despite evidence and the consensus of the World Society of Emergency Surgery, which supports the use of nonoperative management, clinicians continue to seek the most appropriate treatment strategies for complicated appendicitis. [2] The results of our study, performed busing a modeling method, provide valuable information to help surgeons decide the ideal strategy to treat complicated appendicitis, with complex tradeoffs between financial resources and patient utility.
Each country has its own health insurance system. In Japan, the government uses a universal health insurance system; therefore, once included in the health insurance system’s listing by the governmental council, expensive imaging studies and emergent surgery can be performed easily in Japan [31]. This has caused a drastic increase in treatment costs, without necessarily indicating feasibility within the public health system. We must maximize the benefits obtained from the available resources, within the system; however, in Japan, evidence is limited regarding the cost-effectiveness of clinical therapeutic strategies. [32] [33] [34] Our findings suggest that Japan’s government may need to adjust the clinical recommendations based on cost-effectiveness in acute appendicitis therapy.
Sensitivity analyses in our study indicated that variation in the probability and HRQoL factors for ELA with perioperative complications for complicated appendicitis had a significant influence on outcomes for both nonoperative management with ILA and nonoperative management without ILA. Therefore, we suggest that ELA and its perioperative complications is an important factor in choosing a therapeutic strategy for complicated appendicitis. Randomized control trials have reported postoperative complications following laparoscopic appendectomy for complicated appendicitis. [35] [36] Surprisingly, there were no differences in the incidence of complications compared with open appendectomy, including surgical site infections and intra-abdominal abscess, which are the most common complications following appendectomy. Regarding cost-effectiveness, intra-abdominal abscess is an especially serious complication and a reported primary drawback of laparoscopic appendectomy. [37] Some authors reported that insufflation and irrigation during laparoscopic appendectomy for complicated appendicitis may increase the incidence of intra-abdominal abscess. [38] [39] This complication leads to a prolonged hospital stay, possible readmission, and the need for subsequent treatment, which increases costs and decreases utility of laparoscopic appendectomy in patients with complicated appendicitis. Therefore, we speculate that in patients with higher risk of postoperative intra-abdominal abscess, such as older patients, nonoperative management could be a preferred and cost-effective strategy compared with operative management.[40]
It should be noted that no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's national health policy. Previously, Shiroiwa et al reported that <¥5–6 million per QALY is considered cost effective in Japan. [41] However, the study did not consider patient quality of life, and it is impossible to accurately determine cost-effectiveness. Therefore, we adopted the World Health Organization's WTP recommendation for ICER threshold, in our model. This metric is meant to be used solely as a common cognitive anchor rather than as a method of dictating clinical decision-making. Nevertheless, we consider our conclusions in this study robust based on the results of the sensitivity analyses. An acceptability curve showed that the probability of nonoperative management with ILA being the most cost-effective strategy was approximately 50% when WTP was ¥20,000,000. Additionally, the possibility of nonoperative management without ILA being the most cost-effective strategy was always < 25% regardless of WTP, demonstrating that both nonoperative management strategies were not cost-effective over a pragmatic range of values for Japanese health care payers. Therefore, operative management remains a standard strategy, and a price reduction would be necessary for nonoperative management strategies to be considered cost-effective.
This study has several limitations. First, because we focused on cost-effectiveness for a relatively short duration, we did not consider the risk of appendiceal cancer. Some authors recommend routine interval appendectomy to rule out the possibility of malignancy rather than to avoid the risk of recurrence. [7] [42] [43] Recent retrospective studies report that the rate of appendiceal neoplasms in patients undergoing interval appendectomy is especially high in patients with complicated appendicitis ≥ 40 years of age.[42] [43] The rate is substantial, and surgeons should be aware of the risk of malignancy in patients with complicated appendicitis. However, a systematic review and meta-analysis showed a 7.4% incidence of recurrent appendicitis and a 1.2% incidence of malignant neoplasm in patients undergoing successful nonoperative management for complicated appendicitis. Based on these findings, the authors concluded that interval appendectomy is not necessary. [4] The role of appendectomy in complicated appendectomy for oncological reasons is debated. Investigating the cost-effectiveness of appendectomy in complicated appendectomy with a long-term follow-up regarding the possibility of malignancy in the appendix is an area requiring future research.
Second, because of the lack of Japanese studies on this subject, in the present study, the costs of the strategies were estimated using a micro-costing method to obtain precise information of the actual costs paid by the national insurance in a municipal hospital. However, these estimates may be subject to variations in treatment options between hospitals, even though the variations were included in the sensitivity analysis.
Third, few studies have evaluated quality of life in the early postoperative period after appendectomy. Therefore, we estimated utilities for the treatment strategies based on data related to other diseases and surgical procedures. If the utility of the procedures in patients with complicated appendicitis differed from our assumptions, our model outcomes could be compromised. Further studies are needed to better characterize the health states associated with the treatment of complicated appendicitis.
Finally, our study did not provide sufficient data to assess minor and major complications individually. The impact on cost and utility is strongly influenced by the type of complication; therefore, it should be emphasized that substantial differences in cost and utility of complications could affect the model outcome.
In conclusion, we found that nonoperative management with ILA and nonoperative management without ILA were not cost-effective strategies compared with operative management in the treatment of complicated appendicitis. Nonoperative management deserves serious consideration as a treatment option, but should not be performed routinely in treating complicated appendicitis because of its lower cost-effectiveness.