Successful surgical management of non-perforating acute appendicitis with septic disseminated intravascular coagulation: A case report and review of the literature

Highlights • Non-perforating acute appendicitis with septic DIC is extremely rare.• Nowadays, interval appendectomy has become popular.• However, judging the limit of conservative treatment for acute appendicitis is a critically important matter.• Appendectomy should be performed for non-perforating acute appendicitis with septic DIC.


Introduction
Acute appendicitis is one of the most common gastrointestinal emergencies. Appendectomy is still considered the gold standard for acute appendicitis treatment. Nowadays, interval appendectomy is often used [1]. Many cases are relieved by conservative Abbreviations: DIC, disseminated intravascular coagulation; CT, Computed tomography.
* Corresponding author at: 2-1-1 Kabeminami, Asakista-ku, Hiroshima, 731-0293, Japan. E-mail addresses: toshiaki-k-tkt@car.ocn.ne.jp (T. Komo), tkohashi0303@gmail.com (T. Kohashi). 1 2-1-1 Kabeminami, Asakista-ku, Hiroshima, 731-0293, Japan. treatment, even those with perforating appendicitis without peritoneal irritation and abscess in the abdominal cavity. Needless to say, it is very important not to miss the time point when conservative treatment should stop and conversion to surgery should occur. Generally, perforating appendicitis and abscess-forming appendicitis may cause septic disseminated intravascular coagulation (DIC). However, it is difficult to assume that acute appendicitis lacking abdominal symptoms and without perforation and abscess may cause septic DIC. We report herein a rare case of non-perforating acute appendicitis with septic DIC. The present work has been reported in accordance with the SCARE criteria [2].
The patient was diagnosed with non-perforating acute appendicitis with septic DIC. The patient was distressed regarding whether he should be treated conservatively with an antibiotics-first strategy or undergo an appendectomy, because he had few symptoms, no perforation, and no abscess. Ultimately, laparoscopic appendectomy was performed due to anxiety about exacerbation of septic DIC. The resected specimen revealed a necrotized appendiceal mucous membrane. There was no evidence of appendiceal wall perforation (Fig. 2). Histopathological examination showed non-perforating gangrenous appendicitis. He required DIC therapy (thrombomodulin administration, antithrombin administration, and nafamostat mesilate) for 2 days postoperatively. Preoperative blood culture detected Bacteroides thetaiotaomicron. He was discharged on postoperative day 9, and remained in good health 1 month after surgery.

Discussion
Acute appendicitis is one of the most common gastrointestinal emergencies. There are two types of appendicitis: non-perforating (uncomplicated) and perforating (complicated) appendicitis. Appendectomy is still considered the gold standard for acute appendicitis treatment. Therefore, it is recommended that appendectomy be performed as soon as possible.
Nowadays, interval appendectomy has become popular as an elective surgical strategy for acute appendicitis following curative antibiotic treatment [1]. Interval appendectomy can avoid extended surgery (cecectomy or ileocecal resection rather than appendectomy alone) and reduce postoperative complications [4]. The indication for interval appendectomy includes patients with perforating appendicitis without general peritonitis and abscessforming appendicitis, though it is controversial [5]. However, delaying an appendectomy increases the risk of perforating appendicitis with general peritonitis, which is associated with a higher incidence of short and long-term morbidity [6]. Judging the limit of conservative treatment and determining the best time to perform surgery is a critically important matter. Some factors may help to identify the need for a conversion to surgery with an antibiotics-first strategy of appendicitis treatment, such as physical factors (fever, cardiorespiratory, and peritoneal irritation), laboratory parameters (white blood cell count and C-reactive protein), and CT (appendix diameter, ascites, intraperitoneal free air, and abscess). However, there is no absolute index. Therefore, determination of the best time to perform surgery is dependent heavily on the decision of the physician.
In the present case, physical examination revealed stable cardiorespiratory dynamics, no abdominal distension, and only slight spontaneous abdominal pain without tenderness and peritoneal irritation. Contrast-enhanced CT demonstrated an enlarged appendix (10 mm in diameter) without fecalith, ascites, intraperi-  toneal free air, and abscess (Fig. 1). There was no evidence of perforating appendicitis. Laboratory analysis revealed septic DIC. The patient was diagnosed with non-perforating acute appendicitis with septic DIC. The patient was distressed regarding whether he should be treated conservatively with an antibiotics-first strategy or undergo appendectomy, because he had few symptoms, no perforation, and no abscess. Ultimately, laparoscopic appendectomy was performed due to anxiety about exacerbation of septic DIC. Histopathological examination showed non-perforating gangrenous appendicitis. It was thought that non-perforating acute appendicitis with septic DIC was caused by the draining of intestinal bacteria from the necrotized appendiceal mucous membrane into the portal venous system due to a rise in the internal pressure of the appendix and necrosis of its mucous membrane. In the present case, preoperative blood culture detected Bacteroides thetaiotaomicron. Bacteroides thetaiotaomicron, a gram-negative anaerobic bacillus, belongs to the genus Bacteroide. Most of the time, Bacteroides thetaiotaomicron is part of the normal flora of the gastrointestinal tract, oral cavity, and respiratory tract. The mortality rates of Bacteroides thetaiotaomicron sepsis have been reported very high as 17-100% [7]. The patient might not be saved from septic DIC if determination of performing surgery was late.
To the best of our knowledge, non-perforating acute appendicitis with septic DIC is extremely rare, and only a few cases have been reported; only 3 [8][9][10] and 10 cases [11][12][13][14][15][16][17][18][19][20] are reported in the English and Japanese literature, respectively. Fourteen cases, including the present case of non-perforating acute appendicitis with septic DIC, were reviewed in the present study (Table 1). There were 11 (79%) males and 3 (21%) females with a mean age of 50 (range: 26-79) years. Of these 14 patients, 11 did not have peritoneal irritation. There was no evidence of perforating appendicitis with contrast-enhanced CT. The median duration from symptom onset to a diagnosis of septic DIC was 24 (range: 2-48) hours. Nine patients required an estimated 24 h or more for a diagnosis of septic DIC from the onset. Thirteen patients who underwent surgery were alive, and 1 patient who did not was dead. Namely, all 13 of the patients who underwent surgery were saved from septic DIC due to appendectomy; in contrast, 1 patient without appendectomy was not saved from septic DIC. Therefore, appendectomy should be performed for patients with non-perforating acute appendicitis with septic DIC, even if they have few symptoms and no perforation.

Conclusions
We report herein a rare case of non-perforating acute appendicitis with septic DIC. Nowadays, conservative treatment precedes surgery, as non-operative management with an antibiotics-first strategy of acute appendicitis treatment is increasing, even if the patient has perforating appendicitis without general peritonitis and abscess-forming appendicitis. However, it is thought that appendectomy should be performed when acute appendicitis is complicated by septic DIC, even if it is a non-perforating appendicitis in which improvement with conservative treatment is anticipated.

Conflicts of interest
The authors declare that they have no Conflicts of interest.

Funding
The authors declare that this study was not funded externally.

Ethical approval
The study such as this case report was exempted from ethical approval by the Institutional Review Board of Hiroshima City Asa Citizens Hospital.

Consent
When obtaining informed consent for surgical procedures, general consent for publication and presentation was obtained from the patient.

Author contribution
TK drafted the manuscript. TK, TK and YA reviewed and edited the manuscript. TK, KO, TK, NT, MK, AN, MS, and MM participated in the care of the patients. MK provided the histopathological examination and diagnosis. YA, JH, TK, MF, HM, and NH participated in critical revision of the manuscript. All authors read and approved the final manuscript.

Registration of research studies
This is case report not research study.

Provenance and peer review
Not commissioned, externally peer-reviewed.