Lower gastrointestinal perforation is one of the diagnoses of acute abdomen. Unlike in appendicitis and diverticulitis, a myriad of bacteria in the stool spread from the colon to the abdominal cavity, causing acute diffuse peritonitis, bacterial toxin absorption, and infectious shock, leading to multiple organ failure with a high mortality rate of 30–50% [11, 13–14]. Therefore, lower gastrointestinal perforation requires prompt diagnosis and therapeutic intervention [11]. However, it has no specific symptoms and is often misdiagnosed. Previous case series have reported that only about 10% of cases are diagnosed before surgery [11]. We conducted the first large-scale multicenter retrospective study on lower gastrointestinal perforation.
In this study, delayed diagnosis occurred in about 31% of the cases; this was less than the rates reported in previous studies [11]. In a previous study, the rate of accurate diagnosis before surgery was approximately 10% [11]; however, in this study, 60–70% of the patients had timely diagnosis. This may be because the prevalence of CT in Japan is extremely high [15] and the fact that the definition of timely diagnosis included cases in which although the initial diagnosis was wrong, the patients were referred immediately, resulting in timely diagnosis (near miss) and cases in which the immediate diagnosis was difficult (no fault).
There are no previous studies on factors associated with diagnostic errors of lower gastrointestinal perforation. Yang and Ni reported that this disease was more common in the elderly and bedridden patients, with 70% of the patients having a history of chronic constipation and 20% developing the disease after laxatives were administered [11]. Therefore, acute abdominal pain with signs of peritoneal irritation in the elderly with chronic constipation or in long-term bedridden patients should be considered as a symptom of lower gastrointestinal perforation [11]. The results of this study indicate that bedridden patients and those with a history of constipation are at risk for lower gastrointestinal perforation; however, these cases were not directly related to delayed diagnosis. Other factors such as antipsychotic use, analgesic use, use of immunosuppressive drugs including steroids, history of psychiatric disorders, and history of diabetes mellitus were also unassociated with delayed diagnosis.
In our study, the multivariate logistic regression analysis revealed that examination by practitioners other than general physicians was significantly associated with delayed diagnosis. Furthermore, presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports tended to be associated with delayed diagnosis.
In Japan, the training of general practitioners and emergency physicians has only just been established, and there is an urgent need to train them further. Currently, most of the primary care and emergency room services are provided by domain-specific specialists [16]. As a result, primary care and emergency medicine in Japan is provided by doctors who are not well trained in these areas. Additionally, the level of accuracy of diagnosis by gastroenterologists and non-gastroenterologists were similar in this study (OR: 1.258, 95% CI: 0.786–2.014). Although this is a problem unique to Japan, the results suggest that training of the general practitioners and emergency physicians who are skilled in dealing with various symptoms decreases the risk of delayed diagnosis of lower gastrointestinal perforations and possibly of other acute illnesses.
The reason that lower gastrointestinal perforations with fever is more likely to be missed is that the presence of fever may anchor the working diagnosis to the occurrence of an infection. With some exceptions, lower gastrointestinal perforation should result in abdominal pain with signs of peritoneal irritation. In the presence of abdominal pain with peritoneal irritation signs, the differential diagnoses include appendicitis, diverticulitis, pancreatitis, or gastrointestinal perforation. Therefore, when patients have abdominal pain with peritoneal irritation signs with or without fever, the strategy to reduce delayed diagnosis is not to treat empirically with antimicrobial agents, but to perform imaging studies to confirm the diagnosis.
This study revealed that the absence of tenderness was associated with delayed diagnosis of lower gastrointestinal perforation, and the finding of an absence of abdominal tenderness in about 10% of the cases is consistent with that in Yang and Ni's study [11]. Lower gastrointestinal perforation without abdominal findings presents a diagnostic difficulty. Repeated reevaluation and follow-up of patients with abdominal pain or positive inflammatory reaction without a clear diagnosis is desirable to avoid missing these cases.
In Japan, the availability of urgent radiology reports is low, with only 26.9% cases reported in this study. Communication barriers between physicians and radiologists are due to a variety of factors, such as system factors (eg, health information technology, crowding, shift-based work, and interruptions) [17, 18]. In our study, the results suggested that the unavailability of urgent radiology reports may be related to delayed diagnosis. To solve these problems, various factors such as training of the radiologists, improvement of the information technology systems including remote reading, and reform of the medical system are necessary.
In our study, the most common initial misdiagnoses were infectious enteritis, small bowel obstruction, constipation, diverticulitis, and appendicitis. In a previous study, upper gastrointestinal perforation was a common diagnosis, while colonic swelling, appendicitis, and pancreatitis were also reported [11]. The tendency for fatal diseases to be overlooked under the diagnosis of gastroenteritis in Japan is consistent with the finding of a previous study by Watari et al. [19]. It is understandable that constipation is a common initial diagnosis due to the presenting characteristics of the patients. The frequencies of small bowel obstruction, diverticulitis, and appendicitis among initial misdiagnoses are one of the features of this study. If there is small bowel obstruction with fever, increased inflammatory response, and peritoneal irritation signs, it is advisable to review the differential diagnoses. If there is abdominal pain with peritoneal irritation signs, it is advisable to request for imaging tests for a definitive diagnosis rather than simply judging the case as diverticulitis or appendicitis and treating it empirically with antimicrobial agents.
The greatest strength of this multicenter Japanese study is its large sample size; however, there are certain limitations to this study. First, the retrospective study design cannot fully exclude several common biases, including information bias, selection bias, and unexpected confounding factors. Second, we did not determine the causes of lower gastrointestinal perforation, because this disease is more common in the elderly and the bedridden, and we presumed many cases to have been managed conservatively or palliatively without surgery. In fact, only about half of the perforation sites could be identified at surgery, and many cases were treated conservatively. Additionally, previous literature has shown that the causes of non-traumatic intestinal perforation are diverse and that it is not necessary to determine them before surgery. Since the main purpose of this study was to determine the accuracy of the initial diagnosis of lower gastrointestinal perforation, and because of the abovementioned limitations, causal analysis was excluded from the design. Third, since the objective of this study was to mainly identify epidemiological characteristics of delayed diagnosis of lower gastrointestinal perforation, we did not examine the prognosis of the patients. There were many prognostic factors of acute abdomen, and most of the patients with this disease were elderly. Therefore, if we are to accurately analyze whether delayed diagnosis is associated with the prognosis, we must consider the clinical course, detailed data on patient factors and hospital factors, and even palliative cases of perforation due to advanced colorectal cancer.
In the future, we hope to conduct a retrospective analysis of error cases wherein the errors might have occurred, to determine what error patterns exist and whether they are preventable or not. In summary, delayed diagnosis of lower gastrointestinal perforation occurs in about one-third of the cases. Factors associated with delayed diagnosis probably include the presence of fever, absence of abdominal tenderness, unavailability of urgent radiology reports, and examination by a non-generalist.