Mini-laparoscopy as a diagnostic tool for abdominal tuberculosis: a retrospective series of 29 cases

This study is the largest case series of patients with abdominal TB diagnosed by mini-laparoscopy. Four patients with splenic tuberculosis in this case series are also part of a previously published study by our group on the effectiveness and safety of mini-laparoscopy-guided spleen biopsy [11]. To the best of our knowledge, there are no other case series on the feasibility of mini-laparoscopy in the diagnosis of abdominal TB to date. Our results confirm earlier reports about the difficulties of diagnosing abdominal TB due to the protean and insidious nature of clinical symptoms and the lack of specific laboratory, radiological, or clinical findings [3].

In line with previous studies [19], the most consistent laboratory features in patients with abdominal TB were anemia, elevated CRP, and elevated ESR. These features are highly unspecific and not able to distinguish abdominal TB from the wide range of differential diagnoses. Since neither tuberculin skin tests nor IGRAs can accurately discriminate between latent and active disease, they are not recommended for the diagnosis of active TB in low- and middle-income countries [20]. Also, IGRAs cannot provide sufficient sensitivity for the diagnosis of extrapulmonary TB [21], which is underlined by the finding that less than half of patients in our study had a positive test result. While radiological investigations may play an important role in the diagnosis of both pulmonary and extrapulmonary forms of TB, our study also highlights the limitations of CT and ultrasound and demonstrates the overall diagnostic value of mini-laparoscopy in patients with abdominal TB. CT is generally regarded as the most informative radiological modality in the diagnosis of abdominal manifestations and CT abnormalities have been reported in 69% to 78% of patients with visceral or peritoneal TB [8, 22]. Common findings are often nonspecific and include thickening of the peritoneum, ascites, lymphadenopathy, hepatomegaly, hepatic, or splenic lesions, and calcifications [8, 22, 23]. It has been proposed that PET/CT imaging may be useful in diagnosing extrapulmonary TB [24], but this warrants further investigation in larger studies. Besides, the cost and accessibility of this imaging modality limit its utility in resource-limited TB-endemic settings. Abdominal ultrasound is usually the first imaging study obtained in the assessment of patients with abdominal symptoms. A meta-analysis including 879 HIV-positive individuals with abdominal TB recently showed that abdominal ultrasound has a diagnostic sensitivity of 63% for any abnormality [9]. It has therefore been proposed to be a feasible diagnostic tool in the investigation of patients with suspected abdominal TB in resource-limited healthcare settings with a high pre-test probability for TB [9, 25]. Remarkably, in our study, neither abdominal ultrasound nor abdominal CT detected the majority of focal lesions that were observed by visual inspection of the peritoneum and visceral organs during mini-laparoscopy.

While clinical, laboratory, and radiological findings can raise suspicion of abdominal TB, tissue biopsies are generally required to make a definite diagnosis and fresh native tissue specimens should be sent for AFB stain, mycobacterial culture and M. tuberculosis PCR. Mycobacterial culture is essential since it is the only diagnostic modality to reliably allow for drug susceptibility testing to exclude drug-resistant TB. In our cohort, mycobacterial culture of tissue samples obtained during mini-laparoscopy grew M. tuberculosis in 15 patients, one of which was resistant to isoniazid. While mycobacterial culture is paramount to perform susceptibility testing and thus ensure effective treatment, it has a low diagnostic yield of only 10 to 35% for abdominal TB, and the results may require several weeks due to the slow growth rate of M. tuberculosis [26]. AFB stain has an even lower sensitivity ranging between 3 and 25% [4, 26]. Tissue PCR from fresh native tissue specimens has been demonstrated to be the most specific diagnostic test for abdominal tuberculosis with an overall sensitivity of 58% to 86% [4, 27]. The classic histology of caseating granulomas can be found in 51 to 83% of patients with hepatic TB [28], 76 to 100% of patients with tuberculous peritonitis [29‐32], and the majority of reported cases of splenic TB [33, 34]. Our study highlights that no single diagnostic method reliably identifies all cases of abdominal TB and can serve as a sufficiently sensitive gold standard. Rather, a combination of microbiological results, histopathological findings, and a good response to anti-tuberculous treatment should be used to diagnose abdominal TB. The frequent discrepancies between microbiological and histological results from tissue samples may be explained by the fact that not all examinations were necessarily performed on the same specimen and by a heterogeneous distribution of mycobacteria in infected organs. Therefore, ideally several tissue biopsies should be obtained for both microbiological and histopathological analyses. In patients with suspected abdominal TB, conventional laparoscopy has been considered the investigation of choice. It presents the opportunity to visualize the surface of the liver, the spleen, and the peritoneal cavity and offers the option of obtaining targeted tissue specimens from suspicious focal lesions [35]. Mini-laparoscopy represents a cheaper and less invasive alternative to conventional laparoscopy which requires smaller insertions to the abdominal wall due to ultra-fine instrumentation and can be safely conducted outside of the operation room with the patient under conscious sedation. Compared to percutaneous fine-needle aspiration biopsies, laparoscopy allows targeted core needle biopsies with the acquisition of larger tissue samples, which may be required to perform not only reliable histological analyses but also microbiological culture and M. tuberculosis PCR. Several studies demonstrated a high diagnostic yield of more than 80% in patients with suspected abdominal TB [26, 35]. In addition, while percutaneous biopsies are considered by many to be contraindicated in patients with high bleeding risk, laparoscopic techniques can be performed safely even in patients with severe coagulopathies [16] and enable termination of post-biopsy bleeding with various coagulation methods. This is of particular relevance for patients with suspected abdominal TB since mycobacterial infection has been identified as a significant risk factor for bleeding complications after percutaneous liver biopsy [36]. In our study cohort, minor post-biopsy bleeding occurred in 19 (66%) patients and was subsequently successfully controlled using argon plasma coagulation, fibrin glue, or both. Since abdominal TB is virtually always associated with intra-abdominal adhesions, laparoscopic techniques have a certain risk of intestinal perforation. In our cohort, intestinal perforation occurred in 2 patients, neither of whom required secondary interventions or admission to the ICU. These uncomplicated clinical courses demonstrate that mini-laparoscopy is a safe alternative to conventional laparoscopy due to the ultra-fine instrumentation. However, these findings also highlight that mini-laparoscopy should only be conducted by experienced physicians at hospitals equipped to handle complications that may potentially arise. Intraabdominal adhesions may hypothetically limit the feasibility of laparoscopic techniques since visualization may be impaired and biopsies may not be carried out. In our cohort visualization of the liver and the peritoneum was possible and tissue biopsies could be performed in all individuals. However, visualization of the spleen was only possible in around half the patients, so isolated splenic lesions may potentially be missed. While mini-laparoscopy has already been demonstrated to be relatively safe and efficient in the diagnosis and staging of a variety of hepatic [10, 12, 14‐16], splenic [11, 17], and peritoneal [13] diseases, our study provides evidence that this technique can also be useful in the diagnostic work-up of patients with suspected abdominal TB.

Our study is subject to several limitations that are mainly inherent to the retrospective study design. Firstly, we included patients that received mini-laparoscopy for suspected abdominal TB but no control group that was diagnosed by other means. While we demonstrate the principle feasibility of mini-laparoscopy for diagnosing abdominal TB, this study was not designed to identify patient subgroups who benefit from mini-laparoscopy or to compare mini-laparoscopy to other techniques like conventional laparoscopy or image-guided puncture techniques. For example, mini-laparoscopy may have limitations in cases in which suspected lesions are not easily accessible. Secondly, since no standardized study protocol was used, not all microbiological, histopathological, and radiological analyses were performed on all tissue samples in our cohort, so we were not able to assess the diagnostic sensitivity of the different diagnostic methods. Thirdly, the feasibility and relative safety of mini-laparoscopy, which we demonstrated at our tertiary care center with experience with this technique and specialization in infectious diseases may not apply to other healthcare settings. Fourthly, the patient number of this case series is rather small given the low overall incidence of abdominal TB in Germany. Prospective studies on larger patient cohorts including low-resource settings with a higher incidence of TB are needed to establish practical diagnostic algorithms including mini-laparoscopy for patients with suspected abdominal TB.

In conclusion, our study emphasizes that mini-laparoscopy is a safe and valuable tool in patients with suspected abdominal TB that allows visual assessment of the abdominal viscera and peritoneum and guided biopsies from suspicious focal lesions. It has a higher diagnostic yield than radiologic imaging and allows for drug susceptibility testing to select therapy and improve treatment outcomes in patients with drug-resistant tuberculosis. Regular and timely use of this diagnostic modality could prevent unnecessary procedures or invasive surgery and improve patient outcomes.