Acta Chir Belg, 2009, 109, 65-70

Peritoneal Tuberculosis in Laparoscopic Era

E. Trcoveanu, G. Dimofte, C. Bradea, C. Lupas cu, R. Moldovanu, A. Vasilescu First Surgical Clinic, University Hospital St. Spiridon Ias i, Romania.

Key words. Laparoscopy ; peritoneal tuberculosis ; ascites ; tuberculosis. Abstract. Peritoneal tuberculosis is uncommon in developed countries, but as the general incidence of tuberculosis is on the rise in Romania so is the case with peritoneal localization of the disease. The present study retrospectively analyzed 18 patients (8 males and 10 females, mean age 50 years, range 17-74 years) diagnosed in our department with peritoneal tuberculosis between 1995 and 2007. Results : Ascites was present in all but one case. Other common findings were weight loss (12 cases), weakness (5 cases), abdominal pain (16 cases), anorexia (6 cases) and night sweat (3 cases). Abdominal ultrasound has been used to demonstrate ascites in 16 cases. Only two patients had chest radiography suggestive for active tuberculosis. Laparotomy was performed in four cases, laparoscopy in 14 cases (two conversions). Intraoperative findings included multiple diffuse involvements of the visceral and parietal peritoneum, white miliary nodules or plaques, enlarged lymph nodes, ascites, violin string fibrinous strands, and omental thickening. Biopsy specimens showed granulomas, while ascitic fluid showed numerous lymphocytes. We conclude that the symptoms of abdominal tuberculosis vary greatly, and laparoscopy can be essential for diagnosis and management. The operation is safe, reliable with few complications and permits a prompt diagnosis, necessary to cure the patient.

Introduction The worldwide incidence of tuberculosis (TB), particularly the extra-pulmonary form, is increasing (1). This is attributed to poverty, poor health care, migration from endemic areas and the increased prevalence of multi drug-resistant TB (1). Peritoneal tuberculosis has an incidence of 0.5-1.5% and a prevalence of 4-10% within cases of extra-pulmonary TB (2). In developing countries it is associated with a low socio-economic status and malnutrition, while in developed countries it is significantly associated with HIV infection and immigration. The symptoms and signs of peritoneal TB are nonspecific and as such early diagnosis is difficult. In countries with high incidence of TB infection physicians maintain a high index of suspicion aiming for an early diagnosis, low morbidity and low mortality. Modern laparoscopy has changed the perspective of a surgical procedure for diagnostic purpose and the minimal access approach is easily accepted in the diagnostic protocol of ascites of unknown origin. Still there are very few studies reporting experiences with laparoscopic diagnosis of peritoneal tuberculosis (1, 3, 4). Material and method Between 1995 and 2007 abdominal tuberculosis was diagnosed in 26 patients admitted in our department : 18 with peritoneal tuberculosis, 7 with intestinal involvement and one with mesenteric lymph node disease.

Laparoscopy with biopsy has been used in 14 out of 18 patients in the study. All patients underwent clinical examination and screening laboratory tests, chest radiograph, abdominal ultrasound, biochemical and bacteriological analysis of ascitic fluid during preoperative assessment. Laparoscopy was indicated in 14 patients for ascites of uncertain cause. We used standard laparoscopy technique with a 10-mm optical trocar and a 5-mm trocar for the biopsy forceps. Abdominal visual examination was performed with a 30 laparoscope for a comprehensive evaluation of the peritoneal surface (Fig. 1). Samples of ascites (50 mL) were taken and sent for microbiological examination. Abnormalities on the parietal serosa were sampled using a biopsy forceps. Bacteriology studies for Mycobacterium tuberculosis were performed on ascitic fluid and/or tissue samples. Liver biopsies were associated when major hepatic lesions were discovered (liver cirrhosis). In four patients we choose classic laparotomy for acute generalized peritonitis due to peptic ulcer perforation (one case), previous abdominal surgery (two patients) and plastic peritonitis associated with pelvic abscess secondary to a peritoneal dialysis in a woman with end-stage renal failure. Patients were followed up by the specialist medical team for at least 6 months. Results During the study period peritoneal TB was diagnosed using laparoscopy in 18 patients (8 males, 10 females).

66

E. Trcoveanu et al.

Fig. 1 Free intraperitoneal fluid with significant thickening of the peitoneal layer

Table I Demographic and hospital data of 18 patients with peritoneal tuberculosis

Characteristics Female / Male Mean age (years) Laparoscopic / open approach Readmission Mean postoperative hospital stay laparoscopic / open approach No of patients 10 / 8 50.2 (17-74) 14 / 4 1 5.6 / 13

Table II Clinical features of 18 patients with peritoneal tuberculosis

Symptoms Mean duration of illness (weeks) Abdominal distension Anorexia Pain Weight loss Vomiting Malaise Night sweats Diarrhea Pulmonary symptoms patients N 25 (8-56) 3 6 16 12 4 5 3 1 3 Signs % 100 17 33 89 67 22 28 17 6 17 Ascites Pallor Abdominal tenderness Hepatomegaly Splenomegaly Cachexia Lymphadenopathy Abdominal mass Pleural effusion N 16 4 13 1 2 3 2 2 2 patients % 89 22 72 6 11 17 11 11 11

We found that the disease affected a relatively young population with a mean age of 50.2 years (range 17-74). Table I presents the demographic and hospital data regarding the 18 patients, while clinical features and laboratory results are summarized in Table II and III respectively. In 16 cases abdominal ultrasound revealed ascites, usually in large quantity. We found alterations in liver structure in three cases with chronic liver disease, gallstones in one case and abdominal lymph node enlarge-

ment in two cases. Figure 1 depicts significant ultrasonic aspects. Table IV summarizes imaging investigations of patients with peritoneal tuberculosis. Laparoscopy is the final stage in our diagnostic protocol and macroscopic aspects can be suggestive (Fig. 2). Diagnosis of TB peritonitis was based on the classical findings of peritoneal miliary tubercles, ascites, and adhesions (violin strings) supported by typical histology (Table V). Tuberculosis was confirmed in all 18 patients based on identification of epitheliod granulomas (Fig. 3)

Peritoneal Tuberculosis in Laparoscopic Era

Table III Preoperative laboratory results of 16 patients with peritoneal tuberculosis
Test Anemia Raised WBC (over 10000/mm3) Low serum albumin Abnormal liver function tests Raised erythrocyte sedimentation rate Ascitic fluid straw color exudative AFB* Patients tested N % 18 100 16 89 14 78 17 94 17 94 13 72 13 13 1 72 72 6 Positive findings N % 4 22 14 78 10 56 14 78 14 78

67

* acid-fast bacilli staining in preoperative sample.

Table IV Imaging finding of 18 patients with peritoneal tuberculosis

Imaging Chest radiograph pleural effusion pulmonary fibrosis pulmonary TB Abdominal ultrasound ascites large quantity medium minimal liver cirrhosis peritoneal thickening mesenteric adenopathy gallbladder stones Abdominal CT scan ascites mass mesenteric adenopathy peritoneal thickening Patients tested N % 18 100 2 8 1 18 100 16 3 10 3 3 3 2 1 1 5 1 1 1 1 5 5 5 5 89 17 55 17 17 17 11 5 11 44 5 Positive findings N %

Table V Laparoscopic and histological data

Parameter N Operative findings tubercles ascites cirrhosis Peritoneal histopathology caseating granuloma non-caseating granuloma Liver abnormalities cirrhosis 16 16 3 12 6 3 Patients % 89 89 17 67 33 17

and presence of acid fast bacilli in the specimen (Fig. 4). In three cases liver biopsy demonstrated liver cirrhosis associated with peritoneal tuberculosis. Postoperative regimens included isoniazid 5 mg/kg, rifampicin 10 mg/kg and pyrazinamide 30 mg/kg for 2 months, followed by 4 months of isoniazid 10 mg/kg with rifampicin 30 mg/kg in a 3/7 sequence. All patients were followed in the specialized network for extra-pulmonary tuberculosis with complete response. Anyhow they remain on long term follow-up. Only one case required an unrelated laparotomy for a pancreatic pseudocyst, showing no active lesions and minimal adhesions between liver and diaphragm.

68

E. Trcoveanu et al.

Fig. 2 Peritoneal tuberculosis laparoscopic aspects : tubercles, ascites, adhesions

Fig. 3 Biopsy specimen in peritoneal tuberculosis demonstrating chronic inflammation with epithelioid granulomas formation (col HE 10).

Fig. 4 Biopsy specimen in peritoneal tuberculosis demonstrating epithelioid granulomas and acid fast bacilli (col. Ziehl-Nielsen 40).

Discussion Most reported cases with peritoneal tuberculosis are related with AIDS and are frequently associated with liver cirrhosis, which is not reproduced in our series although chronic alcohol intake, poverty and malnutrition are major co-morbidities in our population (5). Abdominal tuberculosis is not unusual in Eastern Europe and the peritoneal localization is the most common form, being seen in more than 50% of patients admitted with abdominal TB (3). As in most secondary tuberculoses the primary lung infection is healed. In our series only one case presented active pulmonary tuberculosis and seven had pulmonary sequels suggestive for a past history of primary pulmonary tuberculosis. Typically the bacillary spread in the peritoneum develops early in life during the primary infection with latent foci

that are later reactivated. Hematogenous spread from an active pulmonary lesion is the classical source of peritoneal TB. In rare situations, a direct infection of the peritoneal cavity is possible through contiguous spread from an active lesion involving the bowel, abdominal lymph nodes or fallopian tubes. Intestinal TB occurs as a result of swallowing the sputum of active lung TB or of ingestion of contaminated milk. More than 90% of patients have an exudative (moist) type of peritoneal TB presenting with ascites (1). Tuberculosis is a relatively frequent cause of ascites in developing countries and more often ascites in noncirrhotic patients becomes a major indication for laparoscopy (1). The other 10% present with fibroadhesive type of lesions and present with the typical doughy abdomen, only one being described in our series.

Peritoneal Tuberculosis in Laparoscopic Era

As reported herein, peritoneal TB in most cases has an insidious onset of several months duration. The slow development of ascites is the cause of late presentation. Acute onset has been reported requiring urgent laparotomy (1). Our series have one case mimicking perforated peptic ulcer and one case with pelvic abscess. While lowgrade fever and ascites are typical (1, 2, 6, 24), nonspecific symptoms and signs characterize peritoneal tuberculosis. Fever is present in 30% and weight loss in 80% of all cases. Abdominal symptoms are generally mild and patients describe more often an abdominal discomfort associated with abdominal distension. Fever, anorexia and fatigue have also been described in various proportions (6, 7, 24). Pulmonary symptoms in our series are present in 17 % of all patients, and 11 % were associated with active pulmonary disease, which is consistent with other reported series showing this association in 2.6 to 21% of cases (1, 2, 3, 6). Physical examination is non-relevant demonstrating diffuse abdominal pain in 65% of cases and clinical signs of ascites in 75% of cases (1). It is usual to identify pseudotumoral lesions produced by inflammatory changes in the omentum or the mesentery. Peritoneal TB should be considered in any patient with significant risk for tuberculosis and susceptible to opportunistic infections (immunodepression, malnutrition, AIDS, hemodialysis, liver cirrhosis, family history of TB, TB at other sites) presenting with ascites, fever and nonspecific general and abdominal signs (1, 21). Routine blood tests are not helpful and frequently the diagnosis of peritoneal TB is delayed or missed because of its subtle presentation and its insidious course (1, 8). Patients present only a mild anemia and a raised ESR. While skin test with purified protein derivate (PPD) has been reported to be positive in 55-100% in other series (1, 9), only four out of ten tested patients in our series were positive. Immunological anergia in these frail patients can explain the false negative skin tests. Also immunization in the general population with BCG, as it is the case in Romania, will return significant percentages of false positive responses (10). Clear standards should be established for skin testing with PPD. Nevertheless, the low positive predictive value should obviate the clinician from placing undue importance to this test (11, 15). Chest X-Ray abnormalities accompany peritoneal TB in around 48% of cases, (1, 3, 9) but a normal finding and a negative PPD do not rule out peritoneal disease. Ultrasound and CT-scan examination confirm ascites but are non-specific for the diagnosis. Lymphadenopathy, peritoneal thickening and inflammatory masses may suggest tuberculosis (3). Examination of ascites should be routinely performed. Low level albumin associated with low levels of glucose and LDH in the fluid are suggestive for tuberculosis (2, 12). While direct staining of ascites samples are rarely

69
diagnostic (one patient in our series), positive cultures are certainly more helpful but difficult to obtain except for techniques that use at least 1000 mL of ascitic fluid concentrated by centrifugation. In such cases positive cultures were reported in excess of 80% of cases (13). We believe that this technique is impractical in patients with a small volume of ascites. The measurement of the ascitic fluids c-interferon (c-IFN) concentration has been found to be valuable in the diagnosis of peritoneal TB (1, 14). Adenosine deaminase activity in ascitic samples at levels above 30 U/L predict tuberculosis with high sensitivity and specificity (above 90% in most studies) and should be introduced in the diagnostic protocol (14, 15, 21). PCR in ascitic fluid can be used as a major diagnostic tool with a high positive ratio mostly when two primers are used. As such laparoscopy or laparotomy may be reserved for PCR negative cases with symptoms and preoperative work-up suggestive for tuberculosis (16, 17, 19). Needless to say that diagnostic strategy should be tailored according to hospital budget as the new tools bring significant costs. Peritoneal TB can mimic a variety of other abdominal disorders, particularly advanced malignancy and Crohns disease (1). In this series peritoneal carcinomatosis needed exclusion in six of the 16 patients (37.5%). Peritoneal tuberculosis can also mimic acute appendicitis, perforated peptic ulcer, acute cholecystitis, pelvic inflammatory disease or ovarian cancer (1, 18, 19) and diagnostic procedures are even more difficult in patients with liver cirrhosis. Presence of ascitis in females should trigger the evaluation of CA-125 levels mostly when US scan reveals an ovarian mass. High levels can produce confusion with ovarian cancer but have been suggestive for abdominal tuberculosis in females and some even consider the use of this marker as a diagnostic tool in peritoneal TB (19, 20, 21). Diagnostic standards should include laparoscopically guided peritoneal biopsy and microbiological cultures of ascitic fluid (18, 22). Most typical macroscopic lesions are exudative ascites (100%), miliary peritoneal nodules (69%), adhesions (69%), and peritoneal congestion (63%). This macroscopic aspect to mimic peritoneal carcinomatosis (23). Histological evaluation is compulsory to rule out other causes of nodular lesions on the peritoneal surface. Frozen section can bring immediate results as it can establish a high rate of positive TB diagnosis and trigger appropriate early treatment (24). Technically, diagnostic laparoscopy is easily done in the presence of ascites, but access can be a problem in the dry form and cases with massive adhesions (1). This approach adds the advantage of a short hospital stay and avoids unnecessary investigations. A draw-back is that it is an invasive investigation, requiring general anaesthesia in these frail patients. The complication rate of laparoscopy is actually less than 1%.

70
Peritoneal TB is associated with 7% mortality if adequate anti-TB therapy is instituted timely. But it can increase seven folds if evaluation fails to establish a correct diagnosis or if adequate treatment is not available (1). It has been established that 6 month of treatment with isoniazid and rifampicin, with pyrazinamide added for the first 2 month, usually cures tuberculosis. Rate of multidrug resistance strains varies a lot according to national prevalence of tuberculosis from as low as 5% to as high as 48% (25). A fourth drug, usually ethambutol, or a fifth, such as streptomycin, may be added to the initial 2-months intensive phase if drug-resistance is suspected. Compliance with medical treatment, although essential, is always a problem and may alter the outcome. In this series, anti-TB drugs were effective in all patients with rapid and effective resolution of symptoms. Conclusion In the era of minimally invasive surgery early laparoscopy is recommended to establish the diagnosis of peritoneal TB, a condition in which undue diagnostic delay is no longer justified.

E. Trcoveanu et al.
11. HUEBNER R. E., SCHEIN M. F., BASS J. B. Jr. The tuberculin skin test. Clin Infect Dis, 1993, 17 : 968-75. 12. MANSOUR GHANAEI F., SHAFAGHI A., BAGHERZADEH A. H., FALLAH M. S. Low gradient ascites : a seven-year course review. World J Gastroenterol, 2005, 11 : 2337-9. 13. SINGH M. M., BHARGAVA A. N., JAIN K. P. Tuberculous peritonitis : an evaluation of pathogenetic mechanisms, diagnosticprocedures and therapeutic measures. N Engl J Med, 1969, 281 : 1091-1094. 14. SATHAR M. A., SIMJEE A. E., COOVADIA Y. M., SONI P. N., MOOLA S. A. H., INSAM B., MAKUMBI F. Ascitic fluid c interferon concentrations and adenosine deaminase activity in tuberculous peritonitis. Gut, 1995, 36 : 419-421. 15. SANAI F., BZEIZI K. Systematic review : tuberculosis peritonitis : presenting features, diagnostic strategies and treatment. Aliment Pharmacol Ther, 2005, 22 : 685-700. 16. PROTOPAPAS A., MILINGOS S., DIAKOMANOLIS E., ELSHEIKH A., PROTOGEROU A., MAVROMMATIS K., MICHALAS S. Miliary tuberculous peritonitis mimicking advanced ovarian cancer. Gynecol Obstet Invest, 2003, 56 : 89-92. 17. TZOANOPOULOS D., MIMIDIS K., GIAGLIS S., RITIS K., KARTALIS G. The usefulness of PCR amplification of the IS6110 insertion element of M. tuberculosis complex in ascitic fluid of patients with peritoneal tuberculosis. Eur J Intern Med, 2003, 14 : 367-371. 18. VOLPI E., CALGARO M., FERRERO A., VIGANO L. Genital and peritoneal tuberculosis : potential role of laparoscopy in diagnosis and management. J Am Assoc Gynecol Laparosc, 2004 May, 11 : 269-72. 19. UZUNKOY A., HARMA M., HARMA M. Diagnosis of abdominal tuberculosis : experience from 11 cases and review from the literature. World J Gastroenterol, 2004, 10 : 3647-3649. 20. THAKUR V., MUKHERJEE U., KUMAR K. Elevated serum cancer antigen 125 levels in advanced abdominal tuberculosis. Med Oncol, 2001, 18 : 289-291. 21. POYRAZOGLU O., TIMURKAAN M., YALNIZ M. et al. Clinical review of 23 patients with tuberculous peritonitis. Presenting features and diagnosis. J Dig Dis, 2008, 9 : 170-174. 22. GIARDIELLO C., SCOTTI L., ANGELONE G., PROTA C. A case of tubercular peritonitis : diagnostic value of laparoscopy. Chir Ital, 2003, 55 : 125-8. 23. KHARRAT J., GARGOURI D., OUAKAA N. et al. Laparoscopic aspects of peritoneal tuberculosis. Report of 163 cases. Tunis Med, 2003, 81 : 558-62. 24. KRISHNAN P., VAYOTH S. O., DHAR P. et al. Laparoscopy in suspected abdominal tuberculosis is useful as an early diagnostic method. ANZ J Surg, 2008, 78 (11) : 987-9. 25. COHN D. L., BUSTREO F., RAVIGLIONE M. C. Drug-resistant tuberculosis : review of the world-wide situation and the WHO/IUATLD global surveillance project. Clin Infect Dis, 1997, 24 : S121-30.

References
1. AL-MULHIM A. A. Laparoscopic diagnosis of peritoneal tuberculosis. Surg Endosc, 2004, 18 (12), 1757-61. 2. GHEORGHE L., GHEORGHE C. Tuberculoza peritoneala n Peritonitele (sub red. I. Popescu, C. Vasilescu), Ed. Celsius 1998, 77-83. 3. ASTON N. O. Abdominal Tuberculosis. World J Surg, 1997, 21 : 492-499. 4. MES INA C., PASALEGA M., VALCEA D., VASILE I. Tuberculoza abdominala : evalua ri clinico-terapeutice. Chirurgia (Bucuresti). 2004, 99 : 323-3288. 5. POP M., POP C., HOMORODEAN D. et al. Abdominal miliary tuberculosis in a patient with AIDS : a case report. Rom J Gastroenterol, 2003, 12 : 231-4. 6. TANRIKULU A. C., ALDEMIR M., GURKAN F., SUNER A., DAGLI C. E., ECE A. Clinical review of tuberculous peritonitis in 39 patients in Diyarbakir, Turkey. J Gastroenterol Hepatol, 2005, 20 : 906-9. 7. ROBADAY S., BELIZA C., KERLEAU J. M. et al. Tuberculosis peritonitis : an always present disease. About 4 new cases. Rev Med Interne, 2005 Jun 7 ; (Epub ahead of print). 8. LINGENFELSER T., ZAK J., MARKS I. N., STEYN E., HALKETT J., PRICE S. K. Abdominal tuberculosis : still a potentially lethal disease. Am J Gastroenterol, 1993, 88 : 744-750. 9. MARSHALL J. B. Tuberculosis of the gastrointestinal tract and peritoneum. Am J Gastroenterol, 1993, 88 : 989-999. 10. AL-KASSIMI F. A., ABDULLAH A. K., AL-HAJJAJ M. S. et al. Nationwide community survey of tuberculosis epidemiology in Saudi Arabia. Tuber Lung Dis, 1993, 74 : 254-60.

E. Trcoveanu, M.D., Ph.D. Clinica 1 Chirurgie Spitalul Universitar Sf. Spiridon Ias i Bd-ul Independen ei nr.1 700106 Ias i, Romnia Tel. / fax : 0040 232 218 272 E-mail : etarco@iasi.mednet.ro