Hepatobiliary and pancreatic tuberculosis: A two decade experience

Background Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis. Methods The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli. Results Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak [1] intraabdominal abscess [1]) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months). Conclusion Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.


Background
Abdominal tuberculosis (TB) commonly affects the intestinal tract, lymph nodes, peritoneum and solid organs in varying combinations. Up to two-thirds of patients with abdominal TB have abdominal lymphadenopathy or peritoneal disease in addition to intestinal involvement. Onethird may have extra-intestinal involvement also [1]. Isolated hepatobiliary or pancreatic TB is rare and the preoperative diagnosis is difficult. The available literature related to hepatobiliary or pancreatic tuberculosis is mostly in the form of case reports or series. Therefore we reviewed our experience with this rare form of abdominal TB in a tertiary health care centre and referral hospital situated in an area endemic for TB.

Methods
In this retrospective study, the records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic TB over a period of 20 years (January1986-December 2006) were reviewed. The data pertaining to demographic features, sign and symptoms, duration of illness, imaging (X-ray chest, ultrasonography [US], contrast enhanced CT scan and magnetic resonance imaging [MRI]), side-viewing endoscopy, cytology and/or histopathology, operative findings, therapeutic procedures, postoperative outcome and follow up with anti tubercular therapy (ATT) were obtained. The samples for cytology and/or histology were obtained by US or CT guided aspiration, bile cytology and during exploratory laparotomy. The histological findings of granuloma with caseation necrosis or identification of acid fast bacilli was used as the criteria for diagnosis of tuberculosis.

Results
Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Of the 11 patients with hepatobiliary TB, 4 had biliary involvement secondary to involvement of the adjacent periportal and pericholedochal lymph nodes. Of the 7 patients with pancreatic TB, 4 had pancreatic involvement secondary to involvement of the adjacent peripancreatic lymph nodes (Table I). The mean age of the patients was 41.7 (range 19-70 years) and twothirds of them were between third and fourth decade. The duration of symptoms varied between 2 weeks and 2 years (mean: 20 weeks).

Imaging
Chest X-ray t was normal in all patients except two who had evidence of old, healed pulmonary TB. All patients underwent abdominal US as the first investigation for obstructive jaundice or upper abdominal pain. It showed dilated intrahepatic biliary radicals in 10 patients (lower end block in 6 and hilar or suprapancreatic block in 4). The other findings were a space occupying lesions (SOL) in the liver (n = 2), gallbladder mass (n = 3), gallbladder polyp (n = 1), hyperechogenecity of the gallbladder (n = 1) and a pancreatic mass (n = 3). Only 2 patients had enlarged periportal and/or peripancreatic lymph nodes on USG.
Abdominal computed tomography (CT) done in all cases, confirmed the findings on US and also showed enlarged periportal, peripancreatic and/or coeliac lymph nodes in 4 patients. Only one patient, who had a pancreatic head mass with enlarged lymph nodes, was suspected to have pancreatic tuberculosis based on CT scan alone. In all others the findings suggested an alternative diagnosis.
Endoscopic retrograde cholangiopancreatography (ERCP) was attempted in 5 patients and bile was aspirated in all patients. In one patient with a hilar stricture, bile cytology demonstrated acid-fast bacilli and the patient was treated with ATT. Magnetic resonance cholangiopancreatography (MRCP) done in 4 patients (hilar block [n = 2], postcholecystectomy (n = 1) and suspected chelodocholithiasis [n = 2]), did not show any mass or filling defect.

Management
Only 4 patients (22%) could be diagnosed preoperatively, 3 had pancreatic TB and 1 had bile duct TB (presented with hilar stricture). Among 3 patients with pancreatic TB, 1 patient had history of abdominal pain since 2 years and enlarged matted right supraclavicular lymph node on physical examination. Fine needle aspiration cytology (FNAC) from the SC Lymph node showed evidence of TB and a subsequent US-guided FNAC from the pancreatic head mass revealed TB. In the other 2 patients, the diagnosis was made incidentally as CT scan of these patients showed a large, unresectable pancreatic head mass with enlarged para-aortic lymph nodes. Hence, they were considered for palliative chemoradiotherapy. The US-guided FNAC done to confirm the diagnosis of malignancy suggested TB. The patient with a hilar stricture had a history of spinal TB and imaging did not show any mass. He was subjected to ERCP and stenting to decrease the jaundice and a specimen of bile obtained at showed cytological evidence of TB. ATT was started in all four patients. On subsequent follow up, symptoms of these patients resolved completely.
There was no mortality related to surgery. Two patients developed major postoperative complications; one patient following a Whipple's pancreaticoduodenectomy developed a leak from the pancreaticojejunostomy and full thickness wound dehiscence (treated with regular dressing, antibiotics and maintainence of nutrition through feeding jejunostomy), and the other patient who had resection of segment VIII, developed an intra-abdominal abscess requiring percutaneous drainage. Three patients developed ATT-induced hepatotoxicity (elevated level of transaminases [2], jaundice [1]), which required modification in the drugs and dose of ATT. These patients recovered completely and remained asymptomatic on follow up.
The median follow up period was 12 months (9 -96 months). Two patients developed recurrent jaundice. One patient with bile duct TB who underwent hepatojejunostomy developed recurrent cholestatic jaundice 9 months after surgery. She underwent percutaneous transhepatic drainage for cholangitis and was later taken up for surgical decompression. At re-exploration a kink in the Roux-limb was unraveled to relief the obstruction to biliary outflow. However, the patient continued to deteriorate and succumbed to sepsis and multiple organ dysfunction syndrome 1 year after the primary procedure. The second patient with hepatic TB developed jaundice at 8 years of follow up. On evaluation he was detected to have a single stone in the common bile duct which was removed endoscopically. One patient with pancreatic TB developed an incisional hernia.

Discussion
In regions with high prevalence of pulmonary TB, abdominal TB is not uncommon. Its prevalence in developing countries has been estimated to be as high as 12% [2].   Although abdominal TB is thought to be frequently associated with active pulmonary TB, evidence of active pulmonary TB has been reported to occur in 6-38% [3] of cases. Only 2 of our patients had evidence of old healed pulmonary TB. Abdominal TB is distinct from pulmonary tuberculosis in that it affects young adults more commonly (mean age in India, 31 years) [4], and is due to ingestion rather than inhalation of pathogen. Following ingestion the bacilli gain access to the gastrointestinal tract where necrotizing granulomas may develop and then spread to the lymphatics affecting any organ in the GI tract, including hepatobiliary and pancreatic tissue [5].
The primary site of TB is usually not evident in most cases of hepatobiliary and pancreatic TB. The liver is affected most commonly as a part of a miliary spread of tuberculosis from lung via hepatic artery [6]. Infection can also spread through the portal vein or lymphatics especially in patients with concomitant TB of the gastrointestinal tract [7]. The infection reaches the gallbladder by either a hematogenous or lymphatic spread from the primary site, by direct involvement and/or secondary involvement from a pre-existing infection in the liver [8]. The much rarer biliary tract infection is again secondary to excretion of acid-fast bacilli from the liver into the bile [9][10][11] or secondary to involvement of periportal lymph nodes by TB [12][13][14]. We encountered 2 patients with direct involvement of the bile duct while 4 others had enlarged lymph nodes causing secondary biliary obstruction. Pancreatic TB is uncommon and isolated involvement is rare. [1,[15][16][17] It can be affected either by the hematogenous route in miliary tuberculosis or by direct spread from contiguous lymph nodes.
The clinical presentation of hepatobiliary and pancreatic TB is slow and insidious, with non-specific symptoms and signs. In a large review of 300 patients with abdominal TB from India, men and women developed the disease with Fig1d equal frequency, and although pain was the most common presentation, the symptomatology was variable and nonspecific [18]. In our patients too, abdominal pain was the most common presentation (n = 13) associated with non-specific symptoms such as anorexia, weight loss and fever. Presence of active extra-abdominal TB is an important indicator for suspecting a tubercular aetiology in a patient with abdominal complaints. This enabled us to diagnose 2 patients preoperatively and treat with ATT.
Hepatic TB can occur in miliary, nodular and solitary abscess form [19][20][21]. Series from Philippines [22] and China [23] showed that patients with hepatic TB presented with fever, abdominal pain and hepatomegaly and both patients in this series had similar complaints. In addition one patient presented with melaena, which is a rare manifestation.
Gallbladder TB may present with features of cholecystitis, [24] a gallbladder mass [9] or with obstructive jaundice due to associated enlarged pericholedochal lymph nodes. Three of our patients had TB of the gallbladder; one presented with a mass in the gallbladder, the second with a polyp in the gallbladder and the third with a hemobilia. Similarly, symptomatic biliary tract TB mimics a primary bile duct or gallbladder cancer or even primary sclerosing cholangitis [10,11]. Of the 6 patients with biliary tract TB, the working diagnosis in 5 patients was biliary tract malignancy (gallbladder carcinoma [2], cholangiocarcinoma [2] and periampullary carcinoma [2]. One patient with spinal TB and obstructive jaundice with a block at the confluence of the right and left hepatic ducts was suspected to have biliary TB and was diagnosed preoperatively. Xia et al. [25] showed in a series of 16 patients with pancreatic TB, abdominal pain (75%), anorexia/weight loss (69%), malaise/weakness (64%), fever (50%) and jaundice (31%) were the common symptoms. Our patients with pancreatic TB had abdominal pain (n = 5) as the most common manifestation followed by anorexia, weight loss and jaundice (n = 3). These patients mimic carcinoma pancreas or focal pancreatitis [26].

Imaging
Tubercular liver abscess or tuberculoma may be detected as a SOL on US (hypoechoic lesions with hyperechoic rims and complex masses) and CT (hypodense lesions) [27][28][29], but only FNAC or a trucut biopsy can confirm the diagnosis. Two of our patients presented with SOL in the liver, the first was diagnosed as infected hydatid cyst and the second as hepatocellular carcinoma based on CT findings. Maglinte et al. [30] reported that more than 50% of patients with hepatic TB had characteristic calcification on X-ray. However, we did not see this finding in our patients.
In patients with gallbladder and bile duct TB, imaging modalities such as US, CT, MRCP and ERCP are useful to define the mass, the level and extent of bile duct obstruction but almost never suggest a diagnosis of TB. Patients with pancreatic TB may show an enlarged pancreas with focal hypodense lesions and irregular borders, most commonly in the head region or enlarged peripancreatic lymph nodes on CT [31]. However these findings are nonspecific and may be seen in focal pancreatitis or pancreatic carcinoma. The definitive diagnosis rests on histological and bacteriological evidence of tuberculosis. In view of the nonspecific presentation and imaging appearance of the disease, a high index of suspicion is required to obtain a preoperative diagnosis. However, the diagnosis is usually established at laparotomy, as happened in 14 of 18 of our series. Positive yield of AFB from bile cytology on ERCP is low; only 1 of 5 of our patients had AFB positivity on biliary cytology. Techniques for biopsy include endoscopic US-guided biopsy, CT/US-guided percutaneous biopsy, and surgical biopsy [32]. Mallery et al. had shown that there is no difference in accuracy between these three techniques of pancreatic biopsy [33].

Treatment
In patients with hepatobiliary and pancreatic TB, once the diagnosis is established, ATT will cure the disease in nearly all patients. However, patients with evidence of biliary obstruction would need either endoscopic or surgical intervention to relieve the obstruction as the ductal narrowing might persist despite treatment with ATT [9,10,[34][35][36]. Most of our patients required a surgical intervention (14/18) because the preoperative diagnosis was not TB but malignancy. The results of surgery in these patients were satisfactory with no postoperative mortality and low morbidity.

Conclusion
In conclusion, a high index of suspicion in young patients with non-specific symptoms residing in areas with a high prevalence of TB should prompt vigorous attempts at obtaining a preoperative histological or bacteriological diagnosis. In those with no definite diagnosis preoperatively tissue for frozen section should be obtained. However, in those in whom neither a preoperative nor an intraoperative diagnosis of tuberculosis can be made, a surgical excision may be required. This is usually associated with low morbidity and mortality and good long term outcome after adequate ATT.

Competing interests
The author(s) declare that they have no competing interests.

Authors' contributions
SS, SP: Acquisition data, analysis and drafted the manuscript, SR acquisition data and helped in drafting DS: Case 4 A 23-year-old woman presented with pain abdomen, weight loss and enlarged supraclavicular lymph nodes for 2 years Figure 4 Case 4 A 23-year-old woman presented with pain abdomen, weight loss and enlarged supraclavicular lymph nodes for 2 years. Radiologist interpreted imaging, MK: Pathologist provided histological diagnosis PS and TKC: revised it critically. All authors read and approved the final manuscript.