HOD : Prof. Dr. Vasanthakumar MS., UNIT CHIEF : Prof. Dr.Ravindran MS., ASSISTANT PROFESSORS: Dr.Vishwanathan MS., Dr.Muthulakshmi

MS.,PRESENTED BY Dr.Pradeep – Pathogenesis & Investigations Dr.Dhanaraj – Gastrointestinal TB Dr.Sudish- Peritoneal & Solid Organ TB Dr.Adarsh- Surgery in TB

ABDOMINAL TUBERCULOSIS

TUBERCULOSIS

ETIOPATHOGENESIS AND INVESTIGATIONS

WHY SHOULD WE KNOW ABOUT

TB??

40% of Indians harbour tb bacilli In 2010, Global Incidence – 9.4million In india – 2.3millionPrevalence in India is 3.1 million3,20,000 deaths… -WHO

TB declared as notifiable disease by INDIAN GOVERNMENT on

may9th 2012

http://articles.timesofindia.indiatimes.com/2012-05-09/india/31640562_1_mdr-tb-tb-cases-tb-diagnosis

Risk Factors Case series involving 60 patients

38% Cirrhosis

33% Renal Failure with Peritoneal Dialysis

27% Diabetes Mellitus

18% Underlying Malignancy

10% Systemic Corticosteroids

2% AIDS

12% No Risk Factorshttp://www.med.unc.edu

24th march 1882

World TB DAY

PATHOGENESIS

STAGE 1 ESTABLISHMENT

ALVEOLAR MACROPHAGE INGESTS TB BACILLI

M. tuberculosis blocks phagolysosome formation by inhbiting Ca2+ signals and the recruitment and assembly of the proteins that mediate phagosome-lysosome fusion

Fratti RA, et al. J cell Biol 2001

Racial differences in macrophages

microbicidal enzymes. Africans have macrophages less capable of destroying tb bacilli.

Mutations in NRAMP-1 gene involved in pushing out Fe2+ ions from the phagolysosome.

Cellier MF, et al.

Microbes Infect 2007; 9:1662.

STAGE 2 SYMBIOSIS

Tubercle bacilli ingestedBy non activated newly recruitedMonocytes.

STAGE 2 SYMBIOSIS

Incapable alveolar macrophage bursts. New monocytes from blood are recruited to

the site mainly by c5a, Monocyte Chemoattractant protein-1(MCP-1)

TB bacilli multiplies in these non activated monocytes.

7-21 days (<3weeks) – primary TB. Comes to an end when Th1 cells enters the

site

T-CELL

Secrete IFN γ

Activates Macrophages

Kills the inactivated macrophages which were allowing the tb bacilli growth inside them…

WHAT IS THE INITIAL RESPONSE

OF THE HOST??

CMI or DTH???

Main difference is concentration of antigen required….

STAGE 3 EARLY STAGES OF CASEOUS NECROSIS

Non activated Macrophages which allowed the growth of TB bacilli are killed by DTH mediated by T-cellsForming solid caseous necrosis

If DTH is directed towards the TB bacilli then why so

much of tissue destruction occurs??

 up-regulation of ICAM-1, ELAM-1, VCAM-1, and other adhesion molecules

Activated endothelial cells presents tuberculin like antigen to macrophage

Leading to endothelial injury and its consequences

J Leukoc Biol. 1996;60:692–703.

DTH AND CMI

•T-CELLS•DESTROYS INACTIVATED MACROPHAGES IN WHICH BACILLI MULTIPLIES•INITIALLY BENEFICIAL

DTH

•MACROPHAGES and T-CELLS•BACILLI MULTIPLYING INSIDE ACTIVATED MACROPHAGES ARE DESTROYED•BENEFICIAL TO THE HOST

CMI

STAGE 3 EARLY STAGES OF CASEOUS NECROSIS

TB bacilli remains live but cannot multiply in solid caseous material.

TB bacilli escaping from the edges of caseous necrosis are engulfed by macrophages and caseous centre enlarges.

STAGE 4 INTERPLAY OF CMI AND DTH

ACTIVATED MACROPHAGESWALLS OFF THE EXPANDINGCAVITY AND PREVENTS FURTHER INCREASE INSIZE IN HOST WITH GOODCMI.

POOR CMI

IN HOST WITH POOR CMIDTH CONTINUES DESTROYS THE BACILLI AND LUNG TISSUE TOO.

TB BACILL SPREADS THROUGHLYMPHATIC AND HEMATOGENOUS ROUTE TO OTHER ORGANS.

1.ARE HOSTS WITH POOR CMI ARE MORE INFECTIVE??2.ROLE OF STEROIDS IN

ABDOMINAL TB??

STAGE 5 LIQUEFACTION AND CAVITY FORMATION

 the large quantities of bacilli and their antigens in the liquefied caseum overwhelm a formerly effective CMI, causing progression of the disease and the destruction of local tissues, including the wall of an adjacent bronchus.

when the caseum liquefies, the entering

macrophages do not function effectively. Possibly, the entering macrophages are killed

by toxic fatty acids originating from host cells, or the bacilli, or both.

CAUSE OF LIQUEFACTION???

REF: Hemsworth GR, Kochan I. Secretion of antimycobacterial fatty acids by normal and activated macrophages. Infect Immun. 1978;19:170–177.

GENERAL INVESTIGATIONS

. Types of specimens:1.Pulmonary specimens -Sputum -Gastric lavage -Transtracheal aspirations -Bronchoscopy -Laryngeal swabbing2.Urine specimens3.Tissue and body fluid specimens4.Blood specimens5.Wounds, skin lesions, and aspirates

Microscopy

Sputum smears stained by Z-N stain

What is Smear Positivity All patients who have

submitted two Specimens and found to be positive for identification of AFB

Detecting AFB by fluorochrome stain using fluorescence microscopy

Culturing for isolation of Mycobacterium spp continues to be a Gold standard Agar based egg based BACTEC – 14.8days MGIT- 13.3days

4-6weeks

NEWER METHODS

PCR SENSITIVITY-92% SPECIFICITY-99%

INTERFERON –γ release assays.

QuantiFERON-TB

TB SPOT

SENSITIVITY-81%SPECIFICITY-91.2%

SENSITIVITY-87.5%SPECIFICITY-86.3%

GASTROINTESTINAL TUBERCULOSIS

Epidemiology Pathogenesis Clinical features Diagnosis

Epidemiology

Upto 1% of hospital admissions More common in immuno-suppressed Isolated abdominal tuberculosis:

Unselected autopsy series- 0.02 - 5.1% Higher prevalence in females in India (3:1–4:1)

Mainly disease of young adults

~ 2/3 of pt. are 21-40 yr old

TB & HIV

Incidence severity of abdominal TB will increase with the HIV epidemic

HIV – 50 % develop abdominal TB

Pathogenesis

Mechanisms by which M. tuberculosis reach the GIT:

Hematogenous spread from primary lung focus

Ingestion of bacilli in sputum from active pulmonary focus.

Direct spread from adjacent organs.

Via lymph channels from infected LN

In India, organism from all intestinal lesions – M. tuberculosis and not M. bovis.

Types

Ulcerative Hyperplastic Ulcerohyperplastic Diffuse colitis Sclerotic

PATHOLOGY

Bacilli in depth of mucosal glands

Inflammatory reaction

Phagocytes carry bacilli to Peyers Patches

Formation of tubercle

Tubercles undergo necrosis

Most active inflammation in submucosa.

PATHOLOGY

Submucosal tubercles enlarge

Endarteritis & edema

Sloughing

Ulcer formation

Accumulation of collagenous tissue

Thickening & Stenosis

PATHOLOGY

Lymphatic obstructionof mesentery and bowel Thick fixed mass

Regional lymph nodes• Hyperplasia• Caseation necrosis• Calcification

Bacilli via lymphatics

Inflammatory process in submucosa penetrates to serosa

Tubercles on serosal surface

Bacilli reach lymphatics

Order of Frequency

Ileum > caecum > ascending colon > jejunum

>appendix > sigmoid > rectum > duodenum

> stomach > oesophagus

More than one site may be involved

Bhansali - ileum involved in 102 and caecum in 100 of 196

pt. Prakash - ileocaecal involvement in 162 of 300 pt. Most common site - ILEOCAECAL REGION

WHY?

Increased physiological stasis Increased rate of fluid and electrolyte absorption Minimal digestive activity Abundance of lymphoid tissue at this site.

Clinical features

Constitutional symptoms

Fever (40%-70%) Weight loss (40%-90%) Anorexia Malaise

Pain (80%-95%)

Colicky (luminal stenosis) Continous ( LN involvement)

Altered bowel habits

Ileocecal TB

Colicky abdominal pain

Ball rolling in abdomen

Borborygmi

Right iliac fossa lump - ileocaecal region, mesenteric fat and LN

Isolated Colonic TB

9.2% of all cases

Multifocal involvement in ~ 1/3 (28% to 44%)

Anorectal TB

Hematochezia - most common symp. Due to mucosal trauma by stool

Constitutional symptoms

Constipation

Rectal stricture

Anal fistula – usually multiple

Gastroduodenal TB

Stomach and duodenum each ~ 1% of total cases

Mimics PUD - shorter history, non response to t/t

Mimics gastric Ca.

Duodenal obstruction - extrinsic compression by tuberculous LN

Hematemesis / Perforation / Fistulae / Obstructive jaundice

Cx-Ray usually normal

Endoscopic picture - non specific

Esophageal TB

Rare ~ 0.2% of total cases

By extension from adjacent LN

Low grade fever / Dysphagia / Odynophagia / Midesophageal ulcer

Mimics esophageal Ca

OBSTRUCTION

PERFORATION

MALABSORPTION

Complications

Obstruction

Pathogenesis

Hyperplastic caecal TB

Strictures (napkin ring) of the small intestine

Adhesions

Adjacent LN involvement traction, narrowing and fixation of bowel loops.

In India ~ 3% to 20% of bowel obstruction (Bhansali and Sethna).

Malabsorption

2nd most common cause in India

Pathogenesis

bacterial overgrowth in stagnant loop

bile salt deconjugation

diminished absorptive surface due to ulceration

involvement of lymphatics and LN

75% pt with intestinal obstruction

40% of those without (Tandon et al)

Perforation

5%-9% of SI perforations in India

2nd commonest cause after typhoid

Usually single and proximal to a stricture

Clue - Chest x-ray,

Pneumoperitoneum in ~ 50% cases

Investigations

Intestinal TB cont.

CT scan shows thickening of the cecum with pericecal inflammatory changes. Mesenteric lymph nodes are also evident (arrows).

Endoscopy Nodules

Variable sizes (2 to 6mm) Non friable Most common in caecum especially near IC valve.

Tubercular ulcers Large (10 to 20mm) or small (3 to 5mm) Located between the nodules Single or multiple Transversely oriented / circumferential contrast to

Crohns Healing of these ‘girdle ulcers’ strictures

Deformed and edematous ileocaecal valve

Esophageal TB Nodules

TB mass in stomach T.B. ulceration with narrow lumen

Is endoscopy diagnostic?

8 –10 Bx from ulcer edge

low yield on histopath as mainly submucosal disease

Granulomas in 8%-48%

Caseation in ~ 1/3 (33%-38%) of + cases

AFB stains - variable

Culture positivity in 40%

Combination of histology & culture diagnosis in 80% ( S K Sharma)

Take home message

Ileocecal TB is the most common intestinal TB Combination of histology & culture is necessary for diagnosis. Surgery is the only answer

PERITONEAL TUBERCULOSIS

AN OVERLOOKED DIAGNOSIS

Non specific presentation

Insidious presentation

Mimicks malignancy

Unhelpful labaratory tests

DIAGNOSTIC CHALLENGES

EPIDEMOLOGY

PATHOGENESIS

CLINICAL FEATURES

DIAGNOSIS

TREATMENT

6th most common extra pulmonary site

Incidence- 0.1% to 0.7% worldwide

Rising incidence

sexes are equally affected

35 and 45 years of age.

EPIDEMOLOGY

Activation of quiscent foci of

infection(common)

Direct spread –mesentric Lymph nodes –Intraabdominal organs

•Hematogenous spread from–Primary pulmonary TB–Miliary TB

PATHOGENESIS

CLINICAL PICTURE

wet-ascitic(most common)

• ascites• ±peritonitis

fibrotic-fixed

• Mass formation• Matting of bowel loops

dry-plastic form(less common)

• adhesions• ‘doughy feel’• tender abdominal masses.

Encysted(loculated)

• localized abdominal swelling

CLINICAL PRESENTATION

Case series involving 145 patients

73% Abdominal swelling (ascites) – most common

64% Abdominal pain 54% Fever and night sweats 44% Weight loss 18% both pulmonary & abdominal TB Hepatomegaly and splenomegaly - uncommon

CLINICAL FEATURES

Haematological indices. Microbiological diagnosis. Ascitic fluid analysis. New diagnostic tools-Adenosine deaminase,

Gene amplification. Immunodiagnostic tests. Imaging studies CXR- concomitant TB in less than 25% cases Barium studies . ultrasound and computed tomography.

INVESTIGATIONS

•Gross Appearance: Straw coloured .

EXUDATIVE WBC cell count- 500 and 1500 cells/mm3 – lymphocytosis.

LDH raised-> 90 U/L

Protein > 3g /dl.

SAAG <1.1mg/dl

RBC 7%.

AFB stain +ve < 3 per cent of cases.

positive culture is obtained in less than 20 per cent of cases

Ascitic fluid analysis

New diagnostic tools

Adenosine deaminase.

rapid and non-invasive

Purine-degrading enzyme

Assists with maturation and differentiation of T-lymphoid cells.

Raised-  stimulation of T cells by the mycobacterial antigens. 

Adenosine deaminase

•Cut-off value of 30 U/L 94% Sensitive 92% Specific.

FALSE VALUES- •In coinfection with HIV - normal or low. Falsely high values in malignant ascites.

Gene amplification.- LCR & PCR in detecting AFB in tissues.

serological tests- - ELISA to detect IgG to a 43 kDa antigen of M. tuberculosis found it to be highly sensitive. - High IFN-γ levels - detecting latent TB.

Elevated CA-125 -Not sensitive

Also raised in peritoneal carcinomatosis, ovarian malignancy.

Can use to follow treatment response

in obtaining peritoneal biopsies

safer and inexpensive alternative to diagnostic laparoscopy.

high diagnostic yield approaching 95%

Imaging studies

Ultrasound-

superior to CT in revealing the multiple, fine, mobile septations within the ascitic fluid

1. fluid -free or loculated;(echogenic debris) 2. “Club sandwich” or “sliced bread” sign.3. Lymphadenopathy- caseation and calcification.4. Bowel wall thickening .5. Pseudokidney sign

COMPUTED TOMOGRAPHY-

 ascitic fluid has high attenuation values .

•Peritoneum(white arrow) –Smooth and uniform thickening –If nodular, think Peritoneal

Carcinomatosis.

•Omentum(open arrow) –Smudged, omental cake or

nodular..

•Mesentery –Loss of normal mesenteric

configuration -Thickened mesentery (>15 mm)

with mesenteric lymph nodes- early sign

•Lymphadenopathy.(black arrow)

DIAGNOSTIC TOOL OF CHOICE?

DIAGNOSTIC LAPROSCOPY

specificity in excess of 96% on the laparoscopic appearance alone.

With histological findings-sensitivity- 93% specificity- 98%

Peritoneal biopsies should always be examined whenever possible for culture and sensitivity. - gold standard

DIAGNOSTIC YEILD

Thickened peritoneum with tubercles (66%)

thickened and peritoneum with adhesions (21%);

fibro-adhesive type – with tubercles and adhesions 13%. 

LAP FINDINGS

PIT FALLS Peritoneal carcinomatosis, sarcoidosis,

starch peritonitis and Crohn's disease - MIMICK LAP FINDINGS.

More expensive. Requires expertise. poor isolation of organism complications -bleeding, infection and bowel

perforation

ROLE OF

LAPAROTOMY?

 unnecessary

with fibro-adhesive type of TBP when there

is an indication for a peritoneal biopsy.

 ideal diagnostic test

requires the demonstration of

mycobacteria

 characteristic laparoscopic appearance

itself, even in the absence of bacteriological confirmation, would be sufficient grounds for the diagnosis of TBP.

HIGH SPECIFICITY OF MACROSCOPIC APPEARANCE

BUT…

TREATMENT

MEDICAL vs SURGICAL

solely pharmacological.

Four drug regimen:–Isoniazid–Rifampin–Ethambutol–Pyrazinamide.

CAT I ATT Response to therapy is manifested by resolution of

symptoms and disappearance of ascites

UNCOMPLICATED

 Surgery is reserved for complications or

uncertainty in diagnosis.

MDR-TB not responsive to ATT.

ABDOMINAL COCOON SYNDROME-

rare entity causing intestinal obstruction.

Diagnosis done by imaging studies.

Extensive bowel resection is associated with high morbidity.

Symptomatic relief generally ensues following conservative surgery, although recurrence has been reported.

DREADED COMPLICATION

ROLE OF CORTICOSTEROIDS?

 four trials of adjuvant corticosteroids use in TBP

and all of them cited modest benefit.

Alrajhi et al.85 reported considerably low morbidity and complications in those treated with corticosteroids.

 pending need for prospective, well-controlled clinical trials with long-term follow-ups to identify the category of patients most likely to benefit from such therapy

 requires a high index of suspicion because of

the subtle nature of the symptoms and signs.

culture growth of the Mycobacterium remains the ‘gold standard’ for diagnosis.

It is essential to recognize that a combination of different diagnostic tests is used in order to arrive at the diagnosis of TBP

Tuberculous peritonitis--do not

miss it

 Laparoscopy, however, remains the

best means of diagnosing the

disease

SOLID ORGAN TUBERCULOSIS

the portal of entry :hematogenous

dissemination miliary tuberculosis :hepatic artery focal liver tuberculosis :portal vein.

HEPATIC TB

three forms diffuse hepatic involvement- most common granulomatous hepatitis focal/local tuberculoma or abscess- rare

INVESTIGATIONS

Percutaneous liver biopsy.

laparoscopy liver biopsy- cheesy white irregular nodules.

CT SCAN.

CT abdomen

miliary micronodular with miliary calcifications

Multiloculated cystic mass(cluster sign)

MILIARY TB

lesions are small 1 to 2 mm epitheloid granulomas.

TUBERCULOMA Masses larger than 2mm in diameter

• It can occur due to disseminated or miliary form of

the disease• Most commonly encountered in HIV pt(developed

countries)• Fever, weight loss, diarrhea, left upper abdominal

pain, splenomegaly • Investigations• Image-guided percutaneous needle biopsy is the

gold standard for diagnosis.

CECT-abdomen-multiple hypo echoic foci(<2cm)

SPLENIC TUBERCULOSIS

Gross pathology of resected spleen showing innumerable caseating granulomas consistent with splenic tuberculosis.

Mackowiak P A et al. Clin Infect Dis. 2011;52:418-420

The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Computed tomograph scan of the abdomen showing a spleen diffusely infiltrated by small, hypodense lesions consistent with splenic granulomas.

Mackowiak P A et al. Clin Infect Dis. 2011;52:418-420

The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

It is rare Often associated with miliary TB &

immunocompromised pt Result from lymphohaematogenous

dissemimation after pulmonary exposure Anorexia,malaise fever,weight loss,mass Investication: FNAC & BIOPSY (CT guided)

PANCREATIC TB

CT enhanced conrast-

Microscopic pyuria without bacteruria and with

or without hematuria.

Progression of the disease urine culture may be +ve for tubercle bacilli.

Cavitation of renal parenchyma may be seen.

Standard anti TB therapy

RENAL TB

Ovarian TB

Fallopian tubes are affected in 94% of women with genital tuberculosis.

Salpingitis caused by hematogenous dissemination is almost always bilateral .

A tubo-ovarian abscess that extends through the peritoneum into the extraperitoneal compartment suggests tuberculosis

Ovarian TB Tuberculous tubo-

ovarian abscess

(a) Contrast-enhanced CT scan shows a multiloculated mass with peripheral enhancement around centers .(arrow).

(b) Coronal T2-weighted MR image (7,200/90) shows the abscess (arrows).

Surgeon’s Viewpoint

A 24 yr old female comes with pain RIF,

MANTRELS 7/10 diagnosed as acute appendicitis.

On opening an inflammed appendix is found but studded with tubercles, omentum and caecum show multiple tubercles

Do we do appendicectomy ?

Patient comes with features of perforation

peritonitis On opening TB peritonitis with ileac

perforation with a stricture of about 3 cm 2 feet distal to perforation

Primary closure?Stricturoplasty?

Resection?

A 60 yr old male, known case of pulmonary TB

presenting with acute intestinal obstruction On opening ileocecal mass with peritonium

and omentum showing features of TBRt hemicolectomy?Limited resection?

Bypass?

Patent known case of pulmonary TB ,

presenting with ascites and subacute obstruction.

On diagnostic Lap we find Milliary TB with multiple adhesions

Do we do adhesiolysis?

Removing the appendix is a safe procedure

even if microscopic evidence of tuberculosis is present

Delay in treatment can cause significant morbidity

Appendicectomy

•Singapore Med J 2011; 52(2) : 91•Abrams & Holden, 1964

Stricturoplasty/ Resection

Both procedures were equally effective and had equal morbidity in cases of intestinal tuberculous strictures.

Stricturoplasty is superior to resection anastomosis in cases of multiple strictures as it conserves gut length

Stricturoplasty can even be performed safely in cases with coexistent gut perforation.

J Coll Physicians Surg Pak 2003 May;13(5):277-9

Zafar A et al ,Rawalpindi General Hospital, Rawalpindi

Stricturoplasty

Stricturoplasty is a simple, quick, and safe operative technique to manage tuberculous small intestinal strictures, in combination with limited resection or as a sole procedure

Stricturoplasty is suggested in pyloroduodenal and ileocaecal lesions

Abrar Hussain Zaid et al

Katariya  et al

Perforation primary closure?

The results of oversewing alone are poor Bhansali et al.,1968

Resection anastomosis is the best method in treating perforations

N.O. Aston and A.M. de Costa, Postgraduate Medical Journal (1985) 61, 251-252

In critically ill is oval excision of the perforated area with a transverse anastomosis reinforced by an omental patch

Pujari, 1979

Resection Anastomosis

Is it safe?

Annals of Surgery November 1964

Two-stage procedures Reversal of stoma in a well-prepared gut with

ATT cover

Muhammad Saaiq et al

Turkish Journal of Trauma & Emergency

Surgery vol 17 2011 Rankie et al Recio et al Piechaud et al Asian J Surg 2002:25(2):145-8

Resection is a safe and effective procedure in

treating abdominal TB complications.

Resection of a tuberculous lesion where

feasible is the procedure of choice

With effective ATT limited and conservative

resections give good results

How much to resect?

•Journal of the College of Physicians and Surgeons Pakistan 2008, Vol. 18 (7): 393-396•P Agarwal et al , BHJ 2000

Low output fistulas without distal obstruction

ATT wait and watch High output fistulas Fistulas with distal obstruction Fistulas not responding to conservative

management Surgery

Fistulas

Saudi J Gastroenterol. 2010 October; 16(4): 305.

Adhesiolysis / ATT

Adhesive intestinal lesions may be relieved with antitubercular drugs alone without surgery.

Anand et al Balasubramaniam et al

To summarise

Tuberculous peritonitis once diagnosed is usually not a surgical disease.

Resection of diseased segment is the best method

Stricturoplasty and Resection anastomosis are safe procedures

Limited resection is advised with ATT cover Chemotherapy has no substitute and is

essential after surgery.

Thank You