by Harwood Academic Publishers GmbH Printed in Malaysia Can We Do Away With PTBD?

Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical jaundice to decompress the biliary tree and improve hepatic functions. However, the risk of sepsis is high in these patients due to immunosuppression and surgical outcome remains poor. This raises a question—can we do away with PTBD? To answer this query a study was carried out in 4 groups of patients bearing in mind the high incidence of sepsis and our earlier studies, which have demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B. Serial estimations of bilirubin levels carried out during the course of drainage (3 Wks) revealed a gradual and significant decrease from 12.52 ± 8.3 mg% to 5.85 ± 3.0 mg%. Antipyrine half-life did not change significantly (18.35 ± 4.2 hrs compared to basal values 21.96 ± 3.78 hrs). The phagocytic and intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13 ± 3.68% phago, and 19.1 ± 4.49% ICK; Post drainage: 20 ± 8.48% Phago and 11.15 ± 3.05% ICK). Thus PTBD did not improve the metabolic capacity ofthe liver and mortality was higher due to sepsis. Group (C) patientg received TC during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A significant improvement in PMN functions occurred by 3 weeks in both groups (30.29 ± 4.68% phago, 30 ± 4.84% ICK in Group C and 30.4 ± 2.99% phago, 27.15 ± 6.19% ICK in Group D). The mortality in Groups C and D was 25% and 14.2% respectively during the preoperative period. There was no mortality after surgery. It appears from this study that host defenses as reflected by PMN functions play an important role in influencing prognosis. Further decompression of the biliary tree by PTBD seems unwarranted.


initial repo
ts on preoperative external biliary drainage were of dramatic reduction in post-operative mortality-2.Recent trials have however emphasized the compli- cations of drainage techniques thus questioning the advantages of this method13,14,15.The hazards of the Address for correspondence: R. D. Bapat, Professor and Head, Department ofGastroenterology Surgical Services, Seth G. S. Medical College and K. E. M. Hospital, Parel, Bombay-400 012, India.

technique include cholangitis, haemorrhage, biliary leakage, catheter blockage/dislodgement.

The incidence of sepsis following external biliary drainage has been reported to be between 22- 33/017'18 '19.Impairment of function of the immune sys- tem in patients with obstructive jaundice has been suggested as the underlying cause for sepsis 19-)9.To control infection, antibiotics have been used, compli- cating the therapy with development of resistant organisms.Strengthening of host defences is a novel approach which may be complementary to antibiotics to combat infection in patients with o structive jaundice.

Recently, Tinospora cordifolia, a plant from the traditional Indian system ofMedicine (Ayurveda), has been shown to improve the surgical outcome in patients with obstructive jaundice by strengthening the host defences3.Tinospora cordifolia was adminis- tered to patients after institution of external biliary drainage and was continued during the entire drainage period.It is available in the form ofpills which contain dried aqueous extract of the stem of the plant.Earlier reports 31,32 have shown its protective, effect against a variety of infections and this has been attributed to its immunostimulant property.
The beneficial effect of Tinospora cordifolia in patients undergoing percutaneous drainage prompted us to conduct the present study.In the present study we aimed at evaluating the effects of Tinospora cordi- folia in patients with obstructive jaundice undergoing biliary tract surgery, without preoperative Percutaneous Transhepatic Biliary Drainage (PTBD) and compared the results with those undergoing pre operative PTBD and recieving Tinospora cordifolia.
The changes in bilirubin, antipyrine half-life and polymorphonuclear functions in terms of phagocytosis and intracellular killing capacity of neutrophils, along with perioperative mortality and morbidity were observed and noted.The efficacy of Tinospora cordi- folia was also viewed in the light of changes observed in these parameters in patients who underwent surgery alone or following biliary drainage but did not receive Tinospora cordifolia.


MATERIALS AND METHODS

A prospective study was carried out with the approval of the Hospital Ethics committee, in 57 consecutive patients with suspected malignant extrahepatic biliary tract obstruction.The diagnosis was confirmed by ultrasonography, percutaneous transhepatic cholan- giography and/or ERCP.The

nal proof ofmalignant
isease was obtained by peroperative biopsy (or autopsy in patients who died preoperatively).The patients with disseminated malignancy, hepatocellular carcinoma, patients presenting with complications, those with other associated diseases, pregnant women and those taking other traditional drugs/remedies were excluded from the study.Malignant lesions included carcinoma of head of pancreas (n 27), ampullary carcinoma (n 16), carcin ma gall bladder (n 10), cholangiocarcinoma (n 2) and metastases at porta hepatis (n 2).

There were 37 men and 20 women who were included in the study.The age range was 17 to 73 yrs; median age being 48.5 yrs.The median weight for the group was 42.5 kg.The median duration ofillness was 45 days.Written, informed consent was obtained from each patient before randomly allocating them into 4 groups.

Group A: Patients directly underwent surgery with- out preoperative PTBD (n 14).Group B: Patients underwent PTBD preoperatively for 3 weeks, followed by surgery (n 13).Group C: Patients underwent PTBD and received treatment with Tinospora cordifolia pre- operatively for 3 weeks, followed by surgery (n 16).Group D: Patients received treatment with Tinos- pora cordifolia only, pre-operatively for 3 weeks, followed by surgery (n 14).Tinospora cordifolia was used in the form of pills prepared from dried aqueous extract of the stem of the plant; (1 pill 65 mg).The dose selected was 16 mg/ kg/day in 3 divided dose and was extrapolated from previous animal experiments26.

All patients received Vitamin K and perioperative antibiotics.Biliary enteric bypass surgery was done in all cases.

At the time of admission a profile of liver function te

s, renal
chemistry and haemogram was obtained.Metabolic function of the liver was assessed by determining the half-life ofelimination of antipyrine34. 10ml of enous blood was collected in a sterile heparinized tube for determination of phagocytic and killing capacities of neutrophils3.These values assessed on admitting the patients were considered as basal values.In the groups undergoing PTBD (Group B and C), in addition to above tests, bile was collected for culture and antibiotic sensitivity at the time of insertion of drain, weekly during the period of drain- age and intra-operatively.Weekly assessment was carried out by determining-plasma bilirubin (total and direct), antipyrine half-life (t 1/2) 34,37 and phago- cytic and killing activity ofneutrophils3.Pre and post- operative mortality and morbidity were noted.


RESULTS

All the four groups were matched with respect to clinical features, demographic data and parameters assessed at the time of admission (basal values).

Group A: The basal plasma bilirubin levels were 2.9 + 6.4 mg% total bilirubin and 7.2 + 10.1 mg direct bilirubin.The basal antipyrine half-life was 21.23 + 5.6 hours, which was found to be significantly pro- longed as compared to normal values (APt 1/2 14-16 hrs).The perioperative mortality in this group was 57.14% (8/1.4).Of these 5 patients died of liver cell failure, 2 of septicaemia and of biliary peritonitis which developed secondary to anastomotic leak.Group B: In patients who underwent preoperative PTBD there was a significant decrease in the bilirubin levels at the end of 3 we ks of drainage.The total and direct plasma bilirubin levels decreased to 5.85 + 3 mg% and 3.6 + 2.1 mg% respectively from initial values of 12.52 + 8.3 mg% and 7 + 4.2 mg% (P < 0.05).However the antipyrine half-life did not show any significant change inspite of 3 weeks of drainage (Predrainage value

21.96 + 3.7
hrs and 3 weeks post- drainage value: 18.35 + 4.2 hrs).The basal phagocytic and killing capacities of neutrophils in these patients were found to be depressed as compared to normal values (22.13 + 3.68% phago and 19.1 + 4.49% ICK; P < 0.05).A further suppression of these functions was observed during the drainage period; 20 + 8.48% phago and 11.15 + 3.05% ICK (P < 0.05).

Complications seen during the drainage period were substantial.These were, catheter blockage in 2 patients, cholangitis in 2 patients, bile leak in peri- toneal cavity due to kinking of catheter between abdominal wall and liver in patient, mild renal failure which was reversible in patient, pneumonia in 2 patients and pleural effusion in patient.The peri- operative mortality was 61.54% (8/13). 3patients died of liver cell failure, 4 patients of septicaemia and patient of acute renal failure.

Group C: As was seen in Group B, patients from this group who also underwent preoperative PTBD showed a significant decrease in bilirubin levels.At the end of 3 weeks of drainage total bilirubin decreased from 9.4 + 2.68 mg% to 4.43 + 2.1 mg% and direct bilirubin from 6.96 + 2.19 mg% to 3.5 + 2.4 mg%.However,.antipyrine half-life did not show a signi- ficant change (basal value 19.49 + 3.14 hrs and 3 weeks post drainage value: 17.13 + 0.18 hrs).The basal values of % phagocytosis and % intracellular killing capacity ofneutrophils were significantly lower than normal values (19.4 + 7.07% phago and 18.61 + 8.79% ICK).However at the end of 3 weeks, a significant rise in both the functions was observed (30.29 + 4.68% phago and 30 + 4.84% ICK).These values were comparable to normal values of these functions.

Three patients developed wound infection, had GI haemorrhage and patient developed pneumonia.The perioperative mortality was 25% (4/16).One patient died of bile peritonitis following catheter breakage.Repositioning was with great difficulty.Post-mortem revealed multiple intra-abdominal abscesses.Two patients died of septicaemia ofwhich had severe GI haemorrhage and bleeding from the drain.One patient died of liver cell failure.

Group D: The patients who received only Tinospora cordifolia therapy during preoperative period, showed a decrease in bilirubin levels at the end of 3 weeks of treatment (Total bilirubin: from 10.06 _+ 3.4 mg% to 8.48 _+ 2.82 mg% and direct bilirubin: from 7.4 _+ 2.87 mg% to 5.9 _+ 2.02 mg%) but the difference was not significant.Antipyrine levels did not show any significant change (Basal: 23.23 _+ 3.9 hrs and post Tinospora cordifolia therapy: 19.38 _+ 4.46 hrs).

The basal % phagocytosis and % intracellular killing capacity were significantly depressed (22.72 _+ 6.25% Phago and 18.36 _+ 4.25% ICK) as compared to normal values.At the end of 3 weeks oftreatment with Tinospora cordifolia both functions showed a dra- matic rise to near normal levels (30.4 _+ 299% Phago and 27.51 _+ 6.19% ICK).

One patient developed wound infection and patient had pneumonia which were treated effectively.

The perioperative mortality was 14.2% (2/14).One patient died of septicaemia and the other of liver cell failure.


DISCUSSION

Biliary decompression and curative/palliative surgery are performed in obstructive jaundice.However these procedures are associated with considerable morbidity and mortality.The main complications are sepsis, renal failure, haemorrhage and impaired wound healing 35,36.These have been associated with deranged 36 hepatic function, portal and systemic endotoxaemia

The deranged hepatic function was considered the underlying mechanism responsible for various com- plications in jaundiced patients.Preoperative biliary drainage therefore provided a logical solution to prevent postoperative complications.Biliary decom- pression was thought to allow the hepatocytes to regain their functional capacity.This approach was followed enthusiastically and the initial reports showed a reduction in postoperative mortality from 28% to 80//06.Recent prospective studies 13,14,15 however do not confirm the benefits of preoperative biliary drainage.The hazards of this technique outweigh the possible advantages.Thus there appear to be two schools of thought 1. to carry out surgery taking the risk of postoperative complications 2. to operate after PTBD.In the present study in group A where patients underwent surgery without preoperative drainage the mortality was 57.14%.The high levels of Bilirubin and prolonged half-life of antipyrine indicated deranged hepatic function.Deaths due to septicemia indicate poor host defences.Indeed all patients showed suppression of polymorphonuclear function in terms of phagocytic and intracellular killing capacities of neutrophils (Fig. 1).

In group B where patients underwent preopera ive drainage there was a significant fall in bilirubin levels over a period of 3 weeks ofdrainage.Often the plasma bilirubin level is taken as a guideline for improvement in hepatic function and the patient is taken up for surgery when bilirubin levels decrease.However as seen in our study, the reduction in bilirubin level is not accompanied by improvement in half-life of anti- pyrine.Even though t