Alternatives to Cholecystectomy for Cholelithiasis

This presentation serves to review all the available non-operative treatment options for gall stone disease. It was presented in January 2020 to the HepatoPancreaticoBiliary Surgery Unit, Division of General Surgery, ABUTH Zaria, Nigeria

1. ALTERNATIVES TO CHOLECYSTECTOMY FOR CHOLELITHIASIS DR Kabir, Abdulkareem

2. OUTLINE INTRODUCTION HISTORICAL ACCOUNT EPIDEMIOLOGY PATHOPHYSIOLOGY ETIOLOGY CLINICAL EVALUATION TREATMENT OPTIONS CONCLUSION REFERENCES

3. INTRODUCTION Cholelithiasis is one of the most prevalent GI diseases with a substantial burden to health care systems. It is characterized by the formation of gallstones in the hepatic bile duct, CBD, or gallbladder Until in the 1980s, the only therapeutic option for patients with symptomatic gallstones was surgery However, several new and innovative nonsurgical approaches are currently available.

4. HISTORICAL EVOLUTION Gallstones have plagued man since the dawn of time One of the earliest English essays on biliary stones was by Thomas Coe (1757). 1 John S. Bobbs , was the first to offer definitive treatment for gallstones. 1 He performed an emergency cholecystolithotomy on Mary E. Wiggins, a 30-year-old female J. Marion Sims, a gynecologist is credited with performing the first elective cholecystolithotomy in 1878. 2 Karl Langenbuch , a German, performed the first cholecystectomy in 1882. 3

5. HISTORICAL EVOLUTION cont.. William J. Mayo in 1911, promoted cholecystectomy for both symptomatic and asymptomatic gallstones. Cholecystectomy thus became the gold standard “Post-cholecystectomy syndrome” & fear of increased risks of colon cancer search for alternatives Five new treatment alternatives for gallstones have been introduced over the last half of the 20 th century

6. EPIDEMIOLOGY The prevalence of cholelithiasis is affected by many factors; race, gender comorbidities and genetics. In the US, 10-20% of adults have gallstones. 5 About 500000 people develop complications requiring cholecystectomy Responsible for about 10000 deaths World wide. 5 the prevalence western countries is similar to that in the US lower in Asia and Africa

7. In Nigeria, the prevalence has been reported as 2-2.7 % of adults 6-7 In Zaria, gall bladder comprised 0.31% of all general surgical admissions in between 1980-1999. 8

8. ANATOMY

9. PATHOGENESIS Gallstones can be classified as either cholesterol, pigment gallstones or mixed gallstones It occurs because certain substances in bile are present in concentrations that approach the limits of their solubility. When bile is concentrated in the gallbladder, it can become supersaturated with these substances, which then precipitate as crystals The two main substances involved in gallstone formation are cholesterol and calcium bilirubinate

10. Illustration copied from; https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/pancreas_biliary_tract/gallstone_disease.pdf

11. Cholesterol Gallstones : The pathogenesis of cholesterol gallstones stems from a genetic or acquired defect in the hepatic metabolism of lipids Normally cholesterol is fully solubilized by bile acids and lecithin. A delicate balance exists in the proportion of cholesterol, Bile acids and lecithin Cholesterol gallstones are formed when bile is super saturated with cholesterol.

12. CHOLESTEROL STONE FORMATION

13. Triangular coordinate relationship of bile constituents Illustration copied from; https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/pancreas_biliary_tract/gallstone_disease.pdf

14. PIGMENT STONES Black pigment stones; Form in conditions of high haem turnover  unconjugated bilirubin conc.  formation of Calcium bilirubinate Brown pigment stones; Bacteria hydrolyze lecithin to release fatty acids, which bind calcium and precipitate from the solution. The resulting concretions have a claylike consistency and are termed brown pigment stones. Unlike cholesterol or black pigment gallstones, brown pigment gallstones often form de novo in the bile ducts

15. ETIOLOGY Cholesterol gallstones: Cholesterol gallstones are associated with female sex, European or Native American ancestry, and increasing age. Other risk factors include the following: Obesity Pregnancy Gallbladder stasis Drugs Heredity

16. Black pigment gallstones Occur in individuals with high heme turnover as seen in; Haemolytic disorders like SCA, B Thallasemia , Spherocytosis . Cirrhosis. Brown pigment gallstones Intraductal stasis from strictures or infestations chronic colonization of bile with bacteria.

17. CLINICAL EVALUATION It is essential to understand the natural history of gallstone disease to advise patients on the appropriate management options. At one extreme, gallstones can remain silent for years or even a lifetime. At the other extreme, they can cause life-threatening complications and even death.

18. Gallstones may be present in the gallbladder without causing symptoms or complications Symptoms of symptomatic cholelithiasis include Indigestion Dyspepsia, Belching, Bloating, and fat intolerance

19. Physical examination; Patients with the lithogenic state or asymptomatic gallstones have no abnormal findings on physical examination In uncomplicated biliary colic, The pain is poorly localized and visceral in origin; The patient has an essentially benign abdominal examination without rebound or guarding. Fever is absent

20. Acute cholecystitis leads to a well-localized pain in the right upper quadrant, usually with rebound and guarding. A positive Murphy sign Fever is often present, but it may lag behind other signs or symptoms.

21. INVESTIGATIONS Abdominal Xray  Black pigment or mixed gallstones may contain sufficient calcium to appear radiopaque on plain films Abdominal USS  Ultrasonography is the procedure of choice in suspected gallbladder or biliary disease Other investigations include; CT scan, MRCP, HIDA scintigraphy

22. TREATMENT OPTIONS Surgery has long remained the exclusive form of therapy for GD. Understanding of the pathogenesis of gallstone formation has heralded newer, less invasive alternatives. CHOLECYSTECTOMY Open Laparoscopic Alternatives to Cholecystectomy; DISSOLUTION THERAPY (DT) EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY (ESWL) ESWL + DT PERCUTAENEOUS CHOLECYSTOLITHOTOMY ENDOSCOPIC Techniques

23. DISSOLUTION THERAPY Also known as litholytic therapy Involves administration substances known to dissolve cholesterol bile stones Includes; Oral Dissolution Therapy Percutaneous Contact litholytic therapy

24. ORAL DISSOLUTION THERAPY Involves the oral administration of bile acid preparations Chenodeoxycholic acid (CDCA) Ursodeoxycholic Acid (UDCA) They act principally by: Expanding the bile acid pool Inhibiting hepatic HMG- CoAR activity and thus decreasing the secretion of biliary cholesterol, Reducing the duration of secretion of saturated bile. Drug therapy is performed long-term (from 6 mo to 2 years or more), necessarily with ultrasound guidance every 3 months. 10

25. Chenodeoxycholic acid (CDCA) Its cholelitholitic effect was first demonstrated by researchers at Mayo clinic in 1960s. 9 Administered in doses 250mg 12 hourly initially for 2/52 then increased to 13-16mg/kg/day subsequently Its use is limited by side effects; liver test abnormalities, diarrhea, and increases in serum LDL cholesterol levels.

26. Ursodeoxycholic Acid (UDCA) Developed and first used in Japan in 1970s Safe and equally efficacious No significant adverse side effects or signs of toxicity have ever been reported as a result of UDC treatment in many of the many studies that have been published. 9 Administered in 8-10mg/kg/day divided 12hrl, not to exceed 300mg/dose

27. Patient Selection for ODT For successful litholytic therapy, definite criteria should be met for selection of patients with cholelithiasis. 10 : the stone should be cholesterol or mixed; the size of the stones should not be greater than 1.5 cm; the gallbladder should have its functions preserved be packed with stone not more than ¼ of the fasting volume; the cystic duct and common bile duct should have their patency preserved; enterohepatic circulation of bile acids should be preserved

28. Draw backs of ODT: It has a significant recurrence rate Its use is ineffective in pigment stones

29. PERCUTANEOUS CONTACT LITHOLYTIC THERAPY A substance that dissolves cholesterol stones is injected just into the gallbladder or bile ducts They are infused transhepatically through a catheter into the gallbladder lumen or common bile duct, Only cholesterol stones are prone to dissolution Methyltretbutyl ether (MTBE) monooctanoin Dissolution occurs within 4-16 h. 10

30. This procedure is useful in symptomatic or complicated gallstone disease, especially if the patient refuses surgery or is a high risk patient. Drawbacks: MTBE is a toxic, inflammable anesthetic with considerable side effects

31. EXTRACORPOREAL SHOCK-WAVE LITHOTRIPSY . Is the most innovative new approach in the management of gallstone disease. This method employs high-energy sound waves that produce shock waves. Within minutes, stones are pulverized into small fragments  pass spontaneously out of the gallbladder or can be further dissolved with oral dissolution agents. The efficacy of ESWL is very dependent on proper patient selection.

32. Advantages; No general anesthesia is required Patient may be managed on an outpatient basis Can be used in patients who are poor surgical candidates

33. Drawbacks; The set up is very expensive May require long term ODT High recurrence rates in the late period following lithotripsy It has side effects including abdominal wall and skin changes (ecchymosis, petechiae), pain, hematuria, nausea, emesis, and biliary colic

34. Patient Selection for ESWL 10 Single radiolucent cholesterol stones not more than 3 cm in diameter; Multiple radiolucent stones 1-1.5 cm in diameter; The volume of stones is less than 1/2 of that of the gallbladder; A functioning gallbladder; Normal bile duct patency

35. PERCUTAENEOUS CHOLECYSTOLITHOTOMY Involves puncturing the gallbladder, dilating the tract, and removing any gallstones with a cholecystoscope under C-arm fluoroscope guidance Small stones (less than 7 mm) may be removed with grasping forceps. Larger stones are fragmented with electrohydraulic lithotriptor , ultrasonic lithotriptor , or laser probes. Used in high-risk patients with acute calculous diseases, where surgical intervention may be associated with increased morbidity and mortality

36. The advantages of this procedure are Immediate removal of uncrushed gallstones, Production of little gallstone debris Reduction of danger associated with sludge entering the cystic duct

37. ENDOSCOPIC SPHINCTEROTOMY+ STONE EXTRACTION Was first reported in 1974 It employs the use of ERCP apparatus It enables extraction of biliary stones by enlarging the papillary opening Stones lodged in the CBD can then be removed by a basket It is commonly used for removal of CBD stones in high risk surgical patients.

38. ENDOSCOPIC USS GUIDED GALLBLADDER STENTING Endoscopic gallbladder stenting is useful in high-risk patients. It uses ERCP to insert a stent from the gallbladder to the duodenum to relieve biliary symptoms and complications in high-risk patients. A hydrophilic wire is passed from the ampulla of Vater into the common bile duct and into the gallbladder through the cystic duct.  A trans-gastric or trans-duodenal gallbladder puncture is performed under the EUS guidance lumen apposing metal stents (LAMS) is then introduced through the puncture site

39. Advantages It is less invasive than cholecystectomy Patients may be discharged quickly. Unlike other procedures that leave the gallbladder intact, further stone formation does not hinder the effectiveness of endoscopic stenting.

40. CONCLUSION Given the risks associated with cholecystectomy- both open and laparoscopic, advances in the understanding of cholepoisis as well as ultrasonic technology has led to the development of safer and non invasive alternatives. The surgeon thus have an array of options to consider to tailor his/her patient’s needs.

41. REFFERENCES Cutter IS. Landmarks in surgical progress: John Stough Bobbs and lithotomy of the gallbladder. Int Abstr Surg. 192847:409-411 Sims JM. Remarks on cholecystotomy in dropsy of the gallbladder. Br Med J. 1878. 1: 811 - 815 Langenbuch K. EinFall vonExstirpation der Gallenblasewegen chronischerCholelithiasis . Heilung.BerlKlinWochenschr . (1882) 19:725 Mayo WJ. "Innocent" gallstones: a myth. JAMA. (1911) 56: i021-1024 Halldestm I, Kullman E, Borch K, Incidence of and Poetential for Gallstone Disease in a general population sample. Br J Surg. 2009 Nov. 96(11): 1315-22 Charles UE, Emanuel EE, Christpher CO. Prevalence of Cholelithiasis Among Igbo Adult Subjects in Nnewi, Nigeria: A community- Based Sonographic Study. Journal of Diagnostic Medical Sonography. 2017. Akuto OO, Marinho AO, et al, Prevalence of Galllstones in a group of antenatal women in Ibadan Nigeria. Afr J Med Med Sci. 1999; 28(3-4).

42. REFERENCES 8. MM Dauda, Yusufu LMD, Attah MM. Cholecysitis and Cholelithiasis in Adults in Zaria. Tropical Doctor 2005;35 243-245 9. Albert MB, Hans F. Nonsurgical alternatives in the management of gallstones. J Intensive Care Med. 1989;4:3-10. 10. Reshetnyak VI. Concept of the pathogenesis and treatment of VI. Concept of the pathogenesis and treatment of of the pathogenesis and treatment of cholelithiasis. World J Hepatol 2012(2): 18-3; Available from: URL: http://www.wjgnet.com/1948-5182/full/v/i2/18.htm DOI: http://dx.doi.org/10.25/wjh.v.i2.18 11. Donald PG, Pedro AR, Malachy JG. Percutaneous endoscopic treatment of cholelithiasis. Surg Endosc (1990)4" 141- 149 12. https://www.hopkinsmedicine.org/gastroenterology_hepatology/_pdfs/pancreas_biliary_tract/gallstone_disease.pdf 13. Douglas MH. Gallstones (cholelithiasis). Medscape Article; updated Apr 2019