Surgery, Gastroenterology and Oncology

Hemorrhagic cholecystitis is a rare disease whose etiology is not fully understood. Risk

factors include biliary neoplasms, systemic diseases, uremia, coagulopathies. We present 2 cases of hemorrhagic cholecystitis, found intraoperatively on the background of gallbladder cancer.

Introduction

Hemorrhagic cholecystitis is relatively difficult to diagnose due to its rare occurrence and symptoms similar to those of other gallbladder diseases. Bleeding from the bile ducts first described by B. Nauyn in I892 and confirmed by HJ. Schmidt the following year is usually a complication of another disease of the biliary system, the pathogenesis of which is not fully understood.

We present 2 cases of hemorrhagic cholecystitis, found intraoperatively on the background of gallbladder cancer.

Case Reports

Case 1

A 68-year-old patient was admitted to the clinic as an emergency with a history of pain in the right hypochondrium, general fatigue, nausea, vomiting, dark urine, stool lightening.  Previously done ERCP - without affecting the symptoms. Concomitant diseases - non-insulin-dependent diabetes mellitus, stage III hypertension, chronic stage myocardial infarction, condition after LAD stenting, taking anticoagulant therapy (Sintrom). From the physical examination - jaundice on the skin and sclera, pain in the right hypochondrium during palpation, with palpable in the same area formation with a dense consistency. From the laboratory tests - total bilirubin - 94.0 mcmol / l; direct bilirubin - 66.0 mcmol / l; ALAT – 129.0 U/l; ASAT – 118.0 U/l, GGT – 445 U/l; AP – 253 U/l; without abnormalities in blood count and coagulation status.

Performed imaging studies - ultrasonography and CT of the abdomen. Ultrasound data for significantly enlarged gallbladder 150/85 mm with available stones up to 10 mm in size, a significant amount of sludge, wall hyperechogenic zone with lobulated contours. Choledochus - 7 mm. The other intraabdominal organs – normal finding. CT - dilated IHBD up to 4 mm in the right lobe and up to 3 mm in the left, with aerobilia on the left. Gallbladder size -  122/93 mm, thickened wall in the infundibulum up to 22 mm, filled with echogenic contents (fig. 1). Choledoch - undilated, a stent is placed distally. No other pathological findings.

Figure 1 - CT data for enlarged gallbladder filled with echogenic contents, thickened wall

Intraoperatively - significantly enlarged gallbladder, with dimensions about 12/10 cm, with thickened walls. Cholecystotomy performed - a large amount of coagulum and clear blood mixed with purulent exudate were evacuated. Due to macroscopic data for carcinoma, confirmed by express histological examination performed cholecystectomy with resection of the 5th liver segment, revision of hepaticocholedochus through the ductus cysticus - found stent that is passable.

Histological finding - moderately differentiated adenocarcinoma of the gallbladder, hemorrhagic cholecystitis pT1bNxMx,G2, no data on infiltration of the liver parenchyma (fig. 2).

Figure 2 - Infiltration of atypical adenostructures, in places merging with each other, fibrous stroma, areas of hemorrhage

The patient was discharged on the seventh post-operative day, after a normal postoperative period, presented to the Oncology Committee for continued treatment. Followed for a period of 3 years - two hospitalizations for liver abscess - after 4 months and again 1 year after surgery. In the fourth month, a liquid collection with a diameter of about 2 cm with gas inclusions in the area of liver resection was established - puncture and aspiration were performed. Histologically benign material, microbiology - cultures are sterile. Discharged without complaints, in good general condition.

About a year after the surgery she was hospitalized in the clinic with pain in the right hypochondrium, jaundice of the skin and sclera. No significant finding on physical examination, slightly elevated bilirubin and liver enzymes. Ultrasound and CT data for slightly dilated IHBD, a stent in the choledochus that has partially passed into the duodenum, dilated to 17 mm choledochus, whose lumen is filled with echogenic mass (fig. 3). Endoscopically performed stent extraction followed by antibiotic treatment to control cholangitis.

Figure 3 - CT data for cholangitis and stent in the bile ducts

Surgical intervention performed - established small abscess under the liver, slightly thickened walls of the choledochus, which has a diameter of about 10 - 11 mm. Revision of EHBD performed, new endoprosthesis placed. Histological evidence of chronic nonspecific granulomatous inflammatory process of the liver and reactive lymphadenopathy. Normal postoperative period. Currently no evidence of recurrence of the oncologic disease, more than 3 years after the first operation.

Case 2

A 76-year-old patient with complaints of general weakness, fatigue, pain in the right abdomen, concomitant diseases - hypertension II degree, absolute arrhythmia, takes anticoagulants (Eliquis). During the physical examination - palpable formation in the right abdominal half with dimensions of about 10 cm. From the laboratory data - anemic syndrome - hemoglobin 91 g/l, hematocrit - 0.29 l/l; normal values of bilirubin, elevated values of liver enzymes - ASAT - 72.0 U / I; ALAT - 49.0 U/l; GGTP - 265 U / l; AP - 199 U / l; without significant deviations in coagulation status - prothrombin time - 18.9 sec. INR - 1.29; APTT - 29.7 sec. Performed ultrasonography - the presence of multiple lesions in the liver  - metastases, gallbladder – significantly enlarged with a wall of about 3 mm, into the lumen many polypoid masses ranging in size from 1 to 2.6 cm, 2 large stones - about 2 cm. Common bile duct – non dilated. The other abdominal organs – normal finding. Intraoperatively - significantly enlarged gallbladder - over 20 cm with a bacony structure and thickened walls, numerous liver metastases. During cholecystectomy, 500 ml of hemorrhagic contents of the bladder and 3 stones were evacuated.

Histological result - moderately differentiated adenocarcinoma of the gallbladder with liver metastases, hemorrhagic cholecystitis.

The patient was discharged on the seventh post-operative day in good general condition. Presented to the Oncology Committee for continuing treatment. Followed in another medical institution.

DISCUSSION

Hemorrhagic cholecystitis is a rare disease. After the pioneers Nauyn and Schmidt, in 1948 Sandblom first reported bleeding from the hepatobiliary system in the gastrointestinal tract as hemobilia. In 1979, Shah and Clegg described hemobilia caused by cholecystitis as hemorrhagic cholecystitis (3,11). The etiology of hemorrhagic cholecystitis is not fully understood. Various causes have been described in the literature - gallbladder cancer (as in our cases), lithiasis, renal failure, hemophilia, vasculitis (mainly lupus erythematosus), (6,8). Bleeding into the lumen of the gallbladder may occur after trauma (16), including liver biopsy, aneurysms opening in the bile ducts, and bile parasites. Bleeding resulting from ischemia, such as gangrenous cholecystitis, is less common. According to a report by 222 patients from Green et al. in 2001, gallbladder bleeding was caused by iatrogenic factors, inflammation, tumor, injury, and other factors in approximately 65, 13, 7, 6, and 9% of patients, respectively (2). Gallstone disease has been identified as the cause in about 9% of cases of hemobilia.

Often in patients with this disease anticoagulants or corticosteroids are accepted for concomitant diseases (table 1), (1,14,15). Different classifications have been made in attempts to establish the cause (12). Pathogenetically, impaired blood supply, causing ischemic damage to the gallbladder and bile stasis, is ultimately thought to lead to calcium salt concentrations, erosive changes, and areas of infarction and microabscess formation. Destruction of the mucosa can cause bleeding in the lumen of the gallbladder and mixing of the blood with inflammatory exudate and detrital substances. Gallstones in the gallbladder can directly damage the mucosa, leading to damage to the vessel walls. It is also thought that increased pressure in the gallbladder due to acute cholecystitis can damage the mucosa of the gallbladder, leading to damaged vessel walls and ultimately leading to bleeding (13).

Table 1 - Published cases of patients with hemorrhagic cholecystitis on the background of anticoagulant administration

No typical clinical symptoms have been observed, usually as in acute cholecystitis or a tumor of the biliary system (10). Hemorrhagic cholecystitis is easily overlooked because its symptoms mimic those of ordinary hepatobiliary diseases with abdominal pain in the right upper quadrant, impaired liver function, leukocytosis, and a positive Murphy's symptom. Hemobilia is a rare cause of upper gastrointestinal bleeding, but should be considered in patients who have right upper quadrant pain, jaundice, and acute gastrointestinal bleeding (Quincke's triad).

Diagnosing hemorrhagic cholecystitis is relatively difficult, even with modern imaging methods. Ultrasonographically, hyperechogenic contents are observed in the gallbladder, appearing as sludge, as in own cases, and in computed tomography there is thickening of the bladder wall and heterogeneous content mixed with bile, extravasation can be detected during the contrast enhancing (5,9).

 According to the literature, the majority of cases of hemorrhagic cholecystitis (74%) show sonographic features often observed in acute cholecystitis (7).

The aim of treatment for hemobilia is to improve hemostasis and bile flow. For mild hemobilia, conservative treatment can be provided by correcting the coagulation disorder and performing blood transfusions. In most cases, endoscopic treatment or surgery is required. ERCP plays an important role in the treatment of hemobilia. Initially, the flow of bile secretion is improved by removing the hematoma in the bile ducts, which leads to improved abdominal pain and jaundice (4). In case of haemobilia due to haemorrhagic cholecystitis, cholecystectomy should also be performed, as a clot formed in the gallbladder can cause obstructive jaundice. Depending on the site of clot formation, the resulting obstruction can also lead to acute cholangitis, acute cholecystitis, or even acute pancreatitis.

CONCLUSION

Hemorrhagic cholecystitis is a rare diagnosis characterized by the absence of typical symptoms distinguishing it from other diseases of the gallbladder, requiring careful diagnostic and therapeutic approach in each patient, taking into account the general condition and concomitant diseases. Risk factors include biliary neoplasms, systemic diseases, uremia, coagulopathies.

Conflict of interest

All author declare that they have no conflict ofinterest.

REFERENCES

1. Tarazi M, Tomalieh FT, Sweeney A, Summer D, Abdulaal Y. Literature review and case series of haemorrhagic cholecystitis. J Surg Case Rep. 2019;2019(1):rjy360.
2. Shishida M, Ikeda M, Karakuchi N, Ono K, Tsukiyama N,  Shimomura M, et al. Hemorrhagic cholecystitis in a patient on maintenance dialysis. Case Rep Gastroenterol. 2017;11(2):488-493.
3. García PR, Ruiz DD, López PM, Febrero SB, Navas CD, Parrilla PP. Hemorrhagic cholecystitis and hemobilia: two infrequent complications of systemic lupus erythematosus. Rev Esp Enferm Dig. 2011;103(8):431-3. English, Spanish
4. Araújo Teixeira JP, Ribeiro C, Pinto A, Goulart A, Costa Maia J, Pimenta A. Surgical management of acute cholecystitis (experience of 249 cases). Hepatogastroenterology. 2011;58(106):281-4.
5. Shakespear JS, Shaaban AM, Rezvani M. CT findings of acute cholecystitis and its complications. AJR Am J Roentgenol. 2010; 194(6):1523-9.
6. Lai YC, Taring DC. Hemorrhagic acalculous cholecystitis: an unusual location of uremic bleeding. J Chin Med Assoc. 2009; 72(9): 484-7.
7. Chinn DH, Miller EI, Piper N. Hemorrhagic cholecystitis. sonographic appearance and clinical presentation. J Ultrasound Med. 1987;6(6): 313-7.
8. Rosenow EC. The Etiology of Cholecystitis and GallStones and their Production by the Intravenous Injection of Bacteria. The Journal of Infectious Diseases. 1916;199(4):527-556.
9. Jenkins M, Golding RH, Cooperberg P. Sonography and computed tomography of hemorrhagic cholecystitis. AJR Am J Roentgenol. 1983;140(6):1197-8.
10. Gremmels JM, Kruskal JB, Parangi S, Kane RA. Hemorrhagic cholecystitis simulating gallbladder carcinoma. J Ultrasound Med. 2004;23(7):993-5.
11. Brady E, Welch JP. Acute hemorrhagic cholecystitis causing hemobilia and colonic necrosis. Dis Colon Rectum. 1985;28(3):185-7.
12. Kwon JN. Hemorrhagic cholecystitis: report of a case. Korean J Hepatobiliary Pancreat Surg. 2012;16(3):120-2.
13. 13. Parekh JU, Corvera C. Hemorrhagic cholecystitis. Arch Surg. 2010; 145(2):202-4.
14. Lin HP, Lin YC. Isolated intraluminal gallbladder hemorrhage after anticoagulation therapy: Report of a case. J Intern Med Taiwan 2010;21(1):62-65
15. Brawner J, Trivedi H, Sataline LR. Hemocholecyst. Report of a case associated with anticoagulation therapy. Ohio State Med J. 1966; 62(10):1028-30.
16. Wagner DS, Flynn MA. Hemorrhagic acalculous cholecystitis causing acute pancreatitis after trauma. J Trauma. 1985;25(3):253-6.