Acute non-lithotriptic cholecystitis is an acute inflammatory lesion of the gallbladder in which no gallbladder stones are found on imaging, surgical or pathological examination. ～The incidence of AAC accounts for 2-15% of acute cholecystitis and occurs in critically ill patients, especially after severe trauma, burns, sepsis, major surgery, and in the Intensive Care Unit (ICU). Because most patients with AAC have chronic diseases, their clinical manifestations are easily masked by other co-morbidities, and clinicians do not fully understand and pay attention to AAC, which often leads to death due to delayed diagnosis and treatment. Studies have reported that the mortality rate of AAC is as high as 30%. In this paper, the causes, pathogenesis, diagnosis and treatment of AAC are briefly described as follows, in order to further improve the understanding and treatment of AAC among clinicians.
Causes
The etiology is multifactorial and the main causes are.
① Secondary bacterial infections: certain specific pathogens, such as brucellosis, cytomegalovirus and immunocompromised or immunodeficient individuals susceptible to bacterial infections are prone to induce AAC.
② Factors such as long-term fasting, parenteral nutrition, post-surgical hyperthermia, dehydration and application of sedatives: can cause impaired gallbladder emptying, bile stasis and concentration, while high concentrations of bile salts have a strong irritating effect on the gallbladder mucosa.
③ Factors such as hypotension, shock and anemia: the application of norepinephrine or dopamine in shock, etc., increases the sympathetic excitability of the patient and causes vasoconstriction, which can cause insufficient blood perfusion and aggravate the local ischemia of the gallbladder. In addition, some systemic diseases such as polyarteritis and systemic lupus erythematosus can also cause acute cholecystitis due to ischemic injury.
④ Trauma, blood transfusion, sepsis and malignancy can activate Ⅻ coagulation factors and induce the release of local prostaglandins in the gallbladder wall. The gallbladder is the target organ of Ⅻ coagulation factor activation, which can cause severe damage to the blood vessels of the myocardium and plasma membrane layer of the gallbladder, thus facilitating pathogenic bacterial infection of the gallbladder and promoting rapid development of inflammation resulting in gangrene and perforation of the gallbladder wall.
Therefore, any factor that may lead to hypotonia of the vagus nerve may lead to AAC or become an important additional factor in the development of cholecystitis. In addition, comorbid chronic diseases, such as diabetes, hypertension, atherosclerotic heart disease, and obesity, have a higher than normal chance of developing AAC. owen et al [1] ranked the risk for the development of AAC.
Most of our clinically identified patients with AAC have a combination of 2 or more risk factors, such as patients with prolonged ICU monitoring, combined with other organ infections; elderly patients with prolonged water fasting, combined with hypertension and/or diabetes, and impaired consciousness; and patients with multiple chemotherapy and immune deficiency after tumor surgery.
Pathogenesis
The pathogenesis has not been fully elucidated and may be related to cholestasis, systemic or local blood perfusion deficiency and systemic sepsis. Bile stasis and concentration can directly damage the mucosal epithelial cells of the gallbladder, while insufficient blood perfusion of the gallbladder can damage the entire wall of the gallbladder. McChesney et al [5] hypothesized that the pathogenesis of AAC is: gallbladder ischemia and hypoperfusion → aseptic cholecystitis → biliary stasis and bacterial invasion → AAC. this hypothesis can reasonably explain the common complications of AAC, such as gangrene (local microvascular obstruction), pus accumulation (secondary infection) and perforation (thinning of the gallbladder wall). hakala et al proposed to rename AAC as acute ischemic Laurila et al. systematically compared the pathological changes in 34 cases of AAC and 28 cases of acute calculous cholecystitis and found that the typical pathological changes in AAC were extensive and deep myxomatous biliary infiltration, intravascular leukocyte exudation and lymphatic dilation, which in turn led to gangrene and absence of epithelial tissue, extensive inflammatory cell infiltration and necrosis of the muscular layer. These pathologic alterations counter the plausibility of the above pathogenesis.
Clinical presentation
The clinical presentation is quite similar to that of acute calculous cholecystitis. About 80% of patients have persistent right upper abdominal pain and fever, as well as some nonspecific gastrointestinal symptoms such as nausea and vomiting. Some patients may also develop jaundice. Gallbladder gangrene occurs in about 75% of cases, followed by gallbladder perforation and diffuse peritonitis in about 15% of cases, where Murphy’s sign and signs of peritonitis are evident.
The following conditions are often present in combination.
(i) abdominal pain symptoms following surgery or trauma that mask the symptoms of AAC.
(ii) The elderly are unresponsive and have poor blood supply to the gallbladder, making them prone to gallbladder necrosis and perforation, but the patient’s temperature and blood picture can still be normal.
(iii) In cases of severe illness or traumatic coma, the patient requires sedation, tracheal intubation or is unconscious and unable to provide a correct chief complaint. These complex conditions often obscure their clinical manifestations and tend to delay diagnosis and treatment.
Diagnosis
The clinical presentation of epigastric pain, chills, fever and restrictive muscle tension should be considered for AAC if there are varying degrees of elevation in routine blood and liver function tests. However, these clinical manifestations and laboratory tests are not specific, and with the interference of other related diseases, it is difficult to make a clear diagnosis. Imaging examinations have high sensitivity and specificity and thus play a crucial role in the diagnosis of AAC.
Ultrasound
Ultrasound is the preferred method for the diagnosis of AAC because it is non-invasive, rapid, convenient, and can be performed dynamically and continuously. With the development of AAC, ultrasound sonograms also show corresponding manifestations depending on the pathological changes. In the early stage of lesion, it shows enlarged gallbladder and thickened wall, and the transverse diameter of gallbladder >5 cm or wall thickness ≥3.5 mm has important diagnostic significance. When the subplasma edema of the gallbladder is obvious, the so-called “bilateral sign” can be seen. In the middle stage of the lesion, in addition to the enlargement and wall thickening of the gallbladder, dense foggy dot echoes or thick strong echogenic spots may appear in the gallbladder lumen, which are often signs of concentrated bile or septic turbidity. In advanced stages of the disease, abnormal stagnation and enlargement of the gallbladder, thinning of the cystic wall, and pericystitis may be seen. The literature reports that the sensitivity and specificity of ultrasound examination ranges from 30 to 100%. Such a large variation is mainly due to the subjective nature of ultrasound examination and the different diagnostic criteria of each unit. In addition, colonic inflation, ascites, and the presence of wounds in the abdominal wall can affect the accuracy of the test results.
Examination
The sensitivity of the examination is not better than that of ultrasound, and the diagnostic criteria of both are similar. However, compared with ultrasound, CT still has many irreplaceable advantages, such as.
① strong objectivity, clinicians and radiologists can read the film together.
② easier detection of other organs in the abdomen, and not affected by abdominal gas, thus more conducive to differential diagnosis.
③Diagnosis of complications of AAC, such as perforation or abscess formation. the disadvantage of CT examination is that it cannot be applied at the bedside. CT examination is a supplement to ultrasound examination and is feasible in patients with negative ultrasound examination or in whom it is difficult to exclude other diseases of the abdomen.
Biliary scintigraphy
Biliary scintigraphy is another important technique for the diagnosis of AAC. The examination method is: after intravenous injection of 99mTc-labeled methylbromide, a frame is taken every 5 min in the anterior-posterior position with a scintillation camera. 30-60 min later, the gallbladder, common bile duct and small intestine should be visualized. In patients with prolonged fasting, pancreatitis, alcoholism, liver disease, severe comorbidities or TPN, the uptake and secretion of tracer is abnormal, affecting the development of the biliary tract, with a false positive rate of up to 40% for 60 min. The false-positive rate can be reduced by injecting morphine to cause contraction of the sphincter of Oddi to elevate biliary pressure to overcome partial or functional obstruction of the bile duct.
The shortcoming of biliary scintigraphy is that it can only provide information on the function of the gallbladder and cannot be differentiated from other disorders of the right upper abdomen. Foreign scholars recommend the combination of ultrasound and morphine biliary scintigraphy for the diagnosis of AAC, which can significantly improve the diagnostic accuracy and reduce the false-positive and false-negative rates. It is possible that the lack of sufficient knowledge of AAC among domestic clinicians has limited the use of biliary scintigraphy.
Treatment
Once the diagnosis is confirmed, treatment should be given as soon as possible. Delayed treatment often increases the risk of gallbladder gangrene and gallbladder perforation. Treatment should be individualized according to the severity of the patient’s condition, age and the presence of complications, including conservative treatment, gallbladder aspiration and drainage, and surgical treatment.
Conservative treatment
If the diagnosis is made in time and the patient is in good general condition with mild disease, he/she can often improve with active control of the primary disease, timely correction of the imbalance of water-electrolyte and acid-base balance, gastrointestinal decompression, fasting, anti-inflammatory, antispasmodic, biliary and systemic supportive treatment. During the treatment of non-surgical therapy, changes in the condition must be closely observed, and if the condition worsens, gallbladder puncture and drainage or surgical treatment should be considered immediately.
Regarding the application of antibiotics in AAC, due to the obstruction of the bile duct, antibiotics cannot enter the gallbladder with the bile and cannot play the expected role in controlling the infection in the gallbladder, and the progress of gallbladder inflammation and complications are not affected by the application of antibiotics. However, the application of antibiotics can achieve a certain pharmacotherapeutic concentration in the blood, which can reduce the systemic infection caused by cholecystitis, as well as can effectively reduce the occurrence of infectious complications after surgery. The application of systemic antibiotics is still very necessary in patients with fever and high white blood cell count, especially in some elderly people, or in patients with high susceptibility to infection such as those with diabetes mellitus and long-term immunosuppression. The principle of antibiotic use is empirical combination of drugs with different antimicrobial spectrum, such as third-generation cephalosporins in combination with quinolones, aminoglycosides or metronidazole. The medication should also be reasonably adjusted according to the patient’s bile culture and/or blood culture and clinical response.
Percutaneous transhepatic gallbladder drainage (PTGBD) should be considered as soon as possible in patients with poor systemic condition, severe comorbidities, and rapid progression of AAC. PTGBD, as a simple, effective, minimally invasive, and economical gallbladder or (and) bile duct drainage procedure with definite drainage effect, it is an effective emergency measure for acute, critical and severe biliary tract disorders. For the treatment of AAC, PTGBD can be used to kill multiple birds with one stone. First, PTGBD can serve both diagnostic and therapeutic purposes. If AAC is diagnosed, the success rate of conservative treatment can be significantly increased and the course of antibiotics can be shortened by effectively draining the fluid in the gallbladder and reducing the pressure in the gallbladder; even if the diagnosis of AAC is excluded after PTGBD, it is still It is beneficial and harmless that the bile in the gallbladder is emptied and the chance of gallbladder infection is reduced. Therefore, it is suggested that all ICU patients presenting with abdominal sepsis should undergo prophylactic PTGBD if the diagnosis of AAC cannot be excluded. Second, it avoids the high risk of emergency laparoscopic cholecystectomy and the huge trauma of emergency open cholecystectomy, and plays an important role as a bridge to elective cholecystectomy after the acute attack is controlled. If the primary disease is satisfactorily controlled, AAC may not recur and cholecystectomy is not necessary.
Data show that the failure rate of ultrasound-guided PTGBD is 0-6%, the drainage tube prolapse rate is 5-18%, and the complications associated with the operation are 4-18%, including colonic injury perforation. It is clear that PTGBD, although a simple operation, should be adequately prepared and performed with caution.
PTGBD should be contraindicated or used with caution when the following conditions exist.
(i) Those with a significant bleeding tendency.
②Patients in poor general condition with peritoneal effusion, especially in the presence of prehepatic effusion.
③ those with significant gallbladder atrophy.
④those who have poor visualization of the whole gallbladder on ultrasonography due to obesity, pneumatization of the intestinal cavity, etc.
⑤ Those with obvious gallbladder gangrene, near perforation or already perforated.
The incidence of drainage tube prolapse is high and should be taken seriously and actively prevented. If no bile is drained from the drainage tube, the first step is to determine whether the drainage tube is obstructed, and saline flushing can be tried. Once the drainage duct prolapse occurs, if it is a non-transhepatic route, it is easy to develop biliary peritonitis and it is best to perform PTGBD again within 6 hours or definitive surgical treatment; if it is a transhepatic route, it is less likely to develop biliary fistula and the time period for definitive treatment can be extended to 24 hours.
Laparoscopic cholecystectomy and laparoscopic subtotal cholecystectomy
If the patient is already septic at the time of diagnosis or has combined gangrene or perforation, timely surgery based on treatment of the primary disease and correction of shock is required. Emergency LC has the advantage of being minimally invasive and should be the first choice. However, when inflammatory adhesions are present and the triangular anatomy of the gallbladder is unclear or cannot tolerate cholecystectomy, forcing a classical cholecystectomy may lead to serious medically induced injury and outweigh the losses. In fact, open surgery does not provide a clearer view and anatomy than laparoscopic surgery, and its real significance is only to allow the surgeon to change to a more familiar surgical approach, without really solving the underlying causes of DD adhesions and anatomical difficulties. Moreover, it increases the surgical trauma and operation time. The advantages of LSC are that it is less difficult to perform, more maneuverable, and easier to master. Depending on the local pathology, three types of LSC can be performed: LSC I: preservation of part of the gallbladder bed; LSC II: preservation of part of the gallbladder jugular; LSC III: preservation of part of the gallbladder bed and jugular.
Summary
The disease is complex and difficult to diagnose, and early diagnosis and treatment are the key to cure. Once diagnosed, the primary disease should be actively controlled, shock should be corrected in time, fasting, gastrointestinal decompression, and conservative treatment such as symptomatic support should be given. Patients with critical conditions should undergo PTGBD as soon as possible, and if the patient has septic inflammation or gangrene or perforation at the time of diagnosis, surgical treatment should be performed decisively. Emergency LC should be the first choice because of its minimally invasive advantages. If the anatomy of the gallbladder is difficult, it is not necessary to pursue the “perfection” on the operating table.