published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M.Med.Sc.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 39-45).

Introduction: Despite evidence in favour of cholecystectomy early during first presenting admission for most patients with acute calculous cholecystitis, variation in the timing of cholecystectomy remains evident worldwide. This dissertation characterizes the extent of variation within a large regional healthcare system, as well as addresses gaps in our current understanding of the clinical consequences and costs associated with early versus delayed cholecystectomy for acute cholecystitis. Methods: A population-based retrospective cohort of patients admitted emergently with acute cholecystitis was identified from administrative databases for the province of Ontario, Canada. First, the extent of variation across hospitals in the performance of early cholecystectomy (within 7 days of emergency department presentation) was characterized. Second, among patients discharged without cholecystectomy following index admission, the risk of recurrent gallstone symptoms over time was quantified. Third, operative outcomes of early cholecystectomy were compared to those of delayed cholecystectomy. Finally, a cost-utility analysis compared healthcare costs and quality-adjusted life-year gains associated with three management strategies for acute cholecystitis: early cholecystectomy, delayed cholecystectomy and watchful waiting, where cholecystectomy is performed urgently if recurrent gallstone symptoms arise. Results: The rate of early cholecystectomy varied widely across hospitals in Ontario (median rate 51%, interquartile range 25-71%), even after adjusting for patient characteristics (median odds ratio 3.7). Among patients discharged without cholecystectomy following an index cholecystitis admission, the probability of a gallstone-related emergency department visit or hospital admission was 19% by 12 weeks following discharge. Early cholecystectomy was associated with a lower risk of major bile duct injury (0.28%vs.0.53%, RR=0.53, 95%CI 0.31–0.90, p=0.025). No significant differences were observed in terms of open cholecystectomy (15%vs.14%, RR=1.07, 95%CI 0.99–1.16, p=0.10) or in conversion among laparoscopic cases (11%vs.10%, RR=1.02, 95%CI 0.93–1.13, p=0.68). Early cholecystectomy was on average less costly ($6,905 per person) and more effective (4.20 QALYs per person) than delayed cholecystectomy ($8,511; 4.18 QALYs per person) or watchful waiting ($7,274; 3.99 QALYs per person). Conclusions: Early cholecystectomy offers a benefit over delayed cholecystectomy in terms of major bile duct injury, mitigates the risk of recurrent symptoms, and is associated with the greatest QALY gains at the least cost.

Introduction: Despite evidence in favour of cholecystectomy early during first presenting admission for most patients with acute calculous cholecystitis, variation in the timing of cholecystectomy remains evident worldwide. This dissertation characterizes the extent of variation within a large regional healthcare system, as well as addresses gaps in our current understanding of the clinical consequences and costs associated with early versus delayed cholecystectomy for acute cholecystitis. Methods: A population-based retrospective cohort of patients admitted emergently with acute cholecystitis was identified from administrative databases for the province of Ontario, Canada. First, the extent of variation across hospitals in the performance of early cholecystectomy (within 7 days of emergency department presentation) was characterized. Second, among patients discharged without cholecystectomy following index admission, the risk of recurrent gallstone symptoms over time was quantified. Third, operative outcomes of early cholecystectomy were compared to those of delayed cholecystectomy. Finally, a cost-utility analysis compared healthcare costs and quality-adjusted life-year gains associated with three management strategies for acute cholecystitis: early cholecystectomy, delayed cholecystectomy and watchful waiting, where cholecystectomy is performed urgently if recurrent gallstone symptoms arise. Results: The rate of early cholecystectomy varied widely across hospitals in Ontario (median rate 51%, interquartile range 25-71%), even after adjusting for patient characteristics (median odds ratio 3.7). Among patients discharged without cholecystectomy following an index cholecystitis admission, the probability of a gallstone-related emergency department visit or hospital admission was 19% by 12 weeks following discharge. Early cholecystectomy was associated with a lower risk of major bile duct injury (0.28%vs.0.53%, RR=0.53, 95%CI 0.31–0.90, p=0.025). No significant differences were observed in terms of open cholecystectomy (15%vs.14%, RR=1.07, 95%CI 0.99–1.16, p=0.10) or in conversion among laparoscopic cases (11%vs.10%, RR=1.02, 95%CI 0.93–1.13, p=0.68). Early cholecystectomy was on average less costly ($6,905 per person) and more effective (4.20 QALYs per person) than delayed cholecystectomy ($8,511; 4.18 QALYs per person) or watchful waiting ($7,274; 3.99 QALYs per person). Conclusions: Early cholecystectomy offers a benefit over delayed cholecystectomy in terms of major bile duct injury, mitigates the risk of recurrent symptoms, and is associated with the greatest QALY gains at the least cost.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Many patients present with upper abdominal pain and receive some type of pain relieving therapy prior to gallbladder imaging. The physiologic effect of morphine and other analgesics on gallbladder function has been well‐studied. What hasn’t been studied as much are the implications on clinical practice and the decision about whether morphine is the best option to use in suspected chronic gallbladder disease. This case study serves to illustrate the influence of morphine in a patient who underwent both inpatient and outpatient hepatobiliary scintigraphy with dramatically different results. This case study perfectly shows the considerations that must be taken when using morphine because it eliminates many confounding variables; the only difference in the patient at the time of initial and subsequent presentation was the presence of morphine.

Burkitt lymphoma is a highly aggressive B cell non-Hodgkin lymphoma characterized by the translocation t(8,14) and deregulation of the MYC gene on chromosome 8. The endemic (African) form presents classically as an expanding mass in the jaw. The nonendemic (European/North American) form often presents with an abdominal mass. We present an interesting case of Burkitt’s Lymphoma with atypical features. A thirty-five-year-old lady with no significant medical history presented to the hospital with a three week complaint of vaginal bleeding and lower abdominal pain/cramps associated with night sweats and chills. She underwent gynecologic workup with an ultrasound revealing endometrial thickening followed by a hysteroscopic Dilatation and Curettage procedure. Laboratory workup revealed direct hyperbilirubinemia and elevated liver enzymes. MRCP showed gallbladder wall thickening but no biliary obstruction. A diagnosis of acalculous cholecystitis was considered and she underwent a laproscopic cholecystectomy and liver biopsy. Her initial complete blood count revealed mild leukocytosis. Follow up lab work revealed worsening leukocytosis and a hematology consultation was sought. A peak WBC of 81,000 with peripheral blood blasts as high as 31% was noted. Peripheral smear exam revealed moderate sized immature wbc precursors/blasts with high nuclear-cytoplasmic ratio. Further hematological work up including bone marrow aspirate and biopsy was expedited. Pathology resulted positive for Burkitt's lymphoma/leukemia, positive molecular studies, t(8,14), involving bone marrow, gallbladder, liver and endometrium. Patient was emergently treated with dexamethasone and nitrogen mustard as elevated bilirubin levels precluded standard treatment. She was started on Rituxan as this neoplasm is a CD 20+ B cell malignancy but could not tolerate it. HyperCVAD multi-agent chemotherapy was subsequently initiated along with intrathecal chemotherapy (cytarabine and methotrexate). CSF cytology remained negative for lymphoma. Patient’s clinical condition has improved after 2 cycles of chemotherapy and she is currently receiving on going therapy. Burkitt’s lymphoma is one of the most aggressive neoplasms with a tumor doubling time of a few days. The usual presentation is with constitutional symptoms and adenopathy or a mass lesion, and sometimes may manifest solely in the peripheral circulation as an L3 variant of acute lymphoblastic leukemia. Hepatic parenchymal involvement is rare, but reported. Gallbladder involvement with endoluminal deposits is even rarer. Simultaneous hepatic, gallbladder, uterine, nodal and leukemic involvement at presentation is unique. Treatment is primarily with systemic chemotherapy and multi agent regimens effective in acute lymphoblastic leukemia and/or aggressive lymphomas have been used successfully in this condition with a complete response rate of 80%-90% with a long-term survival rate of approximately 60%. Therapy is fraught with risks of fatal tumor lysis syndrome, pancytopenia, infection/sepsis, and bleeding. Potential progression/relapse in the CNS with the CSF serving as a sanctuary site has been well documented necessitating prophylactic intra thecal chemotherapy administration as in our patient. Aggressive biology of this disease required urgent treatment, as delay in institution of combination chemotherapy could result in poor outcome. This case highlights the need to maintain an open mind while evaluating apparently routine symptoms and the importance of rapid diagnosis and treatment of a hematologic-oncologic emergency.

Background: Treatment decisions for elderly patients with gallbladder pathology are complex. Little is known about what factors go into treatment decisions in this population. We used Medicare data to examine gender-based differences in the use of cholecystectomy vs. cholecystostomy tube placement in elderly patients with acute cholecystitis. Methods: We queried a 5% random sample of Medicare data (2009-2011) for patients >65 admitted for acute cholecystitis (by ICD-9 code) who subsequently underwent a cholecystectomy and/or cholecystostomy tube placement. Demographic information (age, race), clinical characteristics (Elixhauser index, presence of biliary pathology), and hospital outcomes (case fatality rate, length of stay, need for ICU care) were compared by gender. A multivariable model was used to examine predictors of cholecystectomy vs. cholecystostomy tube placement. Results: Of 4063 patients admitted with cholecystitis undergoing the procedures of interest just over half (58%) were women. The majority of patients (93%) underwent cholecystectomy. Compared to women, men were younger (average age 76 vs. 78, p value < 0.01) and had few comorbidities (average Elixhauser 1.2 vs. 1.4 p value < 0.01). Case fatality rate was similar between men (2.5%) and women (2.4% p value 0.48). A higher percentage of men spent time in the ICU (36%) compared to women (31% p value < 0.01). On multivariable analysis men were 30% less likely to undergo cholecystectomy (OR 0.69, 95% CI 0.53-0.91). Conclusion: Elderly men are less likely than elderly women to undergo cholecystectomy for acute cholecystitis despite being younger with less co morbidity and are more likely to spend time in the ICU. More research is needed to determine whether a difference in treatment is contributing to the higher rate of ICU utilization in elderly men with acute cholecystitis.

Abstract Technical improvements in computed tomography (CT) scanners have provided new possibilities to exploit the resources of this imaging modality in the evaluation of patients with multiple injuries or patients being treated in an intensive care unit (ICU). The purpose of this study was to assess the significance of multi-detector computed tomography (MDCT) in diagnostics and treatment decisions concerning multiple trauma and critically ill patients. Findings of MDCT using a dedicated trauma protocol in 133 patients exposed to high-energy blunt trauma were retrospectively evaluated. Diagnostic information about the injuries that would enable planning of treatment was sought. The imaging protocol consisted of axial scanning of the head and helical scanning of the facial bones, cervical spine, thorax, abdomen, and pelvis. Ninety-nine of the patients (74%) had at least one finding consistent with trauma. Nineteen false negative findings and two false positive findings were made. The overall sensitivity of MDCT was 94%, specificity 100%, and accuracy 97%. The reliability of a structured 5-min evaluation of MDCT images from the scanner’s console was prospectively evaluated in 40 high-energy trauma patients. The dedicated trauma protocol covering the thorax, abdomen, and pelvis was used in MDCT scanning. The findings were compared with the final radiological diagnosis of the MDCT data made on a picture archiving and communicating system (PACS) workstation, the operative findings, and the clinical follow-up. The evaluation from the scanner’s console enabled diagnosis of all potentially life-threatening injuries, the sensitivity for all injuries being 60% and specificity 98%. The effects of MDCT on the treatment of patients in a 12-bed medical-surgical ICU were observed prospectively. Sixty-four patients with an ICU stay longer than 48 h had had inconclusive findings with other modalities of radiological imaging. They underwent altogether 82 MDCT examinations. Fifty examinations (61%) resulted in a change in treatment, and 20 (24%) of them otherwise contributed to or supported clinical decision-making. Twelve examinations (15%) failed to provide any additional information relevant to the patient’s treatment. MDCT examination was helpful in general ICU patients, with inconclusive findings with other imaging modalities. CT images of 127 mixed medical-surgical ICU patients were retrospectively reviewed for the previously determined findings. Forty-three of these patients underwent open cholecystectomy, revealing eight cases with a normal gallbladder (GB), 26 with an edematous GB, and nine with necrotic acute acalculous cholecystitis (AAC). Abnormal CT findings were present in 96% of all the ICU patients. Higher bile density in the GB body and subserosal edema were associated with an edematous GB. The most specific findings predicting necrotic AAC were gas in the GB wall or lumen, lack of GB wall enhancement, and edema around the GB. The frequent prevalence of nonspecific abnormal imaging findings in the GB of ICU patients limits the diagnostic value of CT scanning.

Acute cholecystitis is the inflammation of the gallbladder, classically caused by gall stones obstructing the cystic duct. In contrast, acalculous cholecystitis is a gallbladder inflammation occurring in the absence of cholelithiasis with a reported prevalence of 10% of all cases of acute cholecystitis. Reactive acalculous cholecystitis is an extremely rare subset of this disease that results from an adjacent inflammatory or infectious intra-abdominal process that may lead to gallbladder stasis, ischemia, and subsequent wall inflammation. Many factors have been associated with acalculous cholecystitis, including (but not limited to) hemodynamic instability, altered immunity, and biliary tree anomalies. Lack of specific signs and symptoms of this particular entity often delays the diagnosis. Herein, we present a rare case of acute, reactive, acalculous cholecystitis secondary to a perforated duodenal ulcer found incidentally during laparoscopic cholecystectomy.

Abstract Acute acalculous cholecystitis (AAC) is an insidious and increasingly recognized complication of critical illness, whose pathogenesis is poorly understood and clinical picture obscure. Diagnosis is difficult and there is no consensus on treatment. The medical records of all ICU patients who had undergone open cholecystectomy due to AAC during the years 2000–2001 and 2003–2004 were examined for clinical and organ failure data. The indication for open cholecystectomy was a suspicion of AAC based on clinical signs and symptoms of sepsis or deteriorating multiple organ dysfunction without other obvious foci and/or radiological (computed tomography or ultrasound) findings indicative of cholecystitis. A total of 73 patients had operatively treated AAC during the study periods, giving an incidence of 0.9% of all admissions (73/8184) and an incidence of 6.7% among the long-stayers (ICUstay >5 days). The hospital mortality of these patients was 43%. Infection was the most common admission diagnosis followed by cardiovascular surgery. The patients were severely ill, the mean (SD) APACHE II score being 25.5 (6.4) and the mean (SD) SOFA score 10.2 (3.5) on admission. In those patients who had AAC as the only intra-abdominal complication of multiple organ dysfunction, cholecystectomy was followed by a remarkable improvement of individual and total SOFA scores by the seventh postoperative day. The AAC gallbladders were histologically and immunohistologically compared to normal gallbladders and to gallbladders of patients with acute calculous cholecystitis (ACC). The ACC patients were admitted into hospital because of primary acute gallbladder disease, were treated on a normal ward and did not have severe sepsis or multiple organ dysfunction. The typical histopathological features of AAC (34 cases) in the gallbladder wall were bile infiltration, lymphatic dilatation and leucocyte margination of blood vessels, while epithelial degeneration and defects, widespread occurrence of inflammatory cells and extensive and deep muscle layer necrosis were typical features of ACC (28 cases). Tight junction proteins (claudin-1, -2, -3, -4, occludin, ZO-1 and E-cadherin) were uniformly expressed in normal gallbladder epithelium, with the exception of claudin-2, which was present in less than half of the cells. In AAC, the expression of cytoplasmic occludin and claudin-1 was decreased compared to control group. In ACC, the expression of claudin-2 was increased, but the expression of claudin-1, -3 and -4, occludin and ZO-1 was decreased compared to normal or AAC gallbladders. In conclusion, AAC is associated with severe illness, infection, long intensive care unit stay and deteriorating multiple organ dysfunction. Open cholecystectomy is one important contributing factor to reverse the course of multiple organ dysfunction in these patients. Histological and immunohistological studies suggest that AAC is a manifestation of systemic inflammatory disease, while ACC is a local inflammatory and often infectious disease.