I
Projeto de Opção do 6º ano - DECLARAÇÃO DE INTEGRIDADE
Eu, Sofia Alexandra Sousa Moreira, abaixo assinado, nº mecanográfico 201004853, estudante do 6º ano do Ciclo de Estudos Integrado em Medicina, na Faculdade de Medicina da Universidade do Porto, declaro ter atuado com absoluta integridade na elaboração deste projeto de opção.
Neste sentido, confirmo que NÃO incorri em plágio (ato pelo qual um indivíduo, mesmo por omissão, assume a autoria de um determinado trabalho intelectual, ou partes dele). Mais declaro que todas as frases que retirei de trabalhos anteriores pertencentes a outros autores, foram referenciadas, ou redigidas com novas palavras, tendo colocado, neste caso, a citação da fonte bibliográfica.
Faculdade de Medicina da Universidade do Porto, 21/03/2018
II
Projecto de Opção do 6º ano – DECLARAÇÃO DE REPRODUÇÃO
NOME
Sofia Alexandra Sousa Moreira
NÚMERO DE ESTUDANTE E-MAIL
201004853 sofiasousamoreira@gmail.com
DESIGNAÇÃO DA ÁREA DO PROJETO
Cirurgia Geral
TÍTULO DISSERTAÇÃO/MONOGRAFIA (riscar o que não interessa) Tratamento da Colecistite Aguda – Estudo Retrospetivo Acute cholecystitis treatment – Retrospective Study
ORIENTADOR
Dr. Rui Jorge Ferreira Mendes da Costa
COORIENTADOR (se aplicável)
Não aplicável
ASSINALE APENAS UMA DAS OPÇÕES:
É AUTORIZADA A REPRODUÇÃO INTEGRAL DESTE TRABALHO APENAS PARA EFEITOS DE INVESTIGAÇÃO, MEDIANTE DECLARAÇÃO ESCRITA DO INTERESSADO, QUE A TAL SE COMPROMETE.
É AUTORIZADA A REPRODUÇÃO PARCIAL DESTE TRABALHO (INDICAR, CASO TAL SEJA NECESSÁRIO, Nº MÁXIMO DE PÁGINAS, ILUSTRAÇÕES, GRÁFICOS, ETC.) APENAS PARA EFEITOS DE INVESTIGAÇÃO, MEDIANTE DECLARAÇÃO ESCRITA DO INTERESSADO, QUE A TAL SE COMPROMETE.
DE ACORDO COM A LEGISLAÇÃO EM VIGOR, (INDICAR, CASO TAL SEJA NECESSÁRIO, Nº MÁXIMO DE PÁGINAS, ILUSTRAÇÕES, GRÁFICOS, ETC.) NÃO É PERMITIDA A REPRODUÇÃO DE QUALQUER PARTE DESTE TRABALHO.
Faculdade de Medicina da Universidade do Porto, 21/03/2018
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Agradecimentos
Quero agradecer, em primeiro lugar, à Dr.ª Fabiana Sousa, a grande força motriz deste projeto, que, não sendo minha co-orientadora oficial, foi muito mais do que isso durante os meses em que realizei este trabalho. Por toda a ajuda, disponibilidade e amizade, expresso o meu mais profundo e sincero obrigado.
Ao Dr. Rui Costa, o meu orientador, por toda a ajuda, orientação e disponibilidade desde o primeiro dia.
À Dr.ª Daniela Linhares, pela ajuda com a análise estatística.
Ao serviço de Cirurgia Geral do Centro Hospitalar de São João e ao Dr. José Costa Maia, diretor do mesmo, por permitirem e acolherem a realização deste projeto.
Ao departamento de Cirurgia e Fisiologia da Faculdade de Medicina da Universidade do Porto e ao Sr. Professor Doutor José Manuel Amarante, pela autorização da realização deste projeto. À Faculdade de Medicina da Universidade do Porto e à Faculdade de Ciências da Saúde da Universidade da Beira Interior, as minhas duas instituições de formação.
A todos os que direta ou indiretamente contribuíram para a realização deste trabalho.
IV
Dedicatória
V
Abstract
Introduction: Acute cholecystitis (AC) is the acute inflammatory disease of the gallbladder. The Tokyo Guidelines aim to provide guidelines of diagnosis, severity stratification and treatment. Urgent cholecystectomy is the first-line treatment, however, in selected patients, antibiotics and cholecystostomy may be useful.
Material and Methods: Retrospective study of patients with AC treated between January 1st 2012 and December 31st 2015 at Centro Hospitalar de São João. Data were collected by consulting the patient’s clinical file. Statistical analysis was performed using SPSS® version 25.0 and was based on Tokyo Guidelines 2018.
Results: 532 patients were admitted with AC: 339 were treated exclusively with antibiotics (group A); 67 with urgent cholecystostomy (group B); 126 with urgent cholecystectomy (group C). Group C patients increased by 20,9% between 2012 and 2015. Statistically significant differences were found concerning age, co-morbidity and clinical severity amongst the groups, with group B patients being older, with more co-morbidities (diabetes mellitus, chronic kidney disease and cardiovascular disease) and with greatest clinical severity. Statistically significant differences (p<0,001) were found concerning length of hospital stay, which was shorter for group C.
Discussion/Conclusion: Urgent cholecystectomy is the treatment of choice for AC, and it is associated with shorter hospital stay and lowest readmission rate. Antibiotics and cholecystostomy may be considered for high-risk patients (Tokyo Guidelines grade III).
VI
Resumo
Introdução: A colecistite aguda (CA) é uma doença inflamatória aguda da vesícula biliar. As Tokyo Guidelines pretendem orientar o seu diagnóstico, estratificação de gravidade e tratamento. A colecistectomia urgente é o tratamento goldstandard, contudo, em doentes selecionados a antibioterapia e a colecistostomia poderão ter utilidade.
Material e Métodos: Estudo retrospetivo dos doentes com colecistite aguda tratados entre 1 de janeiro de 2012 e 31 de dezembro de 2015, no Centro Hospitalar de São João. Os dados foram obtidos através da consulta do processo clínico dos doentes. A análise estatística foi realizada com o SPSS versão 25.0, com base nas Tokyo Guidelines 2018.
Resultados: Foram admitidos 532 doentes com CA: 339 tratados exclusivamente com antibióticos (grupo A); 67 com colecistostomia urgente (grupo B); 126 com colecistectomia urgente (grupo C). Verificou-se um aumento do número de doentes do grupo C de cerca de 20,9% entre 2012 e 2015. Encontrada diferença estatisticamente significativa na idade, co-morbilidades e severidade clínica entre os grupos, sendo os doentes do grupo B os mais velhos, com mais co-morbilidades (diabetes mellitus, insuficiência renal crónica e doença cardiovascular) e com maior gravidade clínica. Verificou-se diferença estatisticamente significativa (p<0001) na duração do internamento, a qual é menor no grupo C. Sem diferença estatisticamente significativa na mortalidade e re-internamento.
Discussão/Conclusão: A colecistectomia urgente é o tratamento de eleição da CA, associa-se a menor tempo de internamento e menor taxa de re-internamento. A antibioterapia e colecistostomia poderão ser considerados para doentes de alto risco (grau III nas Tokyo Guidelines).
VII
Index
1. Introduction ... 1
1.1 Aims and objectives of the study ... 6
2. Material and Methods ... 7
3. Results ... 8
3.1. Demographics and co-morbidities ... 8
3.2. Charlson co-morbidity index ... 10
3.3. Clinical presentation ... 10
3.4. Severity grading ... 11
3.5. Mortality and readmission rates ... 11
3.6. Evolution through the years ... 12
4. Conclusion/Discussion ... 13
5. References ... 15
6. Attachments ... 17
6.1. Declaração de aceitação da Comissão de Ética para realização do estudo ... 18
VIII
Accronyms
AAC: Acute acalculous cholecystitis AC: Acute cholecystitis
ACC: Acute calculous cholecystitis
ASA-PS score: American Society of Anesthesiologists physical status classification score BDI: Bile duct injury
CCI: Charlson co-morbidity index CKD: Chronic kidney disease
CPOD: Chronic pulmonary obstructive disease CRP: C-Reactive Protein
CT: Computed tomography CVD: Cardiovascular disease DM: Diabetes mellitus
ERCP: Endoscopic retrograde cholangiopanchreatography INR: International normalized ratio
PCT: Procalcitonin PT: Prothrombin ratio TG: Tokyo Guidelines
TG07: Tokyo Guidelines 2007 edition TG13: Tokyo Guidelines 2013 edition TG18: Tokyo Guidelines 2018 edition US: Ultrasonography
IX
List of Tables and Figures
TABLESTable 1. Groups distribution according to demographic characteristics and co-morbidities Table 2. Clinical presentation of patients and treatment performed for each group Table 3. Severity grading and treatment performed in each group
Table 4. Mortality, readmission and length of hospital stay
FIGURES
Figure 1. Boxplot representing co-morbidities and treatment for each group Figure 2. Charlson co-morbidity index for all groups
1
1. Introduction
Definition, etiology and grading
Acute cholecystitis (AC) is the acute inflammatory disease of the gallbladder [1, 2] and represents the second source of complicated intra-abdominal infection and one third of all surgical emergency hospital admissions [3].
The primary etiology of AC is the presence of stones [3]. 10-15% of the population is affected by gallstones [1, 4] which are responsible for 90-95% of all AC cases [1]. 6,5% of men and 10,5% of women have gallstones [3]. Forty-year old, fat and fair females (plus fertile) are more prone to develop gallbladder stones, even though it hasn’t been proven this increases the risk of development of AC [1]. Obesity and pregnancy have also been associated with cholelithiasis. Other factors, such as ischemia, motility disorders, direct chemical injury, infections by microorganisms, protozoon and parasites, collagen disease, and allergic reactions are also involved. Transcatheter hepatic arterial chemotherapy and hormone replacement therapy have been shown to increase the risk of AC; statins may decrease this risk [1].
Biliary colic occurs in 1-4% of patients with gallstones annually; in patients with untreated gallstones, AC was seen in 10-20% of them. The probability of gallstone related events after an untreated episode of acute calculous cholecystitis (ACC) is 14% at 6 weeks, 19% and 12 weeks and 29% at 12 months [4]. According to a review by Friedman, 1–2 % of patients with asymptomatic gallstones and 1–3 % of patients with mild symptoms annually presented severe symptoms or complications [1].
Acalculous cholecystitis is the second most common cause of AC, and up to 49% of acalculous cholecystitis occur after trauma and major surgery [5]. Acalculous cholecystitis also occurs in patients admitted in intensive care units or patients with severe burns. Its mortality is very high in critically ill patients [5]. Risk factors for acute acalculous cholecystitis (AAC) include surgery, trauma, long-term intensive care unit stay, infection, thermal burn, and parenteral nutrition. There are other etiologies for AC, such as pancreatobiliary malignancy or latent cholecystitis after ERCP [5], which happens in 0.2-1.0% of patients [1].
Regarding pathophysiology, there is an obstruction by the stone at the gallbladder neck or cystic duct which causes increase of pressure in the gallbladder. The degree of this obstruction and its duration are two determinant factors of the progression of the disease: with short duration and partial obstruction, the patient will experience biliary colic; if there is complete obstruction of long duration, AC will develop. Early treatment is mandatory in both stages [1].
If left untreated, symptoms can cease. However, complications are common, and development of gallbladder gangrene is the most common (20% of cases); 2% of these patients will have subsequent perforation of the gallbladder, which is associated with high mortality [2]. Other
2 complications include biliary peritonitis, pericholecystic abscesses, biliary fistulas [1], gallstone ileus and emphysematous cholecystitis [2].
The overall mortality rate of acute cholecystitis is less than 1% [1] but for severe cases it was reported to be around 6% [6].
Clinical presentation and diagnosis
To date, the Tokyo Guidelines 2013 (TG13) diagnostic criteria for AC are very effective and their use as the Tokyo Guidelines 2018 (TG18) diagnostic criteria for AC is recommended. Although some studies found that its diagnostic accuracy ranges from 60,4% to 94%, validation studies were conducted and recommend that they be used unchanged as the TG18/TG13 diagnostic criteria [7]. The 2007 and, posteriorly, the 2013 Tokyo Guidelines were developed in order to establish objective parameters for the diagnosis of ACC [4] and have since been widely adopted with high sensitivity and high specificity [6]. However, there is no unique marker capable of definitively indicating the diagnosis of AC with high accuracy [3].
Characteristically, patients with AC present with prolonged, steady and severe right upper quadrant or epigastric pain that may radiate to the right shoulder or back [2]. It is the most typical clinical sign of AC due to obstruction of the gallbladder neck by stones, followed by nausea and vomiting [6, 8]. Tenderness in the right upper quadrant with abdominal guarding, palpable gallbladder, positive Murphy’s sign, fever and leucocytosis are also typical of this condition [2, 8]. Fever, nausea, vomiting and anorexia may be associated [2]. During physical examination, the patient is usually febrile, tachycardic and lies still on the examining table for cholecystitis’ pain is aggravated by movement [2].
AC should be suspected when these findings are present: positive Murphy’s sign (with 79-96% specificity [8], though it may be lower in the elder [2]), local inflammatory findings (right upper quadrant abdominal pain and tenderness, p.e.) and fever and systemic inflammatory reactions (elevated C-Reactive protein [CRP] or white blood cell [WBC] count). Definite diagnosis can only be established based on the imaging of ultrasonography (US), computed tomography (TC) or scintigraphy (HIDA scan) [6].
US is the imaging modality of choice, with a 61,3% rate of use [7], and it should be first performed in every patient if AC is suspected since it is non-invasive [8]. It has an 81% sensitivity and 83% specificity [9] and its diagnostic capacity is thought to be good. Characteristic findings include enlarged gallbladder, thickening of the gallbladder wall, gallbladder stones, debris echo [6], ultrasonographic Murphy’s sign (pain that occurs when the ultrasonography probe is pushed against the gallbladder), pericholecystic fluid and pericholecystic abscess [8].
Diagnosis of AC can be established when these findings are present at the same time: thickening of the gallbladder wall (≥5mm), pericholecystic fluid or positive ultrasonographic Murphy’s sign [6]. Ultrasonographic Murphy’s sign is more accurate than Murphy’s sign [2] and it shows a 90% sensitivity and specificity [8].
3 Other imaging studies may be useful. CT can be used when complications or other diagnosis are suspected [2], such as gangrenous cholecystitis or emphysematous cholecystitis [9]. Magnetic resonance imaging or magnetic resonance cholangiopancreatography (MRI/MRCP) may be useful and are recommended if abdominal US does not provide definitive diagnosis, especially when gangrenous cholecystitis is suspected [9]. HIDA scan has a high sensitivity for AC [6] and it is usually indicated if the diagnosis remains uncertain after ultrasonography [2]. Doppler sonography used to be a helpful exam in the diagnosis of AC [6], however, recent studies found that it is not useful for diagnosing AC [9].
For all reasons mentioned above, US is the modality of choice for the diagnosis of AC since it is inexpensive, available immediately, of easy access, does not use ionizing radiation, has high sensitivity and sensibility, provides information regarding the presence of stones and its use is not limited by the levels of serum bilirubin [4, 6, 9].
There are no specific blood tests for the diagnosis of AC [4], but a hemogram can be helpful if these findings are present: general inflammatory findings (abnormal WBC count or elevated CRP over 3mg/dL), elevated blood cell count (>10000mm3/dL) and mild increase of serum enzymes in the hepato-biliary-pancreatic system(such as serum aminotransferases and amylase) and bilirubin (which may rise up to 4mg/dL if there are no complications) [6]. In uncomplicated AC, serum total bilirubin and alkaline phosphatase concentrations are not usually elevated, and if they are, complicated conditions such as cholangitis, choledocholithiasis or Mirizzi syndrome should be suspected [2].
When suspecting of AC it is important to assess the severity status of the patient at the time of diagnosis, within 24 hours and 24 to 48 hours after diagnosis [10]. Apart from the previous measurements mentioned, it is also important to evaluate platelet count, blood urea nitrogen, creatinine, prothrombin time international normalized ratio (PT/INR) and arterial blood gases [8]. Although some studies considered procalcitonin (PCT) levels as helpful in the assessment of severity of AC, PCT level alone is not effective for this purpose and further studies are needed [11].
Once diagnosis has been confirmed, initial treatment should be started immediately, severity should be assessed according to the severity grading criteria, and the patient’s general status should be evaluated [12].
Diagnosis of AAC is similar to ACC with clinical symptoms and imagiologic findings similar to those found in ACC.
Grading
The TG18 severity grading has not changed compared to the TG13 [7]. The severity grading of AC was classified into three categories, shown below [6, 7]. Moderate cholecystitis is not accompanied by organ dysfunction but has serious local complications requiring immediate cholecystectomy and biliary drainage. Moderate cases are characterized by the presence of
4 leucocytosis, palpable right upper quadrant abdominal pain and persistence of symptoms for more than 72 hours or severe inflammation findings; severe cholecystitis refers to a condition that has developed organ dysfunction and requires intensive care with respiratory and circulatory management [6, 7]. These criteria are a useful indicator and predictor of vital prognosis, length of hospital stay, conversion to open surgery and medical costs [7].
Grade III (severe) AC is associated with dysfunction of any of the following organs/systems: 1. Cardiovascular dysfunction (hypotension requiring dopamine ≥5µg/kg/min or any dose of norepinephrine)
2. Neurological dysfunction (decreased level of counsciousness)
3. Respiratory dysfunction (PaO2/Fi O2 ratio <300)
4. Renal dysfunction (Oliguria, creatinine >2.0mg/dL)
5. Hepatic dysfunction (PT/INR >1.5)
6. Hematologic dysfunction (Platelet count <100,000mm3)
Grade II (moderate) AC is associated with any of the following conditions: 1. Elevated WBC count (>18,000/mm3)
2. Palpable tender mass in the right upper abdominal quadrant 3. Duration of complaints >72h1
4. Marked local inflammation (gangrenous cholecystitis, pericholecystic abscess, hepatic abscess, biliary peritonitis, emphysematous cholecystitis)
1: Laparoscopic surgery should be performed withing 96h of the onset of acute cholecystitis
Grade I (mild) AC does not meet criteria of grade II or III and can be identified in a healthy patient with no organ dysfunction and mild inflammatory changes in the gallbalder. Cholecystectomy is a safe and low-risk operative procedure.
Treatment
There are many controversies concerning ACC treatment, including treatment options, timing and surgical management, management of high risk patients, amongst others [4].
Since TG13 were published, many changes in clinical management happened, and new papers suggesting other management bundles for this condition were published. The recently published TG18, unlike TG13, suggest that grade III patients can undergo laparoscopic cholecystectomy if the surgery is performed at advanced centres with specialized surgeons. Other changes include using the Charlson comorbidity index (CCI) and the ASA-PS score for evaluation of general status [12] and into the decision making for all grades [13].
While assessing surgery or drainage indications, all patients should be maintained in fasting. Early treatments include hydration, electrolyte correction if needed, antibiotics and analgesic agents while maintaining surveillance of respiration and hemodynamics [13].
The first-line treatment of AC is early laparoscopic cholecystectomy [4, 8, 14, 15]. Although a German study recommends that surgery must not be performed within 24 hours of onset of
5 symptoms [16], current guidelines recommend it should be performed as early as possible [4] and regardless of how much time has passed since onset of symptoms [13]. Previous guidelines recommended a 72-hour golden period for surgery [14], although this is no longer applicable. Laparoscopy is associated with less pain at incision site, shorter hospital stays and quicker recovery time [4, 13, 17]. Even though it is accepted as a safe surgical technique, it is not free of risks [14] and surgeons must not hold on converting laparoscopic to open surgery if difficulties arise during surgery, especially to avoid bile duct injury [17]. Overall, laparoscopy has better results than open cholecystectomy and presents many advantages, especially regarding mortality, morbidity, biliary lesion and length hospital stay [18, 19].
Alternative treatments for surgically high-risk patients include conservative treatment with antibiotics, which may be associated with gallbladder drainage [15]. Considering antimicrobial therapy, antibiotics must be administered firstly on an empirical basis before the infectious agents are identified [20] and should cover Gram negative rods and anaerobes [21]. Gallblader drainage is a safe alternative to early cholecystectomy for surgically high-risk patients with AC [15, 22] and should be considered as an alternative to surgery if conservative treatment fails [4]. Grade I (mild) AC patients should undergo laparoscopic surgery as soon as the CCI and ASA-PS scores suggest the patient can withstand surgery. If the patient is not eligible for surgery, conservative treatment may be used followed by surgery once the patient is stable [13]. Grade II (moderate) AC, like grade I patients, should undergo surgery if the CCI and ASA-PS scores are compatible with this treatment, as long as the patient is in an advanced care centre for surgical treatment of AC. Grade II AC is often accompanied by severe local inflammation and surgery in these patients is more challenging. If the patient is not eligible for surgery, conservative treatment with antibiotics and biliary drainage should be considered and elective surgery performed later [13].
Grade III (severe) AC is accompanied by organ dysfunction that requires appropriate organ support and initial medical treatment. Patients can undergo early laparoscopic cholecystectomy if they are in an advanced care centre and the surgeon has extensive experience in these types of surgeries. An intensive care unit must be available. If these requirements are not met, patients should be transferred to an advanced centre. Patients not eligible for surgery must undergo conservative treatment; early biliary drainage should be considered if gallbladder inflammation is difficult to control [8]. For patients with contra-indications to drainage, surgical cholecystectomy under local anaesthesia or endoscopic gallbladder drainage may be an alternative [22]. Elective surgery can be performed after drainage improves the patient’s status [13], reducing operative and anesthesiology-related risks [4], however, optimal timing for subsequent surgery is still controversial [23].
For patients treated conservatively, the recurrence rate varied from 19-36%, and in cases in which cholecystostomy has been performed, it varies from 22-47% [1].
6
1.1
Aims and objectives of the study
We performed a retrospective study, including all patients diagnosed with AC at Centro Hospitalar de São João. The aim of this study was to understand how treatment performed affects the outcomes of these patients, particularly readmission and mortality rates. We also intended to understand how co-morbidities and clinical presentation will affect the treatment performed and its correlated outcomes. Three groups were defined according to treatment performed. We also divided patients according to their severity, as preconized by the TG18, and the correlation between severity grading and treatment performed was studied.
Another main goal of our study is to evaluate if our service abides by the international guidelines, particularly the Tokyo Guidelines, which recommend early cholecystectomy as treatment of choice for AC patients and preconizes conservative treatment and drainage as alternatives for surgically high-risk patients.
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2. Material and Methods
Retrospective study of patients over 18 years old with AC treated between January 1st 2012 and December 31st 2015 at Centro Hospitalar de São João.
Permission was obtained from the Ethics Committee on November 2017.
Data were retrieved by consulting the patient’s clinical file and a database was created with the following parameters:
• Number of episode; • Clinical file number;
• Date of hospital admission and length of hospital stay; • Gender;
• Date of birth;
• Co-morbidities present: diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD)
o With this data, CCI was calculated.
• Clinical presentation: pain, duration of pain (>72h) and days of pain evolution, nausea, vomiting, jaundice, Murphy’s sign and fever;
• Analitical study: CRP, WBC count and total and direct bilirubin;
• Abdominal US: presence of lithiasis, US Murphy’s sign and thickening of gallbladder wall; • Abdominal CT: if performed, presence of peri-vesicular fluid and signs of local
inflammation;
• Severity criteria according to TG18 [7]; • Antibiotics administered;
• Treatment performed: cholecystostomy or cholecystectomy, including timing of surgery and complications during or after surgery;
o With this data, Clavien-Dindo classification of surgical complications was calculated.
• Mortality; • Readmission;
532 patients were included in this study. Exclusion criteria include patients under 18 years old, readmission episodes, misdiagnosis and lack of clinical information needed for the study. Statistical analysis was performed using the software SPSS® (Statistical Package for Social Science) version 25.0.
8
3. Results
3.1.
Demographics and co-morbidities
532 patients were admitted with AC between January 1st 2012 and December 31st 2015. Women represented 49,4% (n=263) of all patients and men 50,6% (n=269).
Three groups were defined:
• Group A: patients treated exclusively with antibiotics (63,7%) o 339 patients were included in this group;
• Group B: patients treated with urgent cholecystostomy (12,6%) o 67 patients were included in this group;
• Group C: patients treated with urgent cholecystectomy (23,7%) o 126 patients were included in this group.
Statistically significant differences were found between the number of patients in each group (p<0.001).
Antibiotics were the most used treatment and urgent cholecystostomy the least used one.
Table 1. Groups distribution according to demographic characteristics and co-morbidities
GROUPS TOTAL GROUP A (n=339) GROUP B (n=67) GROUP C (n=126) AGE
(median, min, max) 69 (20, 97) 69 (20,94) 80 (56,97) 64 (20, 90)
G EN DER MALE 269 (50.6%) 177 (52.2%) 39 (58.2%) 58 (46%) FEMALE 263 (49,4%) 162 (47,8%) 28 (41,8%) 68 (54%) CO -M ORB ID IT IE S DM (%) 28.9% 27.4% 43.4% 25.4% CKD (%) 7.9% 5.3% 19.4% 8.7% CVD (%) 28.2% 24.5% 55.2% 23.8% COPD (%) 9.4% 8.3% 13.4% 10.3%
9 Statistically significant differences were found in the ages for all three groups (p<0.001):
• Statistically significant differences were found between patients treated with antibiotics and with cholecystostomy (p=0.005); statistically significant differences were also found between patients treated with cholecystectomy and cholecystostomy (p<0.001); • No statistically significant differences were found between patients treated with
antibiotics and cholecystectomy (p=0.182).
• Group B are the oldest and the youngest patient in this group was 56 years old. • For group A and group C, the youngest patients were both 20 years old.
Although women were submitted to more cholecystectomies than men, which were more submitted to cholecystostomy, no statistically significant differences were found between genders (p=0.202).
Regarding co-morbidities, statistically significant differences were found between groups: • DM was the most frequent co-morbidity and 25,4% of patients with DM were submitted
to urgent cholecystectomy; CKD was the least frequent one and cholecystostomy was the most used treatment in this group.
• Statistically significant differences were found amongst patients with DM (p=0.020), CKD (p<0.001) and CVD (p<0.001).
• No statistically significant differences were found for CPOD (p=0.650);
10
3.2.
Charlson co-morbidity index
Regarding CCI, group B presented with higher scores (median of 5, minimum of 0 and maximum of 17) and group C presented with lower scores (median of 2, minimum of 0 and maximum of 9). Group A presented with a median of 3, minimum of 0 and maximum of 13. Statistically significant differences were found between group B and group C (p=0.043); no statistically significant differences were found between group A and group C (p>0.05).
3.3.
Clinical presentation
Table 2. Clinical presentation of patients and treatment performed for each group GROUPS
GROUP A GROUP B GROUP C
TOTAL % TOTAL % TOTAL % p
VOMITING Yes 178 63,1% 34 12,1% 70 24,8% >0.05 No 161 64,4% 33 13,2% 56 22,4% PAIN > 72h Yes 108 55,4% 27 13,8% 60 30,8% 0.006 No 221 69,7% 35 11,0% 61 19,2% FEVER Yes 80 53,0% 29 19,2% 42 27,8% 0.002 No 259 68,0% 38 10,0% 84 22,0% JAUNDICE Yes 27 61,4% 6 13,6% 11 25,0% >0.05 No 312 64,2% 61 12,6% 113 23,2% MURPHY’S SIGN Yes 161 62,9% 31 12,1% 64 25,0% >0.05 No 159 63,3% 35 13,9% 57 22,7%
11 Concerning clinical presentation and treatment, statistically significant differences were found between all groups for patients presenting with pain over 72 hours (p=0.006) and fever (p=0.002).
Around 50% of patients submitted to urgent cholecystectomy presented with pain over 72 hours. Of all patients presenting with pain over 72 hours (n=195), approximately 30% were submitted to urgent cholecystectomy, 55% were treated conservatively and the remaining submitted to cholecystostomy.
3.4.
Severity grading
For our study, patients were classified into three groups according to the TG18 [7]. For each group, treatment performed was evaluated as follows:
Table 3. Severity grading and treatment performed in each group GROUPS
GROUP A GROUP B GROUP C
TOTAL n % n % n %
SEVERITY GRADING I 213 158 74,2% 15 7,0% 40 18,8%
II 215 132 61,4% 20 9,3% 63 29,3%
III 104 49 47,1% 32 30,8% 23 22,1%
Statistically significant differences were found for each group (p<0.001).
A total of 104 patients were classified as grade III. Among these, 47,1% were treated conservatively and 22,1% were submitted to urgent cholecystectomy.
3.5.
Mortality and readmission rates
Table 4. Mortality, readmission and length of hospital stay GROUPS
GROUP A GROUP B GROUP C
TOTAL TOTAL % TOTAL % TOTAL %
MORTALITY n 14 11 78,6 2 14 1 7 READMISSION n 41 21 51,2 9 22 11 26,8 LENGTH OF HOSPITAL STAY (days) Mean 8,06 9,58 - 16,43 - 8,06 - Median - 7 - 13 - 6 - Minimum 1 4 - 5 - 1 - Maximum 91 56 - 91 - 91 -
12 Throughout the years of this study, 14 patients died: the highest mortality rate was reported in group A and the lowest in group C. Group A was also associated with the highest readmission rate. However, considering mortality and readmission rates, no statistically significant differences were found amongst the groups submitted to different treatments (p=0.113). Statistically significant differences were found regarding length of hospital stay, especially between patients treated with antibiotics and cholecystostomy (p<0.001) and patients treated with cholecystostomy and cholecystectomy (p<0.001). No statistically significant differences were found between patients treated with cholecystectomy and antibiotics.
3.6.
Evolution through the years
In 2012, 18,2% of 132 patients were submitted to surgery; in 2015, 22,0% of 123 patients were submitted to surgery. Overall, during the four years in which our study took place, there has been a documented increase in the percentage of urgent surgeries performed. Between 2012 and 2015, urgent cholecystectomies increased by 20,9%.
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4. Conclusion/Discussion
AC is the acute inflammatory disease of the gallbladder [1, 2, 4]. Its clinical severity may vary greatly, including patient’s death, especially in more susceptible groups (particularly patients presenting with more co-morbidities) [7]. Prognosis for AC is far from poor, but survival is still determined by severity grading [7]. Although the goldstandard treatment is urgent cholecystectomy, treatment performed must be individualized and respect all patients presenting with this condition. Treatment performed must consider clinical gravity, co-morbidities, risk factors and scores and the experience at the treatment centre, amongst others. Treatments preconized, according to clinical presentation and severity, are urgent cholecystectomy, cholecystostomy or conservative treatment with antibiotics [13].
In our study, we verified that over half of patients were submitted to conservative treatment with antibiotics. Our hospital’s differentiation and qualified teams may represent a higher clinical gravity of patients presenting at the emergency room.
Although the present work was made based on TG18, clinical decision making between 2012 and 2015 was based on TG13 and TG07, which preconized conservative treatment for grade III patients, excluding the possibility of urgent surgery in this group. Despite all these limitations, our sample presented a high number of urgent cholecystectomies performed, with a documented increase in 20,9% throughout the period in which this study took place.
We concluded that group C patients were younger and presented with fewer co-morbidities, especially regarding DM, CKD and CVD. They also presented a lower CCI, which resonates with what’s written in literature. In contrast, group B patients were older, with the youngest patient of this group being 56 years old. This group also presented more co-morbidities and higher CCI. These data also enhance the fact that therapeutic decisions in this group were made in conformity with TG13 and TG07.
Regarding clinical presentation, statistically significant differences were found concerning presence of pain >72 hours and fever. Out of all patients presenting with pain >72 hours, 30,8% of them were submitted to urgent cholecystectomy.
Concerning clinical severity, statistically significant differences were found amongst groups, with group III patients submitted mostly to conservative treatment and/or cholecystostomy. However, we also found that, in this particular group, urgent cholecystectomy was performed in 22,1% of patients.
Despite TG07 and TG13 recommending not to perform urgent cholecystectomy in grade III patients, our teams, when presented with high severity patients, still chose to perform urgent surgery in a significant percentage of them. Of all surgeries performed, 18,3% of patients were classified as grade III.
14 Although we did not find statistically significant differences in mortality among groups, a tendency for lower mortality was found in group C. Readmission rates, also not statistically significant, was higher in group A. However, statistically significant differences were found concerning length of hospital stay, which was shorter in group C.
The patient submitted to cholecystectomy who had the longest hospital stay (91 days), presented with septic shock with multi-organ failure after hospital-acquired pneumonia; the patient submitted to cholecystostomy who had the longest hospital stay (also 91 days) also presented with septic shock with multi-organ failure after intra-abdominal abscess.
In conclusion, AC treatment is very diverse and must be individualized in all patients presenting with this condition. However, according to literature and the results of our study, we conclude that patients submitted to urgent cholecystectomy present better outcomes, especially regarding mortality and readmission (without statistical significance) and length of hospital stay (with statistical significance). This abides by international guidelines, particularly TG13 and TG18.
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5. References
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6. Yokoe, M., et al., TG13 diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci, 2013. 20(1): p. 35-46.
7. Kiriyama, S., et al., Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci, 2018. 25(1): p. 17-30. 8. Miura, F., et al., TG13 flowchart for the management of acute cholangitis and
cholecystitis. J Hepatobiliary Pancreat Sci, 2013. 20(1): p. 47-54.
9. Ambe, P.C., et al., Cholecystectomy vs. percutaneous cholecystostomy for the management of critically ill patients with acute cholecystitis: a protocol for a systematic review. Syst Rev, 2015. 4: p. 77.
10. Okamoto, K., et al., TG13 management bundles for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci, 2013. 20(1): p. 55-9.
11. Yuzbasioglu, Y., et al., Role of Procalcitonin in Evaluation of the Severity of Acute Cholecystitis. Eurasian J Med, 2016. 48(3): p. 162-166.
12. Miura, F., et al., Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci, 2018. 25(1): p. 31-40. 13. Okamoto, K., et al., Tokyo Guidelines 2018: flowchart for the management of acute
cholecystitis. J Hepatobiliary Pancreat Sci, 2018. 25(1): p. 55-72.
14. Yamashita, Y., et al., TG13 surgical management of acute cholecystitis. J Hepatobiliary Pancreat Sci, 2013. 20(1): p. 89-96.
15. Tsuyuguchi, T., et al., TG13 indications and techniques for gallbladder drainage in acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci, 2013. 20(1): p. 81-8.
16. Ambe, P., et al., Cholecystectomy for acute cholecystitis. How time-critical are the so called "golden 72 hours"? Or better "golden 24 hours" and "silver 25-72 hour"? A case control study. World J Emerg Surg, 2014. 9(1): p. 60.
17. Terho, P.M., A.K. Leppaniemi, and P.J. Mentula, Laparoscopic cholecystectomy for acute calculous cholecystitis: a retrospective study assessing risk factors for conversion and complications. World J Emerg Surg, 2016. 11: p. 54.
18. Teixeira, J.A., et al., Colecistectomia por Laparoscopia e por Laparotomia na Colecistite Aguda: Análise Crítica de 520 casos. Acta Médica Portuguesa, 2014. 27(6): p. 685-691. 19. Teixeira, J.P., et al., Surgical management of acute cholecystitis (experience of 249
16 20. Gomi, H., et al., TG13 antimicrobial therapy for acute cholangitis and cholecystitis. J
Hepatobiliary Pancreat Sci, 2013. 20(1): p. 60-70.
21. Vollmer, C.M., S.F. Zakko, and N.H. Afdhal. Treatment of Acute Cholecystitis. March 15 2017 [cited 2017 September 16]; Available from: http://bit.ly/2FpvF7F
22. Venara, A., et al., Technique and indications of percutaneous cholecystostomy in the management of cholecystitis in 2014. J Visc Surg, 2014. 151(6): p. 435-9.
23. Inoue, K., et al., Optimal timing of cholecystectomy after percutaneous gallbladder drainage for severe cholecystitis. BMC Gastroenterol, 2017. 17(1): p. 71.
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6. Attachments
6.1
Declaração de aceitação da Comissão de Ética para realização do estudo18
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