Gall bladder carcinoma - Altmeyers Encyclopedia

Gall bladder carcinoma History SynonymsBiliary carcinoma; malignant biliary carcinoma; biliary tract cancer; First described byAustrian pathologist Maximilian Stoll first described gallbladder tumors as distinct tumors in 1777 (Emde 2020). Definition Gallbladder carcinoma (GB- CA, GBCA or GBC) is a malignant disease of the bile ducts (Sharma 2017).So-called "incisional gallbladder carcinoma" is histologically proven GB- CA after standard cholecystectomy (Blitzer 2021). Classification GB- CA belongs to the inhomogeneous tumor entity of malignant tumors of the gallbladder, bile ducts (Sinn 2021) and tumors of the ampulla vateri (Emde 2020). Gallbladder carcinomas are classified according to the TNM- Classification Gallbladder Carcinoma (8th edition 2020):- TX: primary tumor not assessable (Emde 2020). - T1 a: Infiltration of the lamina propria (tumor confined to the mucosa [Blitzer 2021]). - T1 b: infiltration of the mural musculature (tumor confined to the lamina muscularis mucosa [Blitzer 2021])- T 2: Infiltration of perimuscular connective tissue, but no spread beyond serosa or into liver - T2 a: On the peritoneal side, there is infiltration of the perimuscular connective tissue, but no spread beyond the serosa - T2 b: On the liver side there is infiltration of the perimuscular connective tissue, no spread within the liver- T3: Perforation of the serosa and / or infiltration of the liver and / or a neighboring organ such as extrahepatic bile ducts, stomach, duodenum, pancreas, colon, mesh)- T4: Infiltration of the trunk of the portae vein or hepatic artery or infiltration into 2 or more neighboring organs or structures (Pommer 2022) - NX: Regional lymph nodes are not assessable (Emde 2020).- N0: No regional lymph node involvement- N1: Evidence of metastases in 1 - 3 regional lymph nodes- N2: Evidence of metastases in ≥ 4 regional lymph nodes (Pommer 2022).- pN0: Regional lymph node adenectomy and histologic examination of more than 10 lymph nodes (Pommer 2022) - MX: Presence of distant metastases not to be assessed (Emde 2020).- M0: No evidence of distant metastases- M1: presence of distant metastases (Pommer 2022) UICC- Classification:- G1: Well differentiated- G2: Moderately differentiated- G3: Poorly differentiated- G4: Undifferentiated (Emde 2020) - Stage 0: Tis, N0, M0- Stage I A: T1 a, N0, M0- Stage I B: T1 b, N0, M0- Stage II A: T2 a, N0, M0- Stage II B: T2 b, N0, M0- Stage III A: T3, N0, M0- Stage III B: T1 - T3, N1, M0- Stage IV A: T4, any No, N1, M0- Stage IV B: Any T, N2, M0 and any T, any N, M1 (Pommer 2022) In addition to the stage and degree of differentiation, the R- classification (status of the resected margin) is also added (Blitzer 2021):- R0: No residual tumor- R 1: Microscopically small residual tumor- R 2: Macroscopically visible residual tumor - R 2 a: Macroscopically visible residual tumor, but not confirmed microscopically - R 2 b: Macroscopically visible residual tumor confirmed microscopically- R X: Unconfirmed (Wagner 2013) Occurrence/Epidemiology GB- CA occurs infrequently in developed countries and is most common in northern India, the Middle East, North Africa, and certain regions in Chile, with an incidence of 27 / 100,000 population (Emde 2020).The incidence worldwide (Walter 2020) is about 3 / 100,000 per year (Herold 2022). In Germany, approximately 2,300 men and 3,000 women develop GB- CA per year (Emde 2020).The incidence has been decreasing for about 20 years (Blitzer 2021). GB- CA is the most common malignant disease of the biliary tract (Krell 2019). The disease peak is usually beyond the age of 70. Approximately 80% of patients also have cholecystolithiasis (Herold 2022). Women are - with 2 - 3 x (Sharma 2017) - significantly more frequently affected than men (Kasper 2015), however, the mortality rate for men is higher (Sharma 2017). Incidental GB- CA represents approximately 70% of all GB- CA in non-endemic areas and occurs in 0.2 - 3% of patients undergoing cholecystectomy (Blitzer 2021). Etiopathogenesis A GB- CA develops due to various genetic and environmental factors (Sharma 2017) such as:- Cholelithiasis (but only about 0.2% of patients with cholelithiasis develop GB- CA [Kasper 2015]).- chronic cholecystitis- Salmonella- permanent excretor (Herold 2022).Gallbladder polyps > 1 cm in diameter are also at risk for degeneration (Herold 2022).Calcification of the gallbladder, the so-called porcelain gallbladder, was long considered a precancerous condition. However, this is now considered in a more differentiated manner (Blitzer 2021). The relative risk of developing GB- CA is 4.6 according to studies by Patel (2011) with an odds ratio of cancer risk. According to the guideline, risk factors include:- Anatomic abnormalities of the intra- and extrahepatic bile ducts.- cholelithiasis- Chronic bacterial and parasitic cholangitis- Diabetes mellitus- Gallbladder polyps- Porcelain gallbladder- Primary sclerosing cholangitis (Blitzer 2021)- Contact with certain chemicals- Consumption of fried foods- Obesity- Mirizzi syndrome (Sharma 2017) Pathophysiology The development of gallbladder carcinoma follows the dysplasia-carcinoma sequence after accumulation of genetic mutations (Herold 2022).Any exposure to carcinogens can cause normal gallbladder epithelium to metaplasize. Metaplasia is followed by dysplasia to carcinoma in situ, which develops into invasive carcinoma after approximately 15 years (Sharma 2017). Manifestation GB- CA is most commonly diagnosed in the 7th decade of life (Emde 2020). Localization The fundus of the gallbladder contains approximately 60% of all GB- CAs, with approximately 30% in the corpus and 10% in the collum vesicae biliaris (Sharma 2017). Clinical features Gallbladder carcinoma causes symptoms only at a very late stage in the form of:- palpable tumor in the area of the gallbladder bearing- occlusive icterus (Herold 2022)- pain in the right upper quadrant- weight loss (Kasper 2015)It is not uncommon for the disease to be discovered as an incidental finding during cholecystectomy (Herold 2022). Diagnostics In the diagnosis of gallbladder carcinoma are used:- sonography- endosonography- MRI- MRC- MR angio- Spiral CT- ERC- PTC (percutaneous transhepatic cholangiography)(Herold 2022) Imaging SonographyIn the early stage of GB- CA, sonographic changes of a cholecystitis are found in the form of a simple wall thickening. If there is additional evidence of a lesion, vascularity, etc., further diagnostic imaging is recommended (Wernberg 2014). Laboratory There is usually an increase in cholestasis parameters such as gamma- GT, AP. The tumor marker CA- 19- 9 value may be elevated (Herold 2022). However, a specific tumor marker of GB- CA has not been found so far (Sharma 2017). Differential diagnosis - Cholecystolithiasis- Cholecystitis (Herold 2022) General therapy Sinn (2021) recommends presenting the patient to a molecular tumor board for potential targeted therapy options.More than 50% of affected patients with malignant biliary tumors have treatable genetic alterations (Sinn 2021).Usual treatment may consist of:Chemotherapy (see "Internal therapy")Radiatio:Adjuvant radiotherapy may be used if there is local lymph node involvement. However, this has not been shown to increase survival (Kasper 2015).Palliative measures:If inoperable, palliative measures such as ERC with metal stent insertion for biliary drainage may be useful (Herold 2022).Surgery (see below). In recent years, other therapeutic measures have been developed such as:- Next-generation sequencing (NGS)- Whole Exome Sequencing (WES)- RNA sequencing (RNA-seq)- Single exome sequencing (Song 2020) Internal therapy As of 2017, there have been 2 relevant positive phase III trials for first-line treatment of malignant biliary tumor:1. gemcitabine2. cisplatin (sense 2021).This therapy remains the established standard of care in first-line palliative therapy (Sinn 2021).Patients after curative intended resection should be offered adjuvant chemotherapy with capecitabine for 6 months (Sinn 2021).Similarly, therapy with capecitabine can be given as neoadjuvant therapy before resection or as adjuvant therapy in high-risk constellations (Herold 2022).Dosage recommendation: 1,250 mg / m² 2 x / d on days 1 - 14 with a 21-day cycle duration for a total of 8 cycles. After cholecystectomy, chemotherapy should be given p. o. for approximately 12 weeks (Blitzer 2021).Palliative chemotherapy has not been shown to significantly prolong survival (Herold 2022). Operative therapie Gallbladder carcinomas are rarely resectable (Kasper 2015). The risk of recurrence is between 40-80% (Blitzer 2021) and is lower in incisional GB- CA (Qadan 2016).Only in the stage of carcinoma in situ (Tis) and T1 N0 M0- carcinoma is cholecystectomy oncologically sufficient (Herold 2022). In addition, a complete resection (R0- resection) should appear surgically possible (Blitzer 2021).Otherwise, in more advanced stages, extended resection in special centers have been described curatively (Herold 2022).From stage ≥ T1b, liver resection with systematic lymphadenectomy is indicated in addition to cholecystectomy for operable patients (Blitzer 2021).For incisional GB-CA, early resection is recommended from stage T1b onward, if the patient's general condition permits (Blitzer 2021), because the side of the gallbladder facing the liver does not have peritoneal coverage and therefore the tumor can rapidly infiltrate the liver tissue. In up to 33% of patients with T2 tumors, microtumors are found in the adjacent liver parenchyma (Krell 2019). Progression/forecast In 1958 Fortner and Pack still described: "The 5-year survival of a patient with gallbladder cancer represents a medical curiosity" (Krell 2019).Nowadays, the 5-year survival rate for gallbladder carcinoma is between 5 - 15% (Blitzer 2021). Emde (2020) describes the median overall survival in his clientele as 9.1 months.Only R0- resection has a relatively good prognosis with up to 75% of 5-year survival rates (Blitzer 2021). In all other stages, the prognosis is poor (Herold 2022).The average survival time is about 6 months (Kasper 2015). Literature Bitzer M, Voesch S, Albert J, Bartenstein P, Bechstein W, Blödt S, Brunner T, Dombrowski F, Evert M, Follmann M, La Fougère C, Freudenberger P, Geier A, Gkika E, Götz M, Hammes E, Helmberger T, Hoffmann R T, Hofmann W P, Huppert P, Kautz A, Knötgen G, Körber J, Krug D, Lammert F, Lang H, Langer T, Lenz P, Mahnken A, Meining A, Micke O, Nadalin S, Nguyen H P, Ockenga J, Oldhafer K, Paprottka P, Paradies K, Pereira P, Persigehl T, Plauth M, Plentz R, Pohl J, Riemer J,Reimer P, Ringwald J, Ritterbusch U, Roeb E, Schellhaas B, Schirmacher P, Schmid I, Schuler A, von Schweinitz D, Seehofer D, Sinn M, Stein A, Stengel A, Steubesand N, Stoll C, Tannapfel A. Taubert A. Trojan J, van Thiel I, Tholen R. Vogel A, Vogl T, Vorwerk H, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wittekind C, Wörns M A, Galle P, Malek N (2021) S3 guideline-diagnosis and therapy of biliary carcinomas. AWMF Register Number: 032-053OLEmde C T (2020) Outcomes and prognostic factors of gallbladder carcinoma from the surgical clinic of the University Medicine Greifswald from 2001 to 2009. Inaugural - Dissertation for the degree of Doctor of Medicine (Dr. med.) of the University Medicine of the Ernst-Moritz-Arndt-University Greifswald.Herold G et al (2022) Internal medicine. Herold Publishers 569Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 285, 553Krell R W, Wei A C (2019) Gallbladder cancer: surgical management. Chin Clin Oncol. 8 (4) 36Patel S, Roa J C, Tapia O, Dursun N, Bagci P, Bastürk O, Cakir A, Losada H, Sarmiento J, Adsay V (2011) Hyalinizing cholecystitis and associated carcinomas: clinicopathologic analysis of a distinctive variant of cholecystitis with porcelain-like features and accompanying diagnostically challenging carcinomas. Am J Surg Pathol. 35 (8) 1104 - 1113.Pommer A, Hasenberg T, Zirngibl H (2022) Clinical guide general surgery - visceral surgery. Elsevier GmbH Munich Urban and Fischer Publishers 582.Qadan M, Kingham P (2016) Technical Aspects of gallbladder cancer surgery. Surg Clin North Am. 96 (2) 229 - 245Sharma A, Sharma K L, Gupta A, Yadav A, Kumar A (2017) Gallbladder cancer epidemiology, pathogenesis and molecular genetics: recent update. World J Gastroenterol. 23 (22) 3978 - 3998Sinn M, Wege H, Stein A (2021) Carcinoma of the bile duct and gallbladder: towards personalized therapy. Dtsch Med Weekly 145, 442 - 446.Song X, Hu Y, Li Y, Shao R, Liu F, Liu Y (2020) Overview of current targeted therapy in gallbladder cancer. Signal Transduct Target Ther. 5 (1) 230.Wagner G, Hermanek P (2013) Organ-specific tumor documentation: principles and coding instructions for clinic and practice. Springer Verlag Berlin / Heidelberg 20.17Walter D, Trojan J, Waidmann O (2020) Systems therapy of gallbladder carcinoma. Z Gastroenterol 58, 583 - 589.Wernberg J A, Lucarelli D D (2014) Gallbladder cancer. Surg Clin North Am. 94 (2) 343 - 360.

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