Porcelain gallbladder and its relationship to cancer

original article Eur Surg https://doi.org/10.1007/s10353-021-00710-2 Porcelain gallbladder and its relationship to cancer Natale Calomino · Maximilian Leonardo Philip Federico Scheiterle · Daniele Fusario · Noemi La Francesca · Ignazio Martellucci · Daniele Marrelli Received: 5 March 2021 / Accepted: 27 March 2021 © The Author(s) 2021 Summary Background Porcelain gallbladder (PGB) is defined as calcium deposits encrusting the internal visceral layer, which becomes hard, brittle, and bluish. Porcelain gallbladder is rare and has been found in less than 1% of routine cholecystectomy specimens. Several studies report an incidence of gallbladder carcinoma (GBC) associated with gallbladder calcification varying between 12.5 and 61%, data which have been known for 60 years. There is a lack of information concerning PGB and its association with GBC, and the aim of this study is to better define this relationship. Methods A total of 10 patients were found to have PGB in 1050 consecutive routine surgical cholecystectomies. Clinical and laboratory findings, gallbladder histologic examination, bile culture, and bile pH were related to stone composition analysis performed by X-ray diffraction using Perkin–Elmer (Perkin Elmer Corp. Norwalk, CT, US) 1625 FTIR. Results Among the 10 patients with PGB, complete calcification of the entire gallbladder wall was present in six cases, while four patients had partial calcification. Gallstones were present in all cases of PGB, multiple stones in nine cases and a single stone in one case. Bile culture was performed in all patients of Dr. N. Calomino, MD () · M. L. P. F. Scheiterle, MD · D. Fusario, MD · D. Marrelli, MD Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100 Siena, Italy N. La Francesca, MD Department of Human Pathology and Oncology, University of Siena, Siena, Italy I. Martellucci, MD Oncology, Azienda Ospedaliera Universitaria Senese, Siena, Italy K the series. Among the 10 cases with PGB, culture was positive in two cases. Conclusion PGB is a disease as rare as it is subtle. Moreover, the chronic stimulation by stones can generate an initial dysplasia that will subsequently turn into a neoplasm: the cancerization risk is probably no different from long-standing cholesterol or combined stones, but as risk factor for cancer it requires early cholecystectomy. Keywords Cholecystitis · Cholelithiasis · Surgery · Gallbladder cancer · Gallbladder stones Introduction Porcelain gallbladder (PGB) is defined as calcium deposits encrusting the internal visceral layer, which becomes hard, brittle, and bluish ([1], Figs. 1 and 2). The incidence is low, with PGB found in less than 1% of routine cholecystectomy specimens, with a female predominance of 5 to 1 male. Older age is a risk factor, with most occurring over the age of 60 [1–7]. Gallbladder carcinoma (GBC) is an aggressive biliary tract malignancy, rare in most Western countries, although more widespread in other regions of the world, with a particularly high incidence observed in Japan, Chile, India, and Bolivia [6–8]. PGB in children is extremely rare. Adenocarcinoma accounts for 90% of gallbladder cancers [8], while squamous cell carcinomas of the gallbladder account for 2–12%. Other rarer forms of gallbladder cancer include sarcomas, lymphomas, and carcinoids. Although gallstones are a described risk factor for development of gallbladder carcinoma, Comfort et al. showed that less than 1% of patients with asymptomatic gallstones developed gallbladder carcinoma over a 10–25-year period [9, 10]. PGB is currently considered as a late fate of chronic cholecystitis and is included among the most Porcelain gallbladder and its relationship to cancer original article Fig. 1 Laparoscopic view of porcelain gallbladder Fig. 2 important premalignant conditions for GBC. The extent of gallbladder wall involvement varies from the presence of a single calcified plaque adhered to the mucosal layer to total full-thickness replacement of the tissue of the entire gallbladder wall with calcium [1, 8]. Several studies report an incidence of GBC associated with gallbladder calcification varying between 12.5 and 61%, data which have been known for 60 years [10–13]. Other authors think that the condition is not associated with gallbladder malignancy [1]. Actually, the reported incidence is around 2–8% [4, 5]. The aims of this study are to report not only the pathologic findings in the gallbladder wall (as in most of the retrospective studies) but also findings never reported up to now in a large series, such as stone types, structure, and composition; pattern of calcification; bile analysis (pH, culture); and the presumed time lapse between gallbladder calcification and cholecystectomy, in order to better define the relationship between PGB and GBC. Materials and methods A total of 1050 consecutive patients treated by cholecystectomy for benign gallbladder disease at our department between 2003 and 2018 were included in the study, 395 men (37.6%) and 655 women (62.4%). The mean age was 58.6 years (range 19–94). All patients with hyperbilirubinemia due to any cause, known bile duct lithiasis, or those previously treated by ERCP were excluded. Clinical and laboratory findings, gallbladder histologic examination, bile culture, and bile pH were related to stone composition analysis performed by X-ray diffraction using Perkin–Elmer 1625 FTIR (Perkin Elmer Corp. Norwalk, USA). Light stereomicroscopy of stones and scanning electron microscopy of stones (ISI-SX-25 SEM Pabish, Milan, Italy) were also performed in a subset of cases (85 patients with gallstones and 13 patients with GBC). 95% of the procedures were performed by a laparoscopic Porcelain gallbladder and its relationship to cancer Porcelain gallbladder approach (998 pt). Intraoperative cholangiography was performed in all the laparotomic cases (52 pt). Results The whole series (1050 pt) had ultrasonographically demonstrated lithiasis (Figs. 3 and 4). At histological examination a single stone was found in 15% of cases. In 1040 cases we operated patients with gallstones but without PGB: in these cases, stones were ovoidal, single, or multiple in 34%, multifaceted in 35%, combination in 7.5%, composite or other stones in 6.7%, and pigment stones in 11.4%. However, pigment stones in association with other types of stones were found in 5% of other patients. In particular, stones larger than 12 mm were found in 35% of the study population and in 90% of patients with PGB. GBC was incidentally found in 27 cases (27/1050, 2.6%). Multiple lithiasis with a combination of large (size over 12 mm) cholesterol gallstones was found in 25 (92.6%) cases and small cholesterol faceted stones 3–4 mm in diameter in 2 cases. We found 10 cases with PGB at histological examination (Table 1), 8 females (80%) and 2 males (20%). The mean age was 67 years (range 44–88 years). Seven patients with PGB were aware (...truncated)