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A. Puzziello et al.
20.8 Conversion
In many surgical teams, conversion is mandatory in cases of anatomic difculties or complications. A conversion does not make the operation easier or safer. The con­version rate depends on the surgical team’s experience and work volume. The cor­relation between age and conversion has been previously reported in elective surgery for cholelithiasis [32, 51] as well as in AC [30]. Conversion to open surgery is more frequent in elderly patients and ranges between 5 and 25% [10, 47, 52]. Yetkin etal. [32] report a conversion rate of 8% in the younger age group. Although the conver­sion rates were higher in the elderly group of “young old”, this did not reach statisti­cal signicance (P 0.765) [32]. However, subgroup analysis of group of “young old” and “older old” revealed that patients aged 80 or over had a signicantly higher conversion rate than that of other subgroups (P 0.01), a nding which is also in agreement with the literature. Increased age has been noted in the literature as a preoperative risk factor for conversion, perhaps due to a longer history of gallstones and increased number of cholecystitis attacks [53, 54].
Conclusion
The evaluation of a new technology and/or innovative surgical technique has
many problems, which are related in part to a cultural attitude towards evidence-
based surgery [55]. In addition, some factors can also bias the best randomized
trials with random sampling. Moreover, the success of an intervention is not only
related to the surgeon’s skills and experience but also to the patient’s character-
istics. Diffusion of new techniques in surgery is also related to sociological fac-
tors. Whatever the quality of innovation, these factors affect its adoption on a
large scale, thus making any attempt at objective analysis useless: “It is always
too early (for rigorous evaluation) until, unfortunately, it’s suddenly too late”
(Buxton’s law) [56].
In elderly patient, the laparoscopic approach was initially reserved for low­risk patients, although age has never been a contraindication [47]. It is therefore important to consider the impact that this procedure has had on the fastest grow­ing segment of our population, ageing patients, who are at high risk for surgery [5]. LC can be performed safely in extremely elderly patients. However, the pres­ence of inammation is the main factor that inuences the adverse outcome in the elderly.
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20 Cholecystectomy inElderly: Challenge andCritical Analysis ofAvailable Evidence
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20 Cholecystectomy inElderly: Challenge andCritical Analysis ofAvailable Evidence
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Cancer oftheGallbladder andBiliaryTree
MarcoFilauro, GiulioAngelini, FedericoFazio, andAndreaBarberis
21.1 Introduction
Cancer of the gallbladder and biliary tree are still stimulating challenges of modern surgery; the incidence of such diseases is not decreasing, and surgeons have become more aggressive in the last few years with the aim of radically removing neoplasms of this district. Studies from around the world demonstrate improvement of results in terms of long-term survival and quality of life, in elderly people as well. The purpose of this chapter is to review biliary diseases with emphasis on management in the older adult populations: until recently, age per se was considered the most important factor in the surgical decision-making process. However, efforts have been made to better understand the surgical risk and predict life expectancy of older cancer patients.
21
21.2 Gallbladder Cancer
Gallbladder cancer (GBC) is a form of malignant neoplasia equally rare and aggres­sive; because of its tendency to quickly spread by blood and in the lymphatic and in the intraperitoneal cavity, it’s commonly found in its late presentation, often with disseminated disease. Similarly, gallbladder cancer is often found incidentally after cholecystectomy for benign disease such as cholelithiasis, and this may lead to the necessity of additional surgery. Radical surgery is the only potentially curative treatment.
M. Filauro (*) • G. Angelini • F. Fazio • A. Barberis E.O.Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genova, Italy e-mail: marco.lauro@galliera.it
© Springer International Publishing AG, part of Springer Nature 2018 A. Crucitti (ed.), Surgical Management of Elderly Patients,
https://doi.org/10.1007/978-3-319-60861-7_21
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M. Filauro et al.
21.2.1 Epidemiology, Risk Factor, andPathology
Worldwide the incidence of GBCs correlates with a prevalence of cholelithiasis; countries such as South America and those of Far East Asia have particularly high rates of GBC; in Europe GBC has elevated higher incidence mostly in eastern coun­tries; the incidence data range from 1.5 to 3/100,000 of Northern Europe to
21.5/100,000 of Delhi, India [1]. The pathophysiologic factor underlying GBC is
chronic gallbladder inammation. Predisposing pathologic conditions are gallstone disease, porcelain gallbladder, gallbladder polyps, primary sclerosing cholangitis, abnormal pancreaticobiliary duct junction, and chronic infections such as salmonel­losis or helicobacter colonization. The main associated risk factor identied so far is cholelithiasis (especially untreated chronic symptomatic gallstones) [2]; gallstone dis­ease results typically from oversaturation of cholesterol in bile, even on a genetic background [3]; not only does it demonstrated a higher prevalence of GBC among people with cholelithiasis but also most patients with GBC have gallstone disease [4].
Porcelain gallbladder is characterized by the presence of calcication in the wall of the gallbladder, probably from a chronic inammatory response, and is a risk factor for GBC as well, particularly in those cases where gallbladder wall calcica­tion is not complete where the risk of malignancy rises to 41% [5].
Gallbladder polyps are also a risk factor for GBC, and size >1cm is an indepen­dent factor for malignancy; risk of malignancy is 60–62% for polyps <1cm but reaches 46–70% for polyps >1.5cm [6].
Histologically most GBC are adenocarcinoma (about 90%); other kinds of malignancies are represented by squamous cell carcinoma (4%), neuroendocrine (3%), or sarcoma/others unspecied (3%) [7].
GBC spreads directly to the liver, via lymphatic vessels or by hematogenous means; the extreme facility of its spread is also due, on the side of the liver, to the absence of a serous layer with barrier functions, and, on peritoneal surface, there is only a very thin wall. Commonly it initially invades the liver or porta hepatis structures directly and other adjacent organs; the most common sites of lymphatic metastasis are locoregional lymph nodes. Hematogenous drainage leads to metastasize to the liver (typically IV and V seg­ments) and to other extra-abdominal organs such as lungs [
8].
21.2.2 Diagnosis
GBC can be diagnosed preoperatively, intraoperatively, or postoperatively, inciden­tally at pathological examination following routine cholecystectomy; over two thirds of affected by GBC are diagnosed intra- or postoperatively [9]. Symptoms are nonspecic, such as upper right abdominal quadrant pain, sometimes jaundice, nau­sea, anorexia, and/or weight loss, similar to those of a cholelithiasis or cholecystitis; unfortunately, only 25% of patients who present with symptoms are operable [10]. The most common situation is the discovery of the cancer at the time of pathological examination, which accounts for 30% of cases diagnosed with GBC.In three-large series combined, GBC was found in 0.33% of patients undergoing laparoscopic cholecystectomy [1113].
21 Cancer oftheGallbladder andBiliary Tree
When there is a diagnosis or a clinical suspicion of a GBC, it’s important to make a correct preoperative imaging in order to reduce the number of unnecessary surgi­cal attempts.
After blood tests with liver function, US imaging is recommended, followed by contrast-enhanced CT and/or MRI of the chest and abdomen, to evaluate the tumor extension and distant metastases. Endoscopic ultrasound is for some authors very helpful, allowing for good imaging with possible ne needle aspiration biopsy [14]. PET may be a useful method to detect distant or locoregional lymphonodal metas­tases, particularly in the follow-up, but it is not yet inserted in routine diagnostic work-up of GBC.
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21.2.3 Surgical Management
Radical surgical resection, with negative margins, is the only potentially curative treatment; it consists in cholecystectomy, unless the patient has already undergone cholecystectomy with occasional nding at pathologic review, associated to liver resection of segments IVb and V and locoregional lymphadenectomy, including cystic node (Mascagni’s node) and those of hepatic hilum; common bile duct resec­tion is not recommended tout court but only to achieve radical resection with mar­gins free of disease [15]; it can be useful to obtain an intraoperative frozen section of cystic duct stump to decide the need for further resections. Diagnostic laparos­copy avoids a nontherapeutic laparotomy in about 56% with unrespectable disease, and it demonstrates a higher yield primarily in locally advanced tumors than in early-stage tumors where disseminated peritoneal disease is quite rare [16]. A debated issue was the indication to remove the port site after laparoscopic cholecys­tectomy with successive incidental nding of GBG; this has not been shown to change outcomes, since these types of spreads were found in patients with advanced disease and correlates with peritoneal metastasis [17].
21.2.4 Treatment ofUnresectable Disease
Patients with advanced GCA often have a short survival and need palliation for present or future symptoms such as jaundice, dyspepsia, or duodenal occlusion; the main techniques are based on the interventional or endoscopic approach; surgical bypass was in the past described with bilio-enteric anastomosis or with a segment III bypass when hepatic hilum is involved by tumor [18].
21.3 Cholangiocarcinoma
Cholangiocarcinoma (CCA) is a tumor arising from the epithelium of the biliary tree; it can be anatomically divided into intrahepatic (or peripheral) and extrahepatic CCA, depending on where it arises from: within the liver in the rst case and within the extrahepatic bile ducts in the second; extrahepatic CCA are divided into
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perihilar or distal tumors: perihilar CCA, a more common type, arises from main bile duct conuence and distal CCA is localized between the conuence and the Vater’s ampulla. This disease has a bad prognosis, also due to its late diagnosis.
21.3.1 Epidemiology, Risk Factor, andPathology
First described in 1840 by Durand-Fardel [19], CCA is a rare malignancy and its incidence in autopsies is about 0.01–0.46%; in the USA; the reported incidence is about 1–2 cases per 100,000 population [20]. It is difcult to interpret data from the American Cancer Society: in fact, intrahepatic and extrahepatic CCA are classied, respectively, with primary liver cancer and in a separate subgroup that includes gallbladder cancer; the number of primary liver tumors diagnosed annually in the USA is about 39,000 [21], and about 15% are intrahepatic CCA; 15,500 extrahe­patic biliary tumors are estimated to be one third of non-gallbladder neoplasms. Overall incidence of intrahepatic CCA has been rising; this aspect probably is related to new diagnostic methods but may also be due to the concomitant increase in risk factors. Extrahepatic CCA incidence, on the contrary, is decreasing and is substantially unexplained [22].
There are several risk factors for CCA, associated with chronic inammation of the biliary epithelium.
Primary sclerosing cholangitis is a chronic inammatory disease of the biliary tree that leads to brosis of bile ducts; sometimes it is associated with bowel inam­matory diseases, especially ulcerative colitis [23]; CCA rates of 8–40% have been reported in patients with primary sclerosing cholangitis [22].
Intrahepatic biliary stones are more common in Asia as opposed to the West, andare associated particularly with intrahepatic CCA; about 1/10 of patients with hepatolithiasis develop CCA [24]; the pathophysiological mechanism is thought to be the bile stasis and the recurrent biliary infections and epithelial inammation.
Several chemical agents have been associated with CCA: rubber industry expo­sure to nitrosamines and dioxins which are considered risk factors [ a radiological contrast agent, seems to be an important risk factor as it has shown to increase the general population’s risk by 300 times [26].
Liver cirrhosis has been also linked with CCA, with a tenfold risk compared to the otherwise healthy population [27]; moreover, hepatitis B and C viruses were associ­ated with CCA [28]; in a study of patients with cirrhosis with hepatitis C virus, there were 3.5% risk of developing CCA at 10years, which was about 1000 times higher than the estimated incidence of this cancer in the general population [29].
In Asia, a well-known risk factor is parasitic infection with liver ukes of the genera Opisthorchis and Clonorchis [30]; the infection is contracted via eating un- or undercooked sh; inoculated worms lay their eggs in the biliary tree; these parasites induce a chronic inammation that presumably leads to malignant transformation.
Other abnormalities of biliary tree anatomy that are considered a risk factor include choledochal cysts and Caroli’s disease (a congenital condition associated with biliary and renal cysts) [31]; the malignant transformation mechanism is not
25]; thorotrast,
21 Cancer oftheGallbladder andBiliary Tree
315
completely understood but seems to correlate to biliary stasis, pancreatic juice reux causing activation of bile acids, and chronic inammation [32].
Traditionally CCA are divided in intrahepatic CCA, arising from small biliary ductules present in liver parenchyma and extrahepatic CCA; the latter can be further divided according to their location along the biliary tree. It is possible to identify perihilar CCA (also called Klatskin tumors) that arise near/at the biliary conuence of the main left and right hepatic ducts and distal CCA originating from the com­mon bile duct although they are mostly periampullary tumors; generally, perihilar CCA represents 50% of the total, distal CCA 40%, and intrahepatic CCA about 10% of the total [33]. Perihilar CCA has been further classied following the Bismuth-Corlette classication: type I, tumors below the conuence of the left and right hepatic ducts; type II, reaching the conuence but not involving left or right hepatic ducts; type III, occluding the common hepatic duct and either the right (IIIa) or the left (IIIb) hepatic duct; and type IV, multicentric or involving both right and left hepatic ducts (Fig.21.1) [34].
Most of CCA (more than 90%) are well- or moderate-differentiated adenocarci­nomas. Other carcinomas which is possible to nd in the biliary tree are intestinal­type adenocarcinomas; signet cell carcinomas, with intracellular mucin, mucinous adenocarcinomas, adenosquamous carcinomas, clear-cell carcinoma (with similar morphology to renal cell carcinoma), and sarcomatoid/undifferentiated.
Fig. 21.1 Bismuth-Corlette classication of biliary tract cancers
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Adenocarcinomas are divided in other subgroups: sclerosing (or periductal), nodu­lar (mass-forming), mixed type (sclerosing and mass-forming), or polypoid (intraductal).
21.3.2 Diagnosis
Clinical diagnosis of CCA has to be distinguished from extrahepatic CCA and intra­hepatic type. Extrahepatic CCA typically cause obstruction of biliary system; symptoms include jaundice, pruritus, pale stools, and dark urine; some patients can present abdominal pain (typically in right-upper quadrant), weight loss, and fever; sometimes it’s possible to observe fatigue, night sweats, and malaise [35]. Intrahepatic CCA gives less frequently jaundice; more probably patients will pres­ent with right-upper quadrant pain, weight loss, and elevated alkaline phosphatase; sometimes instead intrahepatic CCA is diagnosed incidentally in the course of clini­cal investigations for other disease.
Blood tests are organized to assess liver function and tumor markers; CEA and CA19.9 can be considered for baseline assessment, bearing in mind that CA 19.9 is elevated in the presence of jaundice [36], and AFP can be utilized to distinguish CCA from hepatocellular carcinoma. After abdominal US, CT, and/or MRI is used to assess tumor stage and resectability (Fig.21.2), the goal of such cross-sectional
Fig. 21.2 CT and MRI imaging of intrahepatic (S8) CCA