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A. Puzziello et al.
20.8 Conversion
In many surgical teams, conversion is mandatory in cases of anatomic difculties 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 etal.
[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 signicance (P 0.765) [32]. However, subgroup analysis of group of “young
old” and “older old” revealed that patients aged 80 or over had a signicantly 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 inammation is the main factor that inuences the adverse outcome in
the elderly.
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Cancer oftheGallbladder
andBiliaryTree
MarcoFilauro, GiulioAngelini, FedericoFazio,
andAndreaBarberis
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
311

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M. Filauro et al.
21.2.1 Epidemiology, Risk Factor, andPathology
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 inammation. 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 identied 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 calcication in the wall
of the gallbladder, probably from a chronic inammatory response, and is a risk
factor for GBC as well, particularly in those cases where gallbladder wall calcication is not complete where the risk of malignancy rises to 41% [5].
Gallbladder polyps are also a risk factor for GBC, and size >1cm is an independent factor for malignancy; risk of malignancy is 60–62% for polyps <1cm but
reaches 46–70% for polyps >1.5cm [6].
Histologically most GBC are adenocarcinoma (about 90%); other kinds of
malignancies are represented by squamous cell carcinoma (4%), neuroendocrine
(3%), or sarcoma/others unspecied (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
nonspecic, 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 [11–13].

21 Cancer oftheGallbladder andBiliary 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.
313
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 ofUnresectable 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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M. Filauro et al.
perihilar or distal tumors: perihilar CCA, a more common type, arises from main
bile duct conuence and distal CCA is localized between the conuence and the
Vater’s ampulla. This disease has a bad prognosis, also due to its late diagnosis.
21.3.1 Epidemiology, Risk Factor, andPathology
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 difcult to interpret data from the
American Cancer Society: in fact, intrahepatic and extrahepatic CCA are classied,
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 inammation of
the biliary epithelium.
Primary sclerosing cholangitis is a chronic inammatory disease of the biliary
tree that leads to brosis of bile ducts; sometimes it is associated with bowel inammatory 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,
andare 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 inammation.
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 10years, 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 inammation 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 oftheGallbladder andBiliary Tree
315
completely understood but seems to correlate to biliary stasis, pancreatic juice
reux causing activation of bile acids, and chronic inammation [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 conuence
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 classied following the
Bismuth-Corlette classication: type I, tumors below the conuence of the left and
right hepatic ducts; type II, reaching the conuence 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 classication 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
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