Early Gallbladder Cancer: Clinical, Morphological, Therapeutic and Evolutionary Aspects

doi:10.4236/ss.2013.411095

Paper Menu >>

Journal Menu >>

Surgical Science, 2013, 4, 486-493

Published Online November 2013 (http://www.scirp.org/journal/ss)

http://dx.doi.org/10.4236/ss.2013.411095

Open Access SS

Early Gallbladder Cancer: Clinical, Morphological,

Therapeutic and Evolutionary Aspects

Berkane Salah*, Abid Larbi

Unit of Visceral and Oncological Surgery, Bologhine Hospital, Algiers, Algeria

Email: *[email protected]

Received September 23, 2013; revised October 20, 2013; accepted October 28, 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Introduction: The early cancer of gallbladder is an entity which is not well recognized currently. It is a cancer which

does not extend beyond the muscularis layer of the gallbladder and it is characterized in almost of cases by the absence

of lymph node and visceral invasion. Patients and Method: We have conducted this retrospective study of all our cases

of early gallbladder cancer treated in our surgical unit. We have studied these through clinical, morphological, thera-

peutical and evolutionary aspects. Results: Of 202 gallbladder carcinoma, 33 cancers were classified as early cancer. 25

were females and 8 were males. The mean age was 56.4 years (41 - 70 years). All patients were free of g allbladder can-

cer symptoms and all except one had normal CEA and CA19.9. 2 patients had synchronous tumors (one colonic cancer

and one rectal cancer). For 16 patients, the diagnosis was done by ultrasonography and 17 by histological examination

of the specimen removed for biliary lithiasis. 8 patients had PT1a tumor (confined only to mucosa) and 25 had PT1b

tumor (tumor infiltration of the muscular layer). For 19 patients who benefited from extensive lymphadenectomy, only

one (5.3%) had lymph node infiltration. 16 patients had a simple cholecystectomy and in two cases, the cholecystec-

tomy was associated with bile duct resection. 17 patients had hepatectomy with extensive lymphadenectomy. 2 patients

had a simultaneous right colectomy and abdominoperineal resection and another one benefited from choledocal cyst

resection. 3 patients benefited from stone removal from bile duct and two had tumor removal from bile duct (ruptured

tumor in the bile duct). 1 patient (3.7%) died in postoperative course (hospital mortality). In the follow-up period, 4

patients died from intercurrent causes. Two patients presented a recurrence at 14 and 36 months and died respectively at

19 and 42 months. One patient presented a bile duct cancer at 66 months. She died at 78 months after palliative treat-

ment. Currently, 22 patients (66.7%) are still alive without recurrence with mean and median survival of 53 and 31

months. Conclusion: Early gallbladder cancer is an entity which must be known by the radiologist and the surgeon.

Recognized on time and well treated, early gallb ladder cancer can be cured and its pro gnosis is excellent.

Keywords: Early Cancer; Gallbladder Cancer; Ultrasonography; Expert Radiologist; Surgical Treatment

1. Introduction

The early gallbladder cancer is an entity which is not well

recognized currently. It is a tumor whose extension does

not extend beyond the muscularis layer of the ga llbladder

and does not have frequent lymph node infiltration and

metastatic spread [1]. Moreover, it represents a proportion

of all gallbladder cancer which could be easily cured. In

spite of modern morphologic examination and specifi-

cally an ultrasonography since twenty years, there is not a

clear improvement in the diagnosis for this disease [2-4].

This form is often diagnosed after histological examina-

tion of specimen removed for biliary lithiasis. Making an

exact diagnosis before surgery has an importance to im-

prove the prognosis of this fatal disease in its invasive

form. Surgery is debated when the muscular layer is in-

vaded (pT1b) between cholecystectomy and radical re-

section whereas the cholecystectomy is the best treatment

for the pT1a (tumor confined to mucosa). In this article,

we present our experience of patients who were managed

in our unit during the fifteen last years and to analyze

immediate and long-term prognosis of this disease.

2. Patients and Method

We analyzed all cases of our patients treated for early

gallbladder cancer. We reported the clinical, morpho-

*Corresponding a uthor.

B. SALAH, A. LARBI 487

logical, biological, surgical and evolutionary features of

these patients. The histological specimen was reanalyzed

for the cancer discovered after cholecystectomy done for

biliary lithiasis. All the following features were asked to

the histologist: histological form and grade (differentia-

tion), parietal extension, perineural, vascular and node

infiltration. In our un it, pT1a tumor (confined to mucosa)

is treated by cholecystectomy and pT1b (muscular infil-

tration) is treated by cholecystectomy alone for the patient

above 70 years and by bisugmen tal IV-V with fatal asso-

ciated disease and extensive lymphadenectomy for pa-

tients under 70 years and without fatal associated disease.

On the postoperative course, the patient is followed

clinically, biologically (Ca 19.9 and CEA) and morpho-

logically (ultrasound) each 3 months during 2 years and

each 6 months during the following 2 years. After 5 years,

we propose only clinically follow up. If a recurrence is

diagnosed, a CT scan or MRI is done to have an exact

diagnosis and if the disease is curable we propose a new

surgery for resection and in the contrary only diversion is

practiced. If there is no need of surgery we propose pal-

liative chemotherapy.

3. Results

Of 202 gallbladder cancer resected since 1996, we report

33 patients with early form (16.3%). There were 25 fe-

males and 8 males, with mean age of 56.4 years (41 - 70

years). No patient had any symptoms related to cancer

before the su rgery and physical examination were normal

or related to lithiasis disease (pain , jaundice and palpable

gallbladder in acute cholecystitis). 20 patients (60.6%)

had associated biliary lithiasis. One patient had a history

of choledocal cyst since 25 years. The diagnosis was done

in the pr eopera tive co urse in 1 6 cases (48 .5%) by the ra di-

ologist with the ultrasonography and CT Scan. 3 last pa-

tients had an endoscopic ultrasonography. 17 cases were

diagnosed on the histologist specimen. All of 24 car-

cino-embryonary antigen (CEA) and carbohydrate anti-

gen 19.9 (CA19.9) measured out were normal except for

one CA19.9 which was at 5618 UI/ml for patient with

ruptured tumor in the bile du ct and jaundice. One patient

was treated for Hodgkin disease 10 years ago; 2 patients

had their polypoid tumors known (diagnosed by ultra-

sonography) respectively 1year and ten years ago. The

tumoral aspect was polypoid in 22 cases (66.7%), thick-

ening wall in 6 cases (18%), unapparent form in 4 cases

(12%) and nodular in 1 case. 2 patients had ruptured tumor

in the bile duct (pT1a and pT1b). Microscopically, all

these cases were adenocarcinoma. 8 cases (24.2%) were

pT1a and 25 cases (75.8%) were pT1b (Table 1: charac-

teristics of 27 cases). 1 patient had a choledocal cyst di-

agnosed and followed by a gastroenterologist during 16

years. 16 patients benefited from a cholecystectomy as-

sociated with bile duct resection in two cases for a tumoral

related cause and another had her choledocal cyst re-

moved with a gallbladder. 2 patients who have had a

cholecystectomy benefited from a lymphadenectomy. For

17 patients, IV-V bisugmental hepatectomy with exten-

sive lymphadenectomy was done. 2 patients had respec-

tively colonic and rectal resection simultaneously. 3 pa-

tients benefited from stone removal from bile duct. Only

one patient presented node infiltration between 19 who

benefited from lymphadenectomy (5.3%). 24 patients

(72.7%) had one op eration and 9 (27.8%) two op erations .

The postoperative course was uneventful for 26 patients

(78.8%) and complicated in 7 cases (21.2%). One patient

(3%) died from myocardial infarction (Table 2: surgical

treatment). Two patients benefited from systemic che-

motherapy, one because she had had cystic infiltrative

node and another had associated liver metastatic lesion.

On the long term follow up, one patient received ex ternal

beam therapy for uterine cervix cancer diagnosed 2 years

after the cholecystectomy. One patient died from a colon

cancer recurrence at 15 months without any evident gall-

bladder cancer recurrence. 2 patients (6%) presented a

recurrence at respectively 14 and 36 months. They were

initially treated by cholecystectomy. One benefited from

bisugmental IV-V with lymphadenectomy and chemo-

therapy and died from a new recurrence at 19 m onths. The

second patient had exploratory laparotomy and died at 42

months. One patient presented a bile duct cancer (upper

part) at 66 months. She refused a surgery and died at 78

months. One patient died from acute diabetes complica-

tions at 5 6 months a nd other di ed from gastri c hemorrhage

secondary to gastric ulcus. One patient died from another

disease at 67 months (portal high pressure). One was lost

for follow up at 39 months. 22 patients (66.7%) are still

alive with mean survival of 51 months and median sur-

vival of 32 months. The global 3 and 5 year survival are

respectively 53% and 34%. 11 patients (33.3%) had more

than 5 year survival and the two oldest had more than 10

years. No recurrence case occurred until nowadays for

PTa tumor.

4. Discussion

The early cancer of gallbladder is a form which can be

recognized by modern morphological examination but it

is still diagnosed after surgery for biliary lithiasis. On

clinical aspect, it is a silent disease (without any symp-

toms). This feature c ould expl ain this absenc e of diagnosi s.

Currently, it can be recognized in 2 situations:

 On preoperative cou rse with ultrasonogr aph y [3-5].

 On the histological exam ination after cholecystectomy

for biliary lithiasis [5-8].

For a clinician to make a diagnosis before a surgical

step, he need s an expert ra diologist w ho should be vigilant

during ultrasound examination. There are two funda-

mentals lesions which are in favor of an early cancer:

Open Access SS

B. SALAH, A. LARBI

Open Access SS

488

Table 1. Characteristics of patients.

Case Age Sex LB D M M’ L D (mm) AP CA19.9CEA

30*

Yes

UNA

NOD

ADKNS

ADK (MIXED)

ADK (WD)

ADK (NS)

ADK (WD)

ADK (MD)

ADK (WD)

ADK (WD) PAP

ADK(WD)

ADK (WD)

ADK (WD) PAP

ADK (MIXED)

ADK (WD)

ADK (WD) PAP

ADK (WD)

ADK (WD) PAP

ADK (WD) + CM

ADK (WD)

ADK (MD)

ADK (WD)

ADKNS

ADK (WD)

ADKWD

F + C

UNA

8 - 9

12 - 15 - 20

30 - 10

Synchronous Colon

cancer

BPM

URC + rectal cancer

BPM: biliary pancreatic maljunction; BL: biliary lithiasis; D: diagnosis; E: elevated; F: fundus; C: corpus; Ne: neck. HD: histological d iscovery; CC: choled ocal

cyst; ADKWD: adenocarcin oma well-differentiated, M: Macr oscopic asp ect. M’: micr oscop y; AMD: adeno carcino ma mean di fferentiated, ADK NS: aden ocar-

cinoma not specified; L: location; N: no rmal; AP: a ssociated path ology; Ca19 .9: carbohy drate antige n 19.9; CEA: c arcino-embry onary antigen; P: polypoid lesion;

TW: thickened wall; NOD: nodal aspect; UD: ultrasound discovery UN: unapparent; URC: ulcerative.

 The most easie r form to be detect ed is a polypoid form

(Figure 1).

It is an image which is appended to the gallbladder wall.

It has the same ultrasound-structure than the liver. It is

immobile at the patient positions changes and does not

give an acoustic shadow. This polyp could be single or

multiple, with or without a pedicle. Some features could

orient to the malignant nature, but the strong element is

the polyp diameter (Table 2: malignant criterion of gall-

bladder polyp). If the polypoid form is easily recognized

in a gallbladder without stones by the radiologist, this last

could misinterpret the diagnosis when the gallbladder

contains several stones. In this case, the tumor lesion

could be hidden by stones and this diagnosis become

difficult if not impossible. For this reason, the ultrasono-

graphy should be done on 2 different positions (lying on

the back and on the side). With the lithiasis, acute chole-

cystitis with the inflammatory changes induced could

impede the polyp detection by the radiologist.

Figure 1. Image of polypoid lesion of the fundus of the gall-

bladder on ultrasound examination.

a thickening wall (infiltrative form). This abnormality

could be localized or generalized in the gallbladder

wall.

 The second image of the early cancer is re presented by

B. SALAH, A. LARBI 489

Table 2. Therapeutic and evolutionary aspec ts.

Case Treatment Postoperative course Current status Cause of death

1 CX Simple AWD at 120 months

2 CX Simple AWD at 126 months

3 IV-V+ lymphadenectomy Simple AWD at 156 months

4 CX Simple DWD at 56 months*

5 IV-V + lym p h a d e nectomy Simple AWD at 140 months

6 IV-V + lymphadenectomy External biliary fistula LOF at 39 months

7 CX Simple AWD at 96 months

8 CX + colonic resection Simple DWD at 15 mon ths* Died from colonic

cancer recurrence

9 CX Simple DWD at 78 months Bile duct cancer

10 CX Simple AWD at 81 months

11 IV-V + lymphadenectomy + tumor

removal from bile duct Residual tumor in bile duct Alive at 69 months

12 CX Simple DOD at 19 months Hepatic recurrence

13 CX + bile duct resection Simple AWD at 68 months

14 CX Simple AWD at 72 months

15 CX Simple DOD at 42 months Hepatic recurrence

16 IV-V + lymphadenectomy + chemoth erapy Simple DWD at 67 months Hypertension portal?

17 CX + IV-V + lymphadenectomy Lymphatic fistula DWD at 20 months Gastric ulcer Hemor-

rhage

18 CX+ IV-V + lymphadenectomy Postoperative death POD Myocardial infarction

19 IV-V + lym p h a d e nectomy + tumor rem o v a l

from bile duct External biliary fistula AWD at 37 months

21 IV-V + lym p hadenectomy Simple AWD at 37 months

20 CX + choledocal cyst resection Simple AWD at 36 months

22 IV-V + lym p hadenectomy Wound sepsis AWD at 28 months

23 IV-V + lymphadenectomy Hepatic necrosis AWD at 28 months

24 CX + abdominoperineal resection Simple AWD at 25 months

25 IV-V + lym p hadenectomy Simple AWD at 27 months

26 CX Simple AWD at 25 months

27 IV-V lymphadenectomy Simple AWD at 20 months

28 CX+IV-V+ lymphadenectomy Simple AWD at 18 mont hs

29 IV-V+ lymphadenectomy + chemotherapy Wound sepsis AWD at 20 months

32 CX+ IV-V+ lymphadenectomy Simple AWD at 10 months

31 CX Simple AWD at 8 months

30* CX+ bile duct resection Simple AWD at 7 months

33 CX + IV – V + lymphadenectomy Acute renal failure AWD at 4 months

AWD: alive without disease; DWD: died witho ut disease; DOD: died with disease; LOF: lost for follow up; POD: postoperative deat h; CX: cholecystectomy;

IV-V: bisugmental he patectomy.

For the radiologist, each lesion of this kind detected

with a meticulous examination of the gallbladder wall

should be considered as a malignant lesion especially

when it is limited to one part of the wall. The difficulty is

represented by the presence of the acute cholecystitis.

Onoyama [3] had used the ultrasonography for 53 patients

with an early cancer. He was able to do the diagnosis in

34% of all form of cases. For the polypoid form, the

preoperative diagnosis had been done in 75% of cases in

the absence of lithiasis whereas it was possible only in

38.1% of cases in presence of lithiasis. For the infiltrative

form (thickening wall), the diagnosis was done respec-

tively in 5.9% et 0%. Tsuchiya [5] founds the same dif-

ficulty in his series in presence of lithiasis and with the

thickening wall. The early cancer of the gallbladder is

suspected b etween the patie nts of the first group (INF 0) of

the Japanese Society of biliary su rgery (JSBS) [9]. In our

series and with the same examination (trans-cutaneous

ultrasonography), the preoperative diagnosis have been

done only in 16 cases (48.5%) and all these cases were

Open Access SS

B. SALAH, A. LARBI

490

polypoid form. Between these, 5cases had lithiasis and 5

did not have. The contribution of the CT scan (Figure 2)

for the diagnostic is good and the endoscopic ultrasono-

graphy seems also to be an excellent tool if well executed

[4,10]. The endoscopic ultrasonography should be done

after the trans-cutaneous ultrasonography (second inten-

tion). This examination could show the degree of parietal

extension and then made a difference between an early

form (pT1) and invasive form (pT2 and pT3) of gall-

bladder cancer [10]. But, few studies had been done with

this examination currently. In our experience, we have

started the prac tice of the endo scopic ultrasonog raphy and

the preliminary results are encouraging.

The second possibility to recognize this form of gall-

bladder cancer is represented by the histological exami-

nation of gallbladder specimen resected for biliary lithi-

asis and it is more common until nowadays. It is well

known that in the almost cases, the surgeon can perfectly

suspect this cancer after opening the gallbladder. It is

macroscopically apparent on the mucosa of the gallblad-

der in almost cases [2,3,6,7,11,12]. I n our se ries, it was the

case (macroscopically visible) in 29 cases (87.8%) after

the opening of the gallbladder by the surgeon . It was easy

for a polypoid form and difficult for the thickening form

especially when it is associated with cholecystitis. This

fact is very important for the treatment and binds the

surgeon to open the gallbladder at the end of the inter-

vention and scr uti nize t he gall bl adder m ucosa and i ts wa ll

[8] (Figure 3). 4 unapparent forms (mucosa apparently

normal in case of acute cholecystitis) were encountered in

our series (intraepithelial adenocarcinoma) and not rec-

ognized. For us, each resected gallbladder should be

opened and carefully ex amined at the end of intervention

and before the abdominal closure or port ablation by the

surgeon. The specimen should have a histological ex-

Figure 2. Image of polypoid lesion of the fundus of the gall-

bladder on CT scan examination.

Figure 3. Specimen of PT1b gallbladder cancer.

amination in a short delay. All parts of the gallbladder

must be examined. In th is series, we encountered infiltra-

tive cystic stump in which high degree of dysplasia was

found after the second operation done 2 months later in

patient who benefited from bile duct resection after a

cholecystectomy.

The treatment of early gallbladder cancer is surgery

[6,11-15]. T he best t reatm ent is cholecystectomy which is

curative for the majority of the authors [8,16-19]. For

others, the cholecyst ectomy is suf ficient only for t he pT1a

form (mucosal tumor). A radical resection (cholecystec-

tomy associated with hepatectomy and lymphadenectomy)

is indicated for the pT1b form (involvement of the mus-

cularis layer) [20-22]. This controversy seems to found its

explanation in the fact that these authors find a node ex-

tension in the PT1b form [14,20]. For Shimizu et al. [23]

and Shukla et al. [24], the best treatment for PT1b is a

radical cholecystectomy and then the reoperation is rec-

ommended. In our series, two patients with pT1b tumor

presented recurrence at 14 and 36 months (6%) after

cholecystectomy alone and on e have an infiltrative cystic

node. No patient has presented any recurrence until now

after radical resection for PT1b. Another explanation of

this controversy could be the imperfection of the histo-

logical examination and som e cases of the PT1b are in fact

invasive form PT2 or even PT3 for which the cholecys-

tectomy is insufficient. We have an example with patient

who had 2 foci of tumor, one PT1b in the corpus of the

gallbladder and another PT3 in the neck (data not shown).

M. A. Abramson et al. [25] demonstrated that the greatest

benefit in gained life-years is achieved for the youngest

ages having radical resection. We agree with this view.

For us, if the patient with pT1b tumor is 70-year-old or

less and without a serious general disease and a long life

Open Access SS

B. SALAH, A. LARBI 491

expectancy, the radical surgery (re-resection) is indicated

but if the age is upon 70 years or the patient has a serious

general disease or a short life expectancy, the radical

surgery in must be avoided. It is what we have chosen for

our patient. A recent and large study has reported a good

prognosis with radical surgery which contains hepatec-

tomy and lymphadenectomy [25].

If the diagnosis is done in the preoperative step, the

radical approach is indicated for us when we do not know

infiltrative degree in the gallbladder wall. We started

recently the use of endoscopic ultrasonography after

trans-cutan eous ultr asonogr aphy in the aim to exp lore th e

wall extension and to not misinterpret an invasive form

(PT2 or PT3) and make a difference between PT1a and

PT1b. In the opposite case, the decision is difficult.

Should we do a simple cholecystectomy or a radical re-

section? During the intervention, the surgeon could lead

himself on the aspect of the serous layer for the tumor

located on peritoneal side of the gallbladder. If it is an

early form, the serous layer is normal but if it is the con-

trary (retraction of serous surface and white color…),

invasi ve f orm m ust be susp ec t ed. I f t he dou b t pers is ts , t he

surgeon could practice a radical cholecystectomy if the

patient can support this surgery. If the diagnosis is done

after the opening of the gallbladder at the end of the op-

eration, it is wiser to wait the definitive histological ex-

amination. If it is a pT1a cancer the cholecystectomy is

sufficient. The invasive form (PT2-T3) and PT1b needs a

second operation [6,8]. The quality of the histological

examination is fundamental. The histologist should verify

with a multiple sections if there is not foci of invasive

tumor or a lesi on in the Rokitanski-As choff sinus and f or a

lesion near cystic channel (tumor of the neck) in which a

surgeon would h ave cut in the tumor [8]. Others criterion

are perineural infiltration and vascular embolus which

must be noted in the histological report. If the patient

presents a node infiltration, we advocate a systemic

chemotherapy as adjuvant therapy. We have used sys-

temic chemotherapy for two of our (one with infiltrative

node and one with small liver metastasis).

The postoperative course is sim ple in almost cases. T he

prognosis of this form of gallbladder cancer is excellent

with a cholecystectomy [2,11,14,16,18] and radical

cholecystectomy. The 5 year survival fluctuates between

70% and 100% [2,7,8,11, 14,16-21,26]. In our experience,

we encountered one death (radical cholecystectomy) not

related to the surgery (myocardial infarction). It is one of

the favorable form in which we can talk about a complete

recovery after a treatment, even if late recurrences have

been reported in the literature [11,21].

5. Conclusion

There is a clear evidence through our experience and

literature that the early gallbladder cancer could be rec-

ognized in the preop erative course with the modern mor-

phologic examination (trans-cutaneous ultrasonography,

CT scan, endoscopic ultrasonography…) and on histo-

logical specimen. This form is without gallbladder cancer

symptoms, and tumor markers (CEA and CA19.9) are

usually normal. A polypoid is the easy recognizable

morpholo gical form by the ra diologist. The t hickened wall

form is more difficult to be diagnosed on ultras onography.

We focus on the fact that all the specialized teams (radi-

ologist, surgeon, gastroenterologist, histologist…) are

concerned in order to have a well conducted diagnosis

approach and treatment. The radiologist is the key-ele-

ment in this way. The trans-cutaneous ultrasonography

examination (referential examination) should be done in

minimally two positions in order to not misinterpret a

tumoral lesion. Each infiltrative lesion (thick wall) must

be addressed to a surgeon for a cholecystectomy. For the

polypoid lesion, each polyp whose the diameter is above

10 mm is an indication of a cholecystectomy. Follow-up

with ultrasonography for a lesion under 10 mm is indi-

cated (Figure 4). The surgeon must do a simple chole-

cystectomy in case of PT1a and radical resection for the

PT1b for the majority of cases. Well treated, almost of

these patients will be cured.

Polypoid lesion

of the gallbladder

Symptomatic Asymptomatic

Cholecystecto my Ultrasound

follow-up

Negative Positive

Abstention

Great polyp > 10 mm Small polyp < 10 mm

Complications Without

complications

Ultrasound

follow-up at

3 - 6 mo nths.

Figure 4. Algorithm of gallbladder polyp follow-up.

Open Access SS

B. SALAH, A. LARBI

492

REFERENCES

[1] R. Mizumoto, Y. Ogura and T. Kusuda, “Definition and

Diagnostic of Early Cancer of Biliary Tract,” Hepato-

Gastroenyterology, Vol. 40, No. 1, 1993, pp. 69-77.

[2] A. Koga, S. Yamaguchi, Y. Izumi and N. Hamanaka,

“Ultrasonographic Detection of Early and Curable Carci-

noma of the Gallbladder,” British Journal of Surgery, Vol.

72, No. 9, 1988, pp. 728-730.

http://dx.doi.org/10.1002/bjs.1800720919

[3] H. Onoyama, M. Yamamoto, M. Takada, T. Urakawa, T.

Ajiki, I. Yamada, T. Fujita and Y. Saitoh, “Diagnostic

Imaging of Early Gallbladder Cancer: Retrospective

Study of 53 Cases,” World Journal of Surgery, Vol. 23,

No. 7, 1999, pp. 708-712.

http://dx.doi.org/10.1007/PL00012373

[4] K. Ouchi, M. Suzuki, S. Saijo, K. Ito and S. Matsuno,

“Do Recent Advances in Diagnosis and Operative Man-

agement Improve the Outcome of Gallbladder Carci-

noma,” Surgery, Vol. 113, 1993, pp. 324-329.

[5] Y. Tsuchiya, “Early Carcinoma of the Gallbladder: Mac-

roscopic Features and Us Findings,” Radiology, Vol. 179,

No. 1, 1991, pp. 171-175.

[6] O. Glehen, O. Czyglik, A. D. V. Donsbeck, S. Isaak, F. N.

Gilly, Y. François and J. Vignal, “Cancers Vésiculaires de

Découverte Fortuite,” Annales de Chirurgie, Vol. 125, No.

2, 2000, pp. 137-143.

http://dx.doi.org/10.1016/S0001-4001(00)00114-8

[7] E. Kraas, D. Frauenschuh and S. Farke, “Intraoperative

Suspicion of Gallbladder Carcinoma in Laparoscopic

Surgery: What to Do?” Digestive Surgery, Vol. 19, No. 6,

2002, pp. 489-493. http://dx.doi.org/10.1159/000067602

[8] Y. Shirai, K. Yoshida, K. Tsukada and T. Muto, “Unap-

parent Carcinoma of the Gallbladder,” Annals of Surgery,

Vol. 215, 1992, pp. 326-331.

http://dx.doi.org/10.1097/00000658-199204000-00004

[9] F. Iida, S. Kajikawa and N. Horigone, “Evaluation of

Imaging Examination for Hepatic Invasion of Carcinoma

of the Gallbladder and Post Operative Outcome,” Journal

of the American College of Surgeons, Vol. 180, No. 1,

1995, pp. 72-76.

[10] T. Azuma, T. Yoshikawa, T. Araida and K. Takasaki,

“Differential Diagnosis of Polypoid Lesions of the Gall-

bladder by Endoscopic Ultrasonography,” American Jour-

nal of Surgery, Vol. 181, No. 1, 2001, pp. 65-70.

http://dx.doi.org/10.1016/S0002-9610(00)00526-2

[11] R. M. Appleman, C. G. Morlock, D. C. Dahlin and M. A.

Adson, “Long Term Survival in Carcinoma of the Gall-

bladder,” Surgical, Gynecology and Obstetric, Vol. 117,

1963, pp. 459- 464.

[12] X. de Aretxabala, I. Roa, L. Burgos, J. C. Araya, L.

Fonseca, I. Wistuba and P. Flores, “Gallblader Cancer in

Chile. A Report on 54 Potentially Resectable Tumors,”

Cancer, Vol. 69, No. 1, 1992, pp. 60-65.

http://dx.doi.org/10.1002/1097-0142(19920101)69:1<60::

AID-CNCR2820690112>3.0.CO;2-N

[13] H. Isman and M. Brisard, “L’espoir de Guérison du

Cancer de la Vésicule Biliaire. Arguments Pour une

Conception Nouvelle des Stades Précoces,” Journal de

Chirurgie, Vol. 121, No. 1, 1984, pp. 51-55.

[14] Y. Ogura, R. Mizumoto, S. Isaji, T. Kusuda, S. Matsuda

and M. Tabata, “Radical Operations for Carcinoma of the

Gallbladder: Present Status in Japan,” World Journal of

Surgery, Vol. 15, No. 3, 1991, pp. 337-343.

http://dx.doi.org/10.1007/BF01658725

[15] K. Ouchi, M. Suzuki, T. Tominaga, S. Saijo and S. Ma-

tsuno, “Survival after Surgery for Cancer of the Gall-

bladder,” Briti sh Journal of Surgery, Vol. 81, No. 11, 1994,

pp. 16655-1657.

http://dx.doi.org/10.1002/bjs.1800811131

[16] T. Wakai, Y. Shirai, N. Yokoyama, S. Nagakura, H. Wa-

tanabe and K. Hatakeyama, “Early Gallbladder Carci-

noma Does Not Warrant Radical Resection,” British

Journal of Surgery, Vol. 88, No. 5, 2001, pp. 675-678.

http://dx.doi.org/10.1046/j.1365-2168.2001.01749.x

[17] M. Yamamoto, H. Onoyama, T. Ajiki, I. Yamada, T.

Fujita and Y. Saitoh, “Surgical Results of Operation for

Carcinoma of the Gallbladder,” Hepato-Gastroenterology,

Vol. 46, No. 27, 1999, pp. 1552-1556.

[18] K. Yamaguchi and M. Tsuneoshi, “Subclinical Gallblad-

der Carcinoma,” American Journal of Surgery, Vol. 163,

No. 4, 1992, pp. 382-386.

http://dx.doi.org/10.1016/0002-9610(92)90038-S

[19] K. Yamaguchi, K. Chijiiwa, S. Saiki, K. Nishihara, M.

Takashima, K. Kawakami and M. Tanaka, “Retrospective

Analysis of 70 Operations for Gallbladder Carcinoma,”

British Journal of Surgery, Vol. 84, No. 2, 1997, pp.

200-204. http://dx.doi.org/10.1002/bjs.1800840217

[20] H. Kinoshita, K. Hashiro, M. Hashimoto, T. Kodama, K.

Nishimura, M. Kawataba, S. Furukawa, T. Tamae, J. Na-

gashima, M. Hara, H. Imayama and S. Aoyagi, “Clinico-

pathological Evaluation of Surgical Treatment for Early

Gallbladder Cancer,” Kurume Medical Journal, Vol. 48,

No. 4, 2001, pp. 267-271.

http://dx.doi.org/10.2739/kurumemedj.48.267

[21] G. Wagholikar, D. Gajanan, A. Behari, N. Krishnani, A.

Kumar, S. S. Sadiq, R. Saxena and V. K. Kapoor, “Early

Gallbladder Carcinoma,” Journal of the American Col-

lege of Surgeons, Vol. 194, No. 5, 2002, pp. 137-141.

http://dx.doi.org/10.1016/S1072-7515(01)01136-X

[22] E. Yildrim, O. Celen, K. Gulben and U. Berberuglu, “The

Surgical Management of Incidental Gallbladder Carci-

noma,” European Journal of Surgery, Vol. 31, N o . 1, 2005,

pp. 45-52.

[23] T. Shimizu, Y. Arima, S. Yokomuro, H. Yoshida, Y.

Mamada, T. Numura , N. Tania i, T. Aimoto, Y. Nakamura,

Y. Mizuguchi, Y. Kawahigashi, E. Uchida, K. Akimaru

and T. Tajiri, “Incidental Gallbladder Cancer Diagnosed

during and after Laparoscopic Cholecystectomy,” Journal

of Nippon Medical School, Vol. 73, 2006, pp. 136-140.

[24] P. J. Shukla, G. Barreto, A. Karade and S. V. Shrikhande,

“Revision Surgery for Incidental Gallbladder: Factors In-

fluencing Operability and Further Evidence for pT1b

Tumors,” HPB, Vol. 10, No. 1, 2008, pp. 43-47.

http://dx.doi.org/10.1080/13651820701867794

[25] M. A. Abramson, P. Pandharipande, D. Ruan, J. S. Gold

and E. E. Whang, “Radical Resection for pT1b Cancer: A

Open Access SS

B. SALAH, A. LARBI

Open Access SS

493

Decision Analysis,” HPB, Vol. 11, No. 8, 2009, pp. 656-

663. http://dx.doi.org/10.1111/j.1477-2574.2009.00108.x

[26] D. M. Hari, J. H. Howard, A. M. Leung, C. G. Chui, M. S.

Sim and A. J. Bilchik, “A 21-Year Analysis of Stage I

Gallbladder Carcinoma: Is Cholecystectomy Alone Ade-

quate?” HPB, Vol. 15, No. 1, 2013, pp. 40-48.

http://dx.doi.org/10.1111/j.1477-2574.2012.00559.x