Open access peer-reviewed chapter

Surgical Advances in the Treatment of Gallbladder Carcinoma at Different Stages

Written By

Nicolae Bacalbasa, Irina Balescu, Simona Dima and Irinel Popescu

Submitted: October 5th, 2018 Reviewed: January 4th, 2019 Published: September 25th, 2019

DOI: 10.5772/intechopen.84154

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Abstract

Gallbladder carcinoma remains the most common cancer originating from the biliary tract, which is associated with poor prognosis and poor survival rates. It is estimated that only one-third of patients with histopathological diagnostic of gallbladder cancer had been correctly diagnosed preoperatively, in the remaining cases the diagnostic being established intraoperatively or postoperatively, based on the histopathological examination. Moreover, although surgery remains the most appropriate therapeutic approach in order to improve survival, it is estimated that only 25% of cases with gallbladder carcinomas present resectable lesions. The current chapter reviews the most appropriate surgical options in patients diagnosed with both early stage and advanced stage gallbladder cancer, by minimally invasive as well as by open approach. In the meantime, the therapeutic strategies in incidentally diagnosed gallbladder cancer will be discussed.

Keywords

  • gallbladder cancer
  • atypical hepatic resection
  • bile duct resection
  • lymph node dissection
  • survival

1. Introduction

Gallbladder carcinoma represents the most frequently encountered malignant tumor originating from the biliary tract, with a low rate of diagnostic, a low rate of surgical treatment, and an extremely poor long-term prognostic [1, 2].

The global incidence of gallbladder cancer is low (<2/100,000 cases), but significant differences given by the regional and racial criteria have been reported [3].

Therefore, it has been demonstrated that women are more commonly affected by this malignancy; in regard to the patients’ age, it seems that the incidence of gallbladder cancer significantly increases after the age of 40. In terms of race, it seems that the highest risk for gallbladder carcinoma has been reported among people from Chile, Poland, India, Japan, and Israel [4].

As for the risk factors incriminated for gallbladder cancer development, it seems that the presence and the dimensions of gallstones increased the body mass index as well as multiparity significantly influence it [5, 6].

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2. Treatment options in gallbladder carcinoma

Surgery remains the most efficient therapeutic strategy in order to achieve long-term survival in gallbladder carcinoma patients. However, only a limited number of cases diagnosed with this pathology are amenable to surgery due to the extent of the disease. A generic observation pointed out that only one-third of gallbladder cancer patients are diagnosed preoperatively, and, among these cases, only one quart present resectable lesions [7, 8].

Incidental gallbladder carcinoma also represents a rare condition, ranging from less than 3% of all cases; however, it seems that that this situation is more common in female patients, over 65 years of age who are known with gallbladder stones or cholecystitis and originating from Asian or African descendants [9, 10, 11]. In order to provide a rapid diagnostic in such cases, intraoperative frozen section examinations have been proposed with good results [12]. As for the diagnostic criteria of incidental gallbladder carcinoma, certain authors proposed that in this category cases in which the diagnostic is not suspected during surgery or on gross examination of the specimen should be included, the neoplastic process being only detected at the histopathological examination [13].

When it comes to the extent of the resection, this parameter is dictated by the stage of the tumor; however, improvement of the surgical techniques in regard to liver resection and even liver transplantation as well as in regard to the perioperative management of these patients conducted to an increasing number of cases who can benefit from radical surgery for gallbladder carcinoma [14, 15]. Cases presenting advanced stage disease which is no longer amenable to surgery with curative intent can also benefit from palliative procedures in order to minimize the effects of gastrointestinal or biliary obstruction [2]. In selected cases adjuvant therapies such as chemotherapy or radiotherapy might be also associated in order to improve the overall outcomes [2].

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3. Surgery as a therapeutic option in gallbladder carcinoma patients

The aggressivity of gallbladder cancer was maybe best defined by Alfred Blalock, an American surgeon who stated in 1924 that “in malignancy of the gallbladder, when a diagnosis can be made without exploration, no operation should be performed, inasmuch as it only shortens the patient’s life” [7]. This statement was unfortunately confirmed by a latter publication which demonstrated that on a group of 6222 patients, the cumulative survival rate was of 5–8 months, while the 5-year survival rate did not surpass 4% [16].

However, in the next decades, due to the improvement of the surgical techniques, more extended resections have been safely performed in order to cure this malignancy. This fact was maybe best demonstrated by a Canadian study which analyzed the outcomes of patients submitted to surgery for gallbladder cancer during a 12-year period; cases submitted to surgery in the second part of this interval reported an overall 5-year survival rate of 35%, significantly higher than the first period (in which the 5-year overall survival rate did not surpass 7%) [17].

Whenever gallbladder cancer is suspected, the therapeutic desiderate consists of complete tumoral resection with negative resection margins. In early stages of the disease, this desiderate is achieved if cholecystectomy en bloc with the surrounding liver bed and the regional lymph nodes are excised. In cases in which surgery is planned for a presumed benign disease and at the time of exploration the suspicion of malignancy is raised, hepatic resection should be associated; however, if the surgical team is not prepared to perform liver resection, the patient should be transferred in a specialized center in order to be submitted to a complete surgical procedure. This sequencing of the surgical procedure seems not to influence the long-term survival of the patient [7, 18].

In cases diagnosed in early stages of the disease, it seems that a simple cholecystectomy is enough in order to achieve a good control of the disease; therefore, in stage T1a tumors, the rate of cure after simple cholecystectomy ranges between 85 and 100% [19, 20], while in stage T1b tumors, a more extended local resection should be performed in order to control the disease [21]. This extended resection usually refers to the necessity of associating a wedge hepatic resection [22].

Whenever a T2 gallbladder carcinoma is suspected, a more aggressive surgical procedure including adjacent liver resection involving the segments IVb and V and regional lymph node dissection should be added to improve the outcomes; therefore, it is estimated that, while in cases diagnosed with stage T2 gallbladder cancer, the 5-year overall survival reaches 80% if an extended surgical procedure is performed, significantly higher than simple cholecystectomy (in these cases, the 5-year overall survival ranges between 20 and 40%) [23, 24]. The necessity of resecting segments IVb/Vb is explained by the venous drainage of the gallbladder, which seems to be directed in this area [25].

An interesting study regarding the most appropriate surgical strategy in cases suspected for early gallbladder carcinoma diagnosed during or after cholecystectomy was conducted by Nitta et al. and was published in the Annals of Medicine and Surgery in 2018 [12]; the study included 529 patients submitted to cholecystectomy in Medico Shunju Shiroyama Hospital, Osaka, Japan, between April 2009 and December 2017. Among these cases, there were eight cases diagnosed with gallbladder cancer; five out of the eight cases were submitted to surgery for stones, while the remaining three cases were submitted to surgery for cholecystitis.

Whenever gallbladder cancer was proven at the frozen section, conversion to open surgery occurred, and the patient was submitted to gallbladder bed resection, liver resection of the segments IVb–Vb alone or in association with lymph node dissection; in the meantime if invasion of the cystic duct stump was found, prophylactic common bile duct excision was associated. After a median follow-up period of 17.9 months, five out of the eight patients were still alive; one patient initially diagnosed with stage IIIA gallbladder cancer died due to peritoneal carcinomatosis, while the other two cases died from other diseases [12].

Another interesting topic when it comes to incidental gallbladder carcinoma regards the timing of reoperation; therefore, if the patient is submitted to surgery for presumed benign pathology of the gallbladder and the histopathological studies demonstrate the presence of a malignant transformation at this level, it seems that the best outcomes are reported if early reoperation is performed. Therefore, in the study conducted by Muratore et al. on 11 patients with incidental gallbladder cancer, the authors demonstrated that the best long-term outcomes were seen if radical resection was performed within the first 2.2 months after cholecystectomy [26].

Moreover, the extent of the liver resection should be established in concordance with the local aspect: if the right portal pedicle seems to be involved, liver resection should consist of a right hepatectomy.

In cases suitable for both wedge resection and typical hepatectomy, the extent of liver resection should be carefully tailored due to the fact that in certain cases wedge resection might be insufficient (and associated with positive resection margins), while typical resection might be associated with increased morbidity rates; moreover, the decision of performing a right hepatectomy in patients associating cirrhosis should be taken after analyzing the risk of an insufficient liver remnant [25].

Whenever extended liver resections are expected with a future liver remnant lesser than 25%, a portal vein embolization might be taken into consideration [27]. Another interesting subject is the one regarding the necessity of routinely association of caudate lobe resection; while the Japanese surgeons stand for routine caudate lobe resection, in the Western countries this practice is not part of the standard protocol [25, 28].

When it comes to the lymphatic spread of gallbladder cancer, anatomy studies demonstrated that the first involved lymph nodes are located along the biliary tree and represented by the cystic, common hepatic, and common bile duct lymph nodes; going further, the next involved stations are located along the pancreaticoduodenal, common hepatic artery, and coeliac axis nodes. The most distant lymph node stations are located at the level of the pancreatic body and tail; whenever tumoral cells are encountered at this level, the case is considered to have distant metastases [29].

As for the extent of the lymph node dissection, different opinions have been proposed so far: since certain authors recommended a local lymph node dissection involving the stations from the hepatoduodenal ligament, other surgeons routinely associate retropancreatic and celiac trunk lymph node dissection [7].

In cases presenting more advanced stages of the disease such as T3 gallbladder carcinomas, more extended upper abdominal resections might be taken into consideration; if the tumoral process involves the biliary duct, bile duct resection and anastomosis should be performed. Moreover if the adjacent organs (such as gastrointestinal tract or colon) are involved, segmental resections might be needed in order to achieve complete resection of the malignant process.

Special care should be provided for cases associating gallbladder cancer and stones; such patients might present local adhesions which might induce a difficult differentiation between the inflammatory and malignant transformations; therefore, a large resection is advisable in order to avoid incomplete resection. Whenever the desiderate of negative resection margins is achieved, long-term survival should be expected; in such cases the rate of 5-year overall survival ranges between 30 and 50% [30, 31].

Contrarily, patients diagnosed with stage T4 gallbladder lesions report a poor outcome, surgery with curative intent being suitable in rare cases. In such patients surgery is most commonly performed with palliative intent, while the overall survival remains extremely poor.

The largest studies, which were focused on the role of surgery in gallbladder cancer patients, are summarized in Table 1.

Study, yearNo of casesStage at surgeryType of surgeryRecurrence rateSites of recurrenceLymph node metastasis rateSurvival rateGallbladder carcinoma related deathFactors influencing survival
Lee (review study) [32]1266T1a—706 cases
T1b—560 cases
Laparoscopic cholecystectomy1.1%Common bile duct2.5% (10.9% of T1b lesions and 1.8% of T1a lesions)100% at 5-year follow-upEight cases with T1a lesions and 52 cases with T1b lesions died due to recurrent disease
Nitta (single-center study) [12]8Tis—2 cases
T1b—1 pt.
T2—3 cases
Laparoscopic cholecystectomy—5 cases
Open cholecystectomy—3 cases
Wedge resection of the gallbladder bed—2 cases
Segmental resection—1 case
12.5%PeritonealNRAfter a median follow-up period of 17.9 months, one case died due to the progression of the disease, while other two cases died due to other causesOne case— peritoneal carcinomatosis
Aldossary (single-center study) [33]76Stage I—3 cases
Stage IIA—13 cases
Stage IIB—1 pt.
Stage IIIB—2 cases
Stage IVB—57 cases
21 cases—resection
55 cases—unresectable lesions
10.5%NRNR20.5% for the entire cohort71% of cases presented with unresectable lesions and died of diseaseResectability of the lesions
Stage at diagnostic
Shen (multicentric study) [2]2379Stage I—3.6%
Stage II—7.3%
Stage III A—341 cases
Stage IIIB—333 cases
Stage IVA—253 cases
Stage IVB—838 cases
NR—108 cases
Radical resection—641 cases
Extended radical resection—82 cases
Palliative surgery—499 cases
Drainage—261 cases
NRNR29.7%NRNRNR
Yildirim (single-center study) [34]65T1a—5 cases
T1b—8 cases
T2—34 cases
T3—18 cases
Extended cholecystectomy—28 cases
Simple cholecystectomy—37 cases
83.00%NRNRMedian survival—41 months
5-year overall survival rate—32%
45 casesLymph node status
Tumor stage
Type of surgery
Vascular/neural invasion
Jin (multicentric study) [35]613NRCholecystectomy—150 cases
Partial hepatectomy—249 cases
Extensive hepatectomy—25 cases
Palliative/other procedures—108 cases
Diagnostic—81 cases
NRNRNRNRNRNR
Creasy, single-center study [36]74IIIA—2 cases
IIIB—10 cases
IVA—6 cases
IVB—43 cases
Surgery with curative intent including resection of segments 4 and 5—6 cases
Hemihepatectomy—2 cases
Extended hepatectomy—2 cases
Bile duct resection—10 cases
NRNRNRMedian overall survival—14.2 months61 cases died due to the progression of the diseaseCompleteness of cytoreduction

Table 1.

The largest studies conducted on the theme of the role of surgical approach in gallbladder cancer patients.

Intraoperative aspects of patients submitted to surgery for gallbladder carcinoma are shown in Figures 1, 2, 3, 4.

Figure 1.

Intraoperative aspect after right hepatectomy extended to the caudate lobe for locally advanced gallbladder carcinoma. Association of common bile duct resection was performed.

Figure 2.

Incidental finding—gallbladder carcinoma.

Figure 3.

Dissection of the cystic duct.

Figure 4.

The final aspect after cholecystectomy en bloc with lymph node excision.

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4. Laparoscopic versus open approach in gallbladder cancer patients

Although laparoscopic cholecystectomy represents one of the most facile to be performed minimally invasive procedures, there is still controversy regarding the feasibility and safety of the laparoscopic approach in gallbladder cancer patients. This fact is explained through the aspect that in such cases multiple upper abdominal resections might be needed in order to control the disease; moreover, another fact that should be taken into consideration when deciding for a minimally invasive approach in gallbladder patients is related to the risk of port-site metastases development.

One of the most recent studies which envisaged the efficacy and safety of the laparoscopic approach in gallbladder cancer patients has been recently published by the Chinese surgeons from Jiangsu [37]. The authors included in their study 102 patients with gallbladder carcinoma who were submitted to surgery between August 2008 and August 2017 in a minimally invasive manner, 41 cases, or via an open approach, 61 cases.

The authors demonstrated that there was no significant difference between the operative blood loss, operative time, postoperative complications, R0 resection, and tumor-related death between the two groups [37]. Moreover, the authors demonstrated an improved postoperative outcome for patients submitted to a minimally invasive procedure, while the long-term outcomes demonstrated similar overall survival rates at 1 year, 3 years, and 5 years postoperatively. Moreover, the authors analyzed the 5-year survival rate according to the stage at the initial diagnostic and demonstrated that there was no significant difference in terms of survival for patients submitted to surgery for Tis, T1b, T2, and T3 tumors in a minimally invasive or open approach.

In terms of recurrences and metastases, the authors reported that there was no difference in regard to the incisional site metastases between the two groups (4.9% in the laparoscopic group and 3.3% in the open approach group). However, the authors demonstrated that the risk of incisional metastases was increased in cases presenting gallbladder rupture.

When it came to the recurrence time, it seems that patients submitted to an open approach experienced relapsed disease earlier than those submitted to a minimally invasive approach; however, this aspect was rather related to the fact that among patients submitted to an open approach, a higher proportion of T3 tumors existed [37].

The subject of port-site metastases has been widely studied so far, in certain cases excision of the port sites being proposed in order to minimize this risk [38, 39].

One of the largest studies which debated the role of port-site resection in laparoscopically treated gallbladder cancer patients was conducted by Fuks et al. and was published in the Journal of Visceral Surgery [40]. The study included 218 patients with incidental gallbladder cancer who had been treated in a minimally invasive manner between 1998 and 2008 in 21 centers in France; among these cases, re-resection with curative intent was performed in 148 cases, 54 cases being also submitted to port-site excision.

Their results were compared to the ones reported in the remaining 94 patients who did not undergo to port-site excision. There was no significant difference between the two groups in terms of tumor stage or extent of resection. Port-site metastases were encountered in a single patient who had been previously submitted to port-site excision; it was the case of a patient who had been initially submitted to surgery for a T3 gallbladder carcinoma and who died 15 months after resection due to the development of peritoneal carcinomatosis.

However, the authors demonstrated that the 1-year, 3-year, and 5-year overall survival rates were similar between the two categories of patients; moreover, patients submitted to port-site excision developed an incisional hernia rate at the site of port excision of 8% [40].

Therefore, the authors concluded that port-site excision should not be routinely performed in such cases; an interesting aspect that was pointed out by the same study was the one regarding the possible protective role, which could be given by peritoneal frozen section surrounding the peritoneal trocar orifices in cases presenting greater or equal to T2 tumors [40].

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5. Postoperative complications after surgery for gallbladder carcinoma

Whenever surgery with curative intent is performed in gallbladder carcinoma patients, the postoperative risk of developing complications seems to remain high at both 30 and 90 days postoperatively. Therefore, although most studies take into consideration the 30-day morbidity/mortality rate, it seems that maybe a more adequate tool in order to quantify the postoperative outcomes is represented by the 90-day morbidity/mortality rate. This fact seems to be true not only in gallbladder cancer patients but also in other malignancies such as pancreatic cancer and esophageal or gastric cancer [41, 42].

A recent study conducted on this theme by Goussous et al. and published in 2017 demonstrated that the postoperative mortality within the first 90 days postoperatively is 2.3-fold higher than the 30-day postoperative mortality [43]. Another interesting aspect underlined by this study was the one that the 30-day and 90-day mortality, respectively, was significantly correlated with the degree of tumoral differentiation, with the presence of vascular and lymphatic invasion, with the stage of the tumor, with incomplete resection, and with low-volume centers. Moreover, the authors demonstrated the fact that even in cases submitted to surgery in a minimally invasive manner, the 90-day mortality rate was significantly higher than the 30-day mortality rate [43].

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6. Factors predicting survival after surgery for gallbladder cancer

It seems that the most important prognostic factors predicting the long-term outcomes after surgery for gallbladder carcinoma remain the stage of the disease at the time of diagnostic (including tumoral and lymph node status) as well as the completeness of resection [7, 18]. In the meantime, association of clinical signs as jaundice is most often a sign of locally advanced/unresectable disease and therefore is associated with poor rates of survival [44].

One of the most recent studies which were conducted on the theme of predictors of curative resection and long-term survival in patients with gallbladder cancer was published by Mishra et al. in the American Journal of Surgery [45]. The study included 385 patients diagnosed with gallbladder cancer between September 2003 and December 2014 in the Academic Block, GB Pant Hospital, New Delhi, India. The authors demonstrated that cases presenting gastric outlet obstruction, weight loss, abdominal lump, and obstructive jaundice were more likely to present unresectable lesions.

Moreover, patients presenting at the time of initial diagnostic obstructive jaundice presented significantly lower rates of 1-year, 3-year and 5-year overall survival than those in whom jaundice had not been present at the time of diagnostic [45].

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7. Palliative surgery for unresectable/metastatic gallbladder cancer

Due to the fact that a large proportion of patients with gallbladder cancer are diagnosed in advanced stages of the disease, when surgery with curative intent is no longer possible, palliative procedures might be needed in order to alleviate the symptoms. In such cases, the most frequently reported symptoms necessitating palliative procedures are represented by pruritus, cholangitis, jaundice, digestive obstruction, or pain. However, in this subgroup of patients, the goal of surgery is a pure palliative one, the overall survival ranging between 2 and 4 months [46, 47].

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8. Conclusions

Gallbladder carcinoma remains an extremely aggressive malignancy which is rarely diagnosed in early stages of the disease; therefore the overall survival rates remain extremely poor, the most important predictors for long-term survival being related to the stage at diagnostic as well as to the completeness of resection. However, it should not be omitted the fact that most often extended upper abdominal resections might be needed in order to achieve an R0 resection; therefore such patients should be addressed in high-volume centers.

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Acknowledgments

This work was supported by the project number PN-III-P1-1.2-PCCDI-2017-0797 and project title “Pathogenic mechanisms and personalized treatment in pancreatic cancer using multi-omics technologies.”

References

  1. 1. Wistuba II, Gazdar AF. Gallbladder cancer: Lessons from a rare tumour. Nature Reviews. Cancer. 2004;4(9):695-706
  2. 2. Shen HX, Song HW, Xu XJ, Jiao ZY, Ti ZY, Li ZY, et al. Clinical epidemiological survey of gallbladder carcinoma in northwestern China, 2009-2013: 2379 cases in 17 centers. Chronic Diseases and Translational Medicine. 2017;3(1):60-66
  3. 3. Hundal R, Shaffer EA. Gallbladder cancer: Epidemiology and outcome. Clinical Epidemiology. 2014;6:99-109
  4. 4. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. International Journal of Cancer. 2006;118(7):1591-1602
  5. 5. Serra I, Calvo A, Baez S, Yamamoto M, Endoh K, Aranda W. Risk factors for gallbladder cancer. An international collaborative case-control study. Cancer. 1996;78(7):1515-1517
  6. 6. Engeland A, Tretli S, Austad G, Bjorge T. Height and body mass index in relation to colorectal and gallbladder cancer in two million Norwegian men and women. Cancer Causes & Control. 2005;16(8):987-996
  7. 7. Miller G, Jarnagin WR. Gallbladder carcinoma. European Journal of Surgical Oncology. 2008;34(3):306-312
  8. 8. Goetze T, Paolucci V. Does laparoscopy worsen the prognosis for incidental gallbladder cancer? Surgical Endoscopy. 2006;20(2):286-293
  9. 9. Sikora SS, Singh RK. Surgical strategies in patients with gallbladder cancer: Nihilism to optimism. Journal of Surgical Oncology. 2006;93(8):670-681
  10. 10. Chan SY, Poon RT, Lo CM, Ng KK, Fan ST. Management of carcinoma of the gallbladder: A single-institution experience in 16 years. Journal of Surgical Oncology. 2008;97(2):156-164
  11. 11. Yamamoto H, Hayakawa N, Kitagawa Y, Katohno Y, Sasaya T, Takara D, et al. Unsuspected gallbladder carcinoma after laparoscopic cholecystectomy. Journal of Hepato-Biliary-Pancreatic Surgery. 2005;12(5):391-398
  12. 12. Nitta T, Kataoka J, Ohta M, Fujii K, Takashima Y, Inoue Y, et al. Surgical strategy for suspected early gallbladder carcinoma including incidental gallbladder carcinoma diagnosed during or after cholecystectomy. Annals of Medicine and Surgery (London). 2018;33:56-59
  13. 13. Behari A, Kapoor VK. Incidental gall bladder cancer. Advances in Surgery. 2013;47:227-249
  14. 14. Nishio H, Nagino M, Ebata T, Yokoyama Y, Igami T, Nimura Y. Aggressive surgery for stage IV gallbladder carcinoma; What are the contraindications? Journal of Hepato-Biliary-Pancreatic Surgery. 2007;14(4):351-357
  15. 15. Hemming AW, Magliocca JF, Fujita S, Kayler LK, Hochwald S, Zendejas I, et al. Combined resection of the liver and pancreas for malignancy. Journal of the American College of Surgeons. 2010;210(5):808-806
  16. 16. Piehler JM, Crichlow RW. Primary carcinoma of the gallbladder. Surgery, Gynecology & Obstetrics. 1978;147(6):929-942
  17. 17. Dixon E, Vollmer CM Jr, Sahajpal A, Cattral M, Grant D, Doig C, et al. An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: A 12-year study at a North American Center. Annals of Surgery. 2005;241(3):385-394
  18. 18. Fong Y, Jarnagin W, Blumgart LH. Gallbladder cancer: Comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Annals of Surgery. 2000;232(4):557-569
  19. 19. Yamaguchi K, Tsuneyoshi M. Subclinical gallbladder carcinoma. American Journal of Surgery. 1992;163(4):382-386
  20. 20. Shirai Y, Yoshida K, Tsukada K, Muto T. In apparent carcinoma of the gallbladder. An appraisal of a radical second operation after simple cholecystectomy. Annals of Surgery. 1992;215(4):326-331
  21. 21. Principe A, Del Gaudio M, Ercolani G, Golfieri R, Cucchetti A, Pinna AD. Radical surgery for gallbladder carcinoma: Possibilities of survival. Hepato-Gastroenterology. 2006;53(71):660-664
  22. 22. Tsuji T, Kanemitsu K, Hiraoka T, Takamori H, Toyama E, Tanaka H, et al. A new method to establish the rational extent of hepatic resection for advanced gallbladder cancer using dye injection through the cystic artery. HPB: The Official Journal of the International Hepato Pancreato Biliary Association. 2004;6(1):33-66
  23. 23. de Aretxabala XA, Roa IS, Burgos LA, Araya JC, Villaseca MA, Silva JA. Curative resection in potentially resectable tumours of the gallbladder. The European Journal of Surgery. 1997;163(6):419-426
  24. 24. Oertli D, Herzog U, Tondelli P. Primary carcinoma of the gallbladder: Operative experience during a 16 year period. The European Journal of Surgery. 1993;159(8):415-420
  25. 25. Pilgrim CH, Usatoff V, Evans P. Consideration of anatomical structures relevant to the surgical strategy for managing gallbladder carcinoma. European Journal of Surgical Oncology. 2009;35(11):1131-1136
  26. 26. Muratore A, Amisano M, Vigano L, Massucco P, Capussotti L. Gallbladder cancer invading the perimuscular connective tissue: Results of reresection after prior non-curative operation. Journal of Surgical Oncology. 2003;83(4):212-215
  27. 27. Reddy SK, Marroquin CE, Kuo PC, Pappas TN, Clary BM. Extended hepatic resection for gallbladder cancer. American Journal of Surgery. 2007;194(3):355-361
  28. 28. Reid KM, Ramos-De la Medina A, Donohue JH. Diagnosis and surgical management of gallbladder cancer: A review. Journal of Gastrointestinal Surgery. 2007;11(5):671-681
  29. 29. Mekeel KL, Hemming AW. Surgical management of gallbladder carcinoma: A review. Journal of Gastrointestinal Surgery. 2007;11(9):1188-1193
  30. 30. Chijiiwa K, Tanaka M. Carcinoma of the gallbladder: An appraisal of surgical resection. Surgery. 1994;115(6):751-756
  31. 31. Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Annals of Surgery. 1996;224(5):639-646
  32. 32. Lee SE, Jang JY, Lim CS, Kang MJ, Kim SW. Systematic review on the surgical treatment for T1 gallbladder cancer. World Journal of Gastroenterology. 2011;17(2):174-180
  33. 33. Aldossary MY, Alayed AA, Amr SS, Alqahtani S, Alnahawi M, Alqahtani MS. Gallbladder cancer in Eastern Province of Saudi Arabia: A retrospective cohort study. Annals of Medicine and Surgery (London). 2018;35:117-123
  34. 34. Yildirim E, Celen O, Gulben K, Berberoglu U. The surgical management of incidental gallbladder carcinoma. European Journal of Surgical Oncology. 2005;31(1):45-52
  35. 35. Jin LX, Pitt SC, Hall BL, Pitt HA. Aggressive surgical management of gallbladder cancer: At what cost? Surgery. 2013;154(2):266-273
  36. 36. Creasy JM, Goldman DA, Dudeja V, Lowery MA, Cercek A, Balachandran VP, et al. Systemic chemotherapy combined with resection for locally advanced gallbladder carcinoma: Surgical and survival outcomes. Journal of the American College of Surgeons. 2017;224(5):906-916
  37. 37. Feng JW, Yang XH, Liu CW, Wu BQ , Sun DL, Chen XM, et al. Comparison of laparoscopic and open approach in treating gallbladder cancer. The Journal of Surgical Research. 2019;234:269-276
  38. 38. Hu JB, Sun XN, Xu J, He C. Port site and distant metastases of gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron emission tomography. World Journal of Gastroenterology. 2008;14(41):6428-6431
  39. 39. Giuliante F, Ardito F, Vellone M, Clemente G, Nuzzo G. Port-sites excision for gallbladder cancer incidentally found after laparoscopic cholecystectomy. American Journal of Surgery. 2006;191(1):114-116
  40. 40. Fuks D, Regimbeau JM, Pessaux P, Bachellier P, Raventos A, Mantion G, et al. Is port-site resection necessary in the surgical management of gallbladder cancer? Journal of Visceral Surgery. 2013;150(4):277-284
  41. 41. Fischer C, Lingsma H, Hardwick R, Cromwell DA, Steyerberg E, Groene O. Risk adjustment models for short-term outcomes after surgical resection for oesophagogastric cancer. The British Journal of Surgery. 2016;103(1):105-116
  42. 42. Swanson RS, Pezzi CM, Mallin K, Loomis AM, Winchester DP. The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: More than 20,000 resections from the national cancer data base. Annals of Surgical Oncology. 2014;21(13):4059-4067
  43. 43. Goussous N, Hosseini M, Sill AM, Cunningham SC. Minimally invasive and open gallbladder cancer resections: 30- vs 90-day mortality. Hepatobiliary & Pancreatic Diseases International. 2017;16(4):405-411
  44. 44. Hawkins WG, DeMatteo RP, Jarnagin WR, Ben Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Annals of Surgical Oncology. 2004;11(3):310-315
  45. 45. Mishra PK, Saluja SS, Prithiviraj N, Varshney V, Goel N, Patil N. Predictors of curative resection and long term survival of gallbladder cancer–A retrospective analysis. American Journal of Surgery. 2017;214(2):278-286
  46. 46. Kapoor VK, Pradeep R, Haribhakti SP, Singh V, Sikora SS, Saxena R, et al. Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the gallbladder. The British Journal of Surgery. 1996;83(12):1709-1711
  47. 47. Miller G, Boman J, Shrier I, Gordon PH. Small-bowel obstruction secondary to malignant disease: An 11-year audit. Canadian Journal of Surgery. 2000;43(5):353-358

Written By

Nicolae Bacalbasa, Irina Balescu, Simona Dima and Irinel Popescu

Submitted: October 5th, 2018 Reviewed: January 4th, 2019 Published: September 25th, 2019