Surgical strategies in patients with gallbladder cancer: nihilism to optimism

INTRODUCTION: Gallbladder cancer is an aggressive disease with dismal results of surgical treatment and a poor prognosis. However, over the last few decades selected groups have reported improved results with aggressive surgery for gallbladder cancer. METHODS: Review of recent world literature was done to provide an update on the current concepts of surgical treatment of this disease. RESULTS: Long-term survival is possible in early stage gallbladder carcinoma. Tis and T1a gallbladder carcinoma can be treated with simple cholecystectomy only. However, in T1b and beyond cancers, aggressive surgery (extended cholecystectomy) is important in improving the long-term prognosis. Laparoscopic cholecystectomy should not be performed where there is a high index of suspicion of malignancy due to the frequent association with factors (such as gallbladder perforation and bile spill) which may lead to implantation of cancer cells and dissemination. Surgical resection for advanced carcinoma gallbladder is recommended only if a potentially curative R0 resection is possible. Aggressive surgery with vascular and multivisceral resection has been shown to be feasible albeit with an increase in mortality and morbidity. However, the true benefit of these radical resections is yet to be realized, as the actual number of long-term survivors of advanced gallbladder carcinoma is few. CONCLUSIONS: Surgery for gallbladder carcinoma, like other malignancies, has the potential to be curative only in local or regional disease. Pattern of loco-regional spread of disease dictates the surgical procedure. Radical surgery improves survival in early gallbladder carcinoma. The long-term benefit of aggressive surgery for advanced disease is unclear and may be offset by the high mortality and morbidity.     

Staging,Treatment, and Future Approaches of Gallbladder Carcinoma

Background

Gallbladder cancer is the most common malignant cancer of the bile ducts and third most common gastrointestinal malignant in the world for public health. Its relatively low incidence and confused symptoms result in advanced disease at the time of presentation, contributing to poor prognosis and reduced survival associated with this disease. The main function of the gallbladder is to store excreted bile acids from the liver in preparation for a meal. Its main risk factor is prolonged exposure to biliary calculations, although bacterial infections and other inflammatory conditions are associated. Chronic inflammatory bowel conditions are associated with gallbladder cancer. T stage translates to identifying residual disease at reoperation for incidental gallbladder cancer and residual disease negatively affects survival.

Conclusion

It is the most common cancer of gallbladder, gallbladder cancer remains a rare disease. Gallbladder cancer is a rare disease that can be accidentally diagnosed after cholecystectomy or accidentally, often with more advanced disease. The prognosis is generally extremely poor and improvements in surgical resection of this approach have to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.

     

19例原发性胆囊癌疗效分析

目的:探讨浸润肌层的胆囊癌是否是局部疾病,行单纯胆囊切除术后是否要行二次根治手术治疗方法:回顾分析了19例浸润肌层的原发性胆囊癌患者,8例行单纯胆囊切除术,11例行根治性淋巴结清扫术68个区域淋巴结被检查平均随访时间97个月结果:组织学检查均未发现血管浸润,1例有淋巴管浸润淋巴结均未见转移10年生存率为89%,单纯胆囊切除术与根治术结果相比,差别无统计学意义.2例行根治术的患者死于肿瘤复发结论:多数浸润肌层的早期原发性胆囊癌仅是局部扩散,行单纯胆囊切除术后不需再行根治术。     

Gallbladder cancer

Gallbladder cancer has a reputation for being aggressive and incurable. Single institution series, however, have defined successful management strategies in which the extent of resection is based on the stage of the tumor at presentation. Careful ultrasound screening for abnormalities in the gallbladder wall, and CA19-9 serum determination prior to routine cholecystectomy may heighten awareness for cancer in this population. For tumors confined to the muscular layer of the gallbladder a simple cholecystectomy is associated with an almost 100% cure rate. Tumors invading through the muscle wall (Stage II) should be managed with extended cholecystectomy, including resection of hepatic segments IVb and V, and an extensive lymph node dissection of the porta hepatis, posterior pancreaticoduodenal, and interaortocaval lymph nodes. This operation for Stage II gallbladder cancer is associated with a 90% to 100% 3-year survival rate. Simple cholecystectomy fails in the majority of Stage II patients. Patients with Stage III and IV tumors may also benefit from an extended cholecystectomy. Patients with bulky primary tumors without lymph node metastases (T4N0) seem to have a better prognosis than those with distant lymph node metastases, and should be treated aggressively when possible. It is advantageous to perform the appropriate extent of surgery for gallbladder cancer at the initial operation. Heightened awareness of the presence of cancer and the knowledge of appropriate management are important. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated for all disease except Stage I. This review will discuss the epidemiology, pathology, and staging of gallbladder cancer and describe the appropriate surgical management based on the stage of the cancer.     

Advanced gallbladder carcinoma: a case report and review of the literature

A case with carcinoma of the gallbladder and recurrent metastases to regional lymph nodes is reported. Following primary surgery, secondary resection of node recurrence, and long term combination chemotherapy, the patient is alive and disease free after 9 years. The possibility of a successful cancer suppression, as mirrored by a depressed RES-function test during the treatment with anticancer drugs, is discussed. Only nine other cases with advanced gallbladder cancer and 5 year survival are found in the literature.     

胆囊癌外科治疗的争议与思考

胆囊癌恶性程度高,易侵犯邻近脏器和发生淋巴结转移,且对放化疗不敏感,是预后最差的胆道恶性肿瘤.根治性手术切除仍然是目前唯一有可能治愈胆囊癌的手段,但是关于胆囊癌的手术方式、肝脏切除范围、淋巴结清扫范围、意外胆囊癌的处理等方面仍存在诸多争议.此外,当前免疫治疗和靶向治疗在多种实体瘤中取得巨大成功的背景下,未来外科手术在进...     

Successful treatment of advanced gallbladder cancer with an anticancer drug S-1: assessment based on intratumoral gene

While surgical resection is the most effective treatment for gallbladder cancer, most of these cancers are not resectable at the time of diagnosis, and therefore, chemotherapy serves as the primary therapy in many cases. However, to date, there is no standard chemotherapy for this cancer. We report a case of advanced gallbladder cancer for which the anticancer drug S-1 was effective. The patient was a 53-year-old woman who presented with a huge ovarian tumor. On workup, all abdominal images revealed the presence of advanced gallbladder cancer that had invaded the liver. Because the gallbladder formed a relatively hard and swollen mass involving the omentum, as revealed during exploration, the surgical resection of the gallbladder was not possible at that time, and only hysterectomy and bilateral salpingo-oophorectomy were performed. She started on the anticancer drug S-1 just after this operation. S-1 is a prodrug of 5-fluorouracil (5-FU), and contains 5-chloro-2-4-dihydroxypyridine (CDHP), an inhibitor of dihydropyrimidine dehydrogenase (DPD) that rapidly degrades 5-FU. Eight months after the first operation, radical cholecystectomy was performed. Pathologically, the tumor was diagnosed as an adenocarcinoma of the gallbladder, and no evidence of liver invasion was found. Intratumoral gene expression analysis of the resected gallbladder revealed significantly elevated DPD expression. We suggest that the rapid degradation of 5-FU mediated by this high DPD in our patient was significantly blocked by the CDHP in S-1, and that the efficacy of 5-FU was consequently maintained at the maximum level.     

Recent trends of gallbladder cancer in Japan: an analysis of 4,770 patients

BACKGROUND: Gallbladder cancer is the most common cancer of the biliary tract and has a particularly high incidence in Chile, Japan, and northern India. Many Japanese surgeons have reported that aggressive surgery improves the outcome of patients with gallbladder cancer. Differences in survival rates between Japan and other countries have been noted. The objective of this study was to determine whether there were any changes over time in the incidence, therapeutic approach, stage at diagnosis, or prognosis of gallbladder cancer in an unselected, community-based series of patients in Japan. METHODS: In total, 4,774 patients with gallbladder cancer were analyzed between 1988 and 1997 based on data from the Biliary Tract Cancer Registration Committee of the Japanese Society of Biliary Surgery. RESULTS: Survival was related closely to surgical stage, with 5-year survival rates of 77% for patients with stage I disease, 60% for patients with stage II disease, 29% for patients with stage III disease, 12% for patients with stage IVA disease, and 3% for patients with stage IVB disease. Patient age also affected survival. The survival rate for patients aged <49 years was significantly better compared with the survival rate for patients in the other groups (P < .05). The 5-year survival rate for patients aged <49 years was 38%. The survival rate for patients aged >79 years was significantly worse compared with the survival rate for patients in the other 4 groups (P < .01). The 5-year survival rate for patients aged >79 years was 21%. Stratifying patients by stage according to the Japanese Society of Biliary Surgery classification showed that women maintained a survival advantage over men among patients with stage I and II disease. Adjuvant chemotherapy did not provide a survival benefit. There were no apparent changes in patient demographics between the period from 1988 to 1992 and the period from 1993 to 1997. CONCLUSIONS: For this study, the authors evaluated the gallbladder cancer trends in Japan. The Classification of Biliary Tract Carcinoma proposed by the Japanese Society of Biliary Surgery reflected the prognosis of patients with gallbladder cancer. Patient outcomes were affected by patient age and sex. No substantial differences in patient survival were apparent over the 10-year study period. The data did not support any advantage for aggressive surgical resection and adjuvant chemotherapy. Further analysis of operative procedures will be necessary to determine conclusively whether there is any survival advantage from aggressive surgery in patients with advanced gallbladder cancer.     

Do the progesterone receptors have a role to play in gallbladder cancer?

Background: Gallstone disease as well as gallbladder cancer are more common in women and female sex hormones may be involved in their etiology. Aim and Methods: To determine whether female sex hormones have a role in the pathogenesis, of gallbladder carcinoma and in its prognosis, we estimated, by enzyme immunoassay, the estrogen and progesterone receptors (ER and PgR) in the gallbladders of 21 patients with gallbladder cancer, 19 patients with cholelithiasis, and 6 patients who underwent incidental removal of essentially normal gallbladder as a component of wider resection. Results: ER were present in the gallbladder mucosa in all the three groups in proportions which were not significantly different (9/21 in carcinoma, 4/19 in gallstones, and 1/6 normal), whereas the expression of PgR was greater in carcinomas (13/18), less in cholelithiasis (4/12), and absent in normal gallbladders. PgR expression was higher in tumors of lower stage (7/7) and lower in advanced disease stage IV tumors (6/11). PgR expression was associated with better disease stage (p=0.05) and significantly longer overall survival (median survival of 301 d vs 54 d) as well as better survival within the same stage (269 d vs 54 d for stage IV disease, p=0.011). Cox’s regression analysis showed that PgR was an independent risk factor (R=0.2283, p=0.0035). Conclusions: Our findings suggest that the female sex hormones may have a role in the pathogenesis of gallbladder cancer and that PgR expression has a prognostic significance. We believe that when this relationship is reaffirmed by larger studies, gallbladder cancer may be treated with appropriate sex hormonal manipulation.     

腹腔镜胰体尾脾联合胆囊切除治疗胰尾癌并胆囊癌探讨

目的：探讨腹腔镜胰体尾脾联合胆囊切除治疗胰尾癌并胆囊癌的可行性。方法：对临床诊断为胰尾癌并胆囊癌、慢性胆囊炎急性发作,继发性脾功能亢进的患者实施腹腔镜胆囊、胰体尾脾切除。结果：手术过程顺利,肿瘤完整切除,术中出血少,创伤小,术后恢复快,患者痊愈出院,随访一年病人生活质量良好。结论：腹腔镜胰体尾脾、胆囊切除治疗胰尾癌并胆囊癌是可行的,其具有传统手术的安全性,又具有微创性的优点,值得进一步推广和应用。     

腹腔镜胰体尾脾联合胆囊切除治疗胰尾癌并胆囊癌探讨

目的:探讨腹腔镜胰体尾脾联合胆囊切除治疗胰尾癌并胆囊癌的可行性。方法:对临床诊断为胰尾癌并胆囊癌、慢性胆囊炎急性发作,继发性脾功能亢进的患者实施腹腔镜胆囊、胰体尾脾切除。结果:手术过程顺利,肿瘤完整切除,术中出血少,创伤小,术后恢复快,患者痊愈出院,随访一年病人生活质量良好。结论:腹腔镜胰体尾脾、胆囊切除治疗胰尾癌并胆囊癌是可行的,其具有传统手术的安全性,又具有微创性的优点,值得进一步推广和应用。     

Frequency of gallbladder cancer in Chile, a high-risk area

We report an autopsy study of gallbladder cancer prevalence in Chile, where the risk of this disease is among the highest reported world-wide. In 14,768 autopsy protocols obtained from 3 university hospitals, 45% of women and 20% of men older than 20 years had gallstone disease (the major known risk factor for gallbladder cancer). The prevalence of gallbladder cancer in Chileans was compared to that found in a Swedish-Czechoslovakian autopsy study previously published. These countries were chosen because of their high frequency of gallstone disease. The comparison was performed by using logistic regression models adjusting for possible differences in the age-sex structure or the true incidence of gallstones in both populations. We found that the most important single risk factor for gallbladder cancer in Chile was gallstone disease, with an estimated effect on the logistic scale meaning that the cancer risk for subjects with gallstones is seven times higher than for those without the disease. Second in importance was the risk for sex, women being 2.8 times higher than for men. The estimated difference in the sex composition and the incidence of gallstones resulted in 17.9% higher odds of cancer in Chile than in Sweden and Czechoslovakia. However, this difference was not significant. This study suggests that the major etiologic factors of gallbladder cancer in Chileans, Swedes and Czechoslovakians are primarily related to gallstone disease.     

Long-term follow-up of surgically treated gallbladder cancer patients

AIMS: Palliative attempts have traditionally led treatment of gallbladder cancer but resection offers the only chance for long-term survival. This study investigates the impact of surgery with curative intent in gallbladder cancer treatment and evaluates prognostic factors for survival. METHODS: Two hundred and sixty-seven patients were admitted for surgical therapy. Sixty received resection with curative intent and form the basis of this analysis. RESULTS: R0 resection (n=45) was a highly significant independent survival predictor (P<0.001). All 5-year survivors (n=10) had tumour-free resection margins. Early T stage (P=0.017) and highly differentiated cancer (P=0.008) had a significant better outcome. Nodal spreading increased by local tumour extension and lymphatic involvement decreased patient survival (P=0.018). Patients' age (>75 years) was without influence on long-term survival. CONCLUSIONS: Long-term survival is possible both in elderly patients and in advanced cancer.     

Gallbladder cancer: Historical treatment and new management options

Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.     

Laparoscopic cholecystectomy and unsuspected gallbladder carcinoma.

Gallbladder cancer is a relatively uncommon malignancy in the United States. Its presentation is similar to that of lithic disease of the gallbladder. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall, gallbladder cancer portends a poor prognosis. However, in select cases, a favorable outcome can be expected and the less favorable predicted expected outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted postoperatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope. The technique of extended cholecystectomy is outlined.     

Radical surgery for gallbladder cancer: a worthwhile operation?

AIMS: Extended operations are the only chance of a cure for patients with advanced gallbladder carcinoma, but there is no consensus about which subset of patients can benefit. The aim of this retrospective study is to evaluate the results of surgical resection with special reference to the prognostic factors and to long-term survival. METHODS: A retrospective review of 70 patients with a diagnosis of gallbladder cancer treated from 1985-1998 was performed: 33 patients had a curative resection and were included in this study. For stage I disease, simple cholecystectomy was considered curative; in most of the other cases, cholecystectomy was associated with lymph node dissection and liver resection. RESULTS: Hospital mortality and morbidity were 6% and 33%, respectively. Curative resection was associated with an actuarial 5-year survival of 27.4%. Survival of pT1-2 patients was significantly better than that of pT3 (P=0.04) or pT4 patients (P=0.002). Patients with lymph node spread had a poorer prognosis (P=0.06) but four were alive and disease-free with a median survival of 22 months. CONCLUSIONS: Depth of the tumour and lymph node metastases are important prognostic factors. Patients with pT3-4 tumours or regional lymph node spread should be considered for curative resection because long-term survival is possible.     

Incidental finding of gallbladder carcinoma detected during or after laparoscopic cholecystectomy.

AIM: Carcinoma of the gallbladder is a rare neoplasm with a dismal prognosis. With the increase of cholecystectomies due to the wide acceptance of laparoscopic cholecystectomy, the incidental diagnosis of gallbladder carcinoma is more frequent. We report our experience with gallbladder cancer diagnosed during or after the performance of laparoscopic cholecystectomy. METHODS: We evaluated 11 patients with gallbladder cancer out of 5539 patients who underwent laparoscopic cholecystectomy. Patient clinical and demographic characteristics were reviewed. RESULTS: Intraoperatively in 297 patients there was the suspicion of adenocarcinoma and frozen sections were performed. In four of them the diagnosis of adenocarcinoma was confirmed. In two of them the procedure was converted to open with gallbladder liver bed resection and regional lymph node dissection while the other two were considered inoperable. Of the remaining 5242 patients, seven were diagnosed postoperatively at the pathologic examination. Of these, five patients refused to undergo a repeat operation. We did not observe port site metastasis in any of our patients. Survival was low and ranged from 3-14 months. CONCLUSION: Gallbladder cancer runs a short course, with a poor prognosis. The use of a meticulous laparoscopic technique seems to be important for the diagnosis and the avoidance of early complications of the disease.     

Laparoscopic bile duct resection with lymph node dissection for gallbladder cancer diagnosed after laparoscopic cholecystectomy

IntroductionLaparoscopic reoperation of postoperatively diagnosed gallbladder cancer is a technically challenging procedure due to inflammatory adhesion or fibrosis around the hepatoduodenal ligament and gallbladder bed [1,2]. Here we describe a technique for laparoscopic bile duct resection with lymph node dissection in a patient with cystic duct cancer diagnosed after laparoscopic cholecystectomy.VideoA 73-year-old woman presented with postoperatively diagnosed gallbladder cancer. She underwent laparoscopic cholecystectomy to treat symptomatic gallbladder stones at another hospital, 2 months earlier. Postoperative pathology revealed a 0.9 × 0.7 cm, T2 lesion of adenosquamous carcinoma located at the cystic duct. The cystic duct margin showed high-grade dysplasia. We planned to perform laparoscopic bile duct resection with lymph node dissection. After adhesiolysis to expose the hepatoduodenal ligament, the lymph nodes were dissected around the retropancreatic area, hepatoduodenal ligament, and common hepatic artery in an en bloc fashion. Combined segmental resection of the bile duct, including the fibrotic scar around the cystic duct stump, was completed with negative resection margins. Retrocolic choledochojejunostomy and side-to-side jejunojejunostomy were then performed intracorporeally.ResultsThe operation time was 195 minutes and the estimated intraoperative blood loss was minimal. The postoperative pathologic report revealed no residual tumor tissue and negative resection margins. Lymph node metastasis was found in one of eight retrieved lymph nodes. The patient was discharged on postoperative day 4 with no postoperative complications.Conclusion.Laparoscopic radical surgery involving bile duct resection and lymph node dissection can be safely performed in patients with postoperatively diagnosed gallbladder cancer.     

Role of laparoscopy in the evaluation of biliary tract cancer

Patients with malignancies of the biliary tract have a dismal prognosis. As in most abdominal cancers, resection is the only effective treatment with potential for cure. Preoperative staging is not completely accurate, however, and a significant number of patients with biliary carcinoma undergo unnecessary laparotomy. As imaging technology improves, more patients with unresectable disease will be identified, avoiding the need for a laparotomy. Laparoscopy is a major addition, but its usefulness in staging of abdominal malignancies continues to evolve. The importance of laparoscopy to better predict the resectability in liver malignancies increasingly has been recognized. Conversely, the use of staging laparoscopy for other cancers has shown little benefit. For hilar cholangiocarcinoma and gallbladder cancer, the authors' analysis of 100 patients supports the use of staging laparoscopy for assessing these tumors. In this series, staging laparoscopy correctly identified unresectable disease and prevented unnecessary laparotomy in one third of patients. Patients with unresectable disease that was not detected at laparoscopy most often had locally advanced tumors. LUS did not contribute to the assessment of resectability in these patients. The yield of laparoscopy was lower for hilar cholangiocarcinoma, but could be improved by targeting patients who are at higher risk for occult unresectable disease, such as patients with T2 or T3 lesions. These patients and patients with primary gallbladder carcinoma have a high incidence of metastatic disease and should undergo laparoscopic staging before attempting at resection.     

Laparoscopic cholecystectomy and unsuspected gallbladder cancer.

Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope. Copyright Harcourt Publishers Limited.