BACKGROUND

Current approaches to adjuvant treatment after resection of gallbladder carcinoma (GBCA) and hilar cholangiocarcinoma (HCCA) are based on an incomplete understanding of the recurrence patterns of these diseases. Through an in-depth analysis of the sites of initial recurrence after resection of GBCA and HCCA, the current study aimed to highlight differences in the biology of these tumors and to provide further insight for adjuvant therapeutic strategies.



METHODS

Patients with either GBCA or HCCA who underwent a potentially curative resection were identified prospectively from a maintained database. Specific sites of initial disease recurrence were identified retrospectively and categorized as locoregional (resection margin, porta hepatis, or retroperitoneal lymph nodes) or distant (peritoneal, extraabdominal, or discontiguous liver metastases). Differences in disease recurrence patterns, time to disease recurrence, and overall and site-specific survival were analyzed.



RESULTS

Between May 1990 and August 2001, 177 patients underwent potentially curative resection, 97 for GBCA and 80 for HCCA. Disease recurrence and follow-up data were available for 156 patients (80 with GBCA and 76 with HCCA). The median time to disease recurrence was shorter for patients with GBCA compared with patients with HCCA (11.5 vs. 20.3 months; P = 0.007). Overall, 52 (68%) patients with HCCA and 53 (66%) patients with GBCA had disease recurrene at a median follow-up of 24 months. Of those who developed disease recurrence, isolated locoregional disease as the first site of failure occurred in 15% of patients with GBCA compared with 59% of patients with HCCA (P < 0.001). By contrast, an initial GBCA recurrence involving a distant site, with or without concomitant locoregional recurrence, occurred in 85% of patients compared with 41% of patients with HCCA (P < 0.001). This pattern of disease recurrence was diagnosis specific and did not change significantly when patients were stratified by several clinicopathologic factors, including disease stage and its component variables. Using multivariate analysis, diagnosis was an independent predictor of the site of disease recurrence. Among patients who experienced disease recurrence, survival was greater among the patients with HCCA compared with patients with GBCA (29 months vs. 20.6 months, respectively; P = 0.037). For both tumors, the site of initial disease recurrence had no apparent impact on survival time.



CONCLUSIONS

After resection, recurrent GBCA is much more likely than recurrent HCCA to involve a distant site. GBCA is also associated with a much shorter time to recurrence and a shorter survival period after recurrence. The results demonstrated significant differences in the clinical behavior of these tumors and suggested that an adjuvant therapeutic strategy targeting locoregional disease, such as radiotherapy, is unlikely to have a significant impact in the overall management of GBCA. Conversely, there is at least some rationale for such an approach in patients with HCCA based on the pattern of initial recurrence. Cancer 2003. © 2003 American Cancer Society.



DOI 10.1002/cncr.11699

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11699

Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies.

Alfred Blalock wrote 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.”1 This pessimistic view of gallbladder cancer is understandable because this rapidly growing tumor has a propensity for early dissemination. Furthermore, due to the proximity of the gallbladder to the liver and major vasculature, extensive hepatic resections are often required to eradicate local disease. Therefore, until recently most reports of cure of gallbladder cancer occurred “by accident” after complete excision of early stage disease by simple cholecystectomy for gallstones. In a review of the literature up to 1978, Piehler and Crichlow 2 reported only a 5% 5-year survival and a median survival of 5 to 8 months for 5,836 cases. Even for the 25% who were treated by resection with curative intent, only 16.5% survived 5 years. These results were echoed recently by a report from the French Surgical Association Survey of 724 carcinomas of the gallbladder, in which Cubertafond et al 3 reported a median survival of 3 months, 5-year survival of 5%, and 1-year survival of 14%. A review of gallbladder cancer from Australia revealed a 12% 5-year survival rate, with all survivors having stage I or II disease. 4 These dismal results reinforced the nihilism that surrounds this disease.

George Pack was the first to advocate radical liver resection as treatment for gallbladder cancer, 5 reporting in 1955 on the first three gallbladder cancers treated by right hepatic lobectomy and portal lymph node dissection. This radical approach was not embraced until recently, however, because of the risk of such extensive surgery. As experience with liver resection for other cancers has demonstrated increasing safety of liver resections and biliary reconstructions, such major resections are increasingly performed for gallbladder cancer. 6–10 Data accumulated over the last decade have clearly suggested the utility of such a radical approach for selected patients with gallbladder cancer. However, there are many unresolved questions. Are such radical resections warranted for advanced stage disease? Which of the many staging systems for gallbladder cancer are the most useful for prediction of prognosis, for selection of patients for adjuvant therapy, and for stratification of patients in clinical trials? Most importantly, because a large number of patients are discovered to have gallbladder cancer during operative therapy for presumed gallstone disease, are reoperative radical resections warranted after prior noncurative cholecystectomy? The current study addresses these question using data from a tertiary cancer referral center.

Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention.

Gallbladder cancer (GBC) represents the most common and aggressive type among the biliary tree cancers (BTCs). Complete surgical resection offers the only chance for cure; however, only 10% of patients with GBC present with early-stage disease and are considered surgical candidates. Among those patients who do undergo "curative" resection, recurrence rates are high. There are no established adjuvant treatments in this setting. Patients with unresectable or metastatic GBC have a poor prognosis. There has been a paucity of randomized phase III data in this field. A recent report demonstrated longer overall survival with gemcitabine in combination with cisplatin than with gemcitabine alone in patients with advanced or metastatic BTCs. Molecularly targeted agents are under development. In this review, we attempt to discuss the current status and key issues involved in the management of GBC.

/pdf/current-management-of-gallbladder-carcinoma-209dzs64sp.pdf

Current Management of Gallbladder Carcinoma

Incidence of Finding Residual Disease for Incidental Gallbladder Carcinoma: Implications for Re-resection

Objectives:We assess how laparoscopy has altered the presentation of patients with gallbladder cancer and determine whether radical resection in patients with gallbladder cancer is beneficial.Summary Background Data:The widespread adoption of laparoscopic cholecystectomy has led to an increased freq

Gallbladder cancer: the role of laparoscopy and radical resection.

OBJECTIVE: The objective of this study was to evaluate the benefit of an aggressive approach to gallbladder carcinoma on long-term survival. SUMMARY BACKGROUND DATA: Recent studies have shown that an aggressive surgical treatment of bile duct carcinoma can be associated with a surprising long-term survival. However, recent data on gallbladder carcinoma are not available. METHODS: Data were obtained from a questionnaire sent to 73 institutions in France, Europe, and overseas, and they were analyzed retrospectively. The review included an analysis of patient sex and age, associated hepatobiliary diseases, symptoms and signs, diagnostic tests, operative management, pathology reports, and survival. RESULTS: Seventy-eight per cent of the patients were women, and 22% were men (p 70 years) had a higher operative risk (p 60 months; T1 to T2, > 22 months, and T3 to T4, 2 to 8 months). No differences were observed among the different surgical procedures adopted. CONCLUSIONS: No progress has been made in the last 10 years in the treatment of gallbladder malignancies.

Surgical treatment of 724 carcinomas of the gallbladder. Results of the French Surgical Association Survey

BACKGROUND/AIMS: Gallbladder carcinoma is a highly lethal disease. The advantages of radical surgery remain controversial. The authors' objective was to evaluate the effectiveness of an aggressive approach to gallbladder carcinoma on long-term survival. METHODOLOGY: A questionnaire was sent to 73 institutions in France, Europe, and overseas. Data, from 724 patients treated between 1980 and 1989, were analyzed for patient sex and age, associated hepatobiliary diseases, symptoms and signs, diagnostic tests, operative management, pathology reports and survival. Seventy-eight percent of the patients were women, and 22% were men. Gallstones were present in 86% of the cases. Four percent of the patients had Tis lesions, 11% had T1 to T2 lesions, and 85% had T3 to T4 lesions. RESULTS: Twenty-three percent of the patients underwent curative operations, and 77% had a palliative treatment (25% of the patients underwent exploratory laparotomy). Exploratory laparotomy was followed by the highest mortality rate (66%), and older patients (>70 years) had a higher operative risk. The overall median survival was 3 months, and long-term survival correlated with cancer stage: Tis >60 months, T1 to T2 >22 months, and T3 to T4 2 to 8 months. Projected five-year survival for cancers limited to the gallbladder and treated by simple cholecystectomy was 93%, 18% and 10% for Tis, T1 and T2 respectively. For T3 to T4, no difference was observed among the different surgical procedures adopted - hepatic resection, trans-tumoral stenting or biliary-enteric anastomosis. CONCLUSIONS: In conclusion, a simple cholecystectomy is effective only for Tis cancer. An extended cholecystectomy for invasive cancer should be performed, but only if there is limited involvement of the immediately adjacent hepatic parenchyma. There is now a need to evaluate more effective adjuvant therapy in the form of radiotherapy or newer chemotherapeutic agents.

Radical surgery for gallbladder cancer. Results of the French Surgical Association Survey.

The lipid mediator platelet-activating factor (PAF) plays a role in cancer. We investigated its presence in human colon carcinoma by assessing the levels of tissue phospholipase A(2) (PLA(2), the key enzyme in the generation of the lyso-PAF precursor), lyso-PAF, PAF and acetylhydrolase activity (AHA, the key enzyme in PAF degradation) in colorectal cancer patients and by correlating them with Dukes' classification. The results highlighted that the tumour tissues of Dukes' A and B patients had significantly higher PLA(2), lyso-PAF, PAF and AHA levels as compared with nontumour tissues. Dukes' C patients had higher PLA(2), lyso-PAF and AHA levels but unchanged PAF. Dukes' D patients had higher AHA levels but unchanged PLA(2), lyso-PAF and PAF. A pathophysiological role for PAF is suggested in human colon carcinoma.

Tissue concentrations of platelet-activating factor in colorectal carcinoma: inverse relationships with Dukes' stage of patients

Éventrations postopératoires: prothèse intraou extrapéritonéale?

This clinical study reports that blood levels of the pro-inflammatory mediator platelet-activating factor (PAF) did not change in colorectal cancer patients. In contrast, plasma levels of two enzymatic activities, one implicated in PAF production (i.e. phospholipase A2) and one in PAF degradation (i.e. PAF acetylhydrolase activity) were significantly elevated.

/pdf/elevated-plasma-phospholipase-a2-and-platelet-activating-3drzdzpaug.pdf

Elevated plasma phospholipase A2 and platelet-activating factor acetylhydrolase activity in colorectal cancer

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