Significance of Ductal Margin Status in Patients Undergoing Surgical Resection for Extrahepatic Cholangiocarcinoma

Sasaki, Ryoko; Takeda, Yuichiro; Funato, Osamu; Nitta, Hiroyuki; Kawamura, Hidenobu; Uesugi, Noriyuki; Sugai, Tamotsu; Wakabayashi, Go; Ohkohchi, Nobuhiro

doi:10.1007/s00268-007-9102-7

Cited by 99 publications

(103 citation statements)

References 35 publications

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“…In 2005, Wakai et al26 reported that invasive carcinoma at the ductal resection margins had a strong adverse effect on survival in patients with extrahepatic cholangiocarcinoma, whereas residual carcinoma in situ did not. Thereafter, similar results were reported in Japan,27, 28, 29, 30, 31, 32, 33, 34, 35, 36 the USA,37 South Korea,38, 39 and Germany 40. These findings indicate that discrimination between carcinoma in situ and invasive carcinoma is critical when the ductal resection margins are found to be positive on intraoperative examination of frozen sections; residual carcinoma in situ may lead to late local recurrence, whereas residual invasive carcinoma results in early local recurrence 26…”

Section: Introductionsupporting

confidence: 84%

“…26, 27, 28, 31, 32, 34, 35, 38 The reported incidences of complete resection with histopathologically negative margins ranged from 69% to 87% 26, 27, 28, 31, 32, 34, 35, 38. All the studies included in Table 1 confirmed that ductal resection margin status was an independent prognostic factor in patients with extrahepatic cholangiocarcinoma.…”

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 80%

“…Differentiation between severe dysplasia and carcinoma in situ may be difficult or impossible. Therefore, in several clinical studies,26, 27, 28, 35, 36, 38, 39 severe (high‐grade) dysplasia has been categorized as carcinoma in situ. Severe dysplastic epithelium or carcinoma in situ may extend into intramural glands such as the sacculi of Beale or metaplastic pyloric type glands 42.…”

Section: “Carcinoma In Situ”: Histopathological Terminologymentioning

confidence: 99%

“…All the studies included in Table 1 confirmed that ductal resection margin status was an independent prognostic factor in patients with extrahepatic cholangiocarcinoma. Residual invasive carcinoma at the ductal resection margins (median survival time, 12‐21 months) has been reported to influence patient survival after surgical resection for extrahepatic cholangiocarcinoma more adversely than residual carcinoma in situ (median survival time, 29‐99 months) 26, 27, 28, 31, 32, 34, 38. Several research groups reported that survival following resection was comparable between patients who had negative ductal margins (median survival time, 33‐55 months) and those who had positive ductal margins with carcinoma in situ (median survival time, 37‐99 months) 26, 27, 28, 31, 32, 35.…”

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 99%

“…Residual invasive carcinoma at the ductal resection margins (median survival time, 12‐21 months) has been reported to influence patient survival after surgical resection for extrahepatic cholangiocarcinoma more adversely than residual carcinoma in situ (median survival time, 29‐99 months) 26, 27, 28, 31, 32, 34, 38. Several research groups reported that survival following resection was comparable between patients who had negative ductal margins (median survival time, 33‐55 months) and those who had positive ductal margins with carcinoma in situ (median survival time, 37‐99 months) 26, 27, 28, 31, 32, 35. Although residual carcinoma in situ at the ductal margins does not have a strong adverse effect on survival in patients with extrahepatic cholangiocarcinoma, it may result in late local recurrence 26, 27, 28, 29, 31, 32, 34, 36, 53, 54, 55, 56, 57…”

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 99%

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Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma

Wakai

Sakata

Katada

et al. 2018

Annals of Gastroent Surgery

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Recent advances in dimensional imaging, surgical technique, and perioperative patient care have resulted in increased rates of complete resection with histopathologically negative margins and improved surgical outcomes in patients with extrahepatic cholangiocarcinoma. However, achieving cancer‐free resection margins at ductal stumps in surgery for this disease remains challenging because of longitudinal extension, which is one of the hallmarks of extrahepatic cholangiocarcinoma. When the ductal resection margins are shown to be positive on examination of frozen sections, discrimination between carcinoma in situ and invasive carcinoma is clinically important because residual carcinoma in situ may lead to late local recurrence whereas residual invasive carcinoma is associated with early local recurrence. Residual invasive carcinoma at the ductal margins should be avoided whenever technically feasible. Residual “carcinoma in situ” at the ductal margins appears to be allowed in resection for the advanced disease because it has less effect on survival than other adverse prognostic factors (pN1 and/ or pM1). However, in surgery for early‐stage (pTis‐2N0M0) extrahepatic cholangiocarcinoma, residual carcinoma in situ at the ductal margins may have an adverse effect on long‐term survival, so should be avoided whenever possible. In this review, we focus on the histopathological term “carcinoma in situ,” the biological behavior of residual carcinoma in situ at ductal resection margins, intraoperative histological examination of the ductal resection margins, outcome of additional resection for positive ductal margins, and adjuvant therapy for patients with positive margins.

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Section: Introductionsupporting

confidence: 84%

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 80%

Section: “Carcinoma In Situ”: Histopathological Terminologymentioning

confidence: 99%

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 99%

Section: Biological Behavior Of Residual Carcinoma In Situmentioning

confidence: 99%

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Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma

Wakai

Sakata

Katada

et al. 2018

Annals of Gastroent Surgery

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Adjuvant chemoradiotherapy for positive hepatic ductal margin on cholangiocarcinoma

Sugiura

Uesaka

Okamura

et al. 2020

Annals of Gastroent Surgery

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Aim This study evaluated the effects of postoperative adjuvant chemoradiotherapy (A‐CRT) for positive hepatic ductal margin (HM+) in extrahepatic cholangiocarcinoma (EHCC). Methods Patients with EHCC who underwent surgical resection between 2002 and 2014 were included in this retrospective study. For patients with HM+, A‐CRT was conducted. The clinical effect of A‐CRT for HM+ on the survival and recurrence and prognostic factors of EHCC was reviewed. Results Among 340 patients, the hepatic ductal margin was negative in 296 and positive in 44. Of the 44 patients with HM+, 22 received postoperative A‐CRT, and 22 did not. Hepatic stump recurrence occurred in 19 patients. The incidence was significantly higher in patients with HM+ (20%, 9/44) than in those with negative hepatic ductal margin (HM−) (3%, 10/296) ( P < .001). Among the patients with HM+, the incidence was almost identical between the patients with and without A‐CRT: 23% (5/22) in HM+/CRT− and 18% (4/22) in HM+/CRT+ patients ( P = .999). The median survival time was 49 months in HM−, 43 months in HM+/CRT−, and 49 months in HM+/CRT+ patients. The differences were not significant among the groups. A multivariate analysis revealed CA 19‐9 ≥ 300 U/mL, combined vascular resection, histologic grade G2/G3, and lymph node metastasis to be significant prognostic factors. However, the performance of postoperative A‐CRT did not contribute to prolonging survival. Conclusion A‐CRT for HM+ in patients with EHCC did not affect the survival or stump recurrence.

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Clinical value of additional resection of a margin-positive distal bile duct in perihilar cholangiocarcinoma

Otsuka

Yokoyama

Mizuno

et al. 2019

British Journal of Surgery

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Background: Little is known about the effect of additional resection for a frozen-section-positive distal bile duct margin (DM) in perihilar cholangiocarcinoma. Methods: Patients who underwent surgical resection for perihilar cholangiocarcinoma between 2001 and 2015 were analysed retrospectively, focusing on the DM. Results: Of 558 consecutive patients who underwent frozen-section examination for a DM, 74 (13⋅3 per cent) had a frozen-section-positive DM with invasive cancer or carcinoma in situ. Eventually, 53 patients underwent additional resection (bile duct resection in 44 and pancreatoduodenectomy in 9), whereas the remaining 21 patients did not. Ultimately, R0 resection was achieved in 30 of the 53 patients (57 per cent). No patient who underwent additional resection died from surgical complications. The 44 patients with additional bile duct resection had a 5-year overall survival rate of 31 per cent. Overall survival of the nine patients who had pancreatoduodenectomy was better, with a 10-year rate of 67 per cent. Survival of the 21 patients without additional resection was dismal: all died within 5 years. Multivariable analyses identified nodal status and additional resection as independent prognostic factors (lymph node metastasis: hazard ratio (HR) 2⋅26, 95 per cent c.i. 1⋅26 to 4⋅07; bile duct resection versus no additional resection: HR 0⋅32, 0⋅17 to 0⋅60; pancreatoduodenectomy versus no additional resection: HR 0⋅08, 0⋅02 to 0⋅29). Conclusion: Additional resection for frozen-section-positive DM in perihilar cholangiocarcinoma frequently yields R0 margins. It offers a better chance of long-term survival, and thus should be performed in carefully selected patients. Prognostic factors in patients with a frozen-section-positive distal marginPrognostic factors were analysed in the 74 patients with a frozen-section-positive DM ( Table 2). On univariable analysis, microscopic venous invasion, pathological tumour

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Significance of Ductal Margin Status in Patients Undergoing Surgical Resection for Extrahepatic Cholangiocarcinoma

Cited by 99 publications

References 35 publications

Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma

Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma

Adjuvant chemoradiotherapy for positive hepatic ductal margin on cholangiocarcinoma

Clinical value of additional resection of a margin-positive distal bile duct in perihilar cholangiocarcinoma

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