K-ras Point Mutation in the Nerve Plexuses Around the Superior Mesenteric Artery in Resectable Adenocarcinoma of the Pancreatic Head

Ohigashi, Hajime; Ishikawa, Osamu; Sasaki, Yo; Yamada, Terumasa; Furukawa, Hiroshi; Imaoka, Shingi; Kasugai, Tsutomu; Ishiguro, Shingo; Ueda, Koji; Miyoshi, Yasuo; Nakamura, Yusuke

doi:10.1001/archsurg.135.12.1450

Cited by 18 publications

(15 citation statements)

References 13 publications

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“…Using a quantitative PNA PCR approach, we detected K-ras mutation in the surgical resection margins of 37 of 70 (53%) patients, all of whom had negative margins by H&E. Ohigashi et al have also detected K-ras mutation in retroperitoneal tissues of patients with pancreatic cancer. 31 Here we correlated K-ras margin status with disease outcome and demonstrated a significant difference in overall survival (fig 2). These findings therefore suggest that the current techniques to determine the adequacy of surgical margins may not be sensitive to identify relevant genetic aberrancies which may be the surrogates of unrecognised disease.…”

Section: Discussionmentioning

confidence: 67%

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Kim

Reber

Dry

et al. 2006

Gut

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Background: Despite intent to cure surgery with negative resection margins, locoregional recurrence is common in pancreatic cancer. Aims: To determine whether detection of K-ras gene mutation in the histologically negative surgical margins of pancreatic cancer reflects unrecognised disease. Patients: Seventy patients who underwent curative resection for pancreatic ductal adenocarcinoma were evaluated. Methods: All patients had surgical resection margins (pancreatic transection and retroperitoneal) that were histologically free of invasive cancer. DNA was extracted from these paraffin embedded surgical margins and assessed by quantitative real time polymerase chain reaction to detect the K-ras gene mutation at codon 12. Detection of K-ras mutation was correlated with standard clinicopathological factors. Results: K-ras mutation was detected in histologically negative surgical margins of 37 of 70 (53%) patients. A significant difference in overall survival was demonstrated between patients with margins that were K-ras mutation positive compared with negative (median 15 v 55 months, respectively; p = 0.0008). By univariate and multivariate analyses, detection of K-ras mutation in the margins was a significant prognostic factor for poor survival (hazard ratio (HR) 2.8 (95% confidence interval (CI) 1.5-5.3), p = 0.0009; and HR 2.8 (95% CI 1.4-5.5), p = 0.004, respectively). Conclusions: Detection of cells harbouring K-ras mutation in histologically negative surgical margins of pancreatic cancer may represent unrecognised disease and correlates with poor disease outcome. The study demonstrates that molecular-genetic evaluation of surgical resection margins can improve pathological staging and prognostic evaluation of patients with pancreatic ductal adenocarcinoma.

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Section: Discussionmentioning

confidence: 67%

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Kim

Reber

Dry

et al. 2006

Gut

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“…Recent histological and molecular studies seem to indicate that resection margin involvement is significantly more frequent than commonly reported 17,44,50,51 . This implies that pancreatic cancer represents for the majority of patients a locally advanced disease, which cannot be cured by surgery alone and requires adjuvant treatment.…”

Section: The Way Forwardmentioning

confidence: 98%

“…Further support for the importance of extensive tissue sampling comes from a study in which the detection of cancer cells in soft tissue around the superior mesenteric artery was compared between conventional histology and K‐ras mutational analysis. In a considerable proportion (43%) of cases that were negative on histology but positive according to the K‐ras analysis, cancer cells were indeed identified when additional tissue sections were examined microscopically 44 …”

Section: Gross Specimen Examinationmentioning

confidence: 99%

Resection margins and R1 rates in pancreatic cancer – are we there yet?

2007

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The prognosis of pancreatic cancer is poor, even for those patients who undergo surgical resection. The rate of local recurrence is high, despite the fact that in most series complete (‘R0’) resection is reported to be achieved in the majority of patients. The discrepancy between pathological assessment and clinical outcome indicates that microscopic margin involvement (R1) is frequently underreported, and potential causes for this are discussed in this review. Special emphasis is given to the variation that exists between currently used dissection techniques and their impact on the assessment of the resection margins in pancreatoduodenectomy specimens.

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“…Instead, p53 deletion detected in peritoneal drainage fluid was associated with early peritoneal metastasis. Pancreatic cancers usually infiltrate into retroperitoneal nerve plexuses [21] or lymphatic tissues [22] on a microscopic level although macroscopic tumors are confined to the pancreas. The data of this study suggest that microscopic residual disease that outflows from the vessels and lymphatics at the operation bed flows into the peritoneal cavity, which results in peritoneal metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cancer cells with p53 deletion detected by fluorescentin situhybridization in peritoneal drainage fluid is correlated with early peritoneal seeding in resectable pancreatic cancer

et al. 2013

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PurposeFree tumor cells in peritoneal fluid in patients with pancreatic cancer may have prognostic significance but there are few reports on methods for the effective detection of free tumor cells. The aims of this study were to identify free cancer cells in peritoneal fluid with fluorescent in situ hybridization (FISH) technique and to investigate its prognostic significance.MethodsTwenty-eight patients with resectable pancreatic cancer who underwent surgical resection were included. Peritoneal washing and peritoneal drainage fluid were examined by FISH for p53 deletion.ResultsAmong the study subjects, the R0 resection rate was 75%. None of the patients had positive cytology with Papanicolaou's method. p53 deletion was detected in 9 peritoneal washings (32.1%) and in 5 peritoneal drainage fluids (17.9%). After a median of 18 months of follow-up, 25 patients (89.3%) experienced recurrence and 14 patients (50.0%) had peritoneal seeding. Patients with p53 deletion detected in the peritoneal drainage fluid had positive radial margin (60.0% vs. 17.4%, P = 0.046) more frequently and a lower peritoneal metastasis free survival (median, 11.1 months vs. 30.3 months; P = 0.030). Curative resection (P < 0.001) and p53 deletion in peritoneal drainage fluid (P = 0.030) were independent risk factors of peritoneal metastasis free survival after multivariate analysis.ConclusionFISH technique detects free cancer cells with higher sensitivity compared to Papanicolaou's method. p53 deletion detected in peritoneal drainage fluid is correlated with positive radial resection margin and results in early peritoneal seeding. Patients with p53 deletion in peritoneal drainage fluid need more aggressive adjuvant treatment.

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K-ras Point Mutation in the Nerve Plexuses Around the Superior Mesenteric Artery in Resectable Adenocarcinoma of the Pancreatic Head

Cited by 18 publications

References 13 publications

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins

Resection margins and R1 rates in pancreatic cancer – are we there yet?

Cancer cells with p53 deletion detected by fluorescentin situhybridization in peritoneal drainage fluid is correlated with early peritoneal seeding in resectable pancreatic cancer

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