Prognostic predictions based on pathological findings of peritoneal dissemination in patients with stage IV colorectal cancer without residual disease (R0 status)

Kono, Koji; Kinoshita, Takashi; Oshiro, Taihei; Ouchi, Akira; Ito, Seiji; T, Abe; Senda, Yoshiki; Misawa, Kazunari; Ito, Y.; Natsume, Seiji; Higaki, Eiji; Okuno, Masataka; Hosoi, Takahiro; An, Byonggu; Hayashi, Daisuke; Uchino, Tairin; Kunitomo, Aina; Oki, Satoshi; Jin, Tao; Suenaga, Yasuhito; Maeda, Shingo; Dei, Hideyuki; Numata, Yoshihisa; Shimizu, Yasuhiro

doi:10.1007/s00595-019-01800-1

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…We found that high tumour necrosis percentage was associated with shorter cancer-specific survival in two independent cohorts, involving more than 1300 patients. Several previous studies have also suggested that tumour necrosis represent a potential prognostic factor in CRC [22,[26][27][28]45]. Still, to our knowledge, our study is the largest so far and also supports the significance of tumour necrosis independent of many parameters currently evaluated in clinical practice such as lymphovascular invasion, tumour grade, MMR status, and BRAF status.…”

Section: Discussionsupporting

confidence: 84%

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Immunological and prognostic significance of tumour necrosis in colorectal cancer

et al. 2023

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Background Colorectal cancer (CRC) causes the second most cancer deaths worldwide, but the disease course varies according to tumour characteristics and immunological factors. Our objective was to examine the associations of tumour necrosis with tumour characteristics, immune cell infiltrates, serum cytokine concentrations, as well as prognosis in CRC. Methods Three independent CRC cohorts, including 1413 patients, were analysed. Associations of the areal percentage of tumour necrosis with clinicopathologic parameters, tumour infiltrating immune cells, cytokine concentrations in systemic and mesenteric vein blood, and survival were examined. Results Higher tumour necrosis percentage associated with shorter colorectal cancer-specific survival independent of tumour grade, T, N or M-class, mismatch repair status, BRAF status, and other possible confounding factors. In the largest cohort (N = 1100), the HR for high tumour necrosis percentage (≥40% vs. <3%) was 3.22 (95% CI 1.68–6.17, Ptrend < 0.0001). Tumour necrosis percentage positively correlated with peripheral serum levels of CXCL8, a proinflammatory chemokine, and negatively correlated with mesenteric serum levels of CXCL10 and mast cell densities in the invasive margin of the tumour. Conclusions Our results support the value of tumour necrosis as a prognostic factor in colorectal cancer. CXCL8 may have a role in the systemic effects of tumour necrosis.

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Section: Discussionsupporting

confidence: 84%

“…In our study, high tumour necrosis percentage was associated with several tumour characteristics such as high TNM stage, high grade, and MMR proficient status. Other studies have reported similar findings [3,22,23,[26][27][28][29]. Apoptotic cell death could be more common in MMR-deficient tumours compared to MMR proficient [30,31].…”

Section: Discussionsupporting

confidence: 64%

Immunological and prognostic significance of tumour necrosis in colorectal cancer

et al. 2023

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“…The 2019 JSCCR guidelines recommend resection for the local recurrence of rectal cancer when R0 resection is possible (12). Many previous studies have reported cases of recurrent lesion resection and their corresponding prognoses (13), particularly that of hepatic, para-aortic lymph node, and peritoneal metastases secondary to colorectal cancer (14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

How many times can patients tolerate reoperation for the local recurrence of colorectal cancer in terms of complications?

Komori,

Kinoshita,

Sato

et al. 2023

J. Med. Invest.

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The frequency of resection for the recurrence of colorectal cancer has not been investigated in previous studies. Likewise, the related postoperative complications and the limit for indicating surgical resection has not been reported. Herein, we reported the complications of a highly frequent surgical approach for rectal cancer recurrence, i.e., exceeding three reoperations, based on our clinical experience. We included 15 cases exceeding two operations for the local recurrence of colorectal cancer from 2014 to 2019. We examined the postoperative complications classified as Clavien-Dindo IIIb. The positive rates of the complications were 0 (0.0%), 0 (0.0%), 2 (13.3%), 3 (37.5%), and 0 (0.0%) for the primary, 1 st recurrent, 2 nd recurrent, 3 rd recurrent, and 4 th recurrent operation group (p = 0.027), respectively. It is important to exercise caution in handling cases exceeding two reoperations (exceeding three reoperations including the primary operation).

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“…Tumour necrosis has been reported to positively associate with poor prognosis and overall survival of CRC patients. 84,85 Necrotic cells may also release proinflammatory and tumour-promoting cytokines that will increase the probability of proto-oncogenic mutations or epigenetic alterations, inducing angiogenesis, cancer cell proliferation and chemoresistance. 86,87 The reduction of tumour necrosis in the combination group may further highlight the therapeutic potential of this adjuvant treatment.…”

Section: Discussionmentioning

confidence: 99%

BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil

et al. 2019

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Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC). Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry. Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC. Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

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Prognostic predictions based on pathological findings of peritoneal dissemination in patients with stage IV colorectal cancer without residual disease (R0 status)

Cited by 3 publications

References 11 publications

Immunological and prognostic significance of tumour necrosis in colorectal cancer

Immunological and prognostic significance of tumour necrosis in colorectal cancer

How many times can patients tolerate reoperation for the local recurrence of colorectal cancer in terms of complications?

BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil

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