bims-netuvo 2022-04-10 papers

Issue of 2022‒04‒10
four papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Ann Med Surg (Lond). 2022 Mar;75 103398

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study.

Gustavo N C Inoue, Ruan Pimenta, Juliana A Camargo, Nayara I Viana, Vanessa R Guimarães, Miguel Srougi, William C Nahas, Katia R M Leite, Sabrina T Reis.

Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines.Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia.
Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group.
Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery.
Institutional protocol number: Animal Ethics Committee 1332/2019.

Keywords: ANOVA, analysis of variance; Anesthesia; Circulating; Cytokines; FC, flow cytometry; ICTC, circulating tumor cells; IFN, interferon; IL, interleukin; IVIS, In Vivo Imaging System; Killer cells; NK, natural killer; NOD/SCID, non-obese diabetic/severe combined immunodeficiency; Natural; Neoplastic cells; PC, prostate cancer; Prostatic neoplasms; SD, standard deviation; Spinal; TNF, tumor necrosis factor

DOI: https://doi.org/10.1016/j.amsu.2022.103398

Int J Colorectal Dis. 2022 Apr 05.

Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.

Hyun Gu Lee, Chan Wook Kim, Jong Lyul Lee, Yong Sik Yoon, In Ja Park, Seok-Byung Lim, Chang Sik Yu, Jin Cheon Kim.

PURPOSE: Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO.METHODS: This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size.
RESULTS: In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups.
CONCLUSIONS: This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.

Keywords: Abdominoperineal resection; Prognostic factor; Rectal cancer; Sphincter-saving operation

DOI: https://doi.org/10.1007/s00384-022-04138-2

Crit Rev Oncog. 2021 ;26(3): 1-41

A Profound Relationship between Circadian Rhythm Dysfunction and Cancer Progression: An Approach to Exploration.

Saptadip Samanta.

Circadian (~ 24-hour) rhythm has been observed in all living organisms. In humans, the circadian system governs different physiological functions such as metabolism, sleep-wake cycle, body temperature, hormone secretion, and cellular proliferation. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the principal circadian pacemaker. The SCN receives input signals primarily from the retinohypothalamic tract (RHT), sends output signals to different parts of the hypothalamus, pineal gland, and the peripheral clocks through the neural or humoral network. The functions of the circadian clock are mediated by the rhythmic expression of the core clock genes through a complex feedback loop. Disruption of clock functions influences the development of several pathologic conditions, including cancer, shift work, chronic or acute jet lag, and light-at-night affect the circadian activity, leading to development of several physiological disorders, more specifically cancer. Circadian dysfunction alters the expression of core clock genes that promote the deregulation of the cell cycle, increase cell proliferation and survival, decrease apoptotic activity, alter metabolic functions, increase metastatic property, collectively induces cancer progression.

DOI: https://doi.org/10.1615/CritRevOncog.2021039731

Oncogene. 2022 Apr 07.

Malignant peripheral nerve sheath tumor: models, biology, and translation.

Bandarigoda N Somatilaka, Ali Sadek, Renee M McKay, Lu Q Le.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8-13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies.

DOI: https://doi.org/10.1038/s41388-022-02290-1