bims-netuvo 2021-10-03 papers

Issue of 2021‒10‒03
six papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Ann Gastroenterol Surg. 2021 Sep;5(5): 623-633

Roles of the nervous system in pancreatic cancer.

Taiichi Wakiya, Keinosuke Ishido, Tadashi Yoshizawa, Taishu Kanda, Kenichi Hakamada.

Pancreatic ductal adenocarcinoma (PDAC), with its extremely poor prognosis, presents a substantial health problem worldwide. Outcomes have improved thanks to progress in surgical technique, chemotherapy, pre-/postoperative management, and centralization of patient care to high-volume centers. However, our goals are yet to be met. Recently, exome sequencing using PDAC surgical specimens has demonstrated that the most frequently altered genes were the axon guidance genes, indicating involvement of the nervous system in PDAC carcinogenesis. Moreover, perineural invasion has been widely identified as one poor prognostic factor. The combination of innovative technologies and extensive clinician experience with the nervous system come together here to create a new treatment option. However, evidence has emerged that suggests that the relationship between cancer and nerves in PDAC, the underlying mechanism, is not fully understood. In an attempt to tackle this lethal cancer, this review summarizes the anatomy and physiology of the pancreas and discusses the role of the nervous system in the pathophysiology of PDAC.

Keywords: axon guidance; nerve growth factors; neurotrophic tyrosine kinase receptor; pancreatic neoplasms; tumor microenvironment

DOI: https://doi.org/10.1002/ags3.12459

Cancers (Basel). 2021 Sep 13. pii: 4594. [Epub ahead of print]13(18):

Perineural Invasion and Associated Pain Transmission in Pancreatic Cancer.

Jialun Wang, Yu Chen, Xihan Li, Xiaoping Zou.

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor-neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.

Keywords: nerve remodeling; pain; pancreatic cancer; perineural invasion

DOI: https://doi.org/10.3390/cancers13184594

World J Gastroenterol. 2021 Sep 07. 27(33): 5610-5621

Radiomics for predicting perineural invasion status in rectal cancer.

Mou Li, Yu-Mei Jin, Yong-Chang Zhang, Ya-Li Zhao, Chen-Cui Huang, Sheng-Mei Liu, Bin Song.

BACKGROUND: Perineural invasion (PNI), as a key pathological feature of tumor spread, has emerged as an independent prognostic factor in patients with rectal cancer (RC). The preoperative stratification of RC patients according to PNI status is beneficial for individualized treatment and improved prognosis. However, the preoperative evaluation of PNI status is still challenging.AIM: To establish a radiomics model for evaluating PNI status preoperatively in RC patients.
METHODS: This retrospective study enrolled 303 RC patients in a single institution from March 2018 to October 2019. These patients were classified as the training cohort (n = 242) and validation cohort (n = 61) at a ratio of 8:2. A large number of intra- and peritumoral radiomics features were extracted from portal venous phase images of computed tomography (CT). After deleting redundant features, we tested different feature selection (n = 6) and machine-learning (n = 14) methods to form 84 classifiers. The best performing classifier was then selected to establish Rad-score. Finally, the clinicoradiological model (combined model) was developed by combining Rad-score with clinical factors. These models for predicting PNI were compared using receiver operating characteristic curve (ROC) analysis and area under the ROC curve (AUC).
RESULTS: One hundred and forty-four of the 303 patients were eventually found to be PNI-positive. Clinical factors including CT-reported T stage (cT), N stage (cN), and carcinoembryonic antigen (CEA) level were independent risk factors for predicting PNI preoperatively. We established Rad-score by logistic regression analysis after selecting features with the L1-based method. The combined model was developed by combining Rad-score with cT, cN, and CEA. The combined model showed good performance to predict PNI status, with an AUC of 0.828 [95% confidence interval (CI): 0.774-0.873] in the training cohort and 0.801 (95%CI: 0.679-0.892) in the validation cohort. For comparison of the models, the combined model achieved a higher AUC than the clinical model (cT + cN + CEA) achieved (P < 0.001 in the training cohort, and P = 0.045 in the validation cohort).
CONCLUSION: The combined model incorporating Rad-score and clinical factors can provide an individualized evaluation of PNI status and help clinicians guide individualized treatment of RC patients.

Keywords: Computed tomography; Model building; Perineural invasion; Preoperative prediction; Radiomics; Rectal cancer

DOI: https://doi.org/10.3748/wjg.v27.i33.5610

J Cancer Res Ther. 2021 Oct 01.

Prognostic factor for recurrence in esophagus cancer patients who underwent surgery for curative intent: A single-institution analysis.

Manjinder S Sidhu, Davinder Paul, Sumeet Jain, Gurpreet S Brar, Sandhya Sood, Kunal Jain.

Objective: The purpose of this study is to analyze predisposing factors for a higher risk of recurrence in esophageal cancer patient who underwent surgery for curative intent and to do survival analysis of prognostic factors.Materials and Methods: Between February 2018 and March 2020, we retrospectively identified 28 cases staged T1b to T4a managed electively at our institute as per multidisciplinary management plan. Demographic, clinical, radiological, operative, histopathological parameters, upfront surgery done or not, type of preoperative, and adjuvant treatment used and whether neoadjuvant or adjuvant therapy was planned along with waiting time for surgery, were assessed as potential risk factors. End point of study was to find potential risk factors for recurrence and to do their subgroup survival analysis.
Results: The recurrence rate in our study was 25% with a mean follow-up of 24 months. The median time of recurrence was 8.5 months, all recurrence occurred within 1 year. Overall DFS at 2 years was 72%. On univariate analysis, following prognostic factors were associated with high risk of recurrence, male sex X2 (1) =4.42, p = 0.035; histology subtype of adenocarcinoma X2 (1) = 7.07, p = 0.008; margin positive X2 (1) =3.76, p = 0.05; presence of lymph vascular invasion (LVI) X2 (1) =7.88, p = 0.005; presence of perineural invasion (PNI) X2 (1) =5.97, p = 0.015; postoperative T size >4 cm X2 (1) =3.86, p = 0.049; and nodal positivity X2 (3) =13.47, p = 0.004.
Conclusions: Male sex, adenocarcinoma histological subtype, positive resected margin, presence of LVI and PNI, postoperative T size >4 cm, and high postoperative nodal positivity and whether neoadjuvant versus adjuvant therapy given (on K. M analysis) were the identified predictors of recurrence which compromised DFS.

Keywords: Mid and lower esophagus; prognostic factors; risk of recurrence

DOI: https://doi.org/10.4103/jcrt.JCRT_1702_20

ANZ J Surg. 2021 Sep 30.

Risk factors for recurrence in colorectal cancer: a retrospective analysis in a regional Australian hospital.

Jonathon Holt, Heinrich Schwalb, Hugh Elbourne, Luc Te Marvelde, Caitlin Reid.

BACKGROUND: Colorectal cancer is the third most commonly diagnosed malignancy in Australia. Up to a third of patients who have undergone surgery with curative intent for colorectal cancer will have a recurrence of disease leading to significant morbidity and mortality. Regional Australians have disproportionately worse outcomes.AIM: To identify factors associated with recurrence in colorectal cancer patients treated at a regional Australian hospital.
METHODS: This study is a retrospective cohort analysis. Consecutive patients who have undergone curative resection at a regional public and private hospital by three surgeons from a single surgical practice for either rectal cancer or colon cancer were included. Prognostic indicators of recurrence were examined via both univariate and multivariate time-to-event analyses.
RESULTS: Three hundred nine patients were included with 43 recurrences. Thirty presented with distant metastases, seven presented with locoregional recurrence and six presented with locoregional as well as distant recurrence. In univariable analysis, higher rates of recurrence were associated with tumour type, higher AJCC summary stage, higher preoperative levels of CA19-9, perineural invasion, lymphovascular invasion, <12 nodes examined, positive lymph nodes and emergency surgery status. On multivariable analysis recurrence remained associated with tumours with a mucinous and/or signet cell component, positive nodes and <12 lymph nodes examined.
CONCLUSION: A combination of patient and treatment factors are relevant in determining the risk of recurrence for stage I-III colorectal cancer. This study emphasises the importance of histology in determining risk, particularly the number of nodes examined. CEA 19-9 may also be a useful pre-operative predictor of recurrence.

Keywords: colorectal cancer; colorectal surgery; recurrence; risk factors; surgical oncology

DOI: https://doi.org/10.1111/ans.17209

Front Oncol. 2021 ;11 618820

Evaluation of Traditional Prognostic Factors for Stage I-III Colorectal Cancer Patients Who Survived for Over Five Years After Surgery.

Dakui Luo, Yufei Yang, Zezhi Shan, Qi Liu, Sanjun Cai, Qingguo Li, Xinxiang Li.

The aim of this study was to explore the prognostic factors in stage I-III colorectal cancer (CRC) patients who had survived for over five years. A total of 9754 stage I-III CRC patients who received curative surgery in the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center were enrolled in this study. Of them, 3640 patients had survived for over five years after surgery. Univariate and multivariate Cox regression analyses were performed in the entire cohort and those who had survived for over five years. Compared with patients in the entire cohort, patients who had survived for over five years were more likely to be younger, have less disease of signet ring cell histology, perineural invasion and vascular invasion, more well differentiated tumors and stage I disease. In the entire cohort, increased age, signet ring cell, poor differentiation, more advanced pathological stage, perineural invasion and vascular invasion were inversely associated with disease-free survival (DFS) and overall survival (OS) using multivariable Cox regression analyses. Only age, pathological stage and perineural invasion remained significant in patients who had survived for over five years. Moreover, tumor location was an independent factor for OS in this subgroup. Predictors for prognosis of CRC change over time. Age, pathological stage and perineural invasion deserve more attention among patients who have survived for over five years.

Keywords: COX; FUSCC; colorectal cancer; prognostic factors; survive over five years

DOI: https://doi.org/10.3389/fonc.2021.618820