bims-netuvo 2023-01-08 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2023‒01‒08
seven papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Lymphovascular invasion represents a superior prognostic and predictive pathological factor of the duration of adjuvant chemotherapy for stage III colon cancer patients.
Vasculitis, CA19-9, and PNI differentially predict response and surgical outcome in pancreatic ductal adenocarcinoma.
Risk factors for lymph node metastasis in patients with pT2 colon cancer in Denmark from 2016 to 2019 - a nationwide cohort study.
Survival outcomes of stage I colorectal cancer: development and validation of the ACEPLY model using two prospective cohorts.
Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway.
The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China.
Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana.

BMC Cancer. 2023 Jan 03. 23(1): 3

Lymphovascular invasion represents a superior prognostic and predictive pathological factor of the duration of adjuvant chemotherapy for stage III colon cancer patients.

Linjie Zhang, Yuxiang Deng, Songran Liu, Weili Zhang, Zhigang Hong, Zhenhai Lu, Zhizhong Pan, Xiaojun Wu, Jianhong Peng.

  BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) can indicate poor survival outcomes in colorectal cancer, but few studies have focused on stage III colon cancer. The current study aimed to confirm the prognostic value of LVI and PNI and identify patients who could benefit from a complete duration of adjuvant chemotherapy based on the two pathological factors.METHODS: We enrolled 402 consecutive patients with stage III colon cancer who received colon tumor resection from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Survival analyses were performed by using Kaplan-Meier method with log-rank tests. Risk factors related to disease-free survival (DFS) and overall survival (OS) were identified through Cox proportional hazards analysis.
RESULTS: 141 (35.1%) patients presented with LVI, and 108 (26.9%) patients with PNI. The LVI-positive group was associated with poorer 3-year DFS (86.5% vs. 76.3%, P = 0.001) and OS (96.0% vs. 89.1%, P = 0.003) rates compared with the LVI-negative group. The PNI-positive group showed a worse outcome compared with the PNI-negative group in 3-year DFS rate (72.5% vs. 86.7%, P < 0.001). Moreover, LVI-positive group present better 3-year DFS and OS rate in patients completing 6-8 cycles of adjuvant chemotherapy than those less than 6 cycles (3-year DFS: 80.0% vs. 64.9%, P = 0.019; 3-year OS: 93.2% vs. 76.3%, P = 0.002).
CONCLUSIONS: LVI is a superior prognostic factor to PNI in stage III colon cancer patients undergoing curative treatment. PNI status can noly predict the 3-year DFS wihout affecting the 3-year OS. Furthermore, LVI also represents an effective indicator for adjuvant chemotherapy duration.

Keywords:  Adjuvant chemotherapy; Lymphovascular invasion; Perineural invasion; Prognosis; Stage III colon cancer

DOI:  https://doi.org/10.1186/s12885-022-10416-7
Int J Radiat Oncol Biol Phys. 2023 Jan 01. pii: S0360-3016(22)03692-6. [Epub ahead of print]

Vasculitis, CA19-9, and PNI differentially predict response and surgical outcome in pancreatic ductal adenocarcinoma.

Miles Piper, Richard Blake Ross, Junxiao Hu, Shuichi Watanabe, Michael Knitz, Sanjana Mehrotra, Richard Shulick, Marco Del Chiaro, Sana D Karam.

INTRODUCTION: Curative intent treatment of pancreatic adenocarcinoma (PDAC) relies on surgical resection. Modern treatment protocols focus on optimizing neoadjuvant therapy to increase resectability and improve oncologic outcomes. To elucidate differences in outcomes, we investigated the relationship between neoadjuvant chemotherapy (NAC), either with or without stereotactic body radiation therapy (SBRT), and vascular inflammation, surgical outcomes, and the resultant transcriptomic changes.METHODS: Clinical data were collected from patients with borderline resectable PDAC (clinical T3-T4N0-1) that underwent NAC or NAC-SBRT followed by curative-intent resection between 2014 and 2019. Vascular structures on surgical specimens were histologically evaluated for vasculitis. RNA-seq was utilized to evaluate differential gene expression and generate enrichment maps. Multivariate analysis was used to analyze the relationship between patient characteristics and oncological outcome.
RESULTS: In total, n=46 patients met inclusion criteria (n=12 NAC, n=34 NAC-SBRT) with a median follow up of 20.1 months. All patients underwent curative resection with 91.3% achieving R0. There was no significant difference in patterns of failure, overall survival (OS) or progression free survival between NAC and NAC-SBRT groups. Patients with vasculitis had a lower median OS compared to those without (14.5 mo vs. 28.3 mo, HR of 12.96 [95% CI 3.55-47.28], p<0.001). There was no significant correlation between inflammation and surgical complications or pathologic response. Neoadjuvant therapy did not have a significant effect on development of vasculitis (OR of 1.64 for NAC-SBRT, 95% CI 0.40-8.43, p=0.52). Predictors of poor survival included perineural invasion (PNI) and high baseline CA19-9 (>191 U/mL). Patients with robust CA19-9 (>20% decrease) responses to neoadjuvant therapy had enrichment in immune response, chemotaxis, and cytotoxic T-cell and NK cell proliferation.
CONCLUSIONS: Vasculitis predicts for poor survival outcomes in PDAC patients; NAC-SBRT did not increase the rate of vasculitis compared to NAC. PNI and CA19-9 remain strong prognosticators. Understanding and optimizing the immune response remains a crucial hurdle in achieving responses in pancreatic cancer.

DOI: https://doi.org/10.1016/j.ijrobp.2022.12.039
Colorectal Dis. 2023 Jan 01.

Risk factors for lymph node metastasis in patients with pT2 colon cancer in Denmark from 2016 to 2019 - a nationwide cohort study.

Morten Hartwig, Andreas Rosen, Rasmus Vogelsang, Anne-Marie Fiehn, Ismail Gögenur.

  AIM: The majority of patients with pT2 colon cancer have no lymph node metastasis (LNM). Knowledge of risk factors for LNM in pT2 colon cancer could identify patients at low risk and thereby potential candidates for local tumor excision. The aim was to identify risk factors for LNM in pT2 colon cancer and describe a subgroup of low-risk patients.METHOD: Retrospective cohort study on patients with pT2 colon cancer from a nationwide Danish colorectal cancer database. Age, tumor size, location, histological type, mismatch repair protein status, venous, lymphatic and perineural invasion were included as potential risk factors in multivariate analysis. Primary outcome was LNM.
RESULTS: We identified 1306 patients with pT2 colon cancer, LNM was present in 244 (19%). Demographic data were comparable in patients with and without LNM, and 864 patients who had complete histological data were included for multivariate analysis. Lymphatic (OR = 3.60, 95% CI 2.14-5.9), venous (OR = 1.70, 95% CI 1.03-2.74) and perineural (OR = 4.61, 95% CI 1.60-13.5) invasion were independent risk factors for LNM. Patients with deficient mismatch repair protein tumors had a decreased risk of LNM (OR = 0.55, 95% CI 0.31-0.95). Patients with clinical stage I colon cancer and without risk factors had 10.5% (47/443) risk of LNM. For patients with tumors with deficient mismatch repair protein status and no risk factors, the risk was 7.9%.
CONCLUSION: Lymphatic, venous and perineural invasion are significant risk factors and we identified a subgroup of patients with a low risk of LNM.

Keywords:  Colon cancer; T2 category; histological risk factors; lymph node metastases

DOI:  https://doi.org/10.1111/codi.16469
BMC Med. 2023 Jan 04. 21(1): 3

Survival outcomes of stage I colorectal cancer: development and validation of the ACEPLY model using two prospective cohorts.

Qingbin Wu, Pengju Chen, Chi Shu, Lin Chen, Zechuan Jin, Jun Huang, Xin Wang, Xue Li, Mingtian Wei, Tinghan Yang, Xiangbing Deng, Aiwen Wu, Yazhou He, Ziqiang Wang.

  BACKGROUND: Approximately 10% of stage I colorectal cancer (CRC) patients experience unfavorable clinical outcomes after surgery. However, little is known about the subset of stage I patients who are predisposed to high risk of recurrence or death. Previous evidence was limited by small sample sizes and lack of validation.METHODS: We aimed to identify early indicators and develop a risk stratification model to inform prognosis of stage I patients by employing two large prospective cohorts. Prognostic factors for stage II tumors, including T stage, number of nodes examined, preoperative carcinoma embryonic antigen (CEA), lymphovascular invasion, perineural invasion (PNI), and tumor grade were investigated in the discovery cohort, and significant findings were further validated in the other cohort. We adopted disease-free survival (DFS) as the primary outcome for maximum statistical power and recurrence rate and overall survival (OS) as secondary outcomes. Hazard ratios (HRs) were estimated from Cox proportional hazard models, which were subsequently utilized to develop a multivariable model to predict DFS. Predictive performance was assessed in relation to discrimination, calibration and net benefit.
RESULTS: A total of 728 and 413 patients were included for discovery and validation. Overall, 6.7% and 4.1% of the patients developed recurrences during follow-up. We identified consistent significant effects of PNI and higher preoperative CEA on inferior DFS in both the discovery (PNI: HR = 4.26, 95% CI: 1.70-10.67, p = 0.002; CEA: HR = 1.46, 95% CI: 1.13-1.87, p = 0.003) and the validation analysis (PNI: HR = 3.31, 95% CI: 1.01-10.89, p = 0.049; CEA: HR = 1.58, 95% CI: 1.10-2.28, p = 0.014). They were also significantly associated with recurrence rate. Age at diagnosis was a prominent determinant of OS. A prediction model on DFS using Age at diagnosis, CEA, PNI, and number of LYmph nodes examined (ACEPLY) showed significant discriminative performance (C-index: 0.69, 95% CI:0.60-0.77) in the external validation cohort. Decision curve analysis demonstrated added clinical benefit of applying the model for risk stratification.
CONCLUSIONS: PNI and preoperative CEA are useful indicators for inferior survival outcomes of stage I CRC. Identification of stage I patients at high risk of recurrence is feasible using the ACEPLY model, although the predictive performance is yet to be improved.

Keywords:  Colorectal cancer; Early stage; Prediction model; Prognosis; Risk factor

DOI:  https://doi.org/10.1186/s12916-022-02693-7
Heliyon. 2022 Dec;8(12): e12468

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway.

Yue-Hong Qi, Lu-Zi Yang, Lan Zhou, Li-Juan Gao, Jia-Yi Hou, Zi Yan, Xiao-Gang Bi, Cai-Ping Yan, De-Ping Wang, Ji-Min Cao.

  Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD).Methods: Sympathetic nerve and its neurotransmitter NE, β-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of β2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics.
Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, β2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of β2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, β2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of β2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9.
Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of β2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression.

Keywords:  Catecholamine; Gastric cancer; Sympathetic nerve; YKL-40; β-adrenoceptor

DOI:  https://doi.org/10.1016/j.heliyon.2022.e12468
Eur J Surg Oncol. 2022 Dec 31. pii: S0748-7983(22)01364-6. [Epub ahead of print]

The role of extra-hepatic bile duct resection in patients with gallbladder carcinoma with peri-neural invasion: A ten-year experience in China.

Tian-Run Lv, Hai-Jie Hu, Fei Liu, Wen-Jie Ma, Yan-Wen Jin, Fu-Yu Li.

  BACKGROUND: Peri-neural invasion (PNI) in gallbladder carcinoma (GBC) has been demonstrated as a vital prognostic factor. However, whether PNI in patients with GBC can be regarded as a surgical indication of bile duct resection (BDR) remains controversial.METHODS: GBC patients with pathologically-confirmed PNI between September 2010 and September 2020 were retrospectively reviewed. Comparative analyses were performed in patients with PNI according to the performance of BDR. SPSS 25.0 software and Graph pad PRISMA 7.0 software were used for statistical analyses.
RESULTS: A total of 70 patients GBC patients with PNI were incorporated. The results of comparative analyses indicated that patients who received BDR were generally in a more advanced stage and often required a more extended radical cholecystectomy. Higher incidences of preoperative jaundice (48.6% vs 2.9%, P < 0.0001), major hepatectomy (25.7% vs 8.6%, P = 0.055), combined multi-visceral resections (48.6% vs 5.7%, P < 0.0001), combined major vascular reconstruction (22.9% vs 2.9%, P = 0.014), and a lower R0 rate (68.6% vs 88.6%, P = 0.039) were detected in patients who received BDR. Even after propensity score matching (PSM), BDR still had no significant survival advantage but only increased the length of postoperative stay and the frequency of postoperative morbidities.
CONCLUSION: BDR seemed to have no significant survival advantage in GBC patients with PNI and was only correlated with a longer postoperative hospital stay and a higher rate of morbidities. PNI should not be regarded as a surgical indication of BDR in patients with GBC.

Keywords:  Gallbladder carcinoma; Peri-neural invasion; Prognosis; Radical cholecystectomy; Surgery

DOI:  https://doi.org/10.1016/j.ejso.2022.12.018
BMC Womens Health. 2023 Jan 03. 23(1): 5

Clinicopathologic characteristics of early-onset breast cancer: a comparative analysis of cases from across Ghana.

Patrick Kafui Akakpo, Emmanuel Gustav Imbeah, Lawrence Edusei, Simon Naporo, Kofi Ulzen-Appiah, Joe Nat Clegg-Lamptey, Florence Dedey, Josephine Nsaful, Nelson Affram, Beatrice Wiafe, Samuel Mensah, Michael Nortey, Mohammed Sheriff, Forster Amponsah-Manu, Kwabena Agbedinu, Evelyn Mawunyo Jiagge.

  BACKGROUND: Breast cancer is the commonest cancer diagnosed globally and the second leading cause of cancer-related mortality among women younger than 40 years. This study comparatively reviewed the demographic, pathologic and molecular features of Early-Onset Breast Cancer (EOBC) reported in Ghana in relation to Late Onset Breast Cancer (LOBC).METHODS: A descriptive, cross-sectional design was used, with purposive sampling of retrospective histopathology data from 2019 to 2021. Reports of core or incision biopsy, Wide Local Excision or Mastectomy with or without axillary lymph node dissection specimen and matched immunohistochemistry reports were merged into a single file and analysed with SPSS v. 20.0. Descriptive statistics of frequencies and percentages were used to describe categorical variables. Cross-tabulation and chi-square test was done at a 95% confidence interval with significance established at p < 0.05.
RESULTS: A total of 2418 cases were included in the study with 20.2% (488 cases) being EOBCs and 79.8% (1930 cases) being LOBCs. The median age at diagnosis was 34.66 (IQR: 5.55) in the EOBC group (< 40 years) and 54.29 (IQR: 16.86) in the LOBC group (≥ 40 years). Invasive carcinoma-No Special Type was the commonest tumour type with grade III tumours being the commonest in both categories of patients. Perineural invasion was the only statistically significant pathologic parameter with age. EOBC was associated with higher DCIS component (24.8% vs 21.6%), lower hormone-receptor-positive status (52.30% vs 55.70%), higher proliferation index (Ki-67 > 20: 82.40% vs 80.30%) and a higher number of involved lymph nodes (13.80% vs 9.00%). Triple-Negative Breast cancer (26.40% vs 24.30%) was the most predominant molecular subtype of EOBC.
CONCLUSION: EOBCs in our setting are generally more aggressive with poorer prognostic histopathological and molecular features when compared with LOBCs. A larger study is recommended to identify the association between relevant pathological features and early onset breast cancer in Ghana. Again, further molecular and genetic studies to understand the molecular genetic drivers of the general poorer pathological features of EOBCs and its relation to patient outcome in our setting is needed.

Keywords:  Breast cancer; Characteristics; Early-onset; Ghana; Pathology; Prognosis

DOI:  https://doi.org/10.1186/s12905-022-02142-w