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Understanding Mental Health in CRC Survivorship

KEY TAKEAWAYS

  • The study aimed to investigate the lived mental health experiences of patients with colorectal cancer across the entire care continuum.
  • Researchers noted that integrating mental health support could enhance patient well-being throughout CRC care.

Colorectal cancer (CRC) diagnosis is linked to significant physical stressors such as surgery, chemotherapy, radiation, and often the creation of an ostomy. Patients with CRC frequently experience increased limitations in physical functioning, compared to the general population, including difficulties with housework, walking half a mile, or navigating stairs. While the physical impacts of CRC are well-documented, there has been growing interest in understanding the mental health effects of this diagnosis.

Vicki Cheng and the team aimed to assess the mental health experiences of patients with CRC and identify opportunities to integrate mental health support into the overall care framework.

They performed an inclusive analysis using a patient-oriented constructivist grounded theory design. English-speaking participants aged 18 and older, diagnosed with CRC within the last 10 years and residing in Canada, were recruited.

Data were collected through semi-structured individual interviews guided by a framework co-constructed with patient research partners. The data collection and analysis were iterative, involving theoretical sampling, and resulted in the development of a theoretical model.

About 28 participants diagnosed with CRC (18 females, 10 males), aged 18-63 years at the time of diagnosis, were interviewed, representing all CRC stages. Of these, 10 participants (36%) were in treatment, 12 participants (43%) were in follow-up, and 6 participants (21%) were in the beyond phase. A patient-oriented theory was developed to illustrate the dynamic relationship between self-identity and mental health experiences across the CRC care continuum.

These mental health experiences, including emotional and cognitive-behavioral responses, varied across phases. Additionally, mental health care experiences were influenced by barriers, facilitators, and individual contextual factors, which impacted access to care.

The study concluded that the developed theory offers valuable insights into the mental health experiences of patients with CRC throughout the care continuum. Understanding patients’ emotional and cognitive-behavioral responses, along with their care experiences, highlights opportunities to integrate mental health support into CRC care.

This study was sponsored by a Project Grant from the Canadian Institutes of Health Research, “Examining the epidemiology, treatment, and outcomes in young-onset colorectal cancer” (Funding reference number: PJT-159467).

Source: https://pubmed.ncbi.nlm.nih.gov/39233669/

Cheng V, McTaggart-Cowan H, Loree JM, et al. (2024). “Mental health in people living with and beyond colorectal cancer: A patient-oriented constructivist grounded theory.” Cancer Med. 2024;13(17):e70203. doi:10.1002/cam4.70203

Clinicopathological Value of Gut Microbial Subtypes in CRC

KEY TAKEAWAYS

  • The study aimed to investigate the development of gut microbial subtypes and their potential as diagnostic targets for CRC.
  • Researchers noticed that gut microbial subtypes show distinct bacterial profiles, which may aid in the early diagnosis of CRC.

Gut bacteria are increasingly recognized as being related to colorectal cancer (CRC) and its clinicopathologic characteristics. CRC is marked by a low 5-year survival rate, high mortality, and a concerning trend of diagnosis at younger ages, adding to the global disease burden.

Metastasis is the leading cause of CRC-related deaths, and although early-stage CRC can be treated effectively with surgery, the subtle nature of symptoms often results in intermediate or late-stage diagnoses, causing patients to miss the optimal treatment window.

Shuwen Han and the team aimed to assess the development of gut bacterial subtypes and explore potential microbial targets for improving CRC diagnosis.

They performed an inclusive analysis using stool samples from 914 volunteers, consisting of 376 patients with CRC, 363 with advanced adenomas (AA), and 175 normal controls. These samples underwent 16S rRNA sequencing to examine gut microbial composition. Through unsupervised learning, gut microbial subtypes were identified and visualized using community composition and clustering plots.

The differences in gut bacterial abundance were analyzed across the groups. Additionally, associations between CRC-related bacteria and the identified subtypes, as well as the relationship between gut bacteria and clinical information, were evaluated. Finally, CatBoost models based on differential gut bacteria were developed to identify CRC and AA cases effectively.

About 4 gut microbial subtypes (A, B, C, D) were identified through unsupervised learning. The characteristic bacteria for each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical factors, such as free fatty acids and total cholesterol, along with CRC pathological details like tumor depth, differed significantly among the subtypes.

A positive correlation was observed between Bacilli, Lactobacillales, and subtype B, while Blautia and Lachnospiraceae were positively correlated with subtype C. In contrast, Coriobacteriia and Coriobacteriales showed a negative correlation with subtype D. Lastly, the predictive power of the CatBoost models for identifying CRC was enhanced when incorporating gut microbial subtypes.

The study concluded that gut microbial subtypes provide distinct bacterial profiles, which are closely associated with both clinical and pathological features of CRC. These subtypes offer valuable insights into the microbial composition linked to CRC and advanced adenomas. The findings suggest that gut microbial subtypes may serve as potential diagnostic tools, contributing to the early detection and classification of CRC.

This study was funded by the Key research and development project of Science and Technology Department of Zhejiang Province (no.: 2022C03026), the Public Welfare Technology Application Research Program of Huzhou (no.: 2023GZ86), the Zhejiang Medical and Health Technology Project (no.: 2023RC274), and China University Industry University Research Innovation Fund (no.: 2023HT078).

Source: https://pubmed.ncbi.nlm.nih.gov/39234654/

Han S, Zhuang J, Song Y, et al. (2024). “Gut microbial subtypes and clinicopathological value for colorectal cancer.” Cancer Med. 2024;13(17):e70180. doi:10.1002/cam4.70180

Transcriptomic Analysis of Microbiota-Cancer Interactions

KEY TAKEAWAYS

  • The study aimed to identify a common regulatory network of transcription factors and target genes in lung, colon, and gastric cancer.
  • Transcriptomic analysis identified key transcription factors that interact with the microbiome, influencing tumor development in cancers.

Lung, colon, and gastric cancers are leading causes of cancer-related deaths worldwide. Current diagnostic and treatment approaches based on histologic features and genomic biomarkers have not significantly improved mortality rates. The complex interplay between the human microbiome and cancer development has garnered increasing attention.

Beatriz Andrea Otálora-Otálora and the team aimed to use global transcriptomic network analysis to identify a common regulatory network of transcription factors and target genes in lung, colon, and gastric cancer. This network’s function might be influenced by crosstalk with the microbiome in the oral-gut-lung axis.

Researchers analyzed 25 transcriptomic datasets (10 lung cancer, 10 gastric cancer, and 5 colon cancer). They employed a bioinformatic pipeline using R language libraries and DAVID’s gene enrichment analyses. This aimed to identify a shared regulatory network of transcription factors and target genes across the cancer types, supported by experimental evidence of its role in cancer development.

The analysis revealed a key role for transcription factors SOX4, TCF3, TEAD4, ETV4, and FOXM1. These factors potentially influence stem cell programming and cancer progression by regulating genes involved in microbe-cancer cell interactions.

Specifically, these genes encode cell membrane receptors that interact with viruses such as HTLV-1, HPV, EBV, and SARS-CoV-2. These interactions can activate the MAPK, non-canonical WNT, and IFN signalling pathways, contributing to the overexpression of key transcription factors and the development of lung, colon, and gastric cancer.

The study highlighted the significant interplay between key transcription factors and the microbiome in lung, colon, and gastric cancer. This interaction, mediated by cancer-cell membrane receptors, may represent a crucial aspect of tumour development.

No financial support was provided.

Source: https://pubmed.ncbi.nlm.nih.gov/39228892/

Otálora-Otálora BA, Payán-Gómez C, López-Rivera JJ, et al. (2024). “Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.” Front Cell Infect Microbiol. 2024;14:1425388. Published 2024 Aug 20. doi:10.3389/fcimb.2024.1425388

Robotic vs Laparoscopic Surgery for Rectal Cancer

Robotic vs Laparoscopic Surgery for Rectal Cancer

KEY TAKEAWAYS

  • The study aimed to analyze outcomes of robotic vs. laparoscopic surgery in patients with rectal cancer.
  • Results suggested that RARS is safe and potentially superior to laparoscopic surgery, but larger trials are needed.

Robotic-assisted rectal surgery (RARS) and laparoscopic techniques are increasingly used in rectal cancer surgery, each with various advantages and disdvantages. Determining the optimal approach requires a thorough comparison of their outcomes.

Muhammad Haris Khan and the team aimed to evaluate and compare the outcomes of RARS and laparoscopic-assisted rectal surgery in patients with rectal cancer.

Researchers conducted a comprehensive search across multiple databases, including PubMed, Cochrane, Scopus, Embase, and Google Scholar. The analysis included randomized controlled trials (RCTs) that compared both surgical techniques for rectal cancer.

About 15 RCTs were included in the meta-analysis. The RARS group showed a significantly lower conversion rate to open surgery. Outcomes like anastomotic leak, postoperative ileus, postoperative urinary retention, surgical site infection, and intra-abdominal abscess were similar between the 2 groups.

However, the RARS group had a lower reoperation rate. While heterogeneity was observed in operative time, length of hospital stay, and blood loss, there were no significant differences in oncological outcomes, including local recurrence, the number of harvested lymph nodes, and distal resection margin between the groups. Notably, RARS was associated with a lower positive circumferential resection margin and a higher rate of total mesorectal excision.

The study suggested that RARS is a safe and feasible option for patients with rectal cancer, potentially offering advantages over laparoscopic-assisted surgery. However, further large-scale, high-quality trials are necessary to confirm these findings and establish the most effective approach.

No funding was received.

Source: https://pubmed.ncbi.nlm.nih.gov/39225912/

Khan MH, Tahir A, Hussain A, et al. (2024). “Outcomes of robotic versus laparoscopic-assisted surgery in patients with rectal cancer: a systematic review and meta-analysis.” Langenbecks Arch Surg. 2024;409(1):269. Published 2024 Sep 3. doi:10.1007/s00423-024-03460-3

Pembrolizumab Combo Shows Promise in T4b ESCC Treatment

KEY TAKEAWAYS

  • The study aimed to investigate the safety and efficacy of pembrolizumab + cisplatin and 5-fluorouracil as 1L therapy in patients with T4b ESCC.
  • Researchers noted significant tumor reduction with fewer AEs, supporting pembrolizumab + chemo for T4b ESCC induction therapy.

Nobukazu Hokamura and the team aimed to focus on evaluating the safety and efficacy of pembrolizumab combined with cisplatin and 5-fluorouracil as first-line (1L) therapy in patients with advanced esophageal squamous cell carcinoma (ESCC).

Previous research has indicated that this regimen offers a better objective response and improved survival rates compared to conventional chemotherapy, while also resulting in fewer severe hematological adverse events. Given these promising outcomes, the study specifically targeted patients with T4b ESCC, a particularly advanced stage of the disease, to determine the potential benefits of this combination therapy.

They performed an inclusive analysis of 8 consecutive patients with T4b ESCC who received pembrolizumab combined with cisplatin and 5-fluorouracil as induction therapy, following the KEYNOTE-590 protocol. The patients were evaluated after receiving 1 to 3 courses of treatment.

In addition, the programmed death-ligand 1 (PD-L1) combined positive score (CPS) was assessed prior to the initiation of chemotherapy. The efficacy of the treatment on the primary tumor was determined using a specialized formula developed to calculate the tumor reduction rate.

The clinical outcomes, the numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients experienced relief from T4b. Two patients underwent conversion surgery with R0 resection. The PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients.

PD-L1 CPS was under 10 in PD patients and 1 patient experienced hyperprogression, leading to the development of an esophago-pulmonary fistula. Adverse events (AEs) greater than grade 3 included a bleeding gastric ulcer in 1 patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient developed febrile neutropenia.

The study concluded that marked tumor reduction was confirmed in 62.5% of patients receiving pembrolizumab + cisplatin and 5-fluorouracil, with fewer AEs compared to conventional treatments. This regimen demonstrates potential as an effective induction chemotherapy option for patients with T4b ESCC.

No funding information was given for this source.

Source: https://pubmed.ncbi.nlm.nih.gov/39223478/

Hokamura N, Fukagawa T, Fukushima R, et al. (2024). “Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.” BMC Gastroenterol. 2024;24(1):295. Published 2024 Sep 2. doi:10.1186/s12876-024-03382-w

Evaluating LODDS for Prognosis in GEC Post-Chemoradiation

KEY TAKEAWAYS

  • The study aimed to assess the prognostic value of the LODDS in staging GEC post-neoadjuvant chemoradiation.
  • Researchers found that TLODDSM better predicts prognosis and guides adjuvant therapy for patients with GEC post-neoadjuvant chemoradiation.

After neoadjuvant chemoradiation, the number of examined lymph nodes in resectable gastroesophageal cancer (GEC) often decreases, potentially compromising the accuracy of N staging.

Shuang Liu and the team aimed to evaluate the clinical relevance of a novel staging model based on the logarithmic odds of positive lymph nodes (LODDS) for patients with GEC who have undergone neoadjuvant chemoradiation.

They performed an inclusive analysis involving 1,130 patients with pathologically diagnosed GEC who received neoadjuvant chemoradiation between 2004 and 2019, sourced from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. Lymph nodes were staged using both the AJCC TNM staging system (eighth edition) and the LODDS model.

Patient prognosis was assessed with the Kaplan-Meier method, and differences in node staging were evaluated using the Akaike Information Criterion and Bayesian Information Criterion. Additionally, 914 patients from the researchers’ center were used for external validation of the findings.

In comparison with the traditional TNM staging system, the new TLODDSM staging system, which includes stages I, II, IIIA, IIIB, and IVA, demonstrated higher benefits at various decision thresholds according to decision curve analysis.

The Akaike Information Criterion and Bayesian Information Criterion for the TLODDSM staging system were lower than those for the traditional TNM system, indicating improved sensitivity in predicting patient prognosis.

Additionally, patients classified as stage IIIB or IVA in the new system showed significant benefit from adjuvant chemotherapy. These findings were corroborated by externally validated data from the center.

The study concluded that the TLODDSM staging system offers significant advantages over the TNM staging system in predicting prognosis for patients with GEC who have completed neoadjuvant chemoradiation. This new system provides better guidance for adjuvant chemotherapy decisions, enhancing patient management and treatment outcomes.

The study was funded by the Department of Science and Technology of Jilin Province (No YDZJ202201ZYTS668).

Source: https://pubmed.ncbi.nlm.nih.gov/39210382/

Liu S, Wang Z, Ge Y, et al. (2024). “Prognostic significance of an innovative staging system based on the logarithmic odds of positive lymph nodes for resectable gastroesophageal cancer after neoadjuvant chemoradiation: a population-based study with external validation of data.” J Transl Med. 2024;22(1):801. Published 2024 Aug 29. doi:10.1186/s12967-024-05448-5

IVIM MRI for Staging and Lymph Node Prediction in ESCC

KEY TAKEAWAYS

  • The study aimed to investigate the diagnostic performance of IVIM with iShim in staging primary ESCC and predicting lymph node metastases.
  • Researchers found IVIM effective for preoperative staging and lymph node prediction in ESCC.

Tao Song and the team aimed to prospectively evaluate the diagnostic performance of intravoxel incoherent motion (IVIM) combined with the integrated slice-specific dynamic shimming (iShim) technique for staging primary esophageal squamous cell carcinoma (ESCC) and predicting lymph node metastases. This study investigates how IVIM can be utilized to enhance the assessment of tumor staging and predict lymph node involvement preoperatively.

They performed an inclusive analysis involving 63 patients with ESCC who were prospectively enrolled from April 2016 to April 2019. MRI and intravoxel incoherent motion (IVIM) imaging using the iShim technique (b = 0, 25, 50, 75, 100, 200, 400, 600, 800 s/mm²) were conducted on a 3.0T MRI system before surgery. Primary tumor apparent diffusion coefficient (ADC) and IVIM parameters, including the true diffusion coefficient (D), pseudodiffusion coefficient (D*), and pseudodiffusion fraction (f), were measured by 2 independent radiologists.

Differences in D, D*, f, and ADC values across various T and N stages were assessed. Intraclass correlation coefficients (ICCs) were calculated to evaluate the interobserver agreement between the 2 readers. The diagnostic performances of D, D*, f, and ADC values for primary tumor staging and lymph node metastasis prediction were determined using receiver operating characteristic (ROC) curve analysis.

The inter-observer consensus was excellent for IVIM parameters and ADC (D: ICC = 0.922; D*: ICC = 0.892; f: ICC = 0.948; ADC: ICC = 0.958). The ADC, D, D*, and f values of group T1 + T2 were significantly higher than those of group T3 + T4a [ADC: (2.55 ± 0.43) ×10⁻³ mm²/s vs. (2.27 ± 0.40) ×10⁻³ mm²/s, t = 2.670, P = 0.010; D: (1.82 ± 0.39) ×10⁻³ mm²/s vs. (1.53 ± 0.33) ×10⁻³ mm²/s, t = 3.189, P = 0.002; D*: 46.45 (30.30, 55.53) ×10⁻³ mm²/s vs. 32.30 (18.60, 40.95) ×10⁻³ mm²/s, z = -2.408, P = 0.016; f: 0.45 ± 0.12 vs. 0.37 ± 0.12, t = 2.538, P = 0.014].

The ADC, D, and f values of the lymph nodes-positive (N+) group were significantly lower than those of the lymph nodes-negative (N0) group [ADC: (2.10 ± 0.33) ×10⁻³ mm²/s vs. (2.55 ± 0.40) ×10⁻³ mm²/s, t = -4.564, P < 0.001; D: (1.44 ± 0.30) ×10⁻³ mm²/s vs. (1.78 ± 0.37) ×10⁻³ mm²/s, t = -3.726, P < 0.001; f: 0.32 ± 0.10 vs. 0.45 ± 0.11, t = -4.524, P < 0.001].

The combination of D, D*, and f yielded the highest area under the curve (AUC) (0.814) in distinguishing group T1 + T2 from group T3 + T4a. D combined with f provided the highest diagnostic performance (AUC = 0.849) in identifying group N+ and group N0 of ESCC.

The study concluded that IVIM is an effective functional imaging technique for evaluating the preoperative stage of primary tumors and predicting the presence of lymph node metastases in ESCC.

This study was funded by the Projects of the General Programs of the National Natural Science Foundation of China (No.81972802, 82271979), Natural Science Foundation of Henan Province (No.182300410355), Henan Province Medical Science and Technology Research Program Provincial Department to jointly build key projects (No.SBGJ202002021), Special funding of the Henan Health Science and Technology Innovation Talent Project (No.YXKC2020011), Henan Province focuses on research and development and promotion(No. 212102310133), and Innovation Scientists and Technicians Troop Construction Projects of Henan Province (No.20160913) in the design of the study, data collection and analysis.

Source: https://pubmed.ncbi.nlm.nih.gov/39210470/

Song T, Lu S, Qu J, et al. (2024). “Intravoxel incoherent motion diffusion-weighted imaging in evaluating preoperative staging of esophageal squamous cell carcinoma : Evaluation of preoperative stage of primary tumour and prediction of lymph node metastases from esophageal cancer using IVIM: a prospective study.” Cancer Imaging. 2024;24(1):116. Published 2024 Aug 29. doi:10.1186/s40644-024-00765-w

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