Stage Invasion Research Articles

Prognostic Factors Among Colonic Adenocarcinomas Invading Into the Muscularis Propria.

Depth of invasion through the intestinal wall, categorized as primary tumor stage (pT), is an important prognostic factor in colorectal cancer. However, additional variables that may affect clinical behavior among tumors involving the muscularis propria (pT2) have not been examined at length. We evaluated 109 patients with pT2 colonic adenocarcinomas (median age: 71y, interquartile range: 59 to 79y) along various clinicopathologic parameters, including invasion depth, regional lymph node involvement, and disease progression after resection. Tumors extending to the outer muscularis propria (termed pT2b) were associated in multivariate analysis with older patient age ( P =0.04), larger tumor size ( P <0.001), higher likelihood of lymphovascular invasion (LVI; P =0.03) and higher lymph node stage (pN; P =0.04), compared with tumors limited to the inner muscle layer (pT2a), and LVI was the single most important variable predicting regional lymph node metastasis at resection in these tumors ( P =0.001). The Kaplan-Meier analysis during a median clinical follow-up of 59.7 months (interquartile range: 31.5 to 91.2) revealed that disease progression was more likely in pT2 tumors that exhibited, at the time of staging: size >2.5cm ( P =0.039), perineural invasion (PNI; P =0.047), high-grade tumor budding ( P =0.036), higher pN stage ( P =0.002), and distant metastasis ( P <0.001). Proportional hazards (Cox) regression identified high-grade tumor budding ( P =0.02) as independently predicting shorter progression-free survival in pT2 tumors. Finally, among cases that would not ordinarily be candidates for adjuvant treatment (ie, pT2N0M0), the presence of high-grade tumor budding was significantly associated with disease progression ( P =0.04). These data suggest that, during the diagnosis of pT2 tumors, pathologists may wish to pay particular attention and ensure adequate reporting of certain variables such as tumor size, depth of invasion within the muscularis propria (ie, pT2a vs. pT2b), LVI, PNI, and, especially, tumor budding, as these may affect clinical treatment decisions and proper patient prognostication.

Serum and Bronchoalveolar Lavage Fluid Levels of Cytokines in Patients with Lung Cancer and Chronic Lung Disease: A Prospective Comparative Study.

The role of chronic inflammation in the initiation and progression of carcinogenesis has been well-established in previous studies, particularly in the stages of malignant conversion, invasion, and metastasis. This study aimed to explore the potential correlation between the levels of cytokines in serum and bronchoalveolar lavage fluid (BALF) by comparing their levels between patients with lung cancer and those with benign lung diseases. The study measured the concentration of IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-12p70, in venous blood and BALF of a total of 33 patients with lung cancer and 33 patients with benign lung diseases. Significant differences were found between the two groups in various clinical parameters. The cytokine levels were significantly higher among patients with malignant disease, while the BALF analysis revealed higher cytokine levels compared with serum analysis. It was discovered that the levels of cancer-specific cytokines in the lavage fluid increased significantly sooner and were present at a greater concentration than those in the peripheral blood. After one month of treatment, the serum markers decreased significantly but slower in the lavage fluid. The differences between serum and BALF markers remained significant. It was observed that the highest correlation was among IL-6 (serum) and IL-6 (lavage), with a coefficient of 0.774 (p-value < 0.001), and IL-1 (serum) and IL-1β (lavage), with a coefficient value of 0.610 (p-value < 0.001). Other significant correlations among serum and lavage cytokines were observed between IL-6 (lavage) and IL-1 (serum) (rho = 0.631, p-value < 0.001) and CRP (rho = 0.428, p-value = 0.001), respectively. This study revealed significant differences and correlations in clinical parameters, serum markers, and BALF inflammatory markers between patients with lung cancer and those with benign lung pathologies. The results highlight the importance of understanding the inflammatory profiles of these conditions and could contribute to the development of targeted therapies or diagnostic approaches in the future. Further research is needed to validate these findings, explore their implications for clinical practice, and determine the diagnostic and prognostic value of these cytokines for lung cancer.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis.

Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

Assessing current diagnostic, staging, and treatment practices in community and academic centers for individuals with stage IB-IIIA non–small-cell lung cancer (NSCLC).

e20608 Background: The five-year survival for individuals with surgically resected, early-stage NSCLC is around 50%. Recent availability of biomarker driven therapy after surgery has the promise of improved outcomes. However, deficits in the quality of diagnostic evaluation, evidence-based treatment delivery, care coordination, and biomarker testing are still barriers to optimal outcomes. Methods: In 2022, the Association of Community Cancer Centers (ACCC) conducted a survey of NSCLC providers to assess current patterns in the diagnosis and treatment of patients with early-stage (IB-IIIA) NSCLC. The survey, which was distributed to ACCC members and their associated networks, collected information about each respondent and their cancer program processes around diagnosis, treatment planning, and care delivery. We administered it Qualtrics and analyzed results with SAS 9.4. Results: We had 124 survey respondents from 33 US states. Respondents’ institutions were 60% urban, 23% suburban, and 17% rural, 53% community cancer programs, 37% academic/NCI designated cancer programs, 9% private practice. On average, initial tissue biopsy was performed by interventional radiologists in 29% of cases, interventional pulmonologist in 22%, and thoracic surgeons in 16%. In stage IIA-IIIA, on average 49% typically perform invasive mediastinal staging before surgery, 17% during surgery, and 18% do not typically perform invasive mediastinal staging. The most frequent barriers to optimal staging and diagnosis included scheduling (73%), cost (51%), tissue quality (46%), limited access to tests or procedures (42%), and missed appointments (36%). Multidisciplinary tumor board use included 31% with a general cancer tumor board, 50% with a thoracic specific tumor board, and 14% have a dedicated molecular tumor board. Tumor board meetings were weekly in 57%, 2-3 times a month in 22%, and once a month in 11%. 66% have a standard biomarker testing protocol for resected NSCLC. 51% typically order EGFR and 31% regularly order PDL1 testing for patients with resected NSCLC. The largest barriers to optimal care included: scheduling (23%), patient refusal (19%), communication breakdowns (17%), inadequate staffing (15%), and limited access to subspecialties (14%). 83% agree their center has the staff and resources to help patients navigating the health system. However, only 45% typically assign a nurse navigator to individuals with early-stage NSCLC. Palliative care service referrals were made sometimes or often in 48% of sites, while 51% refer rarely or never. Conclusions: In this broad sample of oncology practices across the US, we identified several strengths and barriers to optimal care for persons with early-stage NSCLC. Improved care coordination and standardized staging and diagnosis practices could optimize care in this dynamic treatment landscape.

The importance of structural and functional characteristics of tidal channels to smooth cordgrass invasion in the Yellow River Delta, China: Implications for coastal wetland management

Understanding the spatiotemporal landscape dynamics and spread pathways of invasive plants, as well as their interactions with geomorphic landscape features, are of great importance for predicting and managing their future range-expansion in non-native habitats. Although previous studies have linked geomorphic landscape features such as tidal channels to plant invasions, the potential mechanisms and critical characteristics of tidal channels that affect the landward invasion by Spartina alterniflora, an aggressive plant in global coastal wetlands, remain unclear. Here, using high-resolution remote-sensing images of the Yellow River Delta from 2013 to 2020, we first quantified the evolution of tidal channel networks by analyzing the spatiotemporal dynamics of their structural and functional characteristics. The invasion patterns and pathways of S. alterniflora were then identified. Based on the above-mentioned quantification and identification, we finally quantified the influences of tidal channel characteristics on S. alterniflora invasion. The results showed that tidal channel networks presented increasing growth and development over time, and their spatial structure evolved from simple to complex. The external isolated expansion of S. alterniflora played a dominant role during the initial invasion stage, and then they connected the discrete patches into the meadow through marginal expansion. Afterwards, tidal channel-driven expansion gradually increased and became the primary way during the late invasion stage, accounting for about 47.3%. Notably, tidal channel networks with higher drainage efficiency (shorter OPL, higher D and E) attained larger invasion areas. The longer the tidal channels and the more sinuous the channel structure, the greater the invasion potential by S. alterniflora. These findings highlight the importance of structural and functional properties of tidal channel networks in driving plant invasion landward, which should be incorporated into future control and management of invasive plants in coastal wetlands.

Optimal number of lymph node stations associated with improved survival among patients with non-small cell lung cancer (NSCLC).

8571 Background: Good quality pathologic nodal evaluation is associated with improved long-term survival in NSCLC after surgical resection. However, there is no universal definition of quality. We examined the association between number of lymph node stations (NLNS) sampled and overall survival. Methods: We examined the population-based Mid-South Quality of Surgical Resection (MS-QSR) cohort, excluding patients with neoadjuvant therapy, positive margins, and secondary resections. We summarized demographic and clinical characteristics with appropriate statistics. We employed four Cox regression models: 1) including NLNS as the only predictor; 2) model 1, adjusting for age, sex, histology, clinical stage, extent of resection, and surgical technique; 3) examined the impact of pathologic staging (pStage in 3 groups: IA/IB[&lt;4cm tumor size]; IB[&gt;4cm]/II/IIIA[pN2-]; pN2]) by modeling interaction with pStage and NLNS; 4) model 3 plus adjustments (no clinical stage). In a cut point analysis to identify the optimal NLNS for improved survival, we dichotomized the NLNS for cut points 0 to 12. Hazard ratios (HR) were calculated (as above) and plotted for each dichotomization. Results: The 3916 eligible patients were 21% Black, 54% male, 15% on Medicaid and 49% Medicare; 84% and 85% had clinical and pathologic stage I/II, respectively; 84% had no invasive staging; 84% had a PET-CT scan. For every additional lymph node station sampled, the HR decreased by 0.94 (95% confidence interval: 0.92, 0.96). After adjustments, the HR remained significant (Table). Our pStage cohorts comprised of 2474 (64%) IA/IB[&lt;4cm]; 1080 (28%) IB[&gt;4cm]/II/IIIA[pN2-]; and 290 (8%) pN2+. Once stratified, HRs remained significant among those with early stage but not for pN2+ (Table). When further adjusted, only pStage IA/IB[&lt;4cm] patients had a significant HR, 0.94 (0.91, 0.97). The cut point analysis indicated sequential survival improvement up to ≥ 7 total stations sampled, consistently across all models/adjustments. Conclusions: The number of lymph node stations examined is directly associated with survival after lung cancer resection. Examination of a total of 7 intrapulmonary, hilar and mediastinal stations seems optimal. Hazard ratios (95% confidence intervals) for modeling hazards as a function of lymph node stations sampled (model 1), further adjusted for age, sex, histology, clinical stage, extent of resection, and surgical technique (model 2), including interaction with pathologic stage with no adjustments (model 3), and interaction with pathological stage with adjustments (no clinical stage) (model 4). [Table: see text]

Clinical Significance of MMP7 Levels in Colorectal Cancer Patients Receiving FOLFOX4 Chemotherapy Treatment.

Various studies have shown an association between the anti-cancer drug 5-fluorouracil and matrix metalloproteinase 7 (MMP7). The expression of MMP7 in the serum of colorectal cancer patients, as well as their sensitivity to chemotherapy, were examined using the FOLFOX4 chemotherapy treatment. Serum samples were taken from 216 colorectal cancer patients who had undergone four cycles of gemcitabine and cisplatin treatment. The sera of 216 healthy persons were used as controls. MMP7 levels in the serum were measured by ELISA. Demographic and survival data were collected. MMP7 levels were not associated with sex, age, peritoneal dissemination, liver metastasis, lymph node metastasis, lymphatic invasion, or venous invasion in CRC patients, but were associated with histological grade, tumor size, TNM stage, and depth of tumor invasion. Patients' serum MMP7 expression reduced after treatment. MMP7 expression was significantly lower chemotherapy-sensitive patients compared with chemotherapy-resistant patients. Elevated MMP7 expression was associated with worse prognosis and chemotherapy-sensitive patients had markedly better overall survival compared with chemotherapy-resistant patients. MMP7 expression was potentially associated with the development of colorectal cancer and elevated levels were associated with chemoresistance in CRC patients. Serum MMP7 levels can be used to screen for drug resistance during FOLFOX4 chemotherapy treatment.

Re-referral for post-op radiation in elderly breast cancer patients who initially omit RT but are unable to tolerate endocrine therapy.

e12507 Background: Omission of Radiation in the setting of Elderly patients 70 yo and above with ER+, cN0, pT1 tumors who receive adjuvant endocrine therapy (HT) is standard of care per NCCN. However, the average adherence rate of HT ranges from 41% to 72%, which is not optimal for patient outcomes. In our institution, we evaluated the treatments of all patients who qualified for omission of radiation upfront and the number of re-referrals for adjuvant radiation in Elderly Breast cancer patients who were unable to tolerate HT past 6 months. Methods: Data was obtained through the National Cancer Registry at our institution for 2021 and reviewed mid 2022. Inclusion criteria included patients diagnosed with Pathologically Invasive Breast Cancer AJCC Stage I-IIB age 70 and above. A total of 176 patients were eligible for review. 86 patients did not qualify for inclusion into study due to 7 receiving surgical treatment outside our system. Furthermore, 81 patients did not qualify due to the following reasons or combination: Mastectomy (19), Triple Negative, Greater than 2 cm, N+, AI only. A total of 90 patients qualified for omission and review. Six month HT therapy cut off was extrapolated by Barbieri et al who determined a 6 month delay of RT after surgery was not associated with an increased risk of relapse. Results: From the 90 patients who qualified for omission of radiation, 67 % (n = 60) of patients chose radiation omission, 30% (n = 27) of patients chose upfront radiation, and 3% (n = 3) of patients declined all therapy. Of the 60 patients who chose omission, 87% of patients had continued HT, however 2 patients passed away within 1 year of surgery. A total of 13% of patients (n = 8) who omitted radiation did not go past 6 months of HT, and only 2 out of 8 patients (25%) were referred back to radiation oncology and moved forward with treatment. For the 27 patients who chose radiation upfront even though they qualified for omission, the most common reason per records was the patient was unsure after initial multidisciplinary clinic that they would be able to tolerate HT. Interestingly, 27% of these patients ended up stopping HT within 9 months due to side effects. Conclusions: Omission of radiation is an option for Elderly Early stage breast cancer patients in the setting of HT. However, HT compliance is variable due to side effects. In our one year single institution study, only 25% of patients who omitted RT and did not get past 6 months of HT were sent back for radiation. We encourage an increased awareness and communication between Radiation Oncology and Medical Oncology regarding the option of radiation for patients who do not pass 6 months of HT. Our institution has implemented an Epic message system and Breast Navigation to aid in re-referral. It is also imperative at the time of Radiation Oncology consultation to discuss the possibility of intolerance to HT in the setting of omission may indicate radiation therapy at a later date.

Variations in Penile Cancer Management: Results From the Global Society of Rare Genitourinary Tumors Survey.

There is paucity of evidence and consensus on various aspects of management of penile cancer (PeCa), which is intuitive considering the rarity of this disease. We present here the details of an online survey conducted by the Global Society of Rare Genito-urinary Tumors (GSRGT) with the aim of capturing the variations in PeCa care across different regions of the world. An online questionnaire was developed by experts within the GSRGT and then circulated via email in English and Spanish versions to clinicians dealing with PeCa. Respondents were allowed 8 weeks to reply. We received 102 responses; the majority of them were from South America (37.2%) followed by North America and Asia (17.6% each). Only 11.7% of the respondents treated more than 25 patients with PeCa annually. Total penectomy is performed by 21.5% of the respondents in >50% of their patients. Less than a fifth of the experts (19.6%) responded that >50% of their patients are clinically node-negative (cN0) at presentation. For intermediate-risk cN0 patients (T1 G2 cancer), about a third of the experts chose surveillance. For invasive inguinal staging, the options of Dynamic Sentinel Lymph Node Biopsy (DSNB), Modified Inguinal Lymph Node Dissection (MILD), Superficial Inguinal Lymph Node Dissection (SILD), and Video-Endoscopic Inguinal Lymphadenectomy (VEIL) were chosen by 28.4%, 26.4%, 31.3%, and 13.7% of the respondents respectively. Considerable variation was seen in the worldwide use of these techniques. For clinically node-positive patients, respondents were in favor of giving adjuvant chemotherapy instead of neoadjuvant chemotherapy, except for cN3 patients. The results of this questionnaire objectified the variations in global practices in the management of PeCa. This serves as the baseline information which can help prioritize research areas for multinational collaborative efforts, a key mission of the GSRGT.

African American women who carry the BRCA1/2 mutation: Clinical characteristics and prevention strategies.

10554 Background: Carriers of pathogenic variants (PV) in BRCA1/2 have an increased risk of breast, ovarian, and other cancers . The clinical characteristics and uptake of risk-reducing interventions in African American(AA) women with BRCA1/2 PVs are less well studied. Methods: After IRB approval, we performed a retrospective chart review on African American women seen at Nancy and James Grosfeld Cancer Genetics Center at Beaumont Health from January 1, 2006, to December 31, 2021, who tested positive for a BRCA 1/2 mutation. We analyzed demographics, cancer characteristics, outcomes, and prevention strategies. Results: Of 238 African American(AA) women who underwent genetic testing, 69 patients (29%) were identified to be a carrier of BRCA1/2 PVs or likely pathogenic variants (LPVs). The median age at testing was 49 years (range: 24-87). Forty-six women (67%) had a cancer diagnosis, with a median age at diagnosis of 52 years. Four women had two, and one had three cancers, for a total of 52 cancers. Breast cancer was the most common type of cancer (40; 77%), with a median age at diagnosis of 48 years (range 24-73) and a majority (26; 65%) being BRCA2 carriers. Most were invasive ductal carcinoma (87.8%), high-grade (80%), ER-positive (52%), PR-negative (68%), HER2-negative (94%) and stage I or II disease (63%). Fifteen (38%) were triple-negative. Most patients (87%) received adjuvant systemic chemotherapy or endocrine therapy, 31% received neoadjuvant chemotherapy, and 39% received adjuvant radiation. The 3- and 5-year survival was 94% and 91%, respectively, with a median follow-up of 103 months. Three patients (all BRCA2 carriers ) developed contralateral breast cancer (median time to recurrence: 201 months); 3 (all BRCA2) developed local recurrence (median time to recurrence: 60 months), and 4(2 BRCA1, 2 BRCA2) developed metastatic recurrence (median time to recurrence: 34 months). Other cancers observed were ovarian (n = 6; 4 BRCA2, 2 BRCA1), uterine (2), lung (2), kidney (1), and glioblastoma (1). Compared to AA carriers without cancer, those with cancer were more likely to undergo risk-reducing mastectomy (RRM; 68% vs. 23%) and risk-reducing salpingo-oophorectomy (RRSO; 72% vs. 55%). In the non-cancer group, significantly fewer patients elected RRM (23%) compared to RRSO (55%). Conclusions: Our study outlines the characteristics of AA women who carry BRCA1/2 PVs, revealing that most had high-grade invasive ductal breast cancer with excellent survival. Patients without a cancer diagnosis were less likely to undergo risk-reducing surgery, highlighting the importance of effective counseling focusing on primary prevention in these high-risk patients. Further research is needed to better characterize cancer risk and address potential barriers to uptake of risk-reducing interventions in this population.

A phase I dose-escalation clinical trial with PLZ4-coated paclitaxel-loaded micelles (PPM) in patients with recurrent or refractory non-myoinvasive bladder cancer.

TPS4615 Background: Bladder carcinoma is one of the top ten cancers in the US with approximately 75% of patients initially presenting with non-myoinvasive bladder cancer (NMIBC). The current standard of care for NMIBC is transurethral resection (TUR) followed by intravesical instillation, usually with Bacille Calmette-Guérin (BCG). Despite combination treatment, 20-80% of patients' disease recurs and 25% progress to invasive stages. The study drug, PLZ4-coated paclitaxel-loaded micelle (PPM), is a solvent-free injectable nanoscale micelle formulation of paclitaxel (PTX). Preclinical data on bladder cancer-specific targeting ligand named PLZ4 has shown potential to specifically deliver chemotherapeutic micelle into bladder cancer cells, both in vitro and in vivo (Zhang, Urol Oncol 2012). In a toxicokinetic study, female Sprague Dawley rats were given intravesicular injections of PPM once weekly for 6 consecutive weeks. No drug related mortality was reported, and no systematic exposure of PPM was observed in toxicokinetic analysis. The purpose of this phase I trial with PPM is to determine the toxicity and recommended Phase II dose. Methods: This is a single arm, open label, Phase I dose-escalation first-in-human trial with an expansion cohort for the treatment of recurrent or refractory NMIBC with PPM. Eligibility includes BCG unresponsive carcinoma in situ or Ta/T1 urothelial carcinoma. Treatment with pembrolizumab is not an inclusion or exclusion criteria as intravesical taxane has comparable efficacy as intravenous pembrolizumab. Up to 29 patients will be recruited at VA Boston Healthcare system. PPM will be given once weekly for six weeks, 50 ml of solution regardless of patient's size or weight will be administered as intravesical instillation. A 3 + 3 design is adopted for this Phase I trial. There are three dose levels at the dose escalation stage: Dose level I: PTX 25 mg or 0.5 mg/ml; Dose Level II: PTX 50 mg or 1.0 mg/ml; Dose Level III: PTX 75 mg or 1.5 mg/ml. At the expansion cohort, up to 12 patients will be treated with PPM at PTX dose of 50 mg or 1.0 mg/ml to determine the efficacy. The primary objective is to evaluate the safety and tolerability of PPM administered through intravesical instillation and determine the recommended Phase II dose of PPM. The secondary objectives are to evaluate the tumor response at 6 weeks after last treatment, determine systemic absorption within 6 hours after intravesical instillation of PPM and assess progression free survival. The efficacy will be determined by urine cytology and cystoscopy after finishing treatment. Molecular correlative studies will be performed. The toxicity will be assessed by Common Terminology Criteria for Adverse Events v5.0. Patients will be followed at 3 month intervals for 2 years or until disease recurrence or progression. This study is currently open for enrollment. NCT05519241. Clinical trial information: NCT05519241 .

Real de-escalation or escalation in disguise?

The past two decades have seen an unprecedented trend towards de-escalation of surgical therapy in the setting of early BC, the most prominent examples being the reduction of re-excision rates for close surgical margins after breast-conserving surgery and replacing axillary lymph node dissection by less radical procedures such as sentinel lymph node biopsy (SLNB). Numerous studies confirmed that reducing the extent of surgery in the upfront surgery setting does not impact locoregional recurrences and overall outcome. In the setting of primary systemic treatment, there is an increased use of less invasive staging strategies reaching from SLNB and targeted lymph node biopsy (TLNB) to targeted axillary dissection (TAD). Omission of any axillary surgery in the presence of pathological complete response in the breast is currently being investigated in clinical trials. On the other hand, concerns have been raised that surgical de-escalation might induce an escalation of other treatment modalities such as radiation therapy. Since most trials on surgical de-escalation did not include standardized protocols for adjuvant radiotherapy, it remains unclear, whether the effect of surgical de-escalation was valid in itself or if radiotherapy compensated for the decreased surgical extent. Uncertainties in scientific evidence may therefore lead to escalation of radiotherapy in some settings of surgical de-escalation. Further, the increasing rate of mastectomies including contralateral procedures in patients without genetic risk is alarming. Future studies of locoregional treatment strategies need to include an interdisciplinary approach to integrate de-escalation approaches combining surgery and radiotherapy in a way that promotes optimal quality of life and shared decision-making.

Correlation of Pap Smear and Colposcopy in Relation to Histopathological Findings in Detection of Preinvasive Lesion of Cervix in Bangabandhu Sheikh Mujib Medical University Hospital Dhaka Bangladesh

Background: Cervical cancer develops from well-defined precursor lesions in a variable period of time. Detecting in early or pre invasive stages, cervical cancer is preventable and curable, so detection of preinvasive lesions is very important. Objectives: The aim of our study was to correlate of Pap smear and colposcopy in relation to histopathological findings in detection of preinvasive lesion of cervix. Methods: This was a cross-sectional study of 110 women to attend in department of Gynecological Oncology OPD of Bangabandhu Sheikh Mujib Medical University Hospital from July 2016 to June 2017. Inclusion criteria were age of 30 to 60 years, who had unhealthy cervix, intermenstrual or post coital bleeding and excessive vaginal discharge. Exclusion criteria were any cervical growth, bleeding at the time of examination, pregnant women. Result: In present study sensitivity of Pap smear for detecting lesions above LSIL was 11(10.0%), specificity 68.38%, PPV was 94.44%, negative predictive value 71.86%. The incidence of preinvasive lesions (LSIL and HSIL) was 33.64% with LSIL 21(19.09%) and HSIL 16(14.55%) and of carcinoma were 10(9.09%). Conclusion: With a comprehensive approach to make awareness and doing proper screening by Paps smear, colposcopy and colposcopy directed biopsy; cervical cancer can be eliminated as a public health problem within a generation. Bangladesh Medical Res Counc Bull 2022; 48(3): 189-194

Prediction values of tertiary lymphoid structures in the prognosis of patients with left- and right-sided colon cancer: a multicenter propensity score-matched study.

Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood. A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively. For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system. Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.

MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy

BackgroundMammalian infertile-20-like kinase 4 (MST4) plays major roles in the progression of malignant tumor types, but its function in gastric cancer (GC) remains poorly understood. ObjectiveTo investigate the regulatory mechanism of MST4 in GC. MethodsImmunohistochemistry was used to detect MST4 protein in GC tissue. Additionally, the correlation between MST4 expression and the clinicopathological characteristics and prognosis of GC was evaluated. The MST4 expression level in GC cells was measured by western blotting and quantitative real-time polymerase chain reaction. Moreover, the regulatory mechanism of MST4 was investigated in vitro and in vivo. ResultsOverexpression of MST4 was found in GC tissue and cell lines, which correlated to the tumor size, histological type, invasion depth, ulcer, lymph node metastasis, lymphovascular invasion, perineural invasion and TNM stage (all P < 0.01). In terms of MST4 functions in vitro, its upregulation facilitated the proliferation, migration, and invasion of GC cells. Furthermore, MST4 promoted these processes by facilitating autophagy, whereas downregulation of MST4 significantly attenuated these processes. Downregulation of MST4 also attenuated tumor growth in vivo. ConclusionHigh expression of MST4 indicates a poor prognosis and promotes GC cell proliferation, invasion, and metastasis by enhancing autophagy.

Enhancing tomato resistance by exploring early defense events against Fusarium wilt disease

Studying plant early immunity, such as the unique immune mechanisms against pathogens, is an important field of research. Tomato wilt resulting from the infection by Fusarium oxysporum f. sp. lycopersici (Fol) is an important soil-borne vascular disease. In this study, we challenged tomato plants with Fol for a time-course RNA sequencing (RNA-seq) analysis. The result indicated that phenylpropanoid and flavonoid pathway genes were significantly enriched during the early invasion stage. Further study revealed that the flavonoids galangin and quercetin could effectively inhibit Fol growth and enhance wilt resistance in tomato. Moreover, the genes involved in plant-pathogen interactions, the MAPK signaling pathway, and plant hormone signal transduction were significantly enriched. These genes were also involved in plant pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) signaling pathways. Strikingly, the transcription levels of pathogen-related protein 1 (SlPR1) were dramatically increased at 2 days post Fol inoculation, implying that SlPR1 is important in early immunity in tomato. SlPR1 does not have direct antifungal activity. Instead, its C-terminal peptide CAPE1 could activate root defense responses, such as the reactive oxygen species (ROS) burst, salicylic acid (SA)/jasmonic acid (JA) production, and defense-related gene expression, which collectively increased tomato resistance to Fol infection. In addition, CAPE1 could induce systemic acquired resistance (SAR). Application of CAPE1 onto tomato leaves induced local resistance to the pathogen Botrytis cinerea and systemic resistance to Fol infection. These results advanced our understanding for the early immunity against Fol in tomato and provide potential strategy for tomato disease control.

A Reconstructed Human Melanoma-in-Skin Model to Study Immune Modulatory and Angiogenic Mechanisms Facilitating Initial Melanoma Growth and Invasion.

Invasion, immune modulation, and angiogenesis are crucial in melanoma progression. Studies based on animals or two-dimensional cultures poorly recapitulate the tumor-microenvironmental cross-talk found in humans. This highlights a need for more physiological human models to better study melanoma features. Here, six melanoma cell lines (A375, COLO829, G361, MeWo, RPMI-7951, and SK-MEL-28) were used to generate an in vitro three-dimensional human melanoma-in-skin (Mel-RhS) model and were compared in terms of dermal invasion and immune modulatory and pro-angiogenic capabilities. A375 displayed the most invasive phenotype by clearly expanding into the dermal compartment, whereas COLO829, G361, MeWo, and SK-MEL-28 recapitulated to different extent the initial stages of melanoma invasion. No nest formation was observed for RPMI-7951. Notably, the integration of A375 and SK-MEL-28 cells into the model resulted in an increased secretion of immune modulatory factors (e.g., M-CSF, IL-10, and TGFβ) and pro-angiogenic factors (e.g., Flt-1 and VEGF). Mel-RhS-derived supernatants induced endothelial cell sprouting in vitro. In addition, observed A375-RhS tissue contraction was correlated to increased TGFβ release and α-SMA expression, all indicative of differentiation of fibroblasts into cancer-associated fibroblast-like cells and reminiscent of epithelial-to-mesenchymal transition, consistent with A375's most prominent invasive behavior. In conclusion, we successfully generated several Mel-RhS models mimicking different stages of melanoma progression, which can be further tailored for future studies to investigate individual aspects of the disease and serve as three-dimensional models to assess efficacy of therapeutic strategies.

Spotlight on the Expanding Role of DANCR in Tumorigenesis and Tumor Progression

Context: Long non-coding RNA (lncRNA) is a novel set of non-coding RNAs (ncRNA), over 200 nucleotides in length, accounting for the regulation of genes and chromosome structure. There are a few articles, mostly focusing on changes in the expression profile of DANCR. However, this review tried to collect documents to discuss the molecular mechanisms of this lncRNA in different cellular signaling pathways, considering microRNAs, to obtain a better understanding of its mode of action. Evidence Acquisition: Differentiation antagonizing non-protein coding RNA (DANCR) is a cancer-associated lncRNA whose dysregulation, mostly upregulation, has been reported in almost all cancers, particularly in stages of invasion, migration, and progression. The regulatory mechanism of DANCR is mostly working as competitive endogenous RNAs (ceRNAs), leading to the hypothesis that lncRNA DANCR has oncogenic functions in malignancies. LncRNA DANCR harbors a number of MicroRNA Response Elements (MREs) for various microRNAs involved in different pathways, which are responsible for turning the situation toward supremacy for the dissemination of cancerous cells and ultimately metastasis, such as PI3K/Akt, TGF-β, Wnt, JAK-STAT, EMT, and DNA damages. In fact, lncRNA DANCR could potentially sequester microRNAs from their targeted mRNAs, which share the same MREs as DANCR. Conclusion: This review article provides proper evidence, of why the aberrant expression of DANCR pathophysiologically turns the circumstances toward supremacy for the progression, migration, and invasion of cancerous cells, and proposes this lncRNA as a potent and extremely promising prognostic marker for the early detection of tumor progression and metastasis, as well as a therapeutic target for controlling the progression of several human malignancies.

Bombyx mori Tetraspanin A (BmTsp.A) is a facilitator in BmNPV invasion by regulating apoptosis

BmTsp.A (Bombyx mori Tetraspanin A) is one of the four transmembrane proteins which are capable to regulate multiple aspects of the immune response and are involved in various stages of viral invasion of the hosts. This study focused on the sequence features, analysis of expression pattern, as well as the effect of BmTsp.A on BmNPV (Bombyx mori nucleopolyhedrovirus) infection in the apoptotic pathway. BmTsp.A features the typical tetraspanins family, including four transmembrane domains and a major large extracellular loop domain. It is highly expressed specifically in the malpighian tubes, and its expression is increased by BmNPV induction for 48 h and 72 h. Overexpression and RNAi (RNA interference) mediated by siRNA reveal that BmTsp.A can promote the infection and replication of the virus. In addition, the overexpression of BmTsp.A regulates BmNPV-induced apoptosis, leading to changes in the expression of apoptosis-related genes and thus affecting viral proliferation. When subjected to stimulation by BmNPV infection, on the one hand, BmTsp.A inhibits Bmp53 through a Caspase-dependent pathway, which consequently promotes the expression of Bmbuffy, thereby activating BmICE to inhibit apoptosis and causing the promotion of viral proliferation. On the other hand, BmTsp.A inhibits the expression of BmPTEN and BmPkc through the phosphatidylinositol 3 kinase (PI3K)/protein kinaseB(AKT) signaling pathway, thus affecting the regulation of apoptosis. To summarize, our results demonstrate that BmTsp.A promotes viral infection and replication by inhibiting apoptosis, which is fundamental for understanding the pathogenesis of BmNPV and the immune defense mechanism of silkworm.