Recurrence Metastasis Research Articles

Radiotherapy and chemoradiotherapy for postoperative recurrence in patients with esophageal squamous cell carcinoma.

The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post-recurrence survival (PRS) and prognostic factors were evaluated by Kaplan-Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. A total of 170 patients were enrolled, with a median age of 60 years (range 43-77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p < 0.05) for PRS. Salvage treatment was not associated with PRS (p = 0.897). However, in patients with negative LN, CRT was associated with prolonged survival (p = 0.043) and had no significant differences in toxic reactions compared to RT (p = 0.924). In addition, RT showed better prognoses (p = 0.020) and lower toxic reactions (p = 0.030) than CRT in patients with positive LNs. Based on prognosis and toxic reactions, ESCC recurrence patients with negative LNs could benefit from CRT, but RT should be recommended for patients with positive LNs.

The KRAS G12D mutation increases the risk of unresectable recurrence of resectable colorectal liver-only metastasis.

Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM). We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results. We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS. This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.

Expressions and clinical significance of CCN5 and E-cadherin in primary and recurrent lesions of breast cancer.

Breast cancer recurrence and lymph node metastasis significantly impact patient outcomes. Understanding the molecular mechanisms behind these processes is crucial for developing effective treatments. CCN5 and E-cadherin are proteins involved in cell adhesion and epithelial-mesenchymal transition (EMT), playing roles in breast cancer progression. This study aimed to analyze the expression levels and clinical significance of CCN5 and E-cadherin in primary and recurrent breast cancer lesions. Immunohistochemical staining using the SP method was performed to detect CCN5 and E-cadherin expression levels in 28 normal breast tissue samples, 52 primary breast cancer lesions, and paired recurrent chest wall lesions. The expression levels of these proteins were compared across different tissue types and correlated with lymph node metastasis. CCN5 and E-cadherin expression levels significantly differed among normal breast tissues, primary breast cancer lesions, and recurrent lesions (Χ2 = 18.934 and Χ2 = 14.516, p < 0.05). Primary breast cancer lesions exhibited higher CCN5 and E-cadherin expression levels compared with recurrent lesions and normal tissues, although these differences were not statistically significant. Patients without lymph node metastases exhibited significantly higher expression levels of CCN5 and E-cadherin compared with those with lymph node metastases (Χ2 = 9.775, Χ2 = 9.1479, p < 0.05). A positive correlation between CCN5 and E-cadherin expression levels was found in breast cancer tissues (r = 0.398, p < 0.001). CCN5 and E-cadherin were expressed at lower levels in recurrent breast cancer tissues and those with lymph node metastases, indicating their potential roles in breast cancer recurrence and metastasis. These findings suggest that CCN5 and E-cadherin might work synergistically to influence breast cancer progression.

Nasopharyngeal Metastasis of Papillary Thyroid Carcinoma

Background: Papillary thyroid carcinoma (PTC) despite of an indolent clinical behavior is known to cause locoregional recurrence and distant metastasis. Lung and bone are the common site of distant metastasis. Nasopharynx is a very rare site of metastasis. Methods: Case report Results: A case is discussed in which patient was diagnosed with PTC and had undergone total thyroidectomy with lymph node dissection with subsequent radiotherapy. Patient presented with nasopharyngeal metastasis within 3 years of diagnosis. Conclusion: Classic PTC can cause recurrence in the form of metastasis in distant rare sites including nasopharynx. It is necessary to keep patients in regular frequent follow-up after initial management especially when associated with high risk factors.

Clinicopathological features and prognostic analysis of synchronous mucinous metaplasia and neoplasia of the female genital tract

Objective: Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis. Methods: We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University. Results: The mean and median age at onset were 47 and 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and some had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions (P＜0.05). Conclusions: SMMN-FGT had a relatively good clinical prognosis, and even advanced patients could benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions were seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

The intestinal flora and nutritional status and immune function characteristics of obese colon cancer patients

BackgroundThe research aims to explore the characteristics of intestinal flora, nutritional status and immune function in patients with different types of obese colon cancer.MethodsA retrospective analysis is conducted on 64 cases of obese colon cancer diagnosed from June 2018 to January 2020. According to the histological staging of the cancer, they are classified into adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma, with corresponding cases of 24, 22 and 18, respectively. The intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI), immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) are analyzed in the different groups of patients. Survival curves are evaluated by Kaplan-Meier method and log-rank test for tumour death, local recurrence, and distant metastasis.ResultsThere were no statistically significant differences in intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI) and immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) between different groups. There was a significant correlation between intestinal flora, nutritional status and immune function for all three. The survival curves of tumour death, local recurrence and distant metastasis in different groups of obese colon cancer patients were statistically significant. The tumor mortality rate, local recurrence, and distant metastasis rate in adenocarcinoma were 78.65%, 54.25% and 48.26% respectively.ConclusionThere are differences in intestinal flora, nutritional status and immune function among different types of obese colon cancer patients, but adenocarcinoma has the least benefit in intestinal flora, poor nutritional status, and weakest immune function.

Hormone receptor expression in low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma: A case report.

Breast low-grade adenosquamous carcinoma is an uncommon cancer that has been neglected in genetic and pathophysiological research. Consequently, medical practitioners face challenges in the effective diagnosis and treatment of this condition. We present the case of a 57-year-old Asian female patient who presented with bilateral breast masses on physical examination. Ultrasound and an MRI revealed a highly suspicious malignant mass in her right breast that was completely removed surgically. After pathological analysis, the diagnosis was low-grade adenosquamous carcinoma with local high-grade transformation, and some of the tumor components were estrogen receptor positive. The patient underwent appropriate postoperative chemotherapy and achieved a favorable outcome. During the follow-up period after surgical resection, the patient did not experience any local recurrence or distant metastasis. Owing to the rare combination of estrogen receptor positivity and high-grade progression, this patient also required adjuvant chemotherapy. This enhances the essential foundation for diagnosing and treating this rare disease, and facilitates the implementation of treatment plans.

Impact of Tumor Pigmentation in 6934 Patients with Uveal Melanoma at a Single Center

PurposeTo evaluate clinical features and outcomes associated with degree of tumor pigmentation in patients with uveal melanoma (UM) of the choroid and ciliary body. DesignRetrospective observational study. Subjects6,934 consecutive patients with choroidal or ciliary body melanoma between 1971 and 2007 from a single ocular oncology center. MethodsData on patient demographics, tumor characteristics, treatment approach, and clinical outcomes were collected. Comparisons between pigmented (>80% pigmentation by surface area), partially pigmented (20-80%), and non-pigmented tumors (<20%) were performed using relevant hypothesis testing. Survival analyses for metastasis and melanoma-related death were conducted using the Kaplan-Meier method with log-rank tests for univariate comparisons. A multivariate Cox regression analysis was performed to assess the independent effects of multiple covariates on time-to-metastasis. Main Outcome MeasuresExtraocular extension, ocular melanocytosis, time to tumor recurrence, tumor location, and melanoma-related metastasis and death. ResultsThere were 6,934 eyes with UM and the degree of tumor pigmentation was classified as pigmented (n=3,762; 54%), partially pigmented (n=2,115; 31%) or non-pigmented (n=1,057; 15%). Pigmented UM was associated with extraocular extension (p<0.001), ocular melanocytosis (p=0.003), earlier tumor recurrence (p<0.001), and more anterior tumor epicenter location (ciliary body, and equator to ora serrata) (p<0.001). Pigmented UMs also exhibited the highest 10-year metastasis rate at 26%, compared to 19% for partially pigmented UMs and 16% for non-pigmented UMs (p<0.001). Kaplan-Meier survival curves demonstrated differences among the tumor pigmentation groups for melanoma-related metastasis (p<0.001) and melanoma-related death (p<0.001). Multivariate Cox regression analysis for melanoma-related metastasis showed that pigmented UMs had a 29% higher relative risk of developing metastasis compared to partially pigmented UMs (p=0.002) and a 54% higher relative risk of developing metastasis compared to non-pigmented UMs (p<0.001). ConclusionPigmented choroidal and ciliary body melanoma is more often associated with ocular melanocytosis, extraocular extension, anterior tumor epicenter, and earlier tumor recurrence. We also revealed that patients with pigmented UMs demonstrate a higher 10-year rate of metastatic disease and have decreased metastatic survival relative to partially pigmented and non-pigmented UMs.

Children and adolescents with differentiated thyroid cancer from 1998 to 2018: a retrospective analysis.

This study aims to investigate the clinical features of differentiated thyroid carcinoma (DTC) in children and adolescents under 18 years and assess the impact of surgery combined with thyroid hormone and radioactive iodine (RAI) on their prognosis. A retrospective observational study was conducted, involving children/adolescents with DTC who underwent surgery at the Head and Neck Department of Tianjin Medical University Cancer Institute and Hospital from January 1998 toDecember 2018. Among 198 patients, 130 (65.7 %) were female. According to the American Thyroid Association guidelines, cases were categorized as low (106, 53.5 %), intermediate (54,27.3 %), and high (38, 19.2 %) risk. The follow-up duration ranged from 3 to 23 years. Local recurrence and distant metastasis were identified in 21 (10.6 %) and 14 (7.1 %) cases, respectively. All patients received levothyroxine, while RAI therapy was administered to intermediate- and high-risk patients. The local recurrence and distant metastasis rates in these two groups were 33.3 and 39.5 %, respectively, with no recurrence or metastasis in the low-risk group. Persistent without structural evidence of disease were 0.9, 3.7, and 26.3 % at end of follow-up for the low-, intermediate-, and high-risk groups, respectively. The overall survival rates for all three groups were 100 %, while disease-free survival rates were 99.1, 63.0, and 34.2 % for the low-, intermediate-, and high-risk groups, respectively. Children/adolescents with low-risk DTC exhibited a favorable prognosis even without RAI. However, intermediate- and high-risk DTC patients, despite RAI and levothyroxine treatment, showed elevated rates of persistent disease, local recurrence, and distant metastasis.

Investigating the effect of Fusobacterium nucleatum on the aggressive behavior of cancer-associated fibroblasts in colorectal cancer

Fusobacterium nucleatum, (F. nucleatum) as a known factor in inducing oncogenic, invasive, and inflammatory responses, can lead to an increase in the incidence and progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAF) are also one of the key components of the tumor microenvironment (TME), which lead to resistance to treatment, metastasis, and disease recurrence with their markers, secretions, and functions. This study aimed to investigate the effect of F. nucleatum on the invasive phenotype and function of fibroblast cells isolated from normal and cancerous colorectal tissue. F. nucleatum bacteria were isolated from deep periodontal pockets and confirmed by various tests. CAF cells from tumor tissue and normal fibroblasts (NF) from a distance of 10 cm of tumor tissue were isolated from 5 patients by the explant method and were exposed to secretions and ghosts of F. nucleatum. The expression level of two markers, fibroblast activation protein (FAP), and α-smooth muscle actin (α-SMA), and the amount of production of two cytokines TGF-β and IL-6 from fibroblast cells were measured by flow cytometry and ELISA test, respectively before and after exposure to different bacterial components. The expression of the FAP marker was significantly higher in CAF cells compared to NF cells (P < 0.05). Also, the expression of IL-6 in CAF cells was higher than that of NF cells. In investigating the effect of bacterial components on the function of fibroblastic cells, after comparing the amount of IL-6 produced between the normal tissue of each patient and his tumoral tissue under 4 treated conditions, it was found that the amount of IL-6 production from the CAF cells of patients in the control group, treated with heat-killed ghosts and treated with paraformaldehyde-fixed ghosts had a significant increase compared to NF cells (P < 0.05). Due to the significant increase in FAP marker expression in fibroblast cells of tumor tissue compared to normal tissue, it seems that FAP can be used as a very good therapeutic marker, especially in patients with high levels of CAF cells. Various components of F. nucleatum could affect fibroblast cells differentially and at least part of the effect of this bacterium in the TME is mediated by CAF cells.

Management of close/positive margins in cutaneous squamous cell carcinoma of the head and neck: a systematised review

Introduction: The authors reviewed close/positive margins in cutaneous squamous cell carcinoma of the head and neck, ensuing recurrence, regional or systemic metastasis, mortality and follow-up management. Methods: The design was a systematised review from January 2000 to July 2021. The MEDLINE database was searched with 15 articles out of 3104 meeting the inclusion criteria. Pertinent references underpinning the National Comprehensive Cancer Network’s Squamous Cell Skin Cancer Guidelines Version 2.2022 were reviewed. Results: Overall, there were 13,671 cutaneous squamous cell carcinoma lesions. We found pooled rates for positive excision (14.6% at 99% CI [12.97, 16.26]), ensuing recurrence (14.7% at 99% CI [13.51, 15.83]), regional or systemic metastasis (33.8% at 99% CI [33.77, 33.87]), and mortality (46.6% at 99% CI [42.53, 50.65]). Positive excisions most frequently involved the deep margin (73.7%), nose (34.5%) and ear (33.14%). Re-excision of positive margins appeared to confer worse recurrence (35.4%). We found pooled rates for close/positive excision (17% at 99% CI [15.22, 18.84]), ensuing recurrence (17% at 99% CI [15.76, 18.16]), regional or systemic metastasis (30.4% at 99% CI [26.15, 34.73]), and mortality (46.6% at 99% CI [42.53, 50.65]). Mean follow up was 51 months. Surgical re-excision with adequate margins appeared to be most efficacious, followed by radiotherapy. Chemoradiation and chemotherapy appeared less efficacious. Conclusion: Surgical re-excision with adequate margins remains the gold standard for close/positive margins in cutaneous squamous cell carcinoma of the head and neck, followed by radiotherapy.

Long-term Outcome After Surgical Resection of Para-aortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

The significance of resection of para-aortic lymph node metastasis in colorectal cancer is controversial. To clarify the prognosis of colorectal cancer after para-aortic lymph node metastasis resection. Multicenter retrospective study. Thirty-six institutions in Japan participated in this study. Database and medical records at each institution were used for data collection. Patients with resected and pathologically proven para-aortic lymph node metastasis of colorectal cancer between 2010 and 2015 were included. Overall survival after para-aortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of para-aortic lymph node metastasis. A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% CI) was 41.0% (32.0-49.8), and the median survival (95% CI) was 4.1 (3.4-4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs pT1- 3, adjusted HR: 1.91, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.98, p = 0.005), time to metastases (synchronous vs metachronous adjusted HR: 2.02, p = 0.02), and the number of para-aortic lymph node metastasis (3 or more vs less than 3, adjusted HR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5-29.7), with a median (95% CI) of 1.2 (0.9-1.4) years. The primary tumor location (left- vs right-sided colon, adjusted HR: 4.77, p = 0.01; rectum vs right-sided colon, adjusted HR: 5.27, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.90, p = 0.03), number of para-aortic lymph node metastases (3 or more vs less than 3, adjusted HR: 2.20, p = 0.001), and hospital volume (less than 10 vs 10 or more, adjusted HR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Para-aortic lymph node recurrence was the most common at 33.3%. Selection bias cannot be ruled out because of the retrospective nature of the study. Less than 3 para-aortic lymph node metastases were a favorable prognostic factor for overall and recurrence-free survival. However, para-aortic lymph node metastases were considered to be a systemic disease, and the significance of resection was limited. See Video Abstract . ANTECEDENTES:La importancia de la resección de metástasis en los ganglios linfáticos paraaórticos (PALNM) en el cáncer colorrectal (CCR) es controvertida.OBJETIVO:Aclarar el pronóstico del CCR después de la resección PALNM.DISEÑO:Estudio retrospectivo multicéntrico.ENTORNO CLINICO:Treinta y seis instituciones en Japón participaron en este estudio.PACIENTES:Pacientes con PALNM de CCR resecado y patológicamente probado entre 2010 y 2015.FUENTES DE DATOS:Base de datos y registros médicos de cada institución.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general (SG) después de la resección PALNM, supervivencia libre de recurrencia (SLR) y patrones de recurrencia después de la resección R0 de PALNM.RESULTADOS:Se incluyó un total de 133 pacientes en la población de análisis primario de este estudio. La tasa de SG a 5 años (intervalo de confianza [IC] del 95 %) fue del 41,0 % (32,0, 49,8) y la mediana de supervivencia (IC del 95 %) fue de 4,1 (3,4, 4,7) años. Los factores de pronóstico independientes para la SG fueron el estadio T patológico (pT4 vs. pT1-3, índice de riesgo ajustado [aHR]: 1,91, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,98, p = 0,005), tiempo hasta las metástasis (síncronas vs. metacrónicas, aHR: 2,02, p = 0,02) y número de PALNM (≥3 vs. <3, aHR: 2,13, p = 0,001). La tasa de SLR a 5 años (IC del 95%) fue del 21,1% (13,5, 29,7), con una mediana (IC del 95%) de 1,2 (0,9, 1,4) años. La ubicación del tumor primario (colon del lado izquierdo vs. derecho, aHR: 4,77, p = 0,01; recto vs. colon del lado derecho, aHR: 5,27, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,90, p = 0,03), el número de PALNM (≥3 vs. <3, aHR: 2,20, p = 0,001) y el volumen hospitalario (<10 vs. ≥10, aHR: 2,18, p = 0,02) se identificaron como independientes factores pronósticos del SLR. La recurrencia de los ganglios linfáticos paraaórticos fue la más común con un 33,3%.LIMITACIONES:No se puede descartar un sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:Menos de tres PALNM fue un factor pronóstico favorable tanto para la SG como para la SLR. Sin embargo, las PALNM se consideraron una enfermedad sistémica y la importancia de la resección fue limitada. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Risk Factors for Rectal Cancer Recurrence after Local Excision of T1 Lesions from a Decade-Long Multicenter Retrospective Study.

Background: Local surgical excision of T1 rectal adenocarcinoma is a well-established approach. Yet, there are still open questions regarding the recurrence rates and its risk factors. Methods: A retrospective multicenter study including all patients who underwent local excision of early rectal cancer with an open or MIS approach and had a T1 lesion from 2010 to 2020 in six academic centers. Data included demographics, preoperative studies, surgical findings, postoperative outcomes, and local and systemic recurrence. A univariable and multivariable logistic regression analysis was performed to identify risk factors for recurrence. Results: Overall, 274 patients underwent local excision of rectal lesions. Of them, 97 (35.4%) patients with a T1 lesion were included in the cohort. The mean age was 69 ± 10.5 years, and 42 (43.3%) were female. The mean distance of the lesions from the anal verge was 7.8 ± 3.2 cm, and the average tumor size was 2.7 ± 1.6 cm. Eighty-two patients (85%) had a full-thickness resection. Eight patients (8%) had postoperative complications. Kikuchi classification of submucosal (SM) involvement was reported in 29 (30%) patients. Twelve patients had SM1, two SM2, and fifteen SM3. Following pathology, 24 patients (24.7%) returned for additional surgery or treatment. The overall recurrence rate was 14.4% (14 patients), with 11 patients having a local recurrence and 6 having a systemic metastatic recurrence, 3 of which had both. The mean time for recurrence was 2.78 ± 2.8 years and the overall mortality rate was 11%. On univariable and multivariable logistic regression analysis of recurrence vs. non-recurrence groups, the strongest and most significant association and possible risk factors for recurrence were larger lesions (4.3 vs. 2.5 cm, p < 0.001) with an OR of 6.67 (CI-1.82-24.36), especially for tumors larger than 3.5 cm, mucinous histology (14.3% vs. 1.2%, p = 0.004, OR of 14.02, CI-1.13-173.85), and involved margins (41.7% vs. 16.2%, p = 0.003, OR of 9.59, CI-2.14-43.07). The open transanal excision (TAE) approach was also identified as a possible significant risk factor in univariant analysis, while SM3 level penetration showed only a trend. Conclusion: Surgical local excision of T1 rectal malignancy is a safe and viable option. Still, one in four patients received additional treatment. There is an almost 15% chance for recurrence, especially in large tumors, mucinous histology, or involved margin cases. These high-risk patients might warrant additional intervention and stricter surveillance protocols.

Neutrophil extracellular traps in cancer.

Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to bothinfectious and sterile inflammation. Beyond the canonical role in defense against pathogens, the extrusion of NETs also contributes to the initiation, metastasis, and therapeutic response of malignant diseases. Recently, NETs have been implicated in the development and therapeutic responses of various types of tumors. Although extensive work regarding inflammation in tumors has been reported, a comprehensive summary of how these web-like extracellular structures initiate and propagate tumor progression under the specific microenvironment is lacking. In this review, we demonstrate the initiators and related signaling pathways that trigger NETs formation in cancers. Additionally, this review will outline the current molecular mechanisms and regulatory networks of NETs during dormant cancer cells awakening, circulating tumor cells (CTCs) extravasation, and metastatic recurrence of cancer. This is followed by a perspective on the current and potential clinical potential of NETs as therapeutic targets in the treatment of both local and metastatic disease, including the improvement of the efficacy of existing therapies.

The Clinical Utility of the NETest in Patients with Small Intestinal Neuroendocrine Neoplasms (Si-NENs): A "Real-Life" Study.

Current biomarkers do not adequately predict the behaviour of neuroendocrine neoplasms (NENs). This study assessed the NETest, a multianalyte blood biomarker, in patients with small intestinal NENs (Si-NENs). We studied two patient groups: Group 1: metastatic Si-NENs (n = 102) and Group 2: post-operatively disease-free according to 68Ga-DOTATATE PET (n = 16). NETest scores were ≤20% (normal), 21-40% (low), 41-79% (intermediate), or ≥80% (high). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In Group 1, the median NETest score was 40% (IQR: 33.3-46.7%). The NETest value (HR: 1.032, 95% CI: 1.003-1.062, p = 0.033) and high-risk NETest category (HR: 10.5, 95% CI: 1.35-81.7, p = 0.025) were independent predictors of PFS, along with presence of lung metastases, CgA levels > 10 × ULN, and tumour growth rate (TGR). Independent predictors of OS were the NETest value (HR: 1.035, 95% CI: 1.005-1.066, p = 0.024) and high-risk NETest category (HR: 15.2, 95% CI: 1.52-151, p = 0.02), along with presence of lung metastases and CgA levels > 10 × ULN. In Group 2, ROC analysis identified an AUC of 0.909 (95% CI: 0.75-0.100) for prediction of local or metastatic recurrence. Blood NETest scores were associated with PFS and OS in patients with metastatic Si-NENs, along with TGR, CgA > 10 × ULN, and presence of lung metastases.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P= 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P= 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P= 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.

A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis

Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.

Yiqi Wenyang Jiedu prescription for preventing and treating postoperative recurrence and metastasis of gastric cancer: a randomized controlled trial protocol.

Postoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%-80% within 2 years after local treatment and approximately 90% within 5 years. "Yang-deficient toxic node" is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of "nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying" can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence. The study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1-3 years, cumulative annual survival after 1-3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate. There is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery. ClinicalTrials.gov, identifier NCT05229809.

Unraveling Complexity: Delving into a Novel Pigmented Epithelioid Melanocytoma Case

Abstract Pigmented epithelioid melanocytoma (PEM) is a rare and diagnostically challenging skin neoplasm. Differentiating this lesion from melanoma is challenging due to overlapping clinical, histopathological, and immunohistochemical features. Some PEMs have a benign course, while others may be associated with more aggressive behaviour and have potential for local recurrence or distant metastasis. So, careful evaluation and follow-up are crucial for individuals with a diagnosis of PEM. This case study focuses on a 42-year-old woman with a gradually enlarging, dark, pigmented gluteal lesion. Histopathological analysis following complete excision showed nodular proliferation of spindled and epithelioid melanocytes in the dermis, extending into subcutaneous fat. Cellular atypia or mitotic figures were absent, confirming the diagnosis as PEM. This case underscores the intricate balance between monitoring and intervention in complex dermatological cases, shedding light on diagnostic challenges and ultimately striving for improved patient care.