BACKGROUND: The antigen processing machinery (APM) plays a critical role in generating tumor-specific antigens that can be recognized and targeted by the immune system. Proper functioning of APM components is essential for presenting these antigens on the surface of tumor cells, enabling immune detection and destruction. In many cancers, defects in APM can lead to immune evasion, contributing to tumor progression and poor clinical outcomes. However, the status of the APM in sarcomas is not well characterized, limiting the development of effective immunotherapeutic strategies for these patients.
METHODS: We investigated 126 patients with 8 types of bone and soft tissue sarcoma operated between 2001-2021. Tissue microarrays mapped 11 specific areas in each case. The presence/absence of APM protein was determined through immunohistochemistry. Bayesian networks were used.
RESULTS: All investigated sarcomas had some defects in APM. The least damaged component was HLA Class I subunit β2-microglobulin and HLA Class II. The proteasome LMP10 subunit was defective in leiomyosarcoma (LMS), myxoid liposarcoma (MLPS), and dedifferentiated liposarcoma (DDLPS), while MHC I transporting unit TAP2 was altered in undifferentiated pleomorphic sarcoma (UPS), gastrointestinal stromal tumor (GIST), and chordoma (CH). Among different neoplastic areas, high-grade areas showed different patterns of expression compared to high lymphocytic infiltrate areas. Heterogeneity at the patient level was also observed. Loss of any APM component was prognostic of distant metastasis (DM) for LMS and DDLPS and of overall survival (OS) for LMS.
CONCLUSIONS: Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

Hepatocellular carcinoma (HCC), a major form of liver cancer, is characterized by high lethality and a multifactorial etiology that includes hepatitis virus infections, lifestyle factors, and genetic predispositions. This study aimed to explore the impact of ZNF208 gene polymorphisms on the clinicopathological features of Taiwanese HCC patients, focusing on three specific single nucleotide polymorphisms (SNPs): rs2188971, rs2188972, and rs8105767. Our cohort consisted of 438 HCC patients and 1193 control individuals. Clinical staging was determined using the tumor/node/metastasis (TNM) system, and various clinical indicators were collected. Our analysis revealed a statistically significant increase in ZNF208 expression in HCC patients compared to controls, indicating a potential role in HCC progression. Although no substantial association was observed between ZNF208 SNPs and increased HCC risk, specific clinical features such as distant metastasis and vascular invasion showed significant associations with these SNPs, suggesting their influence on disease aggressiveness. Demographic analyses highlighted the importance of factors like alcohol consumption and viral hepatitis markers in HCC. Our study underscores the complexity of genetic influences on HCC, with ZNF208 polymorphisms potentially affecting tumor progression and patient outcomes.

BACKGROUND: Patients with intermediate-risk papillary thyroid carcinoma (PTC) have a favorable prognosis with standard treatment of total thyroidectomy (TT) and adjuvant radioactive iodine therapy (RAIT). However, the benefits of TT or adjuvant RAIT remain undetermined, and they are often omitted in Japan. We investigated risk factors for life-threatening distant recurrence in patients with intermediate-risk PTC who are optimal candidates for adjuvant RAIT.
METHODS: Outcomes without RAIT were retrospectively examined in 4030 intermediate-risk conventional PTC cases underwent initial surgery from 2005 to 22 (IRB approval 20200709-1).
RESULTS: Lobectomy (LT) and TT was performed in 11.5% and 88.5%, respectively. Recurrent laryngeal nerve paralysis and hypoparathyroidism was less commonly observed in LT (1.3% and 0%) than TT (2.4% and 3.5 %). Fifty-six cases (1.4%) had distant recurrence. Recurrence-free survival rates at 10 years was 93.5%. There was no significant difference in recurrence rate between LT and TT. Age ≥55, cN1b, and tumor diameter >30 mm significantly associated with distant recurrence. There was a strong relationship between the number of positive risk factors and recurrence; the distant recurrence rate in cases of 0, 1, 2, and 3 positive factors was 0.3% (4/1203), 1.3% (25/1889), 2.7% (23/830) and 7.1% (4/52) (HR 6.46 (2.34-17.86), Log-rank <0.001).
CONCLUSIONS: For intermediate-risk conventional PTC, there is no difference in prognosis even if LT was selectively conducted. However, in patients with risk factors for distant metastatic recurrence, such as age ≥55 years, cN1b, and tumor size >30 mm, adjuvant RAIT was considered eligible.

OBJECTIVE: This study aims to externally validate a predictive model for distant metastasis (DM) with computed tomography (CT)-based radiomics features in prospectively enrolled non-small-cell lung cancer patients undergoing dynamic tumor-tracking stereotactic body radiation therapy (DTT-SBRT).
METHODS: The study collected retrospective data from 567 patients across 11 institutions as the training dataset and prospectively enrolled 42 patients from four institutions as the external test dataset. Four clinical features were collected, and 944 CT-based radiomic features were extracted from gross tumor volumes. After standardization and feature selection, DM predictive models were developed using fine and gray regression (FG) and random survival forest (RSF), incorporating clinical and radiomic features, and their combinations within the training dataset. Then, the model was applied to the test dataset, dividing patients into high- and low-risk groups based on medians of risk scores. Model performance was assessed using the concordance index (C-index), and the statistical significance between groups was evaluated using Gray\'s test.
RESULTS: In the training dataset, 122 of 567 patients (21.5%) developed DM, compared to 9 of 42 patients (21.4%) in the test dataset. In the test dataset, the C-indices of the clinical, radiomics, and hybrid models with FG were 0.559, 0.544, and 0.560, respectively, whereas those with RSF were 0.576, 0.604, and 0.627, respectively. The hybrid model with RSF, which exhibited the best predictive performance of all models, identified 7 of 23 patients (30.4%) as high risk and 2 of 19 patients (10.5%) as low risk for DM incidence in the test dataset (p = 0.116).
CONCLUSIONS: Although predictive models for DM lack significance when applied to prospectively enrolled cases undergoing DTT-lung SBRT, the model with RSF exhibits a consistent capacity to effectively classify patients at a high risk of developing DM.

BACKGROUND: In retroperitoneal leiomyosarcoma (RP LMS), the predominant issue is distant metastasis (DM). We sought to determine variables associated with this outcome and disease-specific death (DSD).
METHODS: Data were retrospectively collected on patients with primary RP LMS treated at a high-volume center from 2002 to 2023. For inferior vena cava (IVC)-origin tumors, the extent of macroscopic vascular invasion was re-assessed on each resection specimen and correlated with preoperative cross-sectional imaging. Crude cumulative incidences were estimated for DM and DSD and univariable and multivariable models were performed.
RESULTS: Among 157 study patients, median tumor size was 11.0 cm and 96.2% of cases were intermediate or high grade. All patients underwent complete resection, 56.7% received chemotherapy (43.9% neoadjuvant) and 14.6% received radiation therapy. Only tumor size and grade and not site of tumor origin (e.g., IVC vs. other) were associated with DM and DSD (p < 0.05). Among 64 patients with IVC-origin tumors, a novel 3-tier classification was devised based on the level of intimal disruption, which was associated with both DM (p = 0.007) and DSD (0.002).
CONCLUSIONS: In primary RP LMS, only tumor size and grade are predictive of DM and DSD. In IVC-origin tumors, the extent of macroscopic vascular invasion is also strongly predictive of these outcomes.

暂无摘要。

Distant metastasis of oral squamous cell carcinoma to skeletal muscles is an extremely rare entity and is an indicator of poor prognosis for the patient. We present a case of oral tongue squamous cell carcinoma that metastasized to the rectus abdominis muscle and clinically became symptomatic nine months after curative surgery of the primary.

BACKGROUND: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges.
METHODS: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS).
RESULTS: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76).
CONCLUSIONS: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

The purpose of this study was to compare the predictive value of different lymph node staging systems and to develop an optimal prognostic nomogram for predicting distant metastasis in pancreatic ductal adenocarcinoma (PDAC). Our study involved 6364 patients selected from the Surveillance, Epidemiology, and End Results (SEER) database and 126 patients from China. Independent risk factors for distant metastasis were screened by univariate and multivariate logistic regression analyses, and a model-based comparison of different lymph node staging systems was conducted. Furthermore, we developed a nomogram for predicting distant metastasis using the optimal performance lymph node staging system. The lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), age, primary site, grade, tumor size, American Joint Committee on Cancer (AJCC) 7th Edition T stage, and radiotherapy recipient status were significant predictors of distant metastasis in PDAC patients. The model with the LODDS was a better fit than the model with the LNR. We developed a nomogram model based on LODDS and six clinical parameters. The area under the curve (AUC) and concordance index (C-index) of 0.753 indicated that this model satisfied the discrimination criteria. Kaplan-Meier curves indicate a significant difference in OS among patients with different metastasis risks. LODDS seems to have a superior ability to predict distant metastasis in PDAC patients compared with the AJCC 8th Edition N stage, PLN and LNR staging systems. Moreover, we developed a nomogram model for predicting distant metastasis. Clinicians can use the model to detect patients at high risk of distant metastasis and to make further clinical decisions.

BACKGROUND: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance.
METHODS: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses.
RESULTS: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value.
CONCLUSIONS: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis.