Metastasizing pleomorphic adenoma of the parotid gland: A common tumour with a very unusual presentation / Metástasis de adenoma pleomorfo de la glándula parótida: un tumor frecuente con una presentación muy poco habitual

Metastasizing pleomorphic adenoma is recognized as a subtype of pleomorphic adenoma in WHO classification 5th edition of salivary glands. The controversy pertaining to the entity is the benign features of the disease even at a metastatic site. We present a rare case of left recurrent pre-auricular swelling in a young male reported as metastasizing pleomorphic adenoma. A nineteen-year-old male presented with left preauricular swelling seven years ago which was diagnosed as pleomorphic adenoma and underwent complete excision of tumour. The tumour recurred twice – two and five years after the surgery. At the second recurrence, the level II neck dissection showed multiple encapsulated deposits of pleomorphic adenoma having similar morphology in the cervical soft tissue with no features of high-grade transformation. (AU)

La metástasis de adenoma pleomorfo está reconocida como un subtipo de adenoma pleomorfo según la clasificación de tumores de las glándulas salivales de la Organización Mundial de la Salud (OMS), 5ª edición. La controversia sobre la entidad se refiere a las características benignas de la enfermedad, incluso en lugares de metástasis. Presentamos un raro caso, en un varón de 19 años, de inflamación preauricular izquierda recurrente que se comunica como una metástasis de adenoma pleomorfo. El paciente presentó inflamación preauricular izquierda hace siete años, que se diagnosticó como adenoma pleomorfo, y se sometió a una resección completa del tumor, el cual presentó dos recidivas, dos y cinco años después de la cirugía. En la segunda recidiva, la resección a nivel II del cuello mostró múltiples depósitos encapsulados de adenoma pleomorfo de morfología similar en el tejido blando cervical, sin características de transformación de alto grado. (AU)

Extraskeletal myxoid chondrosarcoma metastasis to a Meckel's diverticulum adenocarcinoma / Metástasis de condrosarcoma mixoide extraesquelético a un adenocarcinoma de divertículo de Meckel

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature. (AU)

El condrosarcoma mixoide extraesquelético es un tumor de tejidos blandos poco frecuente, con una elevada tasa de recurrencia y metástasis a distancia y una respuesta limitada a la quimioterapia. El divertículo de Meckel es la anomalía congénita más frecuente y se asocia a un riesgo considerable de transformación maligna. En este caso clínico describimos a una paciente de 50 años con antecedentes de condrosarcoma mixoide extraesquelético de miembro inferior y metástasis en el antebrazo que acudió al servicio de urgencias por dolor abdominal. La exploración reveló un vólvulo cecal. Se descubrió incidentalmente una lesión en el tercio medio del íleon, que se extirpó durante la intervención quirúrgica. El examen patológico reveló un adenocarcinoma de divertículo de Meckel, afectado por metástasis de condrosarcoma mixoide extraesquelético. La resección fue completa; sin embargo, la paciente presentaba enfermedad pulmonar metastásica difusa y falleció ocho meses después debido a la progresión de la enfermedad. Este mecanismo de metástasis entre tumores está descrito en otras localizaciones, pero en lo que respecta al divertículo de Meckel, se trata de una situación única en la literatura. (AU)

Skull Metastasis With Orbital Invasion as a Primary Manifestation of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common worldwide cancer with a poor prognosis despite treatment advancements. Patients typically exhibit signs and symptoms pertaining to the liver. Extrahepatic metastasis of HCC is documented to be as low as 5% of cases. Bone metastasis ranks third following lungs and regional lymph nodes. The typical locations for bone metastasis include the vertebral column, pelvis, femora, and ribs, with skull metastasis, being reported in less than 1.6% of cases. Herein, we describe a case of HCC presenting with skull metastases and orbital invasion as the initial manifestation.

Urothelial Carcinoma With Bone Metastasis Mimicking Sciatica: A Common Neoplasm With an Uncommon Presentation.

Bone metastasis in urothelial cancer is underreported and not well-researched. A case of urothelial carcinoma (UC) with bone metastasis presenting as musculoskeletal pain is reported. The patient presented with persistent lower back pain associated with right lower extremity pain, numbness, and tingling. Initially, a diagnosis of sciatica was suspected, but the patient did not respond to treatment. An MRI spine was done, which revealed a bright signal mass in the vertebral body suspicious for a metastatic lesion, left hydroureteronephrosis, and a nonspecific cystic focus in the right iliacus muscle. Subsequent imaging revealed an irregular soft tissue mass at the left posterolateral bladder base, resulting in apparent obstruction of the left ureter, highly suggestive of neoplasm, along with numerous lytic bone lesions in the pelvic girdle with associated soft tissue masses, consistent with metastatic disease. The patient underwent an interventional radiology biopsy of the right iliac soft tissue mass to evaluate the lytic bony lesions, which revealed metastatic carcinoma, consistent with UC. A prompt referral was made for urology and oncology consultations. The patient underwent left percutaneous nephrostomy placement for obstruction, but he was not a candidate for any systemic therapy because of his poor performance status, and hospice was recommended as his metastatic disease was not curable and the goal of any kind of treatment was palliative. The optimal treatment for UC with bone metastasis remains divergent, and the management options should be determined as part of a shared decision-making process. This case highlights the importance of having a high suspicion of neoplastic pathology in patients presenting with musculoskeletal pain, like back pain, and not responding to treatment. This should alert the physicians to the potential for serious disease processes.

M2-Type Macrophages and Cancer-Associated Fibroblasts Combine to Promote Colorectal Cancer Liver Metastases.

Purpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells. Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases. Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis. Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.

Rectal adenocarcinoma in the eye: An unexpected destination.

Colorectal cancer ranks third in cancer incidence in the United States, commonly metastasizing to the liver and lungs. Despite its high prevalence, colorectal cancer with intraocular metastasis is exceedingly rare, with only a few cases reported in the literature. This study presents a 58-year-old male, previously treated for rectal adenocarcinoma with liver and lung metastases, who developed choroidal metastasis causing visual impairment. Despite radiotherapy, moderate improvement was observed, and subsequent disease progression led to systemic chemotherapy. Intraocular metastasis, primarily affecting the choroid, is infrequent, often originating from breast and lung cancers. The presented case, originating from primary KRAS wild-type rectal cancer, adds to the limited gastrointestinal-tract-related occurrences. This report underscores the importance of recognizing intraocular metastasis in colorectal cancer, contributing valuable insights for improved understanding and potential guidance for future clinical decisions. Choroidal metastasis carries a poor prognosis, emphasizing the need for tailored management strategies.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Case report: Isolated eyelid metastasis of ccRCC 5 years after receiving radical nephrectomy.

Introduction: The most common sites of clear cell renal cell carcinoma(ccRCC) metastasis are the lung, bones, liver and brain; eyelid metastasis is a rare occurrence. Case presentation: We report a case of ccRCC metastasis to the left eyelid after radical nephrectomy, and remission after sunitinib treatment. Conclusions: Although the probability of eyelid metastasis rate is very low, tumor metastasis to the eyelid skin is possible after radical nephrectomy. Therefore, any rash like changes on the skin during the review procedure cannot be ignored by the physician.

Prostate cancer brain metastases: Monitoring response to treatment with PSMA PET/CT.

Prostate cancer brain metastases are rare but increasingly recognized with prostate-specific membrane antigen (PSMA) PET/CT. Distinguishing tumor response from postradiation changes are challenging on MRI. PSMA PET/CT may clarify equivocal brain lesions after radiotherapy. A 71-year-old man with metastatic prostate cancer developed 2 new brain lesions on PSMA PET/CT. Lesions were high PSMA-avid and MRI follow up showed enhancing masses with edema, consistent with metastases. He underwent whole-brain radiation. Follow-up PSMA PET/CT after radiotherapy demonstrated significantly decreased lesion size and activity, with activity lower than blood pool, indicating a treatment response. MRI also showed near-resolution of the lesions. This case highlights the potential utility of PSMA PET/CT for detecting prostate cancer brain metastases and monitoring treatment response. PSMA PET/CT provides valuable complementary information to MRI for managing irradiated prostate cancer brain metastases.

Incidental discovery of metastatic renal cell carcinoma at the vaginal wall: A case report.

Metastasis of renal cell carcinoma (RCC) to the vaginal wall has rarely been reported in the literature. We present a case of a 48-year-old who was found to have a solitary RCC metastasis at the vaginal wall, five years following radical nephrectomy. This case is noteworthy because this late presentation is unique, with prior reports of synchronous metastasis or metastasis within two years of nephrectomy, highlighting the need to consider metastatic RCC to the vagina a possibility even many years after treatment.

Classification of high-grade glioblastoma and single brain metastases using a new SCAT-inception model trained with MRI images.

Background and objectives: Glioblastoma (GBM) and brain metastasis (MET) are the two most common intracranial tumors. However, the different pathogenesis of the two tumors leads to completely different treatment options. In terms of magnetic resonance imaging (MRI), GBM and MET are extremely similar, which makes differentiation by imaging extremely challenging. Therefore, this study explores an improved deep learning algorithm to assist in the differentiation of GBM and MET. Materials and methods: For this study, axial contrast-enhanced T1 weight (ceT1W) MRI images from 321 cases of high-grade gliomas and solitary brain metastasis were collected. Among these, 251 out of 270 cases were selected for the experimental dataset (127 glioblastomas and 124 metastases), 207 cases were chosen as the training dataset, and 44 cases as the testing dataset. We designed a new deep learning algorithm called SCAT-inception (Spatial Convolutional Attention inception) and used five-fold cross-validation to verify the results. Results: By employing the newly designed SCAT-inception model to predict glioblastomas and brain metastasis, the prediction accuracy reached 92.3%, and the sensitivity and specificity reached 93.5 and 91.1%, respectively. On the external testing dataset, our model achieved an accuracy of 91.5%, which surpasses other model performances such as VGG, UNet, and GoogLeNet. Conclusion: This study demonstrated that the SCAT-inception architecture could extract more subtle features from ceT1W images, provide state-of-the-art performance in the differentiation of GBM and MET, and surpass most existing approaches.

A prognostic model for triple-negative breast cancer patients with liver metastasis: A population-based study.

However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

A Rare Coexistence of Hybrid Tumor Low-grade Fibromyxoid Sarcoma/Sclerosing Epithelioid Fibrosarcoma and Hibernoma in the Same Thigh: A Case Report.

Introduction: We encountered a unique case of a patient with two distinct tumors coexisting in the same thigh. To the best of our knowledge, this combination of tumors in the same anatomical region has not been previously described in the literature. Case Report: This case report describes a 38-year-old Caucasian male with a painless mass in his right thigh, which was later diagnosed as a hybrid tumor composed of low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, as well as a second tumor, which was diagnosed as a hibernoma. The patient underwent neoadjuvant chemotherapy and surgical excision, followed by adjuvant radiotherapy and treatment for metastatic recurrence. Conclusion: The rarity of this case highlights the need for interdisciplinary collaboration and further investigations into the behavior and management of hybrid tumors. This case also underscores the importance of an accurate histological diagnosis aided by immunohistochemistry and molecular analyses.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases.

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma.

Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally, we explored the impact of FAK degradation on HCC metastasis through wound healing experiments, transwell invasion experiments, and a xenograft tumor model. The expression of proteins related to epithelial-mesenchymal transition (EMT) was measured to elucidate the underlying mechanisms. The results showed that FAK PROTAC can degrade FAK, inhibit the migration and invasion of HCC cells in vitro, and notably decrease the lung metastasis of HCC in vivo. Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited. Consequently, degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis, holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Case report: Metastatic ovarian mucinous carcinoma to the breast: diagnostic challenges and pitfalls.

Metastases to the breast from extramammary sources are extremely rare, with the ovary, primarily high-grade serous carcinoma, being the most common origin. We report a case of breast metastases from advanced stage ovarian mucinous carcinoma in a 48-year-old female- a case hitherto unreported in the literature. The case is noteworthy for its atypical presentation marked by an areolar rash, clinically suggestive of Paget disease of the nipple. This unique clinical scenario, coupled with histopathological examination revealing in-situ-like carcinoma component, posed a diagnostic challenge in discerning the tumour origin. We emphasize the need for heightened awareness among pathologists to avoid misdiagnosing metastatic carcinomas as primary breast tumours, a potential pitfall with significant clinical implications.

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer.

Enhanced knowledge of the interaction of cancer cells with their environment elucidated the critical role of tumor microenvironment in tumor progression and chemoresistance. Cancer-associated fibroblasts act as the protagonists of the tumor microenvironment, fostering the metastasis, stemness, and chemoresistance of cancer cells and attenuating the anti-cancer immune responses. Gastric cancer is one of the most aggressive cancers in the clinic, refractory to anti-cancer therapies. Growing evidence indicates that cancer-associated fibroblasts are the most prominent risk factors for a poor tumor immune microenvironment and dismal prognosis in gastric cancer. Therefore, targeting cancer-associated fibroblasts may be central to surpassing resistance to conventional chemotherapeutics, molecular-targeted agents, and immunotherapies, improving survival in gastric cancer. However, the heterogeneity in cancer-associated fibroblasts may complicate the development of cancer-associated fibroblast targeting approaches. Although single-cell sequencing studies started dissecting the heterogeneity of cancer-associated fibroblasts, the research community should still answer these questions: "What makes a cancer-associated fibroblast protumorigenic?"; "How do the intracellular signaling and the secretome of different cancer-associated fibroblast subpopulations differ from each other?"; and "Which cancer-associated fibroblast subtypes predominate specific cancer types?". Unveiling these questions can pave the way for discovering efficient cancer-associated fibroblast targeting strategies. Here, we review current knowledge and perspectives on these questions, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer. We also review potential therapeutic approaches to prevent the development and activation of cancer-associated fibroblasts via inhibition of CAF inducers and CAF markers in cancer.

Cabozantinib with immune checkpoint inhibitor versus cabozantinib monotherapy in patients with metastatic clear cell renal cell carcinoma progressing after prior immune checkpoint inhibitor.

INTRODUCTION: Rechallenge with antibodies targeting programmed cell death protein-1 or its ligand (PD-1/L1) after discontinuation or disease progression in solid tumors following a prior PD-1/L1 treatment is often practiced in clinic. This study aimed to investigate if adding PD-1/L1 inhibitors to cabozantinib, the most used second-line treatment in real-world patients with metastatic clear cell renal cell carcinoma (mccRCC), offers additional benefits. METHODS: Using de-identified patient-level data from a large real-world US-based database, patients diagnosed with mccRCC, who received any PD-1/L1-based combination in first-line (1L) setting, followed by second-line (2L) therapy with either cabozantinib alone or in combination with PD-1/L1 inhibitors were included. Patients given a cabozantinib-containing regimen in 1L were excluded. The study end points were real-world time to next therapy (rwTTNT) and real-world overall survival (rwOS) by 2L. RESULTS: Of 12,285 patients with metastatic renal cell carcinoma in the data set, 348 patients met eligibility and were included in the analysis. After propensity score matching weighting, cabozantinib with PD-1/L1 inhibitors versus cabozantinib (ref.) had similar rwTTNT and rwOS in the 2L setting. Hazard ratios and 95% confidence interval (CI) for rwTTNT and rwOS are 0.74 (95% CI, 0.49-1.12) and 1.15 (95% CI, 0.73-1.79), respectively. CONCLUSION: In this study, the results align with the phase 3 CONTACT-03 trial results, which showed no additional benefit of adding PD-L1 inhibitor to cabozantinib compared to cabozantinib alone in 2L following PD-1/L1-based therapies in 1L. These results from real-world patients strengthen the evidence regarding the futility of rechallenge with PD-1/L1 inhibitors.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Effects of palliative intrathecal analgesia on patients with refractory cancer bone pain.

This study examined the effects of intrathecal analgesia (ITA) using an extracorporeal pump with a subcutaneous port system in cancer patients with bone metastasis. Among the patients who died of cancer with bone metastasis at the palliative care unit of our institution, 11 who received ITA were selected. Changes in pain, opioid doses, the palliative prognostic index (PPI), and Eastern Cooperative Oncology Group Performance Scale　after ITA were assessed. Pain, opioid doses, and PPI decreased after ITA (P = 0.002, 0.002, and 0.017). ITA for cancer patients with increased PPI due to refractory cancer bone pain decreased pain, opioid doses, and PPI.(100 words).