CRLF2 and IKZF1 abnormalities in childhood hematological malignancies other than B-cell Acute Lymphoblastic Leukemia.

Rearrangements and overexpression of CRLF2 are hallmarks of poor outcomes in BCR::ABL1-like B-ALL, and CRLF2 overexpression is a high-risk marker in T-ALL. However, CRLF2 alterations in pediatric hematologic malignancies other than B-ALL have not been reported. In this study, we analyzed the CRLF2 overexpression, rearrangements (P2RY8::CRLF2 and IGH::CRLF2), activation (pSTAT5 and pERK), and the expression of dominant-negative IKZF1 isoforms (Ik6 and Ik8), implied in CRLF2 dysregulation, in 16 pediatric patients (AML, n = 9; T-ALL, n = 3; LBL, n = 2; HL, n = 1; cytopenia, n = 1). A high frequency of CRLF2 rearrangements and overexpression was found in the 16 patients: 28.6% (4/14) showed CRLF2 overexpression, 93.8% (15/16) were positive for CRLF2 total protein (cell-surface and/or cytoplasmic), while 62.5% (10/16) were positive for P2RY8::CRLF2 and 12.6% (2/16) for IGH::CRLF2. In addition, 43.8% (7/16) expressed Ik6 and Ik8 isoforms. However, only a few patients were positive for the surrogate markers pSTAT5 (14.3%; 2/14) and pERK (21.4%; 3/14).

Evolution and current trends in the management of colorectal cancer liver metastasis.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Patient's informational needs and outreach preferences: A cross-sectional survey study in patients with hepatobiliary malignancies.

Objective: Hepatobiliary tumors have evolving management guidelines. Patient educational needs and interest in community engagement are unknown. This study serves as a needs assessment. Methods: A prospective, needs assessment, survey study of hepatobiliary patients was performed (2016-2019). Surveys (n = 169) were distributed covering three domains of interest: informational needs, interest in outreach, and engagement preferences. Results: Seventy patients completed the survey (response rate = 41.4%). Most patients had completed surgical treatment (84.3%). Cancer treatment was ranked as their primary topic of interest (n = 39, 55.7bold%), followed by symptom management, nutrition, and survivorship. Most patients did not participate in screening (n = 57, 81.4%), though were interested in learning more about these programs. Thirty-nine patients (55.7%) stated they would want to receive more education. Only 17 (24.3%) were interested in attending in-person events. Patients preferred online methods for education (n = 49, 70%). While patients were aware of their case presentation at tumor board, only 38 (54.3%) felt well-informed about recommendations. Conclusion: Multidisciplinary care is complex and difficult for patients to navigate. Most patients have interest in educational resources and prefer online modalities. Patients understand multidisciplinary tumor boards, but communication could be improved. Innovation: These data inform a new, innovative, approach to outreach efforts in this population.

Global Cancer Surgery: pragmatic solutions to improve cancer surgery outcomes worldwide.

The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.

Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies.

Introduction: The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation: We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR. Discussion: Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose PC, NDUFV1, FGF3, FGF4, and DHCR7 as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of FGF3/4 were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.

Comparison between Wright and Shukla formulas: which is better for the placement of umbilical catheters in newborns ≤ 1500 g?

BACKGROUND: Intravascular venous (VUC) or arterial (AUC) umbilical catheter placement is the most frequent invasive procedure in the neonatal intensive care unit (NICU). Either Wright's or Shukla's formula is used to introduce the catheters. However, Shukla's formula is associated with incorrect insertion, especially for newborns < 1500 g. This study aimed to determine by chest X-ray if Wright's formula is better than Shukla's formula for the correct placement of umbilical catheters in newborns ≤ 1500 g. METHODS: We included patients admitted to the NICU of a secondary-level hospital between 2021-2022 who received VUC or AUC through the Wright or Shukla formulas. RESULTS: A total of 129 newborns were included: 78 with VUC and 51 with AUC. In VUC, 50% with Wright and 36.8% with Shukla formulas had the correct location, (p = 0.24). In AUC, 56.6 % with Wright and 52.4% with Shukla formulas were placed correctly placed, (p = 0.76). VUC with weight < 1000 g were correctly placed in 36.4% with Wright and 33.3% with Shukla formulas (p = 0.58). VUC in newborns > 1000 g were correctly placed in 66.6% with Wright and 38.4% with Shukla formulas (p = 0.065). AUC in newborns < 1000 g were correctly placed in 45% using Wright and 42.9% Shukla formulas (p = 0.63). AUC in newborns > 1000 g were correctly placed in 80% using Wright and 57.1% Shukla formulas (p = 0.23). CONCLUSIONS: We found 13% more correctly placed VUC using Wright's formula. Moreover, Wright's formula was 29% above Shukla's VUC placement in neonates > 1000 g, although there was no significant difference due to the sample size.

INTRODUCCIÓN: La colocación de catéteres intravasculares venosos umbilicales (CVU) y arteriales (CAU) es el procedimiento invasivo más frecuente en la unidad de cuidados intensivos neonatales (UCIN). Para introducirlos se utilizan las fórmulas de Wright y de Shukla, aunque esta última podría estar asociada con una inserción incorrecta, especialmente en neonatos < 1500 g. El objetivo de este estudio fue determinar mediante radiografía de tórax cuál fórmula es mejor para la correcta colocación de catéteres umbilicales en recién nacidos ≤ 1500 g. MÉTODOS: Se incluyeron los pacientes ingresados en la UCIN de un hospital de segundo nivel entre 2021-2022 que recibieron CVU o CAU mediante las fórmulas de Wrigth o Shukla. RESULTADOS: Se incluyeron en total 129 recién nacidos: 78 CVU y 51 CAU. En CVU, Wright 50% y Shukla 36.8% tuvieron localización correcta, p = 0.24. En las CAU, Wright 56.6% y Shukla 52.4% tenían una ubicación correcta, p = 0.76. En CVU con peso < 1000 g, Wright 36.4% y Shukla 33.3% bien situados, p = 0.58. En CVU > 1000 g, Wright 66.6% y Shukla 38.4% bien situados, p = 0.065. En CAU < 1000 g, Wright 45% y Shukla 42.9%, p = 0.63. En CAU con peso > 1000 g, Wright 80% y Shukla 57.1%, p = 0.23. CONCLUSIONES: La colocación del CVU fue 13% mejor con la fórmula de Wright. La fórmula de Wright superó en el 29% la colocación del CVU en los neonatos > 1000 g en comparación con la de Shukla, aunque no hubo diferencia significativa debido al tamaño de la muestra.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Scalable, modular continuous wave functional near-infrared spectroscopy system (Spotlight).

Significance: We present a fiberless, portable, and modular continuous wave-functional near-infrared spectroscopy system, Spotlight, consisting of multiple palm-sized modules-each containing high-density light-emitting diode and silicon photomultiplier detector arrays embedded in a flexible membrane that facilitates optode coupling to scalp curvature. Aim: Spotlight's goal is to be a more portable, accessible, and powerful functional near-infrared spectroscopy (fNIRS) device for neuroscience and brain-computer interface (BCI) applications. We hope that the Spotlight designs we share here can spur more advances in fNIRS technology and better enable future non-invasive neuroscience and BCI research. Approach: We report sensor characteristics in system validation on phantoms and motor cortical hemodynamic responses in a human finger-tapping experiment, where subjects wore custom 3D-printed caps with two sensor modules. Results: The task conditions can be decoded offline with a median accuracy of 69.6%, reaching 94.7% for the best subject, and at a comparable accuracy in real time for a subset of subjects. We quantified how well the custom caps fitted to each subject and observed that better fit leads to more observed task-dependent hemodynamic response and better decoding accuracy. Conclusions: The advances presented here should serve to make fNIRS more accessible for BCI applications.

Comparison between Wright and Shukla formulas: which is better for the placement of umbilical catheters in newborns ≤ 1500 g? / Comparación entre las fórmulas de Wright y de Shukla: ¿cuál es mejor para la colocación de catéteres umbilicales en recién nacidos ≤ 1500 g?

Abstract Background: Intravascular venous (VUC) or arterial (AUC) umbilical catheter placement is the most frequent invasive procedure in the neonatal intensive care unit (NICU). Either Wright's or Shukla's formula is used to introduce the catheters. However, Shukla's formula is associated with incorrect insertion, especially for newborns < 1500 g. This study aimed to determine by chest X-ray if Wright's formula is better than Shukla's formula for the correct placement of umbilical catheters in newborns ≤ 1500 g. Methods: We included patients admitted to the NICU of a secondary-level hospital between 2021-2022 who received VUC or AUC through the Wright or Shukla formulas. Results: A total of 129 newborns were included: 78 with VUC and 51 with AUC. In VUC, 50% with Wright and 36.8% with Shukla formulas had the correct location, (p = 0.24). In AUC, 56.6 % with Wright and 52.4% with Shukla formulas were placed correctly placed, (p = 0.76). VUC with weight < 1000 g were correctly placed in 36.4% with Wright and 33.3% with Shukla formulas (p = 0.58). VUC in newborns > 1000 g were correctly placed in 66.6% with Wright and 38.4% with Shukla formulas (p = 0.065). AUC in newborns < 1000 g were correctly placed in 45% using Wright and 42.9% Shukla formulas (p = 0.63). AUC in newborns > 1000 g were correctly placed in 80% using Wright and 57.1% Shukla formulas (p = 0.23). Conclusions: We found 13% more correctly placed VUC using Wright's formula. Moreover, Wright's formula was 29% above Shukla's VUC placement in neonates > 1000 g, although there was no significant difference due to the sample size.

Resumen Introducción: La colocación de catéteres intravasculares venosos umbilicales (CVU) y arteriales (CAU) es el procedimiento invasivo más frecuente en la unidad de cuidados intensivos neonatales (UCIN). Para introducirlos se utilizan las fórmulas de Wright y de Shukla, aunque esta última podría estar asociada con una inserción incorrecta, especialmente en neonatos < 1500 g. El objetivo de este estudio fue determinar mediante radiografía de tórax cuál fórmula es mejor para la correcta colocación de catéteres umbilicales en recién nacidos ≤ 1500 g. Métodos: Se incluyeron los pacientes ingresados en la UCIN de un hospital de segundo nivel entre 2021-2022 que recibieron CVU o CAU mediante las fórmulas de Wrigth o Shukla. Resultados: Se incluyeron en total 129 recién nacidos: 78 CVU y 51 CAU. En CVU, Wright 50% y Shukla 36.8% tuvieron localización correcta, p = 0.24. En las CAU, Wright 56.6% y Shukla 52.4% tenían una ubicación correcta, p = 0.76. En CVU con peso < 1000 g, Wright 36.4% y Shukla 33.3% bien situados, p = 0.58. En CVU > 1000 g, Wright 66.6% y Shukla 38.4% bien situados, p = 0.065. En CAU < 1000 g, Wright 45% y Shukla 42.9%, p = 0.63. En CAU con peso > 1000 g, Wright 80% y Shukla 57.1%, p = 0.23. Conclusiones: La colocación del CVU fue 13% mejor con la fórmula de Wright. La fórmula de Wright superó en el 29% la colocación del CVU en los neonatos > 1000 g en comparación con la de Shukla, aunque no hubo diferencia significativa debido al tamaño de la muestra.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

The impact of age and comorbidity on localized pancreatic cancer outcomes: A US retrospective cohort analysis with implications for surgical centralization.

Introduction: Age and comorbidity are independently associated with worse outcomes for pancreatic adenocarcinoma (PDAC). However, the effect of combined age and comorbidity on PDAC outcomes has rarely been studied. This study assessed the impact of age and comorbidity (CACI) and surgical center volume on PDAC 90-day and overall survival (OS). Methods: This retrospective cohort study used the National Cancer Database from 2004 to 2016 to evaluate resected stage I/II PDAC patients. The predictor variable, CACI, combined the Charlson/Deyo comorbidity score with additional points for each decade lived ≥50 years. The outcomes were 90-day mortality and OS. Results: The cohort included 29,571 patients. Ninety-day mortality ranged from 2 % for CACI 0 to 13 % for CACI 6+ patients. There was a negligible difference (1 %) in 90-day mortality between high- and low-volume hospitals for CACI 0-2 patients; however, there was greater difference for CACI 3-5 (5 % vs. 9 %) and CACI 6+ (8 % vs. 15 %). The overall survival for CACI 0-2, 3-5, and 6+ cohorts was 24.1, 19.8, and 16.2 months, respectively. Adjusted overall survival showed a 2.7 and 3.1 month survival benefit for care at high-volume vs. low-volume hospitals for CACI 0-2 and 3-5, respectively. However, there was no OS volume benefit for CACI 6+ patients. Conclusions: Combined age and comorbidity are associated with short- and long-term survival for resected PDAC patients. A protective effect of higher-volume care was more impactful for 90-day mortality for patients with a CACI above 3. A centralization policy based on volume may have greater benefit for older, sicker patients. Key message: Combined comorbidity and age are strongly associated with 90-day mortality and overall survival for resected pancreatic cancer patients. When assessing the impact of age and comorbidity on resected pancreatic adenocarcinoma outcomes, 90-day mortality was 7 % higher (8 % vs. 15 %) for older, sicker patients treated at high-volume vs. low-volume centers but only 1 % (3 % vs. 4 %) for younger, healthier patients.

A Case of Hepatic Malignant Solitary Fibrous Tumor: A Case Report and Review of the Literature.

A 73-year-old man with a history of atrial myxoma and basal cell carcinoma presented with unexplained fever. Contrast-enhanced CT abdomen showed a large left hepatic lobe mass with early enhancement and delayed venous washout, concerning for hepatocellular carcinoma. Fine needle aspiration showed numerous spindle cells with malignant nuclear features, suggestive of malignant spindle cell neoplasm. The patient underwent left hepatectomy. The surgical specimen showed a well-circumscribe solid mass (14.6 × 13.0 × 10.0 cm) with necrosis. Histopathological examination revealed a proliferation of spindle tumor cells with characteristic staghorn-shaped blood vessels, frequent mitoses, and necrosis. The tumor cells showed strong and diffuse expression of CD34 and STAT6, confirming the diagnosis of malignant solitary fibrous tumor. Solitary fibrous tumor is a rare fibroblastic tumor characterized by a staghorn vasculature and NAB2-STAT6 gene rearrangement. Solitary fibrous tumor of the liver is a rare occurrence. Although most solitary fibrous tumors behave in a benign fashion, solitary fibrous tumors might act aggressively. This case is unique in that it demonstrates an excellent correlation between radiologic, macroscopic, and microscopic features which can contribute to the improvement of radiologic and pathologic diagnostic accuracy.

Simultaneous Hepatic and Visceral Resection: Preoperative Risk Stratification and Implications on Return to Intended Oncologic Therapy.

PURPOSE: Sequence of therapies for synchronous liver metastasis (LM) is complex, with data supporting individualized approaches, although no guiding tools are currently available. We assessed the impact of simultaneous hepatic and visceral resections (SHVR) on textbook outcome (TO) and return to intended oncologic therapy (RIOT), and provide risk-stratification tools to guide individualized decision making and counseling. METHODS: Patients with synchronous LM undergoing hepatectomy ± SHVR were included (2015-2021). Primary and secondary outcomes were TO and RIOT (days), respectively. Using multivariable modeling, a risk score for TO was developed. Decision tree analysis using recursive partitioning was performed for hierarchical risk stratification. The associations between SHVR, TO, and RIOT were examined. RESULTS: Among 533 patients identified, 124 underwent SHVR. TO overall was 71.7%; 79.2% in the non-SHVR group and 46.8% in the SHVR group (p < 0.001). SHVR was the strongest predictor of non-TO (right colon/small bowel: odds ratio [OR] 4.63, 95% confidence interval [CI] 2.65-8.08; left colon/rectum: OR 6.09, 95% CI 2.59-14.3; stomach/pancreas: OR 6.69, 95% CI 1.46-30.7; multivisceral: OR 10.9, 95% CI 3.03-39.5). A composite score was developed yielding three risk strata for TO (score 0-2: 89% vs. score 3-5: 67% vs. score ≥ 6: 37%; p < 0.001). Decision tree analysis was congruent, identifying SHVR as the most important determinant of TO. In patients with colorectal LM, SHVR was associated with delayed time to RIOT (p = 0.004); the risk-stratification tool for TO was equally predictive of RIOT (p < 0.01). CONCLUSIONS: SHVR is associated with reduced likelihood of TO and in turn delayed RIOT. As SHVR is increasingly performed in order to consolidate cancer care, patient selection considering these different outcomes is critical.

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Clockwise Anterior-to-Posterior-Double Isolation (CAP-DI) Approach for Portal Lymphadenectomy in Biliary Tract Cancer: Technique, Yield, and Outcomes.

Background: Portal lymphadenectomy (PLND) is the current standard for oncologic resection of biliary tract cancers (BTCs). However, published data show it is performed infrequently and often yields less than the recommended 6 lymph nodes. We sought to identify yield and outcomes using a Clockwise Anterior-to-Posterior technique with Double Isolation of critical structures (CAP-DI) for PLND. Methods: Consecutive patients undergoing complete PLND for BTCs using CAP-DI technique were identified (2015−2021). Lymph node (LN) yield and predictors of LN count were examined. Secondary outcomes included intraoperative and postoperative outcomes, which were compared to patients having hepatectomy without PLND. Results: In total, 534 patients were included; 71 with complete PLND (36 gallbladder cancers, 24 intrahepatic cholangiocarcinomas, 11 perihilar cholangiocarcinomas) and 463 in the control group. The median PLND yield was 5 (IQR 3−8; range 0−17) and 46% had at least 6 nodes retrieved. Older age was associated with lower likelihood of ≥6 node PLND yield (p = 0.032), which remained significant in bivariate analyses with other covariates (p < 0.05). After adjustment for operative factors, performance of complete PLND was independently associated with longer operative time (+46.4 min, p = 0.001), but no differences were observed in intraoperative or postoperative outcomes compared to the control group (p > 0.05). Conclusions: Yield following PLND frequently falls below the recommended minimum threshold of 6 nodes despite a standardized stepwise approach to complete clearance. Older age may be weakly associated with lower PLND yield. While all efforts should be made for complete node retrieval, failure to obtain 6 nodes may be an unrealistic metric of surgical quality.

Numerical Analysis of Zirconium and Titanium Implants under the Effect of Critical Masticatory Load.

Dental implants have become an alternative to replace the teeth of people suffering from edentulous and meet the physiological and morphological characteristics (recovering 95% of the chewing function). The evolution and innovation of biomaterials for dental implants have had a trajectory that dates back to prehistory, where dental pieces were replaced by ivory or seashells, to the present day, where they are replaced by metallic materials such as titanium or ceramics such as zirconium or fiberglass. The numerical evaluation focuses on comparing the stress distribution and general displacement between different dental implants and a healthy tooth when applying a force of 850 N. For the analysis, a model of the anatomical structure was developed of a healthy tooth considering three essential parts of the tooth (enamel, dentin, and pulp). The tooth biomodel was established through computed tomography. Three dental implant models were considered by changing the geometry of the abutment. A structural simulation was carried out by applying the finite element method (FEM). In addition, the material considered for the analyses was zirconium oxide (ZrO2), which was compared against titanium alloy (Ti6Al4V). The analyses were considered with linear, isotropic, and homogeneous properties. The variables included in the biomodeling were the modulus of elasticity, Poisson's ratio, density, and elastic limit. The results obtained from the study indicated a significant difference in the biomechanical behavior of the von Mises forces and the displacement between the healthy tooth and the titanium and zirconium implant models. However, the difference between the titanium implant and the zirconium implant is minimal because one is more rigid, and the other is more tenacious.