Adjuvant Therapy Research Articles

JianPiTongLuo (JPTL) Recipe regulates anti-apoptosis and cell proliferation in colorectal cancer through the PI3K/AKT signaling pathway

BackgroundJianPiTongLuo Recipe (JPTL Recipe) is a traditional Chinese medicine formula commonly used in the clinical treatment of colorectal cancer. Clinical studies have found that it can significantly improve the prognosis of patients with colorectal cancer. However, its mechanisms of action are not well understood, which has limited its further clinical application. MethodsWe investigated the potential mechanisms of action of the JianPiTongLuo (JPTL) Recipe on colorectal cancer (CRC) using a multi-step approach. Initially, network pharmacology and bioinformatics analyses were conducted using databases such as TCMSP, HERB, BATMAN-TCM, and STRING to identify active components of JPTL Recipe and predict their therapeutic targets. Interaction networks and functional enrichment analyses were constructed to hypothesize relevant biological processes and pathways. In vitro studies involved treating human CRC cell lines HCT116, LoVo and SW480 with varying concentrations of JPTL Recipe extract, measuring cell viability with the CCK-8 assay, assessing apoptosis via flow cytometry, and analyzing signaling pathways through Western blotting. To corroborate these findings, in vivo experiments were performed on BALB/c nude mice implanted with HCT116 cells, divided into control, JPTL Recipe-treated, 5-fluorouracil (5-FU)-treated, and JPTL Recipe combined with 5-FU groups, with tumor growth and histological changes monitored. Mechanistic studies focused on the PI3K/AKT signaling pathway, examining the phosphorylation status of key pathway proteins using immunofluorescence and Western blot analyses to elucidate JPTL Recipe 's interaction with pathway activity. ResultsWe demonstrated that JPTL Recipe effectively inhibits colorectal cancer cell proliferation, anti-apoptotic ability, and exerts synergistic therapeutic effects with fluorouracil. Further analysis revealed that JPTL Recipe affects the activity of colorectal cancer cells by inhibiting the phosphorylation of the PI3K/AKT signaling pathway. ConclusionIn summary, we have discovered and confirmed that the traditional Chinese medicine compound JPTL Recipe can serve as a novel adjuvant therapy for colorectal cancer, offering a new treatment approach for the integration of traditional Chinese and Western medicine in the treatment of colorectal cancer.

Liver Transplantation for Cholangiocarcinoma

AbstractCholangiocarcinomas (CCAs) are highly aggressive, primary liver cancers with rising incidence and mortality rates. The current 5-year overall survival is less than 20%. There are no standardized screening protocols, and current diagnostic methods include serum biomarkers and imaging techniques with suboptimal sensitivities and specificities. The most commonly used treatment options, including combination systemic therapies, locoregional therapies, and surgical resection, offer improving but nonetheless limited progression-free and overall survival. Liver transplantation has shown promising results as a potentially curative treatment for two types of CCA, namely, perihilar and intrahepatic. However, the evidence is largely from retrospective series of small to moderate sample sizes. There is a need to define optimal types and sequencing of neoadjuvant and adjuvant peritransplant therapies, as well as criteria for CCA patient transplant eligibility. Here, we conduct a granular review of the evidence available on every step of the transplant care pathway for perihilar and intrahepatic CCA patients. We aim to inform best practices to inform future avenues of research and maximize the number of patients eligible for this potentially life-prolonging therapy.

Risk of lymph node metastasis in T1 tonsil squamous cell carcinomas patients according to age stratification at diagnosis

BackgroundThe objective of this study is to assess the association between age and lymph nodes metastasis (LNM) in T1 tonsil squamous cell carcinomas (TSCC) patients. MethodsPatients with T1 TSCC were extracted from the SEER database between 2005 and 2014. Univariate and multivariate logistic regression models were produced to recognize the association between age and risk factors of LNM. ResultsA total of 2430 patients were analyzed. Younger patients more frequently presented with LNM compared to their older peers (P < 0.01, respectively.). In multivariate analyses, older age was associated with a significantly lower risk of LNM. Compared to patients aged 29–39-years-old, the hazard ratios for patients aged 40–49, 50–59, 60–69, and 70–88 years old were 0.911 (95 % confidence interval [CI] 0.370–2.245), 0.641 (95 % CI 0.268–1.535), 0.511 (95 % CI 0.212–1.231), and 0.236 (95 % CI 0.095–0.584), respectively. Subgroups analysis shows that the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients (P < 0.05, respectively). ConclusionOur study demonstrates that younger patients with T1 TSCC had a higher risk of LNM than their old peers and the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients. More accurate assessments of LNM and prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck will be imperative for reducing recurrence in younger T1 TSCC.

Valsartan as a prophylactic treatment against breast cancer development and niche activation: What molecular sequels follow chronic AT-1R blockade?

AimsTransactivation of insulin-growth-factor-receptor (IGF-1R) by angiotensin-II-type-1-receptor (AT-1R) was only demonstrated in vascular-smooth-muscle cells and has never been tested in breast-cancer (BC). This investigation addressed the impact of chronic AT-1R blockade by valsartan (Val) on possible concurrent AT-1R/IGF-1R signaling inhibition, regressing BC-tumor-microenvironment (TME) cellular components activation, and hindering BC development. Main methodsThe effect of different Val doses (10, 20, 40 & 80 mg/kg/day for 490 days) was tested on dimethylbenz(a)anthracene (DMBA)-induced progesterone-promoted-BC in rats. The influence on intratumoral/circulating angiotensin-II (ANG-II) levels and AT-1R/Mas-R immunofluorescent-expression were assessed. The potential AT-1R/IGF-1R crosstalk within TME-BC-stem-cells (BCSCs) and cancer-associated-fibroblasts (CAFs) was evaluated by fluorescently marking these cells and locating the immunofluorescently-stained AT-1R/IGF-1R in them using confocal-laser-microscopy and further quantified by flow cytometry. In addition, the molecular alterations following blocking AT-1R were inspected including determining Src; crucial for IGF-1R transactivation by AT-1R, Notch-1; IGF-IR transcriptional-regulator, and PI3K/Akt &IL-6/STAT expression. Further, the suppression of CSCs' capabilities to maintain pluripotency, stemness features, epithelial-to-mesenchymal-transition (EMT), and angiogenesis was evaluated by assessing NANOG gene, aldehyde-dehydrogenase (ALDH), N-cadherin and vascular-endothelial-growth-factor (VEGF), respectively. Furthermore, the proliferative marker; Ki-67, was detected by immunostaining, and tumors were histologically graded using Elston-Ellis-modified-Scarff-Bloom-Richardson method. Key findingsProphylactic Val significantly reduced tumor size, prolonged latency, reduced tumor histopathologic grade, decreased circulating/intratumoral-ANG-II levels, increased Mas-R, and decreased AT1R expression. AT-1R/IGF-1R were co-expressed with a high correlation coefficient on CAFs/BCSCs. Moreover, Val significantly attenuated IGF-1R transactivation and transcriptional regulation via Src and Notch-1 genes' downregulation and reduced Src/IGF-IR-associated PI3K/Akt and IL-6/STAT3 signaling. Further, Val significantly decreased intratumoral NANOG, ALDH, N-cadherin, VEGF, and Ki-67 levels. SignificanceChronic Val administration carries a potential for repurposing as adjuvant or conjunct therapy for patients at high risk for BC.

Hemoadsorption therapy for myoglobin removal in rhabdomyolysis: consensus of the hemoadsorption in rhabdomyolysis task force

BackgroundRhabdomyolysis describes a syndrome characterized by muscle necrosis and the subsequent release of creatine kinase and myoglobin into the circulation. Myoglobin elimination with extracorporeal hemoadsorption has been shown to effectively remove myoglobin from the circulation. Our aim was to provide best practice consensus statements developed by the Hemoadsorption in Rhabdomyolysis Task Force (HRTF) regarding the use of hemadsorption for myoglobin elimination.MethodsA systematic literature search was performed until 11th of January 2023, after which the Rhabdomyolysis RTF was assembled comprising international experts from 6 European countries. Online conferences were held between 18th April − 4th September 2023, during which 37 consensus questions were formulated and using the Delphi process, HRTF members voted online on an anonymised platform. In cases of 75 to 90% agreement a second round of voting was performed.ResultsUsing the Delphi process on the 37 questions, strong consensus (> 90% agreement) was achieved in 12, consensus (75 to 90% agreement) in 10, majority (50 to 74%) agreement in 13 and no consensus (< 50% agreement) in 2 cases. The HRTF formulated the following recommendations: (1) Myoglobin contributes to the development of acute kidney injury; (2) Patients with myoglobin levels of > 10,000 ng/ml should be considered for extracorporeal myoglobin removal by hemoadsorption; (3) Hemoadsorption should ideally be started within 24 h of admission; (4) If myoglobin cannot be measured then hemoadsorption may be indicated based on clinical picture and creatinine kinase levels; (5) Cartridges should be replaced every 8–12 h until myoglobin levels < 10,000 ng/ml; (6) In patients with acute kidney injury, hemoadsorption can be discontinued before dialysis is terminated and should be maintained until the myoglobin concentration values are consistently < 5000 ng/ml.ConclusionsThe current consensus of the HRTF support that adjuvant hemoadsorption therapy in severe rhabdomyolysis is both feasible and safe and may be an effective method to reduce elevated circulating levels of myoglobin.

Who Can Receive Clinical Benefit from Mid-Term Vericiguat Add-on Therapy Among Patients with Systolic Heart Failure Receiving Quadruple Medical Therapy?

Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing "quadruple medical therapy" comprising administration of a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study involved patients undergoing 3-month vericiguat therapy alongside complete quadruple medical therapy in a contemporary real-world clinical practice. Baseline characteristics associated with the primary outcome, defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the 3-month therapeutic duration, were scrutinized. A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the 3-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03-1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the 3-month vericiguat therapy. In conclusion, preservation of baseline systolic blood pressure emerged as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.

Process and outcome differences in the care of patients undergoing elective and emergency right hemicolectomy.

Up to 30% of patients with colorectal cancer present as an emergency and have worse outcomes than elective patients. Compared with left-sided cancers, malignancies arising in the right colon are significantly under-researched. We sought to compare cancer care quality and clinical outcomes between emergency and elective presentations of right-sided colon cancer (RCC). This multicentre, retrospective study included all patients who underwent operative management for a RCC, from 1 April 2017 to 31 March 2022. Data were collected from electronic patient records, and host and tumour factors as well as outcomes between emergency and elective cohorts were compared. Overall, 806 patients (median age 72 years) were included. Some 175 patients (22%) presented as an emergency: 140 in obstruction and 35 with tumour perforation, compared with 1 patient with tumour perforation in the elective group (p < 0.001). The emergency group had higher rates of postoperative complications (59.1% vs 20.0%, p < 0.001), increased 90-day mortality (13.7% vs 1.3%, p < 0.001) and a longer hospital stay (5 vs 10 days, p < 0.001). From the emergency cohort only 29.2% of eligible patients received adjuvant chemotherapy and in multivariate regression analysis emergency presentation was associated with a decreased likelihood of receiving adjuvant chemotherapy (odds ratio 0.26 [0.14-0.47], p < 0.001). Both short- and long-term outcomes after emergency presentation of RCC are poor, with inadequate access to subsequent chemotherapy. Strategies addressing emergency presentations of left-sided tumours have moved towards temporisation and elective surgery. Delaying major resectional surgery for optimisation may improve outcomes and access to adjuvant therapies for RCC.

Understanding the essentials of photodynamic therapy for dental practitioners: Shining a spotlight

Background: Oral disorders, including tooth decay, periodontal disease, and endodontic infections, are prevalent worldwide. The escalating issue of antibiotic resistance exacerbates the need for alternative treatment modalities. Aim: This review aims to provide a comprehensive overview of advancements in photodynamic therapy (PDT) for dental applications, highlighting its potential as a non-invasive local and adjuvant therapy for various oral infectious disorders. PDT, which originated in the early 20th century, involves three primary components: A photosensitizer (PS), light, and oxygen. The PS selectively targets unwanted eukaryotic cells, such as tumors in the oral cavity, or pathogenic microorganisms, while sparing healthy cells. The efficacy of PDT is significantly influenced by the type of PS utilized. Method: An electronic search was conducted using the PubMed database focusing on peer-reviewed articles up to November 2023 using the keywords “photodynamic therapy,” “photochemotherapy,” “antimicrobial photodynamic therapy,” “antimicrobial photodynamic therapy oral,” resulting in 2341, 1034, 389, 221, and 96 items, respectively. After appropriate review, relevant data from other electronic sources are also included for additional information. Results: Historical and recent studies have demonstrated the effectiveness of porphyrin PSs and temoporfin in treating premalignant and malignant intraoral lesions, particularly as palliative treatments when conventional therapies have failed. In addition, phenothiazinium PSs, such as methylene blue and toluidine blue, have shown substantial antimicrobial activity against bacteria, viruses, and fungi. PDT has been applied successfully to treat specific oral conditions, including caries, endodontic and mucosal infections, periodontal disorders, and periimplantitis. Notably, its antibacterial properties suggest that PDT could reduce the dependency on systemic antibiotics. Conclusion: PDT emerges as a promising alternative to conventional treatments for oral infections, offering a potential solution to the global challenge of antibiotic resistance. Continued research and development are essential to enhance the effectiveness and broaden the application of PDT in dental care.

Efficacy of zinc as an adjuvant therapy in acute pneumonia in children of age 2 months to 2 years: A randomized controlled trial

Background: Pneumonia is the most common Illness affecting infants and children globally. Childhood pneumonia has been identified as the major “forgotten killer of children” by UNICEF and the WHO. The WHO and United Nations Children’s Fund (UNICEF) in 2013, published the integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD) which outlined a framework for ending preventable child deaths due to diarrhoea and pneumonia by 2025. Zinc is a vital micro element that is essential for a variety of fundamental biological processes due to its function as a transition metal, cofactor, structural component, and signalling molecule. Zinc is also an essential component of antibacterial immunity. The impaired immunocompetence due to low zinc states enhances the establishment of a particular infection due to a reduction in the clearance of infectious agents. Recommend zinc nutritional intake is 10-20mg/day for children. It is estimated that 17-20% of the world’s population may be zinc deficient. Zinc deficiency is common among children in developing countries because of inadequate food intake, particularly from animal source and limited bioavailability from local diet. It has been proposed that zinc can be a real potential in the prevention of pneumonia morbidity and mortality. Objective: To study the effect of zinc supplementation as an adjuvant therapy on outcome of pneumonia. Method: We conducted a randomised controlled trial from march 2023 to february 2024. All children in the the age group of 2 months to 2 years, who presented with the features of pneumonia to the department of Paediatrics in Akash institute of medical sciences and research centre Devanhalli, Bangalore rural. Ethics consent was obtained from Institutional ethical committee. Demographic details such as name, age, gender along with clinical profile was taken. After admission, detailed history and physical and systemic examination were carried out and necessary data collected. Sample size being 50 cases, they were divided in two groups as case group (zinc group) and control group by stratified randomisation, 25 participants being in each group. Enrolled children were given standard treatment for pneumonia in the form of oxygen, intravenous fluids, bronchodilators, parenteral antibiotics. Enteral feeds were started once the child respiratory distress improved, oxygen saturations greater than 93%, baby was able to tolerate feed. Zinc group received 20 mg of elemental zinc per day as a single dose for 7 days. Result : Out of the total 50 cases, two groups were divided with 25 cases in zinc group and 25 cases in non-zinc group. In zinc group 6 cases (50%) took 24-48 hours for disappearance of symptoms, another 3 cases (26%) less than 24 hours, in 1 case time for disappearance of symptoms was 48-72 hours, another case which took 72-96 hours. The mean duration of time taken for disappearance of danger signs was 42.33 ± 13.89 hours. In the non-zinc group (36%) 5 cases took 24-48 hours for disappearance of danger signs, 3 cases (22%) which took 48-72 hours and 2 cases (14%) which took 96-120 hours, 2 more cases (14%) which took 120-144 hours. The mean duration of hospital stay in non-zinc group was 62.28 ± 10.84 hours which is comparatively more than that of zinc group. Conclusion: This study concluded that zinc supplementation shortens the time taken for resolution of respiratory distress and resolution of symptoms. However, it was not found to be of much help in improving oxygen saturation. It also did not show any significant decrease in time taken for disappearance of danger signs and duration of hospital stay.

GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer

GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment. At median follow-up of 6.5 years (overall cohort) and 5.7 years (neoadjuvant cohort, N = 593), both regimens showed comparable 5-year OS rates (iddEnPC 90.8%, dtEC-dtD 90.0%, p = 0.320). In the neoadjuvant setting, iddEnPC yielded a higher pCR rate than dtEC-dtD (51.2% vs. 42.6%, p = 0.045). Patients achieving pCR had significantly improved 5-year iDFS (88.7% vs. 70.1%, HR 0.33, p < 0.001) and OS rates (93.9% vs. 83.1%, HR 0.32, p < 0.001), but OS outcomes were comparable regardless of pCR status. Thus, iddEnPC demonstrates superior pCR rates compared to dtEC-dtD, yet with comparable survival outcomes.

MGMT protein expression is a reliable predictive biomarker for temozolomide-containing chemotherapy in osteosarcoma.

The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy.

ASO Author Reflections: Is Adjuvant Therapy Necessary for All Patients with Invasive Mucinous Cystic Neoplasms of the Pancreas? Let's De-escalate.

ASO Author Reflections: Is Adjuvant Therapy Necessary for All Patients with Invasive Mucinous Cystic Neoplasms of the Pancreas? Let's De-escalate.

Pathological complete response after conversion therapy in unresectable hepatocellular carcinoma: a retrospective study

BackgroundHepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients.MethodsThe study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival.ResultsA total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324).ConclusionsConversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response.

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.

Prognostic significance of lymphovascular space invasion in early-stage low-grade endometrioid endometrial cancer: a fifteen-year retrospective Chinese cohort study

ObjectiveIn 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study.MethodsThis retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People’s Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model.Results702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028).ConclusionsLVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.

Pembrolizumab (Keytruda)

CADTH recommends that public drug plans reimburse Keytruda for the treatment of locally advanced unresectable or metastatic biliary tract carcinoma (BTC) if certain conditions are met. Keytruda in combination with gemcitabine-based chemotherapy should only be covered to treat patients with locally advanced unresectable or metastatic BTC who have not received prior treatment or who have completed treatment with nongemcitabine-based neoadjuvant or adjuvant therapy more than 6 months ago. Patients receiving Keytruda should be in relatively good health (i.e., have a good performance status, as determined by a specialist). Keytruda should only be reimbursed if it is used in combination with gemcitabine-based chemotherapy if prescribed by specialists with experience in managing BTC and if the cost of Keytruda does not exceed the cost of durvalumab. Keytruda should not be reimbursed if it is used to treat patients with Ampulla of Vater cancer.

Comparative Analysis of Supratentorial Intraventricular Tumors in Adults and Pediatrics in a Developing Country: Clinicopathological Features, Surgical Management, and Outcomes.

Supratentorial intraventricular tumors, encompassing lateral and third ventricular tumors, are uncommon intracranial neoplasms, typically slow-growing and benign, manifesting symptoms only upon reaching a substantial size. This study aims to identify optimal surgical approaches, assess the prevalence and characteristics of these tumors, and evaluate postoperative outcomes among pediatric and adult age groups. A retrospective comparative study at a tertiary care hospital from January 2014 to June 2020 included 165 patients (68 pediatrics, 97 adults) meeting inclusion criteria for intraventricular tumor management. Data covered demographic factors, clinical history, neurological assessments, neuroimaging, surgical approaches, histopathological diagnoses, immunohistochemical features, adjuvant therapies, follow-up status, postoperative complications, and morbidity/mortality. Ventricular tumor incidence showed male preponderance in both adults (M:F = 1.2:1) and pediatrics (M:F = 3:1). Lateral ventricles were the most common location. Pediatric cases exhibited more frequent calcifications on computed tomography scans (35.6% vs. 29.5%). Grade II and III tumors were more prevalent in adults within the lateral ventricle (27.1 and 1.9%) compared with pediatrics (6.5 and 8.4%). The third ventricle predominantly featured benign lesions, with pediatric patients experiencing significantly longer hospital stays (16.12 ± 21.94 days vs. 9.58 ± 6.21 days) (p = 0.006). Adults and pediatric patients showed a significant difference in high-grade lateral ventricle tumors (p-value = 0.002*). Supratentorial ventricular tumors are relatively more prevalent in children than adults, presenting challenges due to size and bleeding risks. Surgical resection is the primary treatment, with a focus on the optimal approach for gross total excision to reduce recurrence risk.

Intramedullary Metastases to Conus Medullaris: A Review of the Literature with a Case Illustration

Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5–36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

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.