Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis.

Background: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results: The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work: More randomised controlled trials are necessary. Study registration: This study is registered as PROSPERO CRD42019130504. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen ('peritoneal metastases'). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets ('systemic chemotherapy') is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and 'hyperthermic intraoperative peritoneal chemotherapy' (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery ('advanced ovarian cancer'), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from 'advanced ovarian cancer'. Uncertainty in treatment continues for gastric cancer. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

Rethinking Surgical Margins: A New Approach to Predict Outcomes in Oral Squamous Cell Carcinoma.

OBJECTIVE: The traditional categorical division of surgical margins using a 5 mm cutoff in oral cavity squamous cell carcinoma (OCSCC) is controversial. The primary aim of this study was to investigate the presence of an optimal cutoff point or, alternatively, assess the potential improvement in predictive value by considering the surgical margins as a continuum. METHODS: Retrospective analysis of OCSCC patients at a tertiary medical center in 1995-2020. Clinical, pathological, and surgical data were evaluated for effect on survivability by regression analyses. RESULTS: The cohort included 266 patients (48.1% male, mean age 65.4 ± 17.7). Patient stratification by categorical margin status yielded no significant between-group differences in survival (p = 0.54). Significance was achieved when margin distance was reevaluated as a continuous variable (p = 0.0018). Similar results were shown in local control (categorical p = 0.59 vs. continuous p = 0.06). Multivariate model excluded possible confounders. A predictive model was created to provide a more accurate prediction of survival. CONCLUSIONS: The continuum spectrum of margin distance better predicts survival outcomes and locoregional control in OCSCC. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Omission of Axillary Lymph Node Dissection in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy.

BACKGROUND: Axillary management after neoadjuvant chemotherapy (NAC) is evolving but axillary lymph node dissection (ALND) remains the standard of care for patients with residual nodal disease. The results of the Alliance A011202 trial evaluating the oncologic safety of ALND omission in this cohort are pending but we hypothesize that ALND omission is already increasing. METHODS: The National Cancer Database was queried to identify patients diagnosed with cT1-3N1M0 breast cancer who underwent NAC and had residual nodal disease (ypN1mi-2) from 2012 to 2021. Temporal trends in omission of completion ALND were assessed annually. Multivariable logistic and Cox regression models were used to identify factors associated with ALND omission and overall survival (OS), respectively. RESULTS: A total of 6101 patients were included; the majority presented with cT2 disease (57%), with 69% HER2+, 23% triple-negative, and 8% hormone receptor-positive/HER2-. Overall, 34% underwent sentinel lymph node biopsy (SLNB) alone. Rates of ALND were the lowest in the last 4 years of observation. After adjustment, treatment at community centers (vs. academic) and lower pathologic nodal burden were associated with omission of ALND. ALND omission was associated with a higher unadjusted OS (5-year OS: 86% SLNB alone vs. 84% ALND; log-rank p = 0.03), however this association was not maintained after adjustment. CONCLUSIONS: Despite the impending release of the Alliance A011202 results, omission of ALND in patients with residual nodal disease after NAC is increasing. This practice appears more prominent in community centers and in patients with a lower burden of residual nodal disease. No association with OS was noted.

A retrospective single institutional analysis of outpatient chemotherapy in patients with cancer during the COVID-19 pandemic.

Providing treatment to patients with cancer, even during the coronavirus disease (COVID-19) pandemic, is essential. In collaboration with infectious disease specialists, we established guidelines for the management of patients with cancer receiving ambulatory treatment during the pandemic on April 8, 2020. This study examined the practice and management of ambulatory chemotherapy under emergency conditions. Following the guidelines, our Breast and Medical oncology department developed a chemotherapy strategy for the phases. Additionally, to distinguish fever during chemotherapy, we developed a flow chart for fever. As part of a fact-finding survey, the status of outpatient chemotherapy was investigated: (1) whether there was any change in the number of chemotherapies before and after the declaration of a state of emergency by the Tokyo Metropolitan Government and (2) the frequency and severity of febrile neutropenia (FN) cases. Compared to before the first declaration of the state of emergency, the number of chemotherapies decreased except after the declaration, but no decrease was observed during the rest of the period; no difference was observed in the frequency or severity of FN outbreaks or in the use of pegfilgrastim for primary prevention before and after the epidemic. With appropriate treatment guidelines, routine chemotherapy can be performed in an outpatient setting during an outbreak.

Cost and budget impact of mass drug administration compared to expanded school-based targeted preventive chemotherapy for soil-transmitted helminth control in Zamboanga Peninsula, the Philippines.

Background: School-based targeted preventive chemotherapy (PC), the primary strategy for soil-transmitted helminth (STH) control, typically focusing on primary schoolchildren, was expanded to secondary school students in the Philippines in 2016. This program still excludes adults, who may also suffer from considerable morbidity and can be a significant reservoir of infection. Mass drug administration (MDA), where the entire population is treated, would bring additional health benefits but will also increase implementation costs. The incremental cost of implementing MDA for STH control compared to expanded school-based targeted PC, however, is unknown. Methods: A cost survey was conducted in Zamboanga Peninsula region in 2021 to estimate the economic and financial cost of implementing MDA compared to the expanded school-based targeted PC from a government payer perspective. A budget impact analysis was conducted to estimate the financial cost to the government of implementing MDA over a five-year timeframe. Monte Carlo simulation accounted for uncertainty in cost estimates. Costs were reported in 2021 United States Dollars ($). Findings: The economic cost of MDA was $809,000 per year (95% CI: $679,000-$950,000) or $0.22 per person targeted (95% CI: $0.19-$0.26), while the expanded school-based targeted PC would cost $625,000 (95% CI: $549,000-$706,000) or $0.57 per person targeted (95% CI: $0.50-$0.64). Over five years, the financial cost to the government for MDA would be $3,113,000 (95% CI: $2,475,000-$3,810,000); $740,000 (95% CI: $486,000-$1,019,000) higher than expanded school-based targeted PC. Interpretation: Implementing MDA in the region will increase the economic and financial costs by 29% and 31%, respectively, when compared to expanded school-based targeted PC. Implementing MDA would require the Department of Health to increase their total expenditure for STH control by 0.2% and could be key in addressing the ongoing STH burden. Funding: The project was funded by the Australian Centre for the Control and Elimination of Neglected Tropical Diseases (NHMRC GA19028), and JPCDT was supported by a UNSW Scientia PhD Scholarship. SVN is funded by an NHMRC Investigator Grant (APP 2018220).

Prognostic Factors in Uterine Sarcoma Based on the Tumor Size Stratification: A Retrospective Study.

OBJECTIVE: Uterine sarcoma is a rare malignant gynecological tumor with a poor prognosis. Many studies have identified the clinical stage as an important prognostic factor; however, the heterogeneity of patient distribution in the International Federation of Gynecology and Obstetrics (FIGO) stage has reportedly required further revision. Therefore, this study retrospectively investigated the factors related to the prognosis of uterine sarcoma, with particular attention to tumor size, which can be evaluated preoperatively. METHODS: Clinical data were extracted from the medical records of patients with uterine sarcoma treated between January 2010 and January 2023. Kaplan-Meier survival curves were plotted according to clinical factors such as histological type, clinical stage, chemotherapy, and tumor size. Factors that were significant in the univariate analysis were subjected to the multivariate analysis using Cox proportional hazards regression. RESULTS: Thirty-four patients with uterine sarcoma, comprising 24 (70.5%), five (14.7%), three (8.8%), and two (5.9%) with leiomyosarcoma, undifferentiated sarcoma, high-grade endometrial stromal sarcoma, and low-grade endometrial stromal sarcoma, respectively, were included. Based on the FIGO stage, 15 (44.1%), six (17.6%), three (8.8%), and 10 patients had stage I, II, III, and IV disease, respectively, at the time of diagnosis. All patients underwent surgery as initial treatment; 15 received postoperative chemotherapy. Among the 32 patients with uterine leiomyosarcoma, undifferentiated sarcoma, or high-grade endometrial stromal sarcoma, overall survival differed significantly in the univariate analysis based on disease stage (I + II vs. III + IV) and tumor size (≤10 vs. >10 cm). However, only tumor size was an independent prognostic factor in the multivariate analysis. CONCLUSION: Tumor size (≤10 vs. >10 cm) may possibly have a prognostic impact on uterine sarcoma.

Uncommon Presentation of Solitary Plasmacytoma in the Nasal Cavity: Diagnostic and Therapeutic Challenges.

Extramedullary solitary plasmacytoma (SP) is an uncommon tumor and is even rare in the head and neck locations. Here, we report the case of an 82-year-old man admitted to our department for the management of nasal cavity SP. Radiological investigation showed a locally advanced tumor making the patient a non-candidate for surgery. The patient had undergone radiotherapy alone to a total dose of 50 Gy, with 2 Gy per fraction five days a week. After a follow-up of nine months, the tumor recurred, and the patient was managed in the internal medicine department. He received palliative chemotherapy with the cyclophosphamide, dexamethasone, and thalidomide protocol which resulted in a good response. This case illustrates the diagnostic challenges and treatment complexities of SP, particularly in rare locations such as the nasal cavity.

Effect of growth hormone on colonic anastomosis after intraperitoneal administration of 5-fluorouracil, bleomycin and cisplatin: An experimental study.

BACKGROUND: Growth hormone (GH) plays a crucial role in wound healing and tissue repair in postoperative patients. In particular, colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents. AIM: To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU), bleomycin and cisplatin. METHODS: Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon, followed by an end-to-end anastomosis under general anesthesia. The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days. The control group (A) received normal saline. Group B received chemotherapy with 5-FU (20 mg/kg), bleomycin (4 mg/kg) and cisplatin (0.7 mg/kg). Group C received GH (2 mg/kg), and group D received the aforementioned combination chemotherapy and GH, as described. The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscopically examined. Body weight, bursting pressure, hydroxyproline levels and inflammation markers were measured. RESULTS: All rats survived until the day of sacrifice, with no infections or other complications. A decrease in the body weight of group D rats was observed, not statistically significant compared to group A (P = 1), but significantly different to groups C (P = 0.001) and B (P < 0.01). Anastomotic dehiscence rate was not statistically different between the groups. Bursting pressure was not significantly different between groups A and D (P = 1.0), whereas group B had a significantly lower bursting pressure compared to group D (P < 0.001). All groups had significantly more adhesions than group A. Hydroxyproline, as a measurement of collagen deposition, was significantly higher in group D compared to group B (P < 0.05), and higher, but not statistically significant, compared to group A. Significant changes in group D were recorded, compared to group A regarding inflammation (3.450 vs 2.900, P = 0.016) and fibroblast activity (2.75 vs 3.25, P = 0.021). Neoangiogenesis and collagen deposition were not significantly different between groups A and D. Collagen deposition was significantly increased in group D compared to group B (P < 0.001). CONCLUSION: Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis. However, GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.

Information needs preferences of Chinese colorectal cancer patients receiving chemotherapy: A discrete choice experiment.

Objective: The study aims to investigate the information needs and preferences of colorectal cancer (CRC) patients undergoing chemotherapy using a discrete choice experiment (DCE) to optimize and improve the information support strategy for these patients. Methods: Between May and July 2023, 165 patients with CRC who were receiving chemotherapy at a single hospital in China completed the questionnaire. The survey instruments included a general information questionnaire, a DCE questionnaire, and the Brief Health Literacy Screening Scale. A conditional logit model was used with Stata 16.0 software to analyze patients' preferences. Results: A total of 159 valid questionnaires were collected, and the questionnaire response rate was 96.4%. All 7 included attributes had an impact on patients' information needs preference (P < 0.05). Among them, information providers, knowledge content, and social support had high relative importance, which were 12.16%, 7.57% and 2.25%, respectively. Patients showed a preference for attending doctors (ß = 1.9439, P < 0.05) and primary nurses (ß = 1.7985, P < 0.05). Providing knowledge related to disease basis, treatment, and health promotion also had a significant impact (ß = 1.6224, P < 0.05). Conclusions: Healthcare professionals should be the primary information source for patients and improve the accessibility of information by establishing professional information platforms or identifying reliable channels. It is recommended to provide continuous information on treatment and health promotion to CRC patients at various stages of chemotherapy. Attention should be paid to identifying and providing measures to alleviate the economic and psychological burden and to meet the social support needs of patients.

Dendritic nanomedicine enhances chemo-immunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells.

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

Difficulty in differentiating liver injury from an immune checkpoint inhibitor from chemotherapy.

This study investigated the potential of immune checkpoint inhibitors (ICIs) combined with chemotherapy as a promising treatment approach for malignancies. This report focuses on a patient with drug-induced liver injury (DILI) following the administration of chemotherapy and ICIs. A 63-year-old patient with non-small cell lung adenocarcinoma (NSCLC) initially underwent γ-knife treatment and subsequently received a combination of chemotherapy comprising bevacizumab and camrelizumab. Due to liver abnormalities, both chemotherapy and ICIs were stopped on day 21. The patient's liver function improved within a month after methylprednisolone treatment. Subsequently, the patient received carboplatin, pemetrexed, and bevacizumab without complications. This finding supported the notion that DILI was likely triggered by the ICI. This case series details a complex instance of DILI resulting from the use of ICIs and pemetrexed/carboplatin. The alignment of the pathological findings and clinical presentation strongly suggested ICI-induced DILI, which was further supported by the definitive response to steroid treatment. This information is important for clinicians, as it emphasizes the importance of closely monitoring liver function and being aware of potential adverse effects associated with ICIs. Such insights contribute to more effective patient care.

Fruquintinib-Induced Cerebellar Hemorrhage in Left-Sided Descending Metastatic Colorectal Adenocarcinoma: A Case Report and Risk Assessment.

Colorectal adenocarcinoma is the most prevalent form of colorectal cancer, representing the majority of cases in the United States. The disease is driven by a series of genetic mutations, including alterations in the adenomatous polyposis coli (APC), Kirsten rat sarcoma viral oncogene homolog G12D (KRAS), human epidermal growth factor receptor 2 immunohistochemistry 3+ (HER-2 IHC3+), checkpoint kinase 2 (CHEK-2) and tumor protein P53 (TP53) genes, which lead to malignant transformation. While the standard treatment for metastatic colorectal cancer (mCRC) typically involves chemotherapy and targeted therapies, many patients experience disease progression, necessitating the exploration of novel treatments. Fruquintinib, a highly selective vascular endothelial growth factor (VEGFR) inhibitor, has emerged as a promising option for mCRC patients who have exhausted conventional therapies. However, its use is associated with significant bleeding risks, including rare but severe complications such as cerebellar hemorrhage. This case report presents a patient with mCRC who developed a cerebellar hemorrhage shortly after initiating fruquintinib therapy, highlighting the need for careful patient monitoring and individualized risk assessment to mitigate such serious adverse events.

Association between salivary inflammatory mediators and oral mucositis in patients with cancer undergoing chemotherapy.

PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.

An overview of different methods to establish a murine premature ovarian failure model.

Premature ovarian failure (POF)is defined as the loss of normal ovarian function before the age of 40 and is characterized by increased gonadotropin levels and decreased estradiol levels and ovarian reserve, often leading to infertility. The incomplete understanding of the pathogenesis of POF is a major impediment to the development of effective treatments for this disease, so the use of animal models is a promising option for investigating and identifying the molecular mechanisms involved in POF patients and developing therapeutic agents. As mice and rats are the most commonly used models in animal research, this review article considers studies that used murine POF models. In this review based on the most recent studies, first, we introduce 10 different methods for inducing murine POF models, then we demonstrate the advantages and disadvantages of each one, and finally, we suggest the most practical method for inducing a POF model in these animals. This may help researchers find the method of creating a POF model that is most appropriate for their type of study and suits the purpose of their research.

Treatment Outcomes in Patients with Recurrent Adrenocortical Carcinoma.

BACKGROUND: While numerous studies have explored treatment outcomes for the overall ACC patient cohort, data on the subpopulation of patients with recurrent disease are limited. Therefore, the aim of this study was to assess treatment outcomes in patients with recurrent ACC. METHODS: In this retrospective study, we included 18 patients median age 49 years (42-62); 67% female) diagnosed with recurrent ENSAT stage I-III ACC who underwent either R0 (n = 16) or Rx (n = 2) surgical resection of the tumor. RESULTS: The median time from the initial surgery to ACC recurrence was 29 months (IQR 18-50). Seven patients (39%) manifested local recurrence, while 11 patients (61%) developed distant metastases. The median follow-up duration after tumor recurrence was 32 months (IQR 25-53). Regarding the treatment of ACC recurrence, 10 patients underwent a second surgery either as an alone procedure (n = 4), or in combination with mitotane (n = 4), mitotane and chemotherapy (n = 1), or mitotane combined with radiotherapy (n = 1). The remaining patients received treatment involving chemotherapy±mitotane (n = 4) and locoregional therapy ±chemotherapy (n = 3). One patient chose not to proceed with further management and follow-up. The median PFS was 17 (95% CI 8-26) months while the median OS was not reached. In the multivariate model, increased mortality was associated with advanced age (p = 0.04) and a shorter interval to ACC recurrence (p = 0.03). CONCLUSION: A significant proportion of patients with ACC recurrence experience disease progression or second recurrence, despite all treatment efforts. Nevertheless, by integrating diverse treatment modalities, many patients have the potential to attain long-term survival.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Impact of taxanes after PD-1 blockade exposure in advanced esophageal squamous cell carcinoma.

BACKGROUND: Programmed cell death-1 (PD-1) blockade improves survival in patients with advanced esophageal squamous cell carcinoma (ESCC). However, the efficacy of taxanes after exposure to PD-1 blockade remains unclear in patients with advanced ESCC. METHODS: We retrospectively analyzed the clinical outcomes of advanced ESCC patients treated with taxanes (paclitaxel or docetaxel) with/without prior exposure to PD-1 blockade (Exposed /Naïve group) at National Cancer Center Hospital from June 2016 to December 2020. RESULTS: Ninety-nine patients (Exposed group, n = 32; Naïve group, n = 67) were included. The objective response rate (ORR) of the Exposed group was significantly higher than that of the Naïve group (37.5% vs. 13.4%, p = 0.009). The median progression-free survival was similar between the Exposed and Naïve groups (3.8 vs. 2.8 months, HR 1.12, 95% CI 0.65-1.86, p = 0.66). PD-1 blockade exposure independently predicated higher ORR to taxanes in multivariate analysis. Grade ≥ 3 adverse events were comparable between the Exposed and Naïve groups (45.8% vs. 40.3%, p = 0.64). CONCLUSIONS: Taxanes following PD-1 blockade in advanced ESCC showed a higher ORR but similar PFS compared to taxanes without prior PD-1 exposure.

Split-Dose Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days. METHODS: We conducted a systematic literature review (SLR) and network meta-analysis (NMA) to better understand treatment patterns and comparative effectiveness and safety of split-dose GC vs gemcitabine plus carboplatin (GCa), GC, and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). RESULTS: Among 120 identified studies, 16 studies representing 1,767 patients included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function, age > 70 years, comorbidities, and physician preference. Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5-18.1 months. Discontinuation rates due to adverse events were 5%-38%. In the NMA, ORR with split-dose GC was significantly higher than with GCa. PFS and OS for split-dose GC were similar to that observed with the other regimens (GCa, GC, and MVAC). CONCLUSIONS: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, split-dose GC demonstrated comparable effectiveness and safety profile to those seen with other regimens. Split-dose GC thus has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further prospective study.