The combination of chemotherapy and immunotherapy for metastatic cholangiocarcinoma (CCA) offers promising improvements in survival and response rates beyond traditional treatments. TOPAZ-1 and KEYNOTE-966 have demonstrated the efficacy of combining immunotherapy (durvalumab and pembrolizumab) with chemotherapy, even in gallbladder cancer (GBC), with a complete response rate of 2.7% in the TOPAZ-1 trial. Advanced CCA treated with immunotherapy combinations has shown complete responses influenced by high programmed death-ligand 1 (PD-L1) or Epstein-Barr virus expression. These responses were enhanced by combining radiotherapy with programmed cell death protein 1 (PD-1) blockade. A 62-year-old man was diagnosed with unresectable GBC, distant lymphatic metastases, and local invasion of liver segments 4i and 5, the colonic hepatic flexure, the duodenal bulb, and the pancreatic head. Immunohistochemical examination revealed poorly differentiated squamous cell carcinoma, without expression of PD-L1. Next generation sequencing revealed the mutation of ERBB2 R678Q and a microsatellite stable tumour. The patient started chemo-immunotherapy with cisplatin-gemcitabine plus durvalumab in June 2022. After eight cycles, a significant reduction in tumour volume and markers was reported, and therapy with durvalumab was maintained through November 2023. The subsequent computed tomography scans showed further reduction in the tumour volume, and surgical resection was performed. Histological examinations confirmed the absence of residual tumour or lymph node metastases. As of June 2024, the patient has shown no signs of disease recurrence. Several reports of conversion surgery in GBC exist, but data on pre-surgical chemo-immunotherapy are limited. Furthermore, a complete response without pathological confirmation in CCA and GBC raises several questions regarding the need for surgery after immunotherapy. Although effective disease control and tumour regression have been reported in advanced GBC with combined anti-cytotoxic T-lymphocyte associated protein 4 and anti-PD-1 agents and chemotherapy, further studies are needed to identify reliable predictive biomarkers due to unclear associations with PD-L1 expression or tumour mutational burden. Overall, chemo-immunotherapy has been effective in treating metastatic CCA, especially when tailored to specific molecular profiles. These treatments may lead to complete responses and novel strategies.

BACKGROUND: Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear.
METHODS: A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed.
RESULTS: 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%).
CONCLUSIONS: The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone.
BACKGROUND: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

BACKGROUND: Hepatocellular 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.
METHODS: The 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.
RESULTS: A 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).
CONCLUSIONS: Conversion 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.

暂无摘要。

UNASSIGNED: The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear.
UNASSIGNED: Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed.
UNASSIGNED: The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006).
UNASSIGNED: Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

暂无摘要。

Over the last ten years, there has been a substantial increase in the number of children and adolescents referred to gender clinics for possible gender dysphoria. The gender affirming model of care, a dominant treatment approach in Canada, is based on low quality evidence. Other countries are realizing this and making psychosocial treatments and/or exploratory psychotherapy a first line of treatment for gender related distress in young patients. Psychodynamic (exploratory) psychotherapy has established efficacy for a range of conditions, and has been used in youth and adults with gender dysphoria. In Canada, the adoption of psychodynamic psychotherapy for gender dysphoria is impeded by some academics who argue that it may violate laws against conversion therapy. Psychodynamic psychotherapy is not conversion therapy and should be made available in Canada as a treatment modality for gender dysphoria.

Sexual orientation and gender identity/expression change efforts (SOGIECEs) are discredited practices that are associated with serious negative effects and incompatible with modern standards for clinical practice. Despite evidence linking SOGIECEs with serious iatrogenic effects, and despite support for LGBTQ+-affirmative care alternatives, SOGIECE practices persist. In the 1970s and 1980s, Behavior Therapy published articles testing and/or endorsing SOGIECEs, thereby contributing to their overall development, acceptance, and use. The Behavior Therapy Task Force on SOGIECEs was assembled to conduct a rigorous review of the SOGIECE articles published in Behavior Therapy and to decide whether, and what, formal action(s) should be taken on these articles. This report provides a detailed review of the historic SOGIECE literature published in Behavior Therapy and outlines the Task Force\'s deliberative and democratic processes resulting in actions to: (1) add prominent advisory information to k = 24 SOGIECE papers in the form of digital \"black box\" disclaimers that caution readers that the SOGIECE practices tested or described in these papers are inconsistent with modern standards, (2) offset organizational financial benefits from the publication of these papers, and (3) promote LGBTQ+-affirmative practices. SOGIECEs are not the only concerning practices across the field\'s history, and the pages of today\'s scientific journals include practices that will be at odds with tomorrow\'s moral standards and ethical guidelines. This report calls for precautionary measures and editorial safeguards to minimize the future likelihood and impact of problematic published scholarship, including the need to fully include those with relevant lived experiences in all aspects of clinical science and peer review.

UNASSIGNED: Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.
UNASSIGNED: We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023.
UNASSIGNED: Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens, it is encouraging that a few of studies have concentrated on this field, and moreover, the methods and parameters noted on other cancer types are also worthy of reference. For the pathologic assessment of HCC specimens underwent immunotherapy, a suitable sampling scheme, identifying immunotherapy-related pathologic response, and quantification of pathologic response rate should be emphasized. For the patients of HCC who are scheduled to receive immunotherapy, tumor-infiltrating lymphocyte, intratumoral tertiary lymphoid structure, programmed cell death ligand 1, Wnt/β-catenin, microsatellite instability and mismatch repair, tumor mutational burden and tumor neoantigen, as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.
UNASSIGNED: The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report. Albeit many related researches are preclinical or insufficient, they may tremendously alter the immunotherapy strategy of HCC in future.

BACKGROUND: Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC).
METHODS: A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints.
RESULTS: After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62).
CONCLUSIONS: TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.