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Background: Hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen has demonstrated efficacy in patients with unresectable hepatocellular carcinoma (HCC). The combined targeted and immunotherapy has emerged as a first-line treatment for liver cancer. In this study, we investigated the clinical efficacy and safety of FOLFOX-HAIC in combination with targeted immunotherapy in patients with untreated, unresectable HCC. Materials and methods: Data were collected from patients with initially unresectable HCC treated at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, from June 2022 to June 2023. Tumor response and survival outcomes were assessed following the FOLFOX-HAIC combined with targeted immunotherapy, The safety was also evaluated through the incidence of related adverse events. Results: A total of 51 eligible patients were recruited. The objective response rate (ORR) based on mRECIST and RECIST 1.1 criteria were 60.8% and 45.1%, respectively. The surgical conversion rate was 25.5%. The median progression-free survival (PFS) was 15.2 months. The 1-year overall survival rate was 88.2%. Adverse events were observed in 98% patients, with 23.5% experiencing grade 3 or 4 adverse events. Conclusion: The FOLFOX-HAIC combined with targeted immunotherapy regimen is effective in patients with unresectable HCC, demonstrated by a high surgical conversion rate and manageable adverse effects. This regimen represents a potential novel first-line treatment option for HCC. [ABSTRACT FROM AUTHOR]

Les thérapies de conversion sont des pratiques pseudo-scientifiques visant à modifier l'orientation sexuelle ou l'identité de genre en usant de procédés violents. Depuis le 31 janvier 2022, la loi française vient expressément interdire la pratique des thérapies de conversion. Toute la difficulté quant à légiférer sur ce sujet tend à ne pas atteindre le droit des individus à bénéficier aux opérations de réassignation sexuelle, si bien que modifiant l'identité des personnes, interventions dont les justifications médicales sont clairement établies. Conversion therapies are pseudo-scientific practices aimed at changing sexual orientation or gender identity using violent methods. Since January 31, 2022, French law has expressly prohibited the practice of conversion therapy. All the difficulty in legislating on this subject tends to not affect the right of individuals to benefit from sexual reassignment operations, which although modifying the identity of people, an intervention whose medical justifications are clearly established. [ABSTRACT FROM AUTHOR]

Summary: Aim: This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases. Methods: In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023. Results: Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance (p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage (p = 0.045), absence of macrovascular invasion and extrahepatic spread (p = 0.045), and a low value of neutrophil to lymphocyte ratio (p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group (p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group (p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR (p = 0.7, 1.0 and 0.3, respectively). Conclusions: Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the leading causes of cancer-related death in China, and with the extensive development of conversion therapy, the treatment of advanced unresectable gastric cancer (AUGC) patients has ushered in a new dawn. This study aimed to analyze the efficacy of conversion therapy in AUGC patients and explored the relevant factors affecting the efficacy. Method: We collected information from GC patients who received conversion therapy from this center and designed a retrospective study. Results: We collected relevant clinical data from 160 patients with AUGC. A total of 120 patients who underwent routine R0 resection were identified as conversion cases. A total of 25 patients (15.6%) achieved pCR, 92 patients (57.5%) achieved objective response rate (ORR), 140 patients (87.5%) achieved disease control rate (DCR), and 20 cases (12.5%) observed tumor progression. There were 86 patients who achieved pathological downgrading, with a total downgrading rate of 53.8%. Among the 160 patients, 37 patients (23.1%) had postoperative complications of varying degrees. A total of 72 patients (45.0%) had tumor recurrence/progression at the end of follow-up. The last chemotherapy and surgery (CST) (OR = 1.046, 95% CI 1.013–1.081, p = 0.006), tumor invasion (OR = 32.096, 95% CI 5.091–202.349, p < 0.001), and distant metastasis (OR = 7.050, 95% CI 1.888–26.323, p = 0.004) were independent factors influencing the efficacy of conversion therapy. Conclusion: Conversion therapy may have a good therapeutic efficacy for AUGC, and some clinical factors affect the efficacy response. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of head and neck undifferentiated carcinoma (HNUC) present significant challenges. Herein, we present the case of a patient with advanced HNUC who underwent conversion surgery following treatment with a combination of pembrolizumab and nimotuzumab. During therapy, histological transformation from undifferentiated to sarcomatoid carcinoma was detected at the primary site. This case not only highlights the potential of immune combination-targeted therapy to reduce tumour burden and increase the surgical options for patients, but also reveals the complex alterations in tumour biology that may occur during treatment. It emphasizes the necessity for routine pathological assessments throughout the therapeutic regimen to guide personalised therapeutic strategies and optimise patient prognoses. [ABSTRACT FROM AUTHOR]

Despite the growing recognition of their harmful effects, sexual orientation change efforts (SOCE) continue to be practiced in various societies. This study examines the experiences of 11 sexual minority individuals in Hong Kong who have undergone SOCE. The findings reveal the pervasive influence of deeply ingrained homonegativity values within religious, family, educational, and soiocultural contexts during LGBTQ+ individuals' formative years. These prevailing stigmas compelled them to pursue SOCE through different methods. However, these methods have been proven ineffective and psychologically harmful, leading to increased distress and internalized homonegativity. The availability of knowledge and access to affirming LGBTQ+ values within religious, community, and sociocultural spheres played a crucial role in helping the respondents come to accept their sexual orientation and cease their attempts at SOCE. This study shed light on how the interplay of Chinese familial values and Christian doctrine in Hong Kong contributes to the promotion of homonegativity, consequently restricting the diverse expressions of sexuality. It is important to recognize that the notion of individuals actively "choosing" to undergo SOCE is misguided, as these decisions are often driven by social stigma and external pressures. Progress in this area requires confronting the systemic heteronormativity embedded within Hong Kong's cultural fabric. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is the best therapy for most patients with non-metastatic HCC. In recent years, the management of patients with HCC has considerably changed, thanks to the improvement of molecular biology knowledge and the introduction of immunotherapy. To date, systemic therapy is authorized in the Western world only in patients with advanced HCC. However, this therapy could not only stabilize the tumour disease or improve survival but could display excellent response and lead to downstaging of the tumour that finally permits LT. There are increasing reports of patients that have performed LT after pretreatment with immune checkpoint inhibitors (ICIs). However, due to the intrinsic mechanism of ICIs, graft rejection might be favoured. In addition, chronic adverse effects affecting other organs may also appear after the end of therapy. This review aims to evaluate the readiness and outcomes of LT in patients with advanced HCC who have previously undergone treatment with ICIs. It seeks to identify the challenges, risks, and benefits associated with this conversion therapy. The integration of ICIs into the treatment paradigm for advanced HCC necessitates a nuanced approach to LT. While early evidence supports the feasibility of LT following ICIs therapy, there is an urgent need for standardized guidelines and more extensive longitudinal studies to optimize patient selection, timing, and post-transplant management. [ABSTRACT FROM AUTHOR]

Traditional psychoanalytic approaches view excessive parental, social or relational involvement in human development as an opportunity for linking complex gender and identity experiences. The analyst's unconscious bias might present them with an opportunity for interpretation that might resemble something akin to conversion therapy. All of which leaves the patient feeling alienated thereby confirming their exiled Self. Early relational trauma affects every gender and sexual identity. In turn each traumatic situation, from inappropriate interference to traumatic abuse, affects how an individual forms and experiences relationships. Gender and sexual identity are fluid agencies of the Self within all human development. For people who are non‐normative when it comes to their gender, identity or sexuality, evidence of early relational trauma should not unthinkingly be treated alongside mental health struggles. This clinical paper explores the once‐weekly analytic work with a young trans man who was exiled and lived in a dysregulated state of mind from his early relational trauma. This paper uses images from the artist Louise Bourgeois to explore the early development of projective identification and to propose that this becomes a way of exiling unwanted feelings into the Other with the hope of finding a place of belonging as if through a psychic umbilical. [ABSTRACT FROM AUTHOR]

Background: Intraoperative conversion to open surgery is an adverse event during minimally invasive distal pancreatectomy (MIDP), associated with poor postoperative outcomes. The aim of this study was to develop a model capable of predicting conversion in patients undergoing MIDP. Methods: A total of 352 patients who underwent MIPD were included in this retrospective analysis and randomly assigned to training and validation cohorts. Potential risk factors related to open conversion were identified through a literature review, and data on these factors in our cohort was collected accordingly. In the training cohort, multivariate logistic regression analysis was performed to adjust the impact of confounding factors to identify independent risk factors for model building. The constructed model was evaluated using the receiver operating characteristics curve, decision curve analysis (DCA), and calibration curves. Results: Following an extensive literature review, a total of ten preoperative risk factors were identified, including sex, BMI, albumin, smoker, size of lesion, tumor close to major vessels, type of pancreatic resection, surgical approach, MIDP experience, and suspicion of malignancy. Multivariate analysis revealed that sex, tumor close to major vessels, suspicion of malignancy, type of pancreatic resection (subtotal pancreatectomy or left pancreatectomy), and MIDP experience persisted as significant predictors for conversion to open surgery during MIDP. The constructed model offered superior discrimination ability compared to the existing model (area under the curve, training cohort: 0.921 vs. 0.757, P < 0.001; validation cohort: 0.834 vs. 0.716, P = 0.018). The DCA and the calibration curves revealed the clinical usefulness of the nomogram and a good consistency between the predicted and observed values. Conclusion: The evidence-based prediction model developed in this study outperformed the previous model in predicting conversions of MIDP. This model could contribute to decision-making processes surrounding the selection of surgical approaches and facilitate patient counseling on the conversion risk of MIDP. [ABSTRACT FROM AUTHOR]

The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n = 104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n = 51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥ 10, the largest size ≥ 50 mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment. [ABSTRACT FROM AUTHOR]

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Introduction: Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5–15.3 months with a 39.1–42.5% tumor response rate. In comparison, ICIs have a 12–14 month OS rate with a 26–33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. Methods: We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. Results: Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B versus A (HR = 2.21, p = 0.041), BCLC stage C versus B (HR = 4.38, p = 0.011), and elevated alpha-fetoprotein levels (HR = 5.02, p < 0.001). Positive responders saw substantial survival benefits (HR = 0.26, p = 0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p = 0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. Conclusion: Conversion therapy with curative intent following HAIC or ICIs might enhance survival in patients with advanced or TACE-unsuitable intermediate-stage HCC. [ABSTRACT FROM AUTHOR]

Some special therapeutic responses may appear during immunotherapy, such as hyperprogression, pseudoprogression and so on. Dissociated response of immunotherapy has been clinically reported in recent years mainly in lung cancer and kidney cancer. Since there were poor prognosis and simple treatment of advanced head and neck cancer, the application of immunotherapy in head and neck cancer has risen in recent years. But the dissociated response of immunotherapy in head and neck cancer is rarely reported. We reported two series of cases of advanced head and neck cancer that showed dissociated response after immunotherapy, tumor progression was assessed by imaging methods such as PET-CT, enhanced CT and enhanced MR, and reviewed the literature related to dissociated response in immunotherapy. We propose that the dissociated response of immunotherapy may affect the treatment strategy of advanced head and neck cancer, but more clinical analyses and researches are needed to confirm it. [ABSTRACT FROM AUTHOR]

Aim: The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods: A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results: A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions: With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration: This was a retrospective study and it did not interfere with treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of This study is exploring the intraoperative and perioperative differences between patients undergoing conversion surgery and those undergoing direct surgery, so as to improve preoperative preparation. Methods: The retrospective study was approved by an ethics review committee. A total of 232 patients with hepatocellular carcinoma who underwent surgical resection at the First Affiliated Hospital of Chongqing Medical University from September 2022 to December 2023 were included, comprising 210 operating patients and 53 conversion patients. Propensity score matching was employed for comparison in order to minimize bias. Results: The conversion group had more intraoperative bleeding (each P=0.001), longer operation time (P=0.033; PSM p=0.025), and higher intraoperative blood transfusion rate (p=0.001; PSM p=0.044). The incidence of perioperative complications, including perioperative ascites formation (p=0.011; PSM p=0.005), moderate to severe anemia (p=0.001; PSM p=0.002), postoperative blood transfusion (p=0.004; PSM p=0.036), and postoperative ICU transfer (p=0.041; PSM p=0.025), was higher in the conversion group compared to the operation group. The postoperative hospital stay (p=0.001; PSM p=0.003) was prolonged in the conversion group. Conclusion: Post-conversion operations carry a higher risk of bleeding and are more likely to result in moderate to severe anemia and ascites formation in the perioperative period. However, the risk is reversible with adequate preoperative blood preparation and prompt postoperative symptomatic treatment. Conversion patients should be encouraged to undergo operating therapy when they can withstand surgical resection. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics. Methods: We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group. Conclusion: Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care. [ABSTRACT FROM AUTHOR]

Abstract Aim The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy. Methods A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed. Results A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively. Conclusions With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery. Trial registration This was a retrospective study and it did not interfere with treatment decisions.

Ruyu Han,1,&ast; Leijuan Gan,1,&ast; Liyu Sun,1 Mengran Lang,2 Xindi Tian,1 Kangwei Zhu,1 Lu Chen,1 Guangtao Li,1 Tianqiang Song1 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 2Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-22-23340123, Fax +86-22-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data.Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently.Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.Keywords: hepatocellular carcinoma, conversion therapy, recurrence-free survival, hepatic resection

Zhong-Tai Lin,1,2,&ast; Shao-Ming Wei,1,3,&ast; Jun-Yi Wu,1,3,&ast; Zhi-Bo Zhang,4 Shuang-Jia Wang,5 Jian-Yin Zhou,6 Meng-Chao Luo,1,3 Zhen-Xin Zeng,1 Xiang-Ye Ou,1 Yang-Kai Fu,1 Han Li,1 De-Yi Liu,1 Jia-Yi Wu,1,3 Mao-Lin Yan1,3 1The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 0591-88217140, Fax +86 0591-87557768, Email tyhjwjy@163.com; yanmaolin74@163.comBackground: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229– 1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119– 1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092– 0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079– 0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373– 4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147– 372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.Keywords: unresectable, hepatocellular carcinoma, conversion therapy, adjuvant therapy, recurrence-free survival, overall survival

Abstract 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. Trial registration International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Abstract 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.

The weak evidence base and profound consequences of gender-affirming interventions for youth call for a particularly sensitive and complex psychoanalytic exploration. However, prohibitions on knowing at the individual and social levels significantly constrain psychoanalytic work with trans-identified youth. Barriers to exploration and thinking that patients bring to treatment are reinforced and reified by the dominant socio-political trends that saturate the contexts in which young people dwell. These trends increasingly frame any attempt to deeply explore why a young person is seeking medical or surgical gender-affirming interventions as “off-limits” and a form of conversion therapy. Furthermore, politically driven clinicians who promote medical gender-affirming interventions misrepresent and attempt to discredit clinicians who explore the meaning and function of trans identification, or who express concern that transitioning may be a drastic solution to various forms of psychic pain. In doing so, they minimise the significance of the weak evidence base for these interventions and their serious, known risks. At the same time, they obscure or deny the psychic pain that is sometimes humming beneath the experience of gender dysphoria. The author asks: If there are significant uncertainties and risks of harm associated with medical interventions for young people, do we want to know? [ABSTRACT FROM AUTHOR]

With the development of comprehensive treatment, locoregional transarterial chemotherapy has become an alternative conversion therapy, palliative therapy, and neoadjuvant therapy for many solid malignant tumors. Locoregional transarterial chemotherapy, which is most frequently used for treating liver cancer, has the characteristics of high regional efficacy and few systemic adverse reactions. In recent years, the number of relevant reports of locoregional chemotherapy for treating initially inoperable colorectal cancer (CRC), including non-metastatic and metastatic CRC, has gradually increased. However, the specific treatment options for such locoregional therapy are not the same, and its indications, medication regimens and combined treatments have not reached any consensus. In this review, the application status of locoregional transarterial chemotherapy in primary and metastatic CRC patients has been reviewed and summarized to provide a reference for future clinical work and scientific research. [ABSTRACT FROM AUTHOR]

"I Spoke to You with Silence: Essays from Queer Mormons of Marginalized Genders" is a collection of essays edited by Kerry Spencer Pray and Jenn Lee Smith that delves into the experiences of queer Mormons navigating their identities within the Church. The essays cover themes of self-discovery, relationships, shame, suicide, and the challenges of living authentically within a heteronormative religious environment. The authors share their vulnerabilities, pain, and resilience, highlighting the complexities and contradictions of queer Mormon lives. The anthology calls for introspection and allyship from both LGBTQIA+ individuals and Mormon communities to create spaces of acceptance and celebration for all identities. [Extracted from the article]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. Due to the lack of typical clinical manifestations in the early stage, most patients in China are in the advanced stage at the time of confirmed diagnosis and thus lose the opportunity for surgical resection, which leads to a poor prognosis. Therefore, it is necessary to explore related therapies for converting unresectable HCC into resectable HCC. In recent years, the improvement in local therapy such as transarterial interventional therapies and radiation therapy technology, together with the clinical application of new targeted therapies and immune checkpoint inhibitors, has brought new opportunities and challenges in the conversion therapy for advanced HCC, and local therapy combined with systemic therapy may have a good synergistic effect, improve the conversion rate of surgery. This article investigates the value of local therapy combined with systemic therapy in the conversion therapy for HCC, in order to provide a basis for the clinical treatment of unresectable HCC. [ABSTRACT FROM AUTHOR]

Due to the insidious onset and poor prognosis of primary liver cancer, most patients are found to have unresectable primary liver cancer at initial diagnosis. In recent years, with the advent of targeted therapy, immunotherapy, and local therapy, some patients with advanced liver cancer have achieved successful conversion and undergone radical surgical resection, but at the same time, such treatment has brought many issues, such as the identification of potential population for conversion, the selection of conversion regimen, the necessity and timing of surgical resection after conversion, and the necessity and duration of adjuvant therapy after conversion surgery. This article discusses the above problems in conversion therapy for liver cancer based on the author’s own experience. [ABSTRACT FROM AUTHOR]

Simple Summary: Potential curative options for hepatocellular carcinoma include liver transplant, surgical resection, and ablation. Unfortunately, only 15–30% of patients are eligible for curative options at the time of presentation. Therefore, it is crucial to explore and evaluate treatment methods than can potentially convert nonsurgical candidates into surgical candidates. One such treatment option that can be used as a conversion strategy is yttrium-90 radioembolization. This study examines the success rate of using boosted dose radiation segmentectomy to convert nonsurgical candidates into eligible candidates for transplant or surgical resection. Background/Objectives: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). Methods: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Results: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child–Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. Conclusions: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection. [ABSTRACT FROM AUTHOR]

This review essay is prompted by Rustam Alexander's monograph Gay Lives and 'Aversion Therapy' in Brezhnev's Russia, 1964–1982 , which explores the under-researched history of gay lives and conversion therapy practices in the USSR. The essay critically interrogates the discourse surrounding Soviet repressive psychiatry (karatel'naiia psikhiatriia), highlighting its exclusionary narrative toward LGBTIQ+ individuals. Drawing on Alexander's exploration of the conversion therapy practice of the Soviet psychiatrist Yan Goland, who employed suggestive methods to attempt to alter sexual orientation, the article places Goland's practice within broader Soviet medical history and post-Soviet political psychiatry. The essay further underscores the relevance of this history in contemporary Russia, where LGBTIQ+ individuals continue to face medicalization and repression, echoing past practices. It concludes by calling for the incorporation of queer and critical psychiatry perspectives into the discourse on psychiatric abuse in Russia. [ABSTRACT FROM AUTHOR]

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients. Plain Language Summary: The combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels. [ABSTRACT FROM AUTHOR]

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. Trial registration: International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289). [ABSTRACT FROM AUTHOR]

Despite empirical evidence documenting its harms and substantial legislative efforts to ban its practice, conversion therapy remains a tragically prevalent practice in the United States. Recently, a circuit split between the Ninth and Eleventh Circuits has developed, raising questions about the future of conversion therapy regulation. This Note takes a retrospective look at the last ten years of conversion therapy bans and related legal challenges, questions the effectiveness of enacted bans, and explores routes for more effective regulation. This Note ultimately argues that conversion therapy bans must shift their focus to the regulation of unlicensed practitioners in order to better protect minors from the empirically demonstrated harms of conversion therapy. [ABSTRACT FROM AUTHOR]

Aim: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. Methods: Ninety‐five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non‐simple nodular (non‐SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. Results: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non‐SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non‐SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non‐SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non‐SN lesions underwent sequential local therapy. Conclusions: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non‐SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non‐SN lesions. [ABSTRACT FROM AUTHOR]

Background This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies. Methods The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT. Results Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P  = .370 and.334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS. Conclusions For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT. [ABSTRACT FROM AUTHOR]

Peritoneal metastasis in gastric cancer has a poor prognosis and is increasing in prevalence. Neoadjuvant chemotherapy is used for advanced tumors; however, surgery is generally not considered for metastatic and unresectable diseases. Recently, conversion surgery, a treatment which aims for an R0 resection following chemotherapy, has become a novel therapeutic option with better survival rates. In addition to surgery, hyperthermic intraperitoneal chemotherapy (HIPEC) leads to significant tumor reduction, but it is limited by its morbidity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) delivers high concentrations of chemotherapy, but does not remove the tumor, making it useful mostly in palliative settings. Intraperitoneal (IP) therapy, known for its minimally invasive nature and repeatability, shows promise but requires further research. Ultimately, an integrated approach involving systemic chemotherapy, radical gastrectomy, HIPEC, PIPAC and IP chemotherapy can be used to optimize treatment outcomes of gastric cancer patients with peritoneal metastasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Method: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The literature on reparative justice focuses for the most part on the grounds and limits of wrongdoers' duties to their victims. An interesting but relatively neglected question is that of what – if anything – victims owe to wrongdoers. In this paper, I argue that victims are under a duty to accept wrongdoers' apologies. I claim that to accept an apology is to form the belief that the wrongdoer's apologetic utterance or gesture has the requisite verdictive, commissive and expressive dimensions; to communicate as much to him; and to recognise that his apology changes one's normative status in relation to him, and to comport oneself accordingly. I then offer a Kantian argument for the duty to accept and qualify that argument in the light of some hard cases. I end the paper by addressing the objection that victims do not owe it to wrongdoers to engage in any form of reparative encounter. [ABSTRACT FROM AUTHOR]

This article addresses the U.S. Supreme Court’s embrace, in 303 Creative LLC v. Elenis, of a First Amendment objection to state public accommodations laws that the Court avoided in Masterpiece Cakeshop v. Colorado Civil Rights Commission: such laws compel governmental orthodoxy. These objections invoke West Virginia Board of Education v. Barnette’s celebrated language: “If there is any fixed star in our constitutional constellation, it is that no official, high or petty, can prescribe what shall be orthodox in politics, nationalism, religion or other matters of opinion or force citizens to confess by word or act their faith therein.” They also cite Barnette’s progeny, including Wooley v. Maynard and Hurley v. Irish-American Gay, Lesbian and Bisexual Group of Boston. Business owners, their lawyers, and judges who have invoked these cases argue that state public accommodations laws requiring that businesses not discriminate based on sexual orientation in providing goods and services compel both speech and silence. In 303 Creative, Justice Gorsuch’s majority (6- 3) opinion quotes the beginning of Barnette’s “fixed star” passage but adapts it: the fixed star becomes “the principle that the government may not interfere with ‘an uninhibited marketplace of ideas.’” Gorsuch moves from the public school room—in which a state law compelled Jehovah’s Witness children to salute the flag, despite their religious beliefs—to the commercial marketplace, but gives little guidance about how broadly the protection of creative expression in this “marketplace of ideas” will extend. While Justice Gorsuch situates the Court’s protection of website designer Lorie Smith against compelled speech— and orthodoxy—in the commercial marketplace as the latest in a series of courageous First Amendment decisions by the Court protecting individuals against an encroaching state, Justice Sotomayor’s dissent excoriates the majority for departing from the long history of the Court courageously defending citizenship-expanding antidiscrimination laws against backlash and repeated First Amendment challenges. This article argues that 303 Creative’s use of Barnette extracts it from its wartime, antitotalitarian context, ignores crucial distinctions drawn in Barnette, and (as Justice Sotomayor’s 303 Creative dissent warns) “‘trivializes the freedom protected in Barnette,’” while also undermining public accommodations laws. The article also considers the recent invocation of Barnette and its progeny to challenge other forms of governmental regulation, including state regulation of crisis pregnancy centers and state bans on conversion therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This is a mixed methods international survey of therapists (n = 89) belonging to Therapy First, an organization supporting the use of exploratory therapy, rather than gender affirmative therapy, with gender-questioning clients. The method used was an electronic questionnaire, producing a 33% response rate from members. Responses were analyzed using thematic analysis. This article reports qualitative responses relating to therapists' experiences of anxiety in working in a hostile professional environment, and their adoption of strategies to minimize risk of allegations of conversion therapy. Therapist strategies included refining existing marketing approaches to serve preferred client groups, and reliance on proven therapy models. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced‐stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post‐surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced‐stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field. [ABSTRACT FROM AUTHOR]

This case study details an innovative conversion therapy strategy in a 58-year-old Asian male with baseline stage cT4N1M1b advanced lung squamous cell carcinoma (SCC) harboring a rare EGFR exon 20 insertion mutation with concurrent high PD-L1 expression who achieved a pathologic complete response (pCR) after preoperative immunotherapy plus chemotherapy. The patient initially presented with coughing and bloody sputum and was comprehensively diagnosed via PET/CT scanning, bronchoscopic biopsy and next-generation sequencing. After four cycles of platinum‒paclitaxel chemotherapy plus immunotherapy with pembrolizumab (a PD-1 blockade), significant primary tumor shrinkage and the disappearance of oligometastasis in the right adrenal gland were discovered via CT scans. The subsequent salvage lung surgery resulted in a pCR, and the patient continued postoperative maintenance immunotherapy. No evidence of disease relapse or immune-related adverse events occurred after a post-surgery follow-up time of 9.4 months. This case highlights the potential value and challenges of immunotherapy plus chemotherapy as conversion therapy strategy in treating patients with non-small cell lung cancer (NSCLC) harboring rare EGFR exon 20 insertions.

BackgroundHepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen has demonstrated efficacy in patients with unresectable hepatocellular carcinoma (HCC). The combined targeted and immunotherapy has emerged as a first-line treatment for liver cancer. In this study, we investigated the clinical efficacy and safety of FOLFOX-HAIC in combination with targeted immunotherapy in patients with untreated, unresectable HCC.Materials and methodsData were collected from patients with initially unresectable HCC treated at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, from June 2022 to June 2023. Tumor response and survival outcomes were assessed following the FOLFOX-HAIC combined with targeted immunotherapy, The safety was also evaluated through the incidence of related adverse events.ResultsA total of 51 eligible patients were recruited. The objective response rate (ORR) based on mRECIST and RECIST 1.1 criteria were 60.8% and 45.1%, respectively. The surgical conversion rate was 25.5%. The median progression-free survival (PFS) was 15.2 months. The 1-year overall survival rate was 88.2%. Adverse events were observed in 98% patients, with 23.5% experiencing grade 3 or 4 adverse events.ConclusionThe FOLFOX-HAIC combined with targeted immunotherapy regimen is effective in patients with unresectable HCC, demonstrated by a high surgical conversion rate and manageable adverse effects. This regimen represents a potential novel first-line treatment option for HCC.

BackgroundGastric cancer (GC) is one of the leading causes of cancer-related death in China, and with the extensive development of conversion therapy, the treatment of advanced unresectable gastric cancer (AUGC) patients has ushered in a new dawn. This study aimed to analyze the efficacy of conversion therapy in AUGC patients and explored the relevant factors affecting the efficacy.MethodWe collected information from GC patients who received conversion therapy from this center and designed a retrospective study.ResultsWe collected relevant clinical data from 160 patients with AUGC. A total of 120 patients who underwent routine R0 resection were identified as conversion cases. A total of 25 patients (15.6%) achieved pCR, 92 patients (57.5%) achieved objective response rate (ORR), 140 patients (87.5%) achieved disease control rate (DCR), and 20 cases (12.5%) observed tumor progression. There were 86 patients who achieved pathological downgrading, with a total downgrading rate of 53.8%. Among the 160 patients, 37 patients (23.1%) had postoperative complications of varying degrees. A total of 72 patients (45.0%) had tumor recurrence/progression at the end of follow-up. The last chemotherapy and surgery (CST) (OR = 1.046, 95% CI 1.013–1.081, p = 0.006), tumor invasion (OR = 32.096, 95% CI 5.091–202.349, p < 0.001), and distant metastasis (OR = 7.050, 95% CI 1.888–26.323, p = 0.004) were independent factors influencing the efficacy of conversion therapy.ConclusionConversion therapy may have a good therapeutic efficacy for AUGC, and some clinical factors affect the efficacy response.