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Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread. [ABSTRACT FROM AUTHOR]

Simple Summary: The response to neoadjuvant treatment in rectal cancer varies among patients, while the evidence of benefit from additional adjuvant chemotherapy, especially in patients with persistent tumor and/or lymph node metastases, is unclear. In our cohort study of 1778 patients, we showed that persistent tumor and/or lymph node metastasis after intensified neoadjuvant treatment, e.g., total neoadjuvant treatment (TNT), was not more strongly associated with an extensive risk of treatment failure (TF, local recurrence and/or distant metastasis) than after less intensive neoadjuvant treatment, e.g., 5-flurouracil-based chemoradiotherapy (5-FU CRT). These results may help clinicians to individualize their surveillance strategies, but do not provide an argument for adding additional chemotherapy in non-responders after TNT. Objectives: Additional adjuvant treatment in patients with rectal cancer with limited response to neoadjuvant treatment to mitigate their higher risk of treatment failure remains controversial. Methods: This is a post hoc analysis of a cohort study of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trial) that included 1948 patients with locally advanced rectal adenocarcinoma. After excluding patients with missing information, 1788 patients (1254 men and 524 women; median age: 62.6 years, age range: 19–84 years) were eligible. We analyzed the extent of tumor response and its association with the incidence of treatment failure after different neoadjuvant treatment approaches. Results: Tumor response was significantly enhanced with more intensive neoadjuvant treatment. After a median follow-up of 55 months for the entire cohort (IQR: 37 months–62 months), the incidence of treatment failure (TF) stratified by tumor response or post-neoadjuvant pathological outcome was not significantly affected by the intensity of neoadjuvant treatment, whereas the ypTNM stage was significantly associated with the risk of treatment failure. Conclusions: In this cohort study, we provide evidence that limited or no response to intensified neoadjuvant treatment protocols is not likely to be more strongly associated with an extensive risk of TF after 5-FU CRT+/− adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Immunotherapy has revolutionised the treatment of advanced hepatocellular carcinoma (HCC). In addition, several phase III trials of immunotherapy in combination with surgical or locoregional therapies for early-to intermediate-stage HCC have recently reported positive results, and other phase III trials in the same patient population are currently in progress. As the application of immunotherapy is shifting to include patients with earlier stages of HCC, one looming question now emerges: What is the role of immunotherapy in the pre-liver transplant population? Liver transplantation is a potentially curative therapy for HCC and confers the additional advantage of restoring a normal, healthy liver. In pre-transplant patients, immunotherapy may improve downstaging success and tumour control at the cost of some immunologic risks. These include immune-related toxicities, which are particularly relevant in a uniquely vulnerable population with chronic liver disease, and the possibility of acute rejection after transplantation. Ultimately, the goal of immunotherapy in this population will be to effectively expand access to liver transplantation while preserving pre- and post-transplant outcomes. In this review, we discuss the mechanisms supporting combination immunotherapy, summarise key recent clinical data from major immunotherapy trials, and explore how immunotherapy can be applied in the neoadjuvant setting prior to liver transplantation in selected high-risk patients. [ABSTRACT FROM AUTHOR]

Opinion Statement: Liver transplantation for hepatocellular carcinoma (HCC) remains an evolving field. Major challenges HCC transplant patients face today include liver organ donor shortages and the need for both better pre-transplant bridging/downstaging therapies and post-transplant HCC recurrence treatment options. The advent of immunotherapy and the demonstrated efficacy of immune checkpoint inhibitors in multiple solid tumors including advanced/unresectable HCC hold promise in expanding both the neoadjuvant and adjuvant HCC transplant treatment regimen, though caution is needed with these immune modulating agents leading up to and following transplant. New options for pre-transplant HCC management will expand access to this curative option as well as ensure patients have adequate control of their HCC prior to transplant to maximize the utility of a liver donor. Machine perfusion has been an active area of investigation in recent years and could expand the organ donor pool, helping address current liver donor shortages. Finally, additional HCC biomarkers such as AFP-L3 and DCP have shown promise in improving risk stratification of HCC patients. Together, these three recent advancements will likely alter HCC transplant guidelines in the coming years. [ABSTRACT FROM AUTHOR]

Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out ‘inclusion criteria’ and defining ‘successful downstaging.’ Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level

Improvements in downstaging therapies have expanded the indications for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients with more advanced disease are now considered candidates due to advancements in radiation therapy, combination therapies, and immunotherapy. Combination stereotactic body radiation therapy (SBRT) and trans-arterial chemoembolization (TACE) has been shown to be superior to the historic treatment, sorafenib, in patients with macrovascular invasion. These patients are now candidates for LT with stable disease after LRT. Patients with ruptured HCC and prolonged stability have also been shown to have acceptable outcomes. The role of neoadjuvant immunotherapy needs to be further defined and has the potential to further improve tumor control prior to transplant.

Improvements in downstaging therapies have expanded the indications for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients with more advanced disease are now considered candidates due to advancements in radiation therapy, combination therapies, and immunotherapy. Combination stereotactic body radiation therapy (SBRT) and trans-arterial chemoembolization (TACE) has been shown to be superior to the historic treatment, sorafenib, in patients with macrovascular invasion. These patients are now candidates for LT with stable disease after LRT. Patients with ruptured HCC and prolonged stability have also been shown to have acceptable outcomes. The role of neoadjuvant immunotherapy needs to be further defined and has the potential to further improve tumor control prior to transplant. [ABSTRACT FROM AUTHOR]

Background: The 9th edition of the lung cancer tumor‐node‐metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. Methods: Stage II non‐small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan–Meier analysis with log‐rank testing compared overall survival (OS) and cancer‐specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)‐based Cox analyses identified prognostic factors. Results: Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p < 0.001; CSS, p = 0.005). LASSO‐based Cox analyses confirmed stage IIA New patients had inferior prognosis compared to stage IIA patients (OS HR: 1 vs. 1.325, p < 0.001; CSS HR: 1 vs. 1.327, p < 0.001). Conclusions: The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging remains unverified in Caucasians. Caution is warranted in assessing the staging and prognosis of these individuals. Further validation of our findings is necessary. The downstaging of T1N1M0 patients from stage IIB to IIA in the 9th edition TNM staging requires validation in the Caucasian population. Utilizing data from the American SEER database, our study revealed that the prognosis of downstaged patients (stage IIA New) resembled that of stage IIB patients but was inferior to that of stage IIA patients. Herein, we proposed that further investigations are warranted to ascertain the optimal staging for the IIA New subgroup. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment—p: <0.001. However, the persistence of adenopathies was not related to the dose of irradiation (p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention—p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage—p: 0.002 and on the lymph node status evaluated during surgical intervention—p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality. [ABSTRACT FROM AUTHOR]

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.

Background: The role of neoadjuvant chemotherapy (NAC) in advanced sigmoid colon carcinoma remains to be further characterized. Rationale for NAC includes downstaging on final pathology and optimization of microscopically negative margins (R0 resection). We investigated rates of neoadjuvant chemotherapy use in advanced sigmoid colon cancer at academic cancer centers and assessed factors associated with likelihood of NAC administration. Methods: The National Cancer Database was queried from 2004 to 2017 for patients with clinical T3 or T4, N0-2, M0 sigmoid colon cancer who underwent surgical resection. Those with neoadjuvant radiation or metastatic disease were excluded. The outcomes of patients who did and did not receive neoadjuvant chemotherapy were evaluated for this retrospective cohort study. Results: There were 23,597 patients of whom 364 (1.5%) received NAC. More patients received NAC at academic (41%, P <.001) and high-volume centers (27%, P <.001). Patients with Medicare/Medicaid (39%) and private insurance (52%) were more likely to receive NAC (P <.001). There was a significantly higher rate of N2 to N1 downstaging in the NAC group. Propensity-score matching demonstrated comprehensive community cancer programs (CCCP) were less likely to provide NAC (OR 0.4; 95% CI 0.23, 0.70, P <.001). There was no difference in survival (P =.20), R0 resection (P =.090), or 30-day readmission rates (P =.30) in the NAC cohort compared to the non-NAC cohort. Conclusions: Access to centers offering multi-disciplinary care with NAC prior to surgical resection is important. This care was associated with academic and high-volume centers and private or government-sponsored insurance. There was no difference in survival between NAC and non-NAC cohort. [ABSTRACT FROM AUTHOR]

About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34‐year‐old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium‐90 resin microspheres was given. At three months post‐SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post‐surgery. This is the first case who underwent SIRT with yttrium‐90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future. [ABSTRACT FROM AUTHOR]

Purpose of Review: Liver transplantation remains the gold-standard treatment for cirrhotic patients with early stage, surgically unresectable hepatocellular carcinoma (HCC). In this review, we describe the current state of liver transplantation (LT) for HCC. Recent Findings: We review recent advances in expanded indications for LT, diagnostics with liquid biopsy and biomarkers, and the emerging role of immunotherapy in this patient population. Summary: Although the shortage of liver allografts necessitates a restrictive HCC selection policy, future advances in patient selection, liquid biopsy technologies and systemic therapies have the potential to improve access to liver transplantation even in patients with expanded indications, without compromising on post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background The 9th edition of the lung cancer tumor‐node‐metastasis (TNM) staging introduced adjustments, including the reclassification of T1N1M0 patients from stage IIB to IIA. This update used data mostly from Asian populations. However, the applicability of these adjustments to Caucasian patients remains uncertain. Methods Stage II non‐small cell lung cancer (NSCLC) patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. Kaplan–Meier analysis with log‐rank testing compared overall survival (OS) and cancer‐specific survival (CSS). Propensity score matching (PSM) balanced baseline characteristics. The least absolute shrinkage and selection operator (LASSO)‐based Cox analyses identified prognostic factors. Results Among 10,470 eligible stage II NSCLC patients (median age: 69 years; male: 53.1%), there were 2736 in stage IIA, 2112 in IIA New, and 5622 in IIB groups. Before PSM, survival outcomes of stage IIA New patients were similar to those of stage IIA patients but better than those of stage IIB. After PSM, stage IIA New and IIB patients showed similar survival rates (OS, p = 0.276; CSS, p = 0.565). Conversely, stage IIA New patients had worse outcomes than stage IIA patients (OS, p

Sequential regimens in patients with epidermal growth factor receptor (EGFR) mutation-positive non–small cell lung cancer (NSCLC) can overcome tyrosine kinase inhibitor (TKI) resistance and maximize clinical benefit. Patients with advanced NSCLC can achieve excellent tumor control after a period of EGFR-TKI treatment. Patients may benefit from additional local treatment, such as surgery or radiation therapy, once the tumor is under control. Here, we present a case of a patient with advanced oligometastatic NSCLC with EGFR mutations who achieved downstaging through sequential EGFR-TKI-based precision medicine allowing resection of residual disease. [ABSTRACT FROM AUTHOR]

Abstract Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. Graphical Abstract

Purpose: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. Methods: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. Results: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. Conclusion: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Reducing time between cancer screening, diagnosis, and initiation of treatment is best achieved when services are available in the same hospital. Yet, comprehensive cancer centers are typically unavailable in low- and middle-income countries (LMICs), where resources are limited and services scattered. This study explored the impact of establishing an in-house pathology laboratory at the largest public cancer hospital in Tanzania on the downstaging of cervical cancer. Methods: We examined clinical datasets of 8,322 cervical cancer patients treated at the Ocean Road Cancer Institute (ORCI). The first period included patients treated from 2002 to 2016, before establishment of the pathology laboratory at ORCI; the second period (post-pathology establishment) included data from 2017 to 2020. Logistic regression analysis evaluated the impact of the pathology laboratory on stage of cervical cancer diagnosis. Results: Patients treated during the post-pathology period were more likely to be clinically diagnosed at earlier disease stages compared to patients in the pre-pathology period (pre-pathology population diagnosed at early disease stage: 44.08%; post-pathology population diagnosed at early disease stage: 59.38%, p < 0.001). After adjustment for age, region of residence, and place of biopsy, regression results showed patients diagnosed during the post-pathology period had higher odds of early stage cervical cancer diagnosis than patients in the pre-pathology period (OR 1.35, 95% CI (1.16, 1.57), p < 0.001). Conclusions: Integrated and comprehensive cancer centers can overcome challenges in delivering expedited cervical cancer diagnosis and treatment. In-house pathology laboratories play an important role in facilitating timely diagnosis and rapid treatment of cervical and possibly other cancers in LMICs. [ABSTRACT FROM AUTHOR]

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. [ABSTRACT FROM AUTHOR]

Abstract Background Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. Methods Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. Results Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. Conclusions The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

Örs Péter Horváth,1 Szabolcs Bellyei,2 Éva Pozsgai,3,4 András Vereczkei1 1Department of Surgery, University of Pécs Clinical Center, Pécs, 7624, Hungary; 2Department of Oncotherapy, University of Pécs Clinical Center, Pécs, 7624, Hungary; 3Department of Public Health, University of Pécs Medical School, Pécs, 7624, Hungary; 4Department of Primary Health Care, University of Pécs Medical School, Pécs, 7623, HungaryCorrespondence: Örs Péter Horváth, Department of Surgery, University of Pécs Clinical Center, Ifjúság Street 13, Pécs, 7624, Hungary, Tel +3672535806, Email horvath.ors.peter@pte.huAbstract: From a surgical point of view, the development of preoperative oncological treatment has had a profound effect on the surgical treatment trends of cancer as well as on the outcomes of cancer patients. Consequently, these changes have challenged formerly entrenched oncological surgical principles. In our short report, we aimed to summarize the main shifts regarding the surgical principles of cancer treatment due to the development of preoperative oncological therapy in recent years. As a result of successful preoperative treatment, surgeons may perform less radical surgeries, the required free resection margin has been narrowed down to a few millimeters in dimension and preoperative treatment is justified in both definitely resectable tumors and in oligometastatic tumors as well. For prognosis assessment, the post-preoperative oncological treatment stage is now considered decisive, rather than the pretreatment stage as previously thought. Other changes include the introduction of the watch and wait strategy and the reverse order of treatment of the primary tumor and metastasis. Observing the continuously improving outcomes of cancer patients and the developments in oncological treatment modalities, a further expansion of the indication of preoperative treatments is to be expected.Keywords: preoperative oncological therapy, neoadjuvant, downstaging, complete remission, surgical principles

Abstract Background The development of systemic chemotherapy including immune checkpoint inhibitors (ICIs) has provided patients with unresectable advanced non-small cell lung cancer (NSCLC) an opportunity to undergo surgical intervention after initial treatment. However, no consensus regarding the indication for salvage surgery in these patients has been reached. Methods We conducted a retrospective study of patients who underwent salvage surgery for advanced NSCLC (cStage IIIA–IVB) after treatment with ICIs from January 2018 to December 2022 at Aizu Medical Center and Fukushima Medical University Hospital. We evaluated the patients’ clinical data, calculated disease-free survival (DFS) and overall survival (OS), and assessed the survival benefit using the Kaplan–Meier method. Results Thirteen patients underwent salvage surgery after immunotherapy. All patients achieved downstaging after initial chemotherapy. Eleven patients underwent lobectomy, and one patient underwent extirpation of intra-abdominal lymph nodes. The mean surgery time and intraoperative blood loss were 242.2 min and 415.1 g, respectively. The mean drainage period was 4.2 days (range, 2–9 days). Grade ≥ 3 postoperative complications were confirmed in three patients. The 2-year DFS rate was 71.2%, and the 2-year OS rate was 76.2%. A pathological complete response compatible with ypStage 0 was achieved in four (30.8%) patients. Patients with ypStage 0 and I achieved significantly better OS than those with ypStage ≥ II (p = 0.044), and patients without severe complications achieved significantly better DFS and OS than those with severe complications (p = 0.001 and p

Simple Summary: This research aimed to compare the outcomes of primary liver transplantation (PLT) and salvage liver transplantation (SLT) for hepatocellular carcinoma (HCC). The aim was to determine which approach offers better oncological outcomes and whether SLT after previous curative treatments such as liver resection (LR) or radiofrequency ablation (RFA) is as effective as PLT. Data analyzed from 141 patients who underwent liver transplantation for HCC found that PLT resulted in significantly longer disease-free survival, overall survival, and cancer-specific survival (CSS) compared to SLT. However, within the SLT group, there was no significant difference in DFS between SLT-LR and SLT-RFA. These findings suggest that PLT may provide superior long-term oncological outcomes, and a shift towards PLT rather than SLT may be worth considering. Further research is needed to confirm these results, but this study provides valuable insights for the research community regarding optimal transplantation strategies for HCC patients. Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered. [ABSTRACT FROM AUTHOR]

Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article. [ABSTRACT FROM AUTHOR]

Background: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. Methods: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. Results: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. Conclusions: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cervical cancer is the fourth most frequent type of neoplasia in women. It is most commonly caused by the persistent infection with high-risk strands of human papillomavirus (hrHPV). Its incidence increases rapidly from age 25 when routine HPV screening starts and then decreases at the age of 45. This reflects both the diagnosis of prevalent cases at first-time screening and the likely peak of HPV exposure in early adulthood. For early stages, the treatment offers the possibility of fertility preservation.. However, in more advanced stages, the treatment is restricted to concomitant chemo-radiotherapy, combined, in very selected cases with surgical intervention. After the neoadjuvant treatment, an imagistic re-evaluation of the patients is carried out to analyze if the stage of the disease remained the same or suffered a downstaging. Lymph node downstaging following neoadjuvant treatment is regarded as an indubitable prognostic factor for predicting disease recurrence and survival in patients with advanced cervical cancer. This study aims to ascertain the important survival role of radiotherapy in the downstaging of the disease and of lymphadenectomy in the control of lymph node invasion for patients with advanced-stage cervical cancer. Material and Methods: We describe the outcome of patients with cervical cancer in stage IIIC1 FIGO treated at Bucharest Oncological Institute. All patients received radiotherapy and two-thirds received concomitant chemotherapy. A surgical intervention consisting of type C radical hysterectomy with radical pelvic lymphadenectomy was performed six to eight weeks after the end of the neoadjuvant treatment. Results: The McNemar test demonstrated the regression of lymphadenopathies after neoadjuvant treatment—p: p: 0.61), the number of sessions of radiotherapy (p: 0.80), or the chemotherapy (p: 0.44). Also, there were no significant differences between the adenopathies reported by imagistic methods and those identified during surgical intervention—p: 0.62. The overall survival evaluated using Kaplan-Meier curves is dependent on the post-radiotherapy FIGO stage—p: 0.002 and on the lymph node status evaluated during surgical intervention—p: 0.04. The risk factors associated with an increased risk of death were represented by a low preoperative hemoglobin level (p: 0.003) and by the advanced FIGO stage determined during surgical intervention (p-value: 0.006 for stage IIIA and 0.01 for stage IIIC1). In the multivariate Cox model, the independent predictor of survival was the preoperative hemoglobin level (p: 0.004, HR 0.535, CI: 0.347 to 0.823). Out of a total of 33 patients with neoadjuvant treatment, 22 survived until the end of the study, all 33 responded to the treatment in varying degrees, but in 3 of them, tumor cells were found in the lymph nodes during the intraoperative histopathological examination. Conclusions: For advanced cervical cancer patients, radical surgery after neoadjuvant treatment may be associated with a better survival rate. Further research is needed to identify all the causes that lead to the persistence of adenopathies in certain patients, to decrease the FIGO stage after surgical intervention, and, therefore, to lower the risk of death. Also, it is mandatory to correctly evaluate and treat the anemia, as it seems to be an independent predictor factor for mortality.

Background: The development of systemic chemotherapy including immune checkpoint inhibitors (ICIs) has provided patients with unresectable advanced non-small cell lung cancer (NSCLC) an opportunity to undergo surgical intervention after initial treatment. However, no consensus regarding the indication for salvage surgery in these patients has been reached. Methods: We conducted a retrospective study of patients who underwent salvage surgery for advanced NSCLC (cStage IIIA–IVB) after treatment with ICIs from January 2018 to December 2022 at Aizu Medical Center and Fukushima Medical University Hospital. We evaluated the patients' clinical data, calculated disease-free survival (DFS) and overall survival (OS), and assessed the survival benefit using the Kaplan–Meier method. Results: Thirteen patients underwent salvage surgery after immunotherapy. All patients achieved downstaging after initial chemotherapy. Eleven patients underwent lobectomy, and one patient underwent extirpation of intra-abdominal lymph nodes. The mean surgery time and intraoperative blood loss were 242.2 min and 415.1 g, respectively. The mean drainage period was 4.2 days (range, 2–9 days). Grade ≥ 3 postoperative complications were confirmed in three patients. The 2-year DFS rate was 71.2%, and the 2-year OS rate was 76.2%. A pathological complete response compatible with ypStage 0 was achieved in four (30.8%) patients. Patients with ypStage 0 and I achieved significantly better OS than those with ypStage ≥ II (p = 0.044), and patients without severe complications achieved significantly better DFS and OS than those with severe complications (p = 0.001 and p < 0.001, respectively). Conclusions: Salvage surgery after chemotherapy including ICIs is a feasible and effective treatment option for patients with advanced NSCLC, especially those who acquire downstaging to pathological stage 0 or I. However, severe perioperative complications might affect patient survival. A prospective study is urgently needed to evaluate the efficacy of salvage surgery. [ABSTRACT FROM AUTHOR]

La resección quirúrgica se considera el tratamiento curativo por excelencia para los pacientes con tumores hepáticos primarios o metastásicos. Sin embargo, menos de 40% de ellos son candidatos a cirugía, ya sea por factores no modificables (comorbilidades, edad, disfunción hepática...), como por la invasión o proximidad del tumor a los principales pedículos vasculares, la falta de un futuro remanente hepático (FRH) adecuado para mantener una función hepática postoperatoria, o criterios de tamaño y numero tumoral. En estos últimos factores, la radioembolización hepática ha mostrado tener un papel como herramienta prequirúrgica, ya sea mediante la hipertrofia del FRH o mediante la reducción del tamaño tumoral que consigue disminuir la estadificación tumoral (término conocido como « downstaging »). A estos se suma un tercer factor, que es su capacidad de aplicar el test del tiempo, que permite identificar aquellos pacientes que presenten en un plazo corto de tiempo progresión de la enfermedad (tanto a nivel local como a distancia), evitándoles una cirugía innecesaria. En este trabajo se pretende hacer una revisión de la radioembolización como herramienta facilitadora de la cirugía hepática, tanto a través de la experiencia de nuestro centro como de la evidencia científica disponible. Surgical resection is considered the curative treatment par excellence for patients with primary or metastatic liver tumors. However, less than 40% of them are candidates for surgery, either due to non-modifiable factors (comorbidities, age, liver dysfunction...), or to the invasion or proximity of the tumor to the main vascular requirements, the lack of a future liver remnant (FLR) adequate to maintain postoperative liver function, or criteria of tumor size and number. In these last factors, hepatic radioembolization has been shown to play a role as a presurgical tool, either by hypertrophy of the FLR or by reducing tumor size that manages to reduce tumor staging (term known as "downstaging"). To these is added a third factor, which is its ability to apply the test of time, which makes it possible to identify those patients who present progression of the disease in a short period of time (both locally and at distance), avoiding a unnecessary surgery. This paper aims to review RE as a tool to facilitate liver surgery, both through the experience of our center and the available scientific evidence. [ABSTRACT FROM AUTHOR]

Introduction: Liver transplantation (LT) is potentially curative for patients with cirrhosis and hepatocellular carcinoma (HCC). However, this procedure is usually reserved for patients with early tumor stages or after successful downstaging with local regional therapies. In patients with locally advanced HCC, current guidelines recommend locoregional and palliative systemic therapies for tumor stages Barcelona Clinic Liver Cancer (BCLC) B and C, respectively. Case Report: In this article, we describe a 63-year-old male patient with locally advanced HCC (BCLC C) and hepatitis C-associated cirrhosis. Following systemic treatment with the immune checkpoint inhibitor atezolizumab and the anti-VEGF antibody bevacizumab, significant downstaging to a tumor stage within the Milan criteria was achieved after which LT was successfully performed. Conclusion: As more effective systemic therapies become available, LT and potential curative treatment could become feasible for selected patients with locally advanced HCC. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein 1 (PD-1) inhibitor is widely utilized in advanced-stage carcinomas including hepatocellular carcinoma (HCC), while its neoadjuvant application plus transarterial chemoembolization (TACE) in HCC remains unexplored. Thereby, the current study aimed to investigate the efficacy and safety of TACE plus PD-1 inhibitor as neoadjuvant therapy bridging to surgical resection in intermediate-stage HCC patients. Methods: Twenty intermediate-stage HCC (China Liver Cancer (CNLC) stage II) patients treated with neoadjuvant TACE plus PD-1 inhibitor (camrelizumab or sintilimab) bridging to surgery were consecutively enrolled. Results: The objective response rate (ORR) and disease control rate (DCR) to neoadjuvant therapy were 75.0% and 100.0%, respectively; meanwhile, alpha-fetoprotein (AFP) was decreased after the neoadjuvant therapy (P < 0.001). Moreover, 14 (70.0%) patients had successful downstaging (patients converted to CNLC stage I). Neither median disease-free survival (DFS) nor median overall survival (OS) was reached; additionally, the 1-year accumulating DFS rate was 86.6%; meanwhile, the 1-year and 2-year accumulating OS rates were 100.0% and 76.4%, separately. Moreover, patients with successful downstaging had a prolonged DFS (P = 0.014) compared to patients with failed downstaging; meanwhile, this trend was also observed in assessing accumulating OS (P = 0.067) (without statistical significance). Main adverse events included pain (50.0%), fever (25.0%), neutropenia (25.0%), nausea and vomiting (25.0%), fatigue (25.0%), peripheral neuropathy (20.0%), anemia (15.0%), thrombopenia (15.0%), diarrhea (15.0%), anorexia (15.0%), and rash (15.0%). Conclusion: Neoadjuvant TACE plus PD-1 inhibitor realizes a satisfying downstaging rate, acceptable survival profile, and tolerance in intermediate-stage HCC patients. [ABSTRACT FROM AUTHOR]

Background Deep regional hyperthermia might have an additional effect on radiotherapy in treating locally advanced rectal cancer (LARC). This study aimed to investigate the role of hyperthermia combined with modern preoperative concurrent chemoradiotherapy (CRT) for LARC.Methods and materials From 2012 to 2018, 152 consecutive patients with LARC treated with neoadjuvant chemoradiation were enrolled and analyzed retrospectively. Pelvic radiotherapy (45–50 Gy) was delivered as volumetric modulated arc therapy (VMAT), concurrently with capecitabine chemotherapy. Fifty patients received hyperthermia combined with CRT (HCRT group) twice a week. Treatment response and outcomes were compared between the two groups. Furthermore, the relationships between peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in response to hyperthermia were analyzed.Results Patients treated with hyperthermia had a significantly higher T-downstaging rate than those without hyperthermia (82.0 vs. 62.7%; p = .016). Hyperthermia was an independent favorable predictor of T-downstaging (odds ratio [OR] = 2.473; 95% confidence interval [CI] 1.050–5.826; p = .038). In the HCRT group, a pre-therapeutic elevated NLR (≥3) was associated with a higher T-downstaging rate (100.0 vs. 73.5%, p = .043). However, NLR was not associated with the T-downstaging rate in the CRT group. Five-year rates of locoregional recurrence-free survival (96.8 vs. 94.7%, p = .959), disease-free survival (DFS; 61.4 vs. 79.3%, p = .242), and overall survival (OS; 92.7 vs. 89.8%, p = .831) were not statistically different between the CRT and HCRT groups.Conclusions Hyperthermia can improve preoperative treatment response in LARC. Pretreatment NLR may be a predictive factor for hyperthermia.

Simple Summary: Response evaluation following neoadjuvant chemotherapy for gastric cancer has been widely debated. Following a full course of preoperative cycles, response evaluation can guide the vigor in delivering postoperative chemotherapy, indicate for whom a shift in regimen following a later relapse may be prudent, and be a tool for scientific use. In the everyday setting, the terms downsizing and downstaging are often used synonymously with response to treatment, but any abilities and limitations in this respect need to be proven. The aim of the present study was to investigate downsizing and downstaging as methods of response evaluation following NAC in gastric cancer. We evaluated whether the response mode translated into strata of long-term survival rates, a prerequisite for a useful method in a neoadjuvant setting. Background: The method of response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer has been widely debated. An essential prerequisite is the ability to stratify patients into subsets of different long-term survival rates based on the response mode. Histopathological measures of regression have their limitations, and interest resides in CT-based methods that can be used in everyday settings. Methods: We conducted a population-based study (2007–2016) on 171 consecutive patients with gastric adenocarcinoma who were receiving NAC. Two methods of response evaluation were investigated: a strict radiological procedure using RECIST (downsizing), and a composite radiological/pathological procedure comparing the initial radiological TNM stage to the pathological ypTNM stage (downstaging). Clinicopathological variables that could predict the response were searched for, and correlations between the response mode and long-term survival rates were assessed. Results: RECIST failed to identify half of the patients progressing to metastatic disease, and it was unable to assign patients to subsets with different long-term survival rates based on the response mode. However, the TNM stage response mode did achieve this objective. Following re-staging, 48% (78/164) were downstaged, 15% (25/164) had an unchanged stage, and 37% (61/164) were upstaged. A total of 9% (15/164) showed a histopathological complete response. The 5-year overall survival rate was 65.3% (95% CI 54.7–75.9%) for TNM downstaged cases, 40.0% (95% CI 20.8–59.2%) for stable disease, and 14.8% (95% CI 6.0–23.6%) for patients with TNM progression, p < 0.001. In a multivariable ordinal regression model, the Lauren classification and tumor site were the only significant determinants of the response mode. Conclusions: Downsizing, as a method for evaluating the response to NAC in gastric cancer, is discouraged. TNM re-staging by comparing the baseline radiological CT stage to the pathological stage following NAC is suggested as a useful method that may be used in everyday situations. [ABSTRACT FROM AUTHOR]

Simple Summary: The usefulness of transarterial radioembolization (TARE) as a treatment has been endorsed by different authors and recommended by a multidisciplinary working group in terms of its safety, efficacy and feasibility for the surgical resection of patients with borderline-resectable hepatocellular carcinoma (HCC). In contrast, in the field of liver transplant (LT), the role of TARE is under debate and there are still no clear and unified guidelines for its indication. Background: Transarterial radioembolization in HCC for LT as downstaging/bridging has been increasing in recent years but some indication criteria are still unclear. Methods: We conducted a systematic literature search of primary research publications conducted in PubMed, Scopus and ScienceDirect databases until November 2022. Relevant data about patient selection, HCC features and oncological outcomes after TARE for downstaging or bridging in LT were analyzed. Results: A total of 14 studies were included (7 downstaging, 3 bridging and 4 mixed downstaging and bridging). The proportion of whole liver TARE was between 0 and 1.6%. Multiple TARE interventions were necessary for 16.7% up to 28% of the patients. A total of 55 of 204 patients across all included studies undergoing TARE for downstaging were finally transplanted. The only RCT included presents a higher tumor response with the downstaging rate for LT of TARE than TACE (9/32 vs. 4/34, respectively). Grade 3 or 4 adverse effects rate were detected between 15 and 30% of patients. Conclusions: TARE is a safe therapeutic option with potential advantages in its capacity to necrotize and reduce the size of the HCC for downstaging or bridging in LT. [ABSTRACT FROM AUTHOR]

Introduction: Locoregional therapies are commonly used as bridging strategies to decrease the drop‐out of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The present paper aims to assess the outcomes of bridging therapies in patients with HCC considered for LT according to an intention‐to‐treat (ITT) survival analysis. Material and methods: Medline and Web of Science databases were searched for reports published before May 2021. Papers assessing adult patients with HCC considered for LT and reporting ITT survival outcomes were included. Two reviewers independently identified, extracted the data, and evaluated the papers according to Newcastle‐Ottawa criteria. Outcomes analyzed were: drop‐out rate; time on the waiting list; 1‐, 3‐, and 5‐year survival after LT and based on an ITT analysis. Results: The search identified 3106 records; six papers (1043 patients) met the inclusion criteria. Patients with HCC, listed for LT and submitted to bridging therapies presented a longer waiting time before LT (MD 3.77, 95% CI 2.07‐5.48) in comparison with the non‐interventional group. However, they presented a raised post LT after 1‐year (OR 2.00, 95% CI 1.18‐3.41), 3‐years (OR 1.47, 95% CI 1.01‐2.15), and 5‐years (OR 1.50, 95% CI 1.06‐2.13) survival. Conclusion: Patients submitted to bridging procedures, despite having a longer interval on the waiting list, presented better post‐LT survival outcomes. Bridging therapies for selected patients at low risk of post‐procedural complications and long expected intervals on the waiting list should be encouraged. However, further clinical trials should confirm the survival benefit of bridging therapies in patients with HCC listed for LT. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of two different therapies on oral lichen planus (OLP) treatment through the analysis of OLP symptoms and signs and to analyze the risk of side effects related to the adopted protocols. Methods: Thirty‐eight patients with OLP were selected according to van der Meij and van der Waal clinical and histopathological criteria. Through a randomized design, 19 patients received Tacrolimus 0.1% ointment (T group) and 19 an anti‐inflammatory mouthwash (M group) composed of calcium hydroxide 10%, hyaluronic acid 0.3%, umbelliferone, and oligomeric proanthocyanidins. The patients were examined on a regular basis for OLP symptoms, signs, and disease severity score changes over a 3‐month follow‐up period. Results: Both treatments were effective in the reduction of OLP signs and symptoms. However, at 3 months (T3), in comparison with the M group, T group patients showed significantly lower mean values of OLP signs (p = 0.035), symptoms (p = 0.045), and disease severity scores (p = 0.041). Moreover, the Spearman test showed that there was a significant correlation between OLP signs and symptoms at each follow‐up session in all patients. Conclusions: Both treatments demonstrated a significant approach to control OLP. However, tacrolimus determined a more effective improvement in OLP signs and symptoms compared to anti‐inflammatory mouthwash at 3‐month follow‐up. [ABSTRACT FROM AUTHOR]

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. Summary of Background Data: Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. Methods: Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006–2015]. Results: Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates (P = 0.05) but had similar incidence of positive CRM (P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. Conclusion: In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients having neoadjuvant systemic therapy (NAST) who have a positive (clipped) lymph node (CN) at presentation must have that CN removed to assess pathologic response at later surgery. Multiple techniques for localizing the CN have been described. We describe a novel ROLL‐based approach. Methods: Consecutive patients between 2018 and 2021, having NAST with biopsy proven positive lymph node(s), had a clip placed into the most abnormal node(s). At later surgery sentinel node and occult lesion localization (SNOLL) was performed with peritumoral radio‐isotope (99mTc‐Nanoscan) injected under ultrasound guidance. Planar and single photon emission computed tomography (SPECT–CT) images were used to identify sentinel nodes (SN) and the CN. If the CN was not a SN, then additional 99mTc‐Nanoscan was injected directly into the CN using ultrasound (ROLL). TAD was performed using a gamma probe and intra‐operative specimen radiographs to confirm excision of the CN. Results: Thirty‐eight patients underwent TAD. 20/38 CNs were SNs on SPECT‐CT. 17/38 CN were localized separately. 1/38 CN was not a SN and could not be identified on ultrasound. The remaining 37/38 (97.4%) of the CNs were removed intra‐operatively. Pathological complete response in the axilla was identified in 18/38 cases. The CN was the only positive node in 10/20 cases. In 18/20 cases the CN contained the largest tumour deposit. Conclusion: Combining SNOLL and ROLL techniques to identify the SNs and, if separate, the CN for TAD is very reliable and logistically robust, especially for units already performing peritumoral lymphoscintigraphy. [ABSTRACT FROM AUTHOR]

Simple Summary: Downstaging therapies provides a viable alternative approach for expanding the MC limits and selecting a subgroup of patients whose LT candidacy would otherwise be disregarded. However, data on downstaging are still controversial due to a variety of reasons, such as differences in LRT, the wide variability in waiting time before LT and, particularly, the lack of intention-to-treat (ITT) analyses. This article is a systematic review and intends to synthesise the existing evidence about the effectiveness of downstaging therapies, aiming to: (a) assess outcomes from ITT analysis of patients with liver cirrhosis and HCC beyond the listing criteria and selected for downstaging protocol, in comparison with HCC within the listing criteria; (b) evaluate outcomes of patients with liver cirrhosis HCC beyond the listing criteria successfully downstaged and transplanted versus those not transplanted. Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45–2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91–2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26–11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15–8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted. [ABSTRACT FROM AUTHOR]

Radical hepatectomy is the main treatment method to improve the prognosis of patients with intermediate and early-stage liver cancer. Most liver cancer patients in China are in the advanced stage at the initial diagnosis, losing the opportunity for surgical treatment. Therefore, it is essential to down-stage unresectable liver cancer to resectable liver cancer clinically, which is an important way to improve patients’ survival and a hotspot of current clinical research. In recent years, with the increase in effective treatment methods for liver cancer, the resection rate of conversion surgery for unresectable advanced liver cancer has been significantly improved, and a growing number of patients benefit from conversion therapy. This article mainly reviews the connotation of conversion therapy for liver cancer, the patient selection, the selection of conversion strategy, the timing of sequential operations, the scheme and safety, etc. [ABSTRACT FROM AUTHOR]

Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for curative therapy after successful downstaging. We aimed to identify the predictors of successful downstaging of unresectable HCC in patient by transarterial chemoembolization (TACE) outside MC. We performed a retrospective study on patients with unresectable HCC outside MC who received downstaging with TACE. Clinical and laboratory variables were recorded. We identified 101 patients with unresectable HCC who underwent initial TACE, who formed the derivation set of this study. Thirty patients who treated by TACE with the same selection criteria served as an external validation set. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging. Then we did the predictive model to predict the efficiency of TACE. Of the 101 patients in the study, 26 patients (25.7%) were successfully downstaging and 75 patients (74.3%) failed downstaging. Multivariate analysis of factors to predict successful downstaging of HCC outside MC the number of tumor (P = 0.01), portal vein tumor thrombosis (PVTT)(p < 0.01), the size of tumor (P = 0.02), hepatitis B surface antigen (HBsAg) (P = 0.01), α-fetoprotein (AFP) (P = 0.02) as significant predictors of successful downstaging. Then we constructed the predictive model. The area under the ROC curve (AUROC) of the predictive equation was 0.90 (95% confidence interval, 0.83–0.95). We found in our study that the number and size of tumors, PVTT, HBsAg, and AFP are good predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC. [ABSTRACT FROM AUTHOR]

As the third leading cause of cancer-related deaths worldwide, hepatocellular carcinoma (HCC) represents a significant global health challenge. This paper provides an introduction and comprehensive review of transarterial radioembolization (TARE) with Yttrium-90 (Y90), a widely performed transcatheter procedure for HCC patients who are not suitable candidates for surgery. TARE involves the targeted delivery of radioactive microspheres to liver tumors, offering a promising treatment option for managing HCC across various stages of the disease. By evaluating Y90 TARE outcomes across early, intermediate, and advanced stages of HCC, the review aims to present a thorough understanding of its efficacy and safety. Additionally, this paper highlights future research directions focusing on the potential of combination therapies with systemic and immunotherapies, as well as personalized treatments. The exploration of these innovative approaches aims to improve treatment outcomes, reduce adverse events, and provide new therapeutic opportunities for HCC patients. The review underscores the importance of ongoing research and clinical trials to optimize TARE further and integrate it into comprehensive HCC treatment paradigms., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and chronic liver disease (CLD) is limited by factors such as tumor size, number, portal venous or hepatic venous invasion and extrahepatic disease. Although previously established criteria, such as Milan or UCSF, have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes, there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation. Immune checkpoint inhibitors (ICI) such as atezolizumab, pembrolizumab, or nivolumab have given hope to this group of patients. We completed a comprehensive literature review using PubMed, Google Scholar, reference citation analysis, and CrossRef. The search utilized keywords such as 'liver transplant', 'HCC', 'hepatocellular carcinoma', 'immune checkpoint inhibitors', 'ICI', 'atezolizumab', and 'nivolumab'. Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT, with acceptable early outcomes comparable to other criteria. Adverse effects of ICI have also been reported during the perioperative period. In such cases, a 1.5-month interval between ICI therapy and LT has been suggested. Overall, the results of downstaging using combination immunotherapy were encouraging and promising. Early reports suggested a potential ray of hope for patients with CLD and advanced HCC, especially those with multifocal HCC or branch portal venous tumor thrombosis. However, prospective studies and further experience will reveal the optimal dosage, duration, and timing prior to LT and evaluate both short- and long-term outcomes in terms of rejection, infection, recurrence rates, and survival., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In the last decade, immunotherapy (IT) has revolutionized oncology and found indications in many cancers, including hepatocellular carcinoma (HCC). In HCC, IT has become the leading systemic therapy for advanced diseases. At the same time, it carries the promise of being a valuable therapy in other settings, including intermediate-stage and unresectable disease, as a downstaging or conversion modality. More controversial is the role of IT in relationship to liver transplantation (LT): on one side, it could be a helpful tool to control or downstage HCC before LT or to treat tumor recurrence after LT, while on the other, it carries the risk of graft rejection and graft loss. This review aims to cover these concerns in depth and unravel the current literature., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)