Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Boron neutron capture therapy for malignant melanoma： first clinical case report in China

A phase Ⅰ/Ⅱ clinical trial for treating malignant melanoma by boron neutron capture therapy（BNCT） was designed to evaluate whether the world＇s first in-hospital neutron irradiator（IHNI） was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography（PET/CT） scan, pathological analysis and gross examination, the patient showed a complete response to BNCT,indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals.

Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.

Immunotherapy of Malignant Tumors Using Antisense Anti-IGF-I Approach: Case of Glioblastoma

The review article describes the criteria established for methodology of antisense anti IGF-I therapy of malignant tumors, particularly of glioblastoma. The cancer patients, after classical therapy of surgery, radiotherapy and chemotherapy, have undergone the injection of genetically modified autologous malignant cells—transfected by IGF-I antisense/triple helix expression vectors. For all cancer patients supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients, the following common immune criteria for “anti IGF-I” strategy were admitted: 1) characteristics of cell “vaccines”—absence of IGF-I and expression of MHC-I in cloned transfected cells;2) the peripheral blood lymphocytes, PBL cells, removed after every of two successive vaccinations, demonstrate an increasing level of CD8+ and CD8+28+ molecules (with a switch from CD8+11b+ to CD8+11b-).

Effects of enteral nutrition intervention on immune and nutritional indexes of patients with gastric malignant cancer during postoperative chemotherapy

Objective The aim of this study was to investigate changes in nutritional status and related indexes in patients with Nutritional Risk Score(NRS)≥3 gastric cancer after nutritional support treatment.Methods A total of 50 patients with gastric cancer were divided into two groups according to the different nutritional support treatment they received during postoperative chemotherapy:immune-enhanced enteral nutrition group(n=25)and conventional enteral nutrition group(n=25).Changes in patient’body mass index(BMI),hemoglobin(HB),serum total protein(TP),serum albumin(ALB),and immune indexes(CD3+,CD4+/CD8+,CD3+/CD8+)were monitored before and after chemotherapy.At the same time,the incidence and classification of gastrointestinal adverse reactions after chemotherapy were assessed.Results Compared with the conventional enteral nutrition group,the nutritional and immune indexes in the immune-enhanced enteral nutrition group were significantly improved.After chemotherapy,the incidence of adverse reactions in the digestive tract was relatively lower and the grade was reduced.Conclusion Immune-enhanced enteral nutrition support can significantly improve the nutritional status of patients,improve immune function,increase the susceptibility of cancer patients to chemotherapy,reduce toxicity and adverse effects,and improve the quality of life of tumor patients compared with conventional enteral nutrition support.

Complex Target Volume Delineation and Treatment Planning in Radiotherapy for Malignant Pleural Mesothelioma (MPM)

Introduction: Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. Materials and Methods: CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178° - 182°, the collimator angles of each arc were set to 90°, Octavius® 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. Results: A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. Conclusion: Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.

In vitro 3D malignant melanoma model for the evaluation of hypericin-loaded oil-in-water microemulsion in photodynamic therapy

Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D culture.These findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.

Laparoscopic duodenojejunostomy for malignant stenosis as a part of multimodal therapy:A case report

BACKGROUND Laparoscopic duodenojejunostomy(LDJ) has become the standard surgical procedure for superior mesenteric artery syndrome due to its sufficient outcome in terms of safety and symptom relief. However, there are only a few reports about LDJ for malignant stenosis and its indication remains uncertain.CASE SUMMARY A 77-year-old woman with a history of pancreatic cancer(PC) treated with distal pancreatectomy with en bloc resection of the transverse colon 7 mo ago was admitted for recurrent vomiting. Imaging upon admission revealed marked distention of the duodenum and a tumor around the duodenojejunal flexure. She was diagnosed with malignant stenosis caused by local recurrence of PC. LDJ was performed with an uneventful postoperative course, followed by chemotherapy which gave her 10 mo overall survival.CONCLUSION We think that LDJ is a valuable method for unresectable malignant stenosis around the duodenojejunal flexure as a part of multimodal therapy.

Clinical Study of Aminolevulinic Acid-mediated Acid Photodynamic Therapy Combined with Surgical Therapy of Skin Malignant Tumor

The purpose of the study was to analyze the effects of aminolevulinic acid-mediated photodynamic therapy(ALA-PDT)combined with surgery and its prognostic implications.Firstly,70 cases of skin malignant tumors admitted to the dermatology department of our hospital from January 2017 to December 2018 were selected and divided into observation group and control group according to the random number table,with 35 patients in each group.Observation group adopted the ALA-PDT combined with surgery therapy,and control group adopted surgery therapy.Two groups of patients were last follow-up to December 2019.The results showed that the total effective rate of clinical treatment in the observation group was significantly higher than that in the control group(P<0.05),indicating that based on the basis of conventional surgical treatment,combined use of ALA-PDT can effectively improve the clinical therapeutic effect and better promote the patient’s health recovery.Therefore,combined with surgical treatment,ALA-PDT can improve the clinical efficacy of skin malignant tumors with fewer adverse reactions,high safety,low recurrence rate and ideal long-term prognosis.

Clinical Efficacy and Adverse Reactions of Photodynamic Therapy in the Treatment of Malignant Skin Tumors and Precancerous Skin Diseases

The purpose of the study was to investigate the efficacy and safety of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases.First of all,100 patients with malignant skin tumor and pre-cancer skin disease admitted to our hospital from January 20,2018 to September 18,2018 were selected,and all of them adopted photodynamic therapy.The 100 patients included 40 cases of basal cell carcinoma,14 cases of squamous cell carcinoma,7 cases of proliferative erythema,9 cases of Bowen’s disease and 39 cases of solar keratosis.Among the 100 patients,77 cases had excellent curative effect,18 cases had good effect and 5 cases had poor effect,and the overall effective rate was 95%(95/100).After 6 months of follow-up,5 cases of basal cell carcinoma,2 cases of squamous cell carcinoma,0 cases of proliferative erythra,1 case of Bowen’s disease and 3 cases of solar keratosis recurred,with an overall recurrence rate of 14%(14/100).The adverse reactions of pruritus were 90%(90/100),81%(81/100),90%(90/100)and 3%(3/100).Therefore,the application of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases is not only effective,but also safe and not easy to relapse.

Clinical Application Significance of Nutritional Support Therapy in Patients with End-stage Malignant Tumor

To analyze the effect of nutritional support on clinical efficacy in patients with end-stage malignant tumors.Sample data collection was conducted from April 2015 to July 2017.54 patients with end-stage malignant tumors were enrolled in the study.They were divided into reference group(n=27)and experimental group(n=27)by double-blind method.Conventional treatment was used in the reference group,while nutritional support therapy was used in the experimental group.The treatment effects of the two groups were compared.Post-treatment effect of the experimental group and the reference group was compared using the parameters including total adverse reaction value,cancer-related fatigue score,quality of life,A/G,AS:AL,alkaline phosphatase(ALP),blood urea nitrogen(BUN),anorexia score,ALB,and uric acid(UA).The parameters such as A/G,AS:AL,ALP,BUN,anorexia score,ALB,and UA were also used to compare between pre-and post-treatment.The value of P<0.05 was used to indicate the statistical significance of the test.Conclusion:Nutritional support therapy had a superior effect in patients with end-stage malignant tumors.

Extra-pleural pneumonectomy in the setting of tri-modality therapy for patients with malignant pleural mesothelioma

Although declining in the US due to restrictions of asbestos exposure, malignant pleura/mesothelioma （MPP） remains a very serious thoracic malignancy that is rising in incidence worldwide （1）. Trirnodality therapy with chemotherapy and radiotherapy combined with extrapleural pneumonectomy （EPP） has gained acceptance given the acceptable mortality rate （〈5%） and long term survival reported in patients with epithelial histology, negative margins, and no extrapleural lymph node involvement after trimodalitv treatment （2）.

Management strategies in malignant glaucoma secondary to antiglaucoma surgery

AIM：To assess the outcomes of various interventions for malignant glaucoma（MG）.·M ETHODS：A retrospective,comparative analysis of case series were performed on 38 eyes of 35 MG patients treated in Aier Eye Hospital of Wuhan between Jan.2009and Dec.2012.Numerous treatments were administered including medical therapy,neodymium：yttriumaluminium-garnet（Nd：YAG）laser posterior capsulotomy and hyaloidotomy as well as 3 surgical options.The characteristic,treatment option and outcome of MG in every individual patient were reviewed and analyzed among all patients who were followed up for an average of 27.1±9.1mo.·RESULTS：Four eyes of 3 patients achieved complete resolution with medical therapy.Nd：YAG laser posterior capsulotomy and hyaloidotomy were performed on 2 eyes,both of which achieved resolution after initial intervention.Thirty-two eyes were given surgical treatments with anterior vitrectomy-reformation of anterior chamber in13 eyes,phacoemulsification-intraocular lens implantation in 10 eyes and phacoemulsification-intraocular lens implantation-anterior vitrectomy in 9 eyes.Resolution of MG was seen in almost all patients.The mean intraocular pressure decreased from 41.87±9.44 mm Hg at presentation to 15.84±3.73 mm Hg at the last visit.The mean anterior chamber depth improved from 0.28±0.27 mm to 2.28±0.19 mm.Twenty eyes with preoperative visual acuity better than counting figure/50 cm had various visual improvements.Complications occurred in 3 eyes of 3 patients including bleeding at the entry site of vitrectomy into vitreous cavity,corneal endothelial decompensation and allergic to atropine respectively.·CONCLUSION：MG occurs as a result of multiple mechanisms involved simultaneously or sequentially.Medical therapy is advocated as the initial treatment,laser therapy is beneficial in pseudophakic eyes,and different surgical regimen is recommended based on different pathogenesis of MG when non-response occurs to nonsurgical management.MG can be managed successfully by appropriate and timely interventions with good visual outcome.

Endoscopic palliation of malignant biliary stricture

Malignant biliary strictures often present late after the window for curative resection has elapsed. In such patients, the goal of therapy is typically focused on palliation. While historically, palliative measures were performed surgically, the advent of endoscopic intervention offers minimally invasive options to provide relief of symptoms, improve quality of life, and in some cases, increase survival of these patients. Some of these therapies, such as endoscopic biliary decompression, have become mainstays of treatment for decades, whereas newer modalities, including radiofrequency ablation, and photodynamic therapy offer additional options for patients with incurable biliary malignancies.

CAR T Cell Therapy for Hematological Malignancies

As a rapidly progressing field in oncology,the adoptive transfer of T cells that have been genetically modified with chimeric antigen receptors(CARs)has shown striking efficacy in the management of hematological malignancies and has been reported in a number of clinical trials.of note,CAR T cell therapy has shown extraordinary potential,especially in relapsed/refractory patients.However,there are still challenges regarding the further development of this strategy,spanning from engineering and manufacturing issues,to limited applications,to accompanying toxicities.In this review,we will summarize the general knowledge of this novel method,including receptor composition,applications,adverse events and challenges.Additionally,we will propose several comprehensive recommendations.

Novel cellular therapies for hepatobiliary malignancies

Background:The mortalities of hepatobiliary malignancies are high.With the failure of conventional chemotherapy and unsatisfactory outcome of molecular targeted drugs,immune-based therapy has become a new focus of research in hepatobiliary cancers treatment.Data sources:We performed a Pub Med search with relevant articles published up to May 2022 and the following keywords:cellular immunotherapy,hepatobiliary cancer,antigen receptor T cell therapy,and receptor-engineered T cell.Information of clinical trials was obtained from https://clinicaltrials.gov/.Results:Cell therapies for hepatobiliary malignancies are at early stage of development.The current review showed that cellular therapies are safe and feasible in patients.These findings provide an important platform for future lager scale clinical trials on immunotherapy in patients with hepatobiliary malignancies.Conclusions:With the continuous advances of cellular immunotherapy,the combination of cellular immunotherapy with surgery,chemotherapy and radiotherapy will be new therapeutic strategies for patients with hepatobiliary cancer.

Diagnostic features and therapeutic strategies for malignant paraganglioma in a patient:A case report

BACKGROUND Paragangliomas and extra-adrenal pheochromocytomas are uncommon neuroendocrine tumors with ubiquitous distribution.Malignant paraganglioma is a relatively rare entity.We report the treatment and pathological characteristics of a patient with malignant paraganglioma,and summarize the latest advances in the treatment of malignant paraganglioma based on a literature review.CASE SUMMARY A 45-year-old Chinese woman presented to the hospital due to pain in the waist(right side) and right buttock,and was diagnosed as malignant paraganglioma after the placement of ureteral stent,implantation of ileus catheter,and transvaginal removal of the vaginal mass.After relief of intestinal obstruction,the patient received intravenous chemotherapy and peritoneal perfusion chemotherapy.Although her pelvic mass disease was stable,she developed multiple liver metastases and bone metastases.Due to the development of spinal cord compression,she underwent orthopedic surgery,followed by radiotherapy,and molecular targeted therapy with apatinib,but with poor disease control.CONCLUSION Clinical management of paraganglioma is challenging for endocrinologists and oncologists.Prospective studies are required to develop standardized therapeutic strategies for malignant paragangliomas.

Efficacy of Recombinant Adenoviral Human p53 Gene in Treatment of Malignant Pleural or Peritoneal Effusions

Background and objective Once the malignant pleural or peritoneal effusion is developed it is difficult to control.This report presents a new method for controlling the malignant effusions.Methods Forty-eight patients,29 males and 19 females with an average age of 61.2 years old,who were satisfied with the study inclusion criteria,were recruited in this study.Twenty-seven and 21 patients had a malignant pleural and peritoneal effusion,respectively.After draining most of fluids,these patients received intra-cavity infusion of rAd-p53 once per week for 4 weeks,at dose of 2×1012 viral particles(VP) diluted into 200 mL of saline solution for pleural effusions,and 4×1012 VP diluted into 500 mL of saline solution for peritoneal effusions.Results Participants were followed up for a median time of 13.6 month.A total of 11 cases,7 with pleural effusions and 4 with peritoneal effusions achieved a complete response(CR),and 20 cases(12 pleural effusions and 8 peritoneal effusions) had a partial response(PR).The overall response rate is 64.6%.Patients' quality of life,assessed by using Karnofsky performance scale(KPS) scores,was improved by an average of 26.4.The one-year of overall survival rate was 54.2% with a median survival time of 12.5 months.There were no serious side effects observed except for self-limited fever found in 79.8% of the cases.Conclusions Intra-cavity infusion of rAd-p53 is an effective and safe treatment for the patients with malignant pleural or peritoneal effusions,especially for those patients who can't tolerate the standard treatments.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.