Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique.

OBJECTIVE: To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. DESIGN: Step-by-step description of the surgical technique with narrated video footage. SETTING: Academic tertiary hospital. PATIENT(S): Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. INTERVENTION(S): After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. MAIN OUTCOME MEASURE(S): Step by step educational video. RESULT(S): The post-operative course was uneventful and the patient was discharge 24 hours after surgery. CONCLUSION(S): Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

A case of complete remission of Hodgkin lymphoma confirmed histopathologically by neck dissection.

BACKGROUND: Hodgkin lymphoma (HL) is diagnosed definitively by biopsy, and treatment is based on stage. Owing to the nature of the disease, post-treatment efficacy is determined mainly by fluorodeoxyglucose-positron emission tomography/computed tomography, and the efficacy of treatment is not confirmed by histopathology. We report a case of tongue cancer after treatment for HL, in which a post-treatment lymph node with complete remission was histopathologically confirmed by neck dissection. CASE: The patient was a 74-year-old man who was referred to our hospital for cancer on the right side of his tongue. He had previously undergone chemotherapy for HL involving the right side of his neck and achieved complete remission. Because he had cT3N2cM0 tongue cancer, glossectomy and bilateral neck dissection were performed. Surprisingly, histopathological examination revealed that there was neither metastatic lymph nodes nor lymphoma cells in his right neck. Moreover, there was no lymphatic structure in his remnant lymph nodes. CONCLUSION: This was a rare case in which complete remission of HL was confirmed by histopathological analysis. The absence of lymph node structure and lymphatic flow led to contralateral neck lymph node metastases of tongue cancer.

Surgical outcomes following breast reconstruction in patients with and without a history of chest radiotherapy for Hodgkin lymphoma: a multicentre, matched cohort study.

BACKGROUND: Breast cancer is the most common treatment-related second malignancy among women with previous chest radiotherapy for Hodgkin lymphoma (HL). Little is known about the effects of this kind of radiotherapy on the outcomes of postmastectomy breast reconstruction (BR). This study compared adverse outcomes of BR after HL-related chest radiotherapy to matched controls. METHODS: The authors conducted a retrospective, matched cohort study in two expert cancer centres in the Netherlands. BRs after therapeutic or prophylactic mastectomy in HL survivors who received chest radiotherapy were matched with BRs in nonirradiated patients without HL on age at mastectomy date, date of BR, and type of BR. The primary outcome was complication-related BR failure or conversion and secondary outcomes were complication-related re-operation, capsular contracture, major donor-site complications, and complication-related ICU admission. The authors analyzed all outcomes univariably using Fisher's exact tests and the authors assessed reconstruction failure, complication-related re-operation, and capsular contracture with multivariable Cox regression analysis adjusting for confounding and data clustering. RESULTS: Seventy BRs in 41 patients who received chest radiotherapy for HL were matched to 121 BRs in 110 nonirradiated patients. Reconstruction failure did not differ between HL survivors (12.9%) and controls (12.4%). The comparison groups showed no differences in number of reoperations, major donor-site complications, or capsular contractures. BR in HL survivors more often let to ICU admission due to complications compared with controls ( P =0.048). CONCLUSIONS: We observed no increased risk of adverse outcomes following BR after previous chest radiotherapy for HL. This is important information for counselling these patients and may improve shared decision-making.

Surgical Management and Contralateral Breast Cancer Risk in Women with History of Radiation Therapy for Hodgkin Lymphoma: Results from a Population-Based Cohort.

BACKGROUND: Women with history of chest irradiation for Hodgkin lymphoma are at increased risk of developing bilateral breast cancer, although contralateral breast cancer risk estimates in this population remain undefined. METHODS: We queried the SEER database for women treated with radiation therapy for Hodgkin lymphoma prior to age 30 years and were diagnosed with a subsequent breast cancer between 1990-2016. Trends in surgical management and the 5- and 10-year cumulative incidence of contralateral breast cancer were evaluated. RESULTS: The cohort included 295 women with a median age of 22 years (range 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range 22-65 years) at breast cancer diagnosis. Overall, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Breast-conserving surgery was performed in 17.3% of patients, while mastectomy was performed in 82.7%. In 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent breast-conserving surgery and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients demonstrated a 40.5% bilateral mastectomy rate. The 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% [95% confidence interval (CI), 5.6-15.4%], increasing to 20.2% (95% CI, 13.7-29.2%) at 10-year and 29.9% (95% CI, 20.8-41.9%) at 15-year follow-up. CONCLUSIONS: Women with a history of prior chest radiation for Hodgkin lymphoma with a diagnosis of breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making for management of this high-risk patient population.

Combined skin-sparing mastectomy and immediate implant-based breast reconstruction: Outcome following mantle field irradiation versus outcome following whole-breast irradiation.

BACKGROUND: Mastectomy may be needed in the context of previous radiotherapy in cases of breast carcinoma following mantle field radiotherapy for Hodgkin lymphoma or in cases of local relapse or second primary tumours after breast conserving therapy including whole-breast irradiation (BCT). The outcome of combined skin-sparing mastectomy and immediate implant-based breast reconstruction (SSM-IIBR) has been reported to be unfavourable in these cases. PURPOSE: To compare the outcome of SSM-IIBR after mantle field radiotherapy to that after BCT and to compare both to the outcome observed in non-irradiated breasts. METHODOLOGY: The prevalences of short-term events, device loss, long-term corrections and secondary reconstructions, and reversion to autologous tissue techniques of 42 SSM-IIBRs performed after mantle field irradiation were compared to those of 47 salvage SSM-IIBRs following BCT. Both outcomes were compared to the outcome in the contralateral, non-irradiated breast of the subgroup of 23 women in the BCT group. RESULTS: The groups were comparable in terms of patient- and procedure-related risk factors, except for time lapse after previous therapy, intraoperative device weight, and the fraction of immediate use of a definitive implant. The outcome of SSM-IIBR after mantle field irradiation significantly differs favourably from that after BCT. It matches the outcome observed in non-irradiated breasts. CONCLUSION: Skin-sparing mastectomy combined with immediate implant-based breast reconstruction is a fully justifiable option for women who previously underwent mantle field irradiation for Hodgkin lymphoma. We feel that the unfavourable outcome observed in women who previously underwent BCT necessitates an alternative reconstructive modality.

Knowledge From London and Berlin: Finding Threads to a Functional HIV Cure.

Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the "Berlin Patient" and the "London Patient". Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.

Outcome of a HIV Positive Patient Infected with COVID-19 After an Autologous Bone Marrow Transplantation: A Case Report.

BACKGROUND: The World Health Organization (WHO) announced the SARS-COV-2 disease pandemic on March 9, 2020. With the advent of this disease, another health burden was added to about 37.9 million people in the world who are infected with HIV and are suffering from various diseases. These people may be at serious risk of COVID-19. Information about the effects of COVID-19 on people living with HIV, is limited. CASE PRESENTATION: We reported a 61-year-old man who was a known case of HIV from 6 years ago that was being treated with HAART (highly active antiretroviral therapy). He also had a history of Hodgkin's lymphoma from 4 years ago who underwent autologous bone marrow transplantation (BMT) 2 weeks before given referral to our hospital. He complained of weakness, anorexia, and fever. RT-PCR for SARS-COV-2-RNA was positive in his nasopharyngeal and oropharyngeal swab. He was diagnosed with COVID-19 infection and treated with atazanavir. After one week, the patient discharged in a good general state. CONCLUSION: To the best of our knowledge, it is the first report of COVID-19 infection in an HIV positive patient after BMT in Iran. Despite his immunodeficiency, COVID-19 disease had mild manifestations and he had a good prognosis. We hope that our report and that of others can remain promising to doctors and HIV patients cross fingers for COVID-19 recovery.

Primary central nervous system Hodgkin's lymphoma: a case report.

Primary central nervous system Hodgkin's lymphoma (CNS-HL) is extremely rare. This current case report describes a 60-year-old male patient that presented with numbness of the left lower extremity and worsening headache. After a full range of investigations and a partial resection of the right cerebellum, external ventricular drainage reservoir placement and cranioplasty, he was diagnosed with primary CNS-HL. The patient was treated with 3 g/m2 methotrexate (intravenous [i.v.], once a day, day 1) and 1 g/m2 cytarabine (i.v., every 12 h, days 2 + 3), followed by anti-programmed cell death protein 1 antibodies (200 mg sintilimab, i.v., once a day, day 1, every 3 weeks). After six courses of treatment with intrathecal injections of 50 mg cytarabine (once a day, day 1) and 5 mg dexamethasone (once a day, day 1), there was no residual lesion on cranial magnetic resonance imaging. No significant drug-related adverse events were observed. The patient has been followed up every 3 months and no relapse has occurred.

Novel Therapies in the Treatment of Hodgkin Lymphoma.

OPINION STATEMENT: Patients with Hodgkin lymphoma (HL) can achieve excellent response and survival rates following frontline combination chemo- and radiation therapy. However, about 10-15% of patients will experience disease relapse which is associated with poor outcomes. Recent breakthroughs in understanding the mechanisms of oncogenicity and interactions within the tumor microenvironment have resulted in development of novel drugs for treatment of patients with HL. Utilizing this information, treatment of newly diagnosed and relapsed HL has become a rapidly evolving field with multiple clinical trials evaluating novel treatment approaches incorporating targeted immunotherapy. In the frontline setting, the use of novel drugs may allow for de-escalation of therapy to avoid long-term complications associated with bleomycin and consolidation radiation therapy. Patients with early-stage, non-bulky disease are candidates for omitting radiation therapy using treatment combinations that include upfront use of brentuximab vedotin or nivolumab. In patients with advanced disease, the addition of brentuximab vedotin to a chemotherapy backbone is currently the standard of care in our practice, particularly in patients with a contraindication for receiving bleomycin. Future investigations in patients with advanced-stage HL will focus on establishing a new standard of care by comparing brentuximab vedotin and nivolumab in combination with chemotherapy (BV-AVD vs. N-AVD) and decreasing the risk of relapse by exploring consolidation therapy in patients with high-risk disease. In patients who have relapsed or are refractory to first-line therapy, salvage treatment has incorporated brentuximab vedotin or PD-1 checkpoint inhibitors to improve response rates of cytotoxic chemotherapy thereby improving the probability of a successful stem cell transplant. Post-transplant consolidation with brentuximab is currently standard of care in patients with high-risk disease. Patients who relapse following autologous stem cell transplant now have an expanded armamentarium of chemo- and immunotherapy options. However, the challenge is to determine the sequence of therapy after prior brentuximab or checkpoint inhibitor exposure.

Diminished expression of 5hmc in Reed-Sternberg cells in classical Hodgkin lymphoma is a common epigenetic marker.

Loss of the epigenetic marker 5-hydroxymethylcytosine (5hmC) has been demonstrated in a variety of neoplasms. Several recent studies have shown epigenetic alteration in Classical Hodgkin lymphoma (CHL), which may impact treatment. We demonstrate near universal depletion of 5hmC in the neoplastic Hodgkin Reed-Sternberg (H/RS) cells in all cases of CHL (49/49). We hypothesized that the addition of vitamin C-a cofactor for the ten-eleven translocation (TET) enzymes which oxidize 5-methylcytosine (5mC) to 5hmC - may replenish levels of 5hmC. The CHL cell line L428 was grown in optimal conditions and then subjected to vitamin C treatment, which demonstrated reduced cell viability as well as caspase activation and increased concentration of 5hmC. A more detailed understanding of the epigenetic landscape of CHL may help guide future therapies.

Hodgkin's lymphoma: post- autologous transplantation consolidation therapy.

A first-line chemotherapy program based on the ABVD regimen is currently considered the golden standard by most hematologists, being able to achieve a cure without any need of subsequent therapies in >70% of patients with advanced-stage Hodgkin's lymphoma (HL). To increase this percentage, efforts in recent decades focused on the development of new therapeutic strategies. A first major effort was the introduction of the BEACOPP chemotherapy regimen, which is able to increase the response rate and to reduce the need of salvage therapies. However, this result did not demonstrate an advantage in terms of overall survival compared to ABVD, mainly due to an excess of non lymphoma-related events in the follow-up phase. Here we describe three clinical cases of young HL patients who had relapsed/refractory disease after the induction chemotherapy. These three clinical cases provide practical and real world evidence in favor of the use of BV in monotherapy as consolidation treatment after autologous stem cells transplantation in patients with relapsed/refractory HL.

Relapsing/refractory HL after autotransplantation: which treatment?

For advanced-stage Hodgkin lymphoma (HL), front-line chemotherapy, alone or in combination with radiotherapy, leads to 5-year progression-free survival (PFS) rates and freedom-from-treatment failure (FFTF) rates of 70-85%, regardless of the chemotherapy regimen applied. Patients with HL experiencing disease progression during or within 3 months of front-line therapy (primary refractory) and patients whose disease relapses after a complete response have a second chance of treatment. The standard of care for relapsed or refractory HL is second-line chemotherapy followed by autologous stem cell transplantation (ASCT), which can induce long-term remission in approximately 40-50% of patients. However, HL recurrence occurs in about 50% of patients after ASCT, usually within the first year, and represents a significant therapeutic challenge. Allogeneic transplantation from HLA-matched donors represents the standard of care for patients with HL relapsing after- or refractory to ASCT.

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

BACKGROUND: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies. AIMS: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards. METHODS: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed. RESULTS: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years. CONCLUSION: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.

PRIMARY HODGKIN'S LYMPHOMA OF THE BREAST INITIALLY TREATED BY SURGICAL EXCISION AND AXILLARY DISSECTION.

Primary breast lymphoma accounts for 0.04%-0.5% of all breast malignancies. Primary non-Hodgkin's lymphomas of the breast are extremely rare and represent approximately 0.38%-0.7% of all cases. Epstein-Barr virus (EBV) has been postulated to play an important role in the pathogenesis of Hodgkin's lymphoma. We present a case of EBV-positive primary Hodgkin's lymphoma of the breast. Although there is no sufficient data on this challenging diagnosis, it is known that it could be misdiagnosed with inflammatory breast carcinoma. A crucial part of the proper histopathologic diagnosis is immunohistochemistry. Different modalities of treatment include operative procedure, chemotherapy and radiotherapy. Recent studies suggest chemotherapy and radiotherapy to be initial treatment for patients with primary breast lymphomas.