Complete, Durable Remission of Advanced Hepatocellular Carcinoma under Treatment with Viscum album Extracts: A Case Report.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths. Early-stage disease is treated with curative intent, but most patients present with advanced HCC, which carries a poor prognosis. Viscum album extracts (VAE) are used by cancer patients as an adjunct treatment or palliation. CASE PRESENTATION: A 51-year-old female presented with relapsing multifocal HCC. She declined palliative treatment and commenced intravenous VAE treatment in conjunction with intravenous hepato-protective L-ornithine-L-aspartate (LOLA). She experienced a significant improvement of life-quality and performance status. After 3 months, a significant regression was noted on computerized tomography, and α-fetoprotein was in normal range. Imaging 11 months later confirmed a complete regression. The VAE and LOLA treatment continues to date. The patient had no other cancer-directed therapy. The regression is sustained for more than 5 years at publication, confirmed by regular imaging and serology. The patient is experiencing an unrestricted quality of life. CONCLUSION: Complete regression of advanced HCC is rare. Responses of HCC to VAE treatment have been reported before. However, this is the first documented case with a complete and durable regression of an HCC under treatment with VAE. Further studies should evaluate VAE treatment in HCC, especially when administered in forms as reported here.

Long-Term Survival of a Patient with Recurrent Dedifferentiated High-Grade Liposarcoma of the Retroperitoneum Under Adjuvant Treatment with Viscum album L. Extract: A Case Report.

CASE PRESENTATION: A 68-year-old male patient underwent a resection of a DDL (T2 N0 M0, FNCLCC grade 2, stage IIIA) in the retroperitoneum. Three months after this first surgery, a recurrence occurred, and was treated with neoadjuvant and adjuvant doxorubicin plus ifosfamide and surgery (resection). A second recurrence-11 months after the second surgery-was treated with surgery and radiotherapy. The patient then began to undergo VAE treatment (0.2 mg-2 mg, subcutaneously, thrice a week). After the VAE treatment was initiated, the patient reported improved quality of life. A third recurrence-12 months after the third surgery-was treated with surgery, radiotherapy, and with an increased dose of VAE (20 mg). Sixty-nine months (5.8 years) after the fourth surgery a fourth recurrence occurred. It was again treated with surgery, along with a month of intravenous VAE infusions and subsequent subcutaneous VAE (20 mg) treatment. Finally, a fifth recurrence-5 months after the fifth surgery-was treated with subcutaneous and intravenous VAE applications and eribulin. The patient died 11 months after the last recurrence; he received a total of 103 months (8.6 years) of VAE treatment and achieved 10.5 years of survival. CONCLUSION: The case presented herein shows a long-time survival and a prolonged recurrence-free interval in a patient with retroperitoneal DDL treated with surgery, chemotherapy, radiotherapy, and VAE injections. On the basis of the antitumoral and immunomodulating effects of VAE and on the reported prolonged survival of VAE-treated patients with other types of tumors, the adjunct VAE treatment is presumed to have contributed to the favorable outcome. Regarding the clinical relevance of VAE treatment, further investigations are needed.

CARE for COVID-19: A Checklist for Documentation of Coronavirus Disease 2019 Case Reports and Case Series.

Coronavirus disease 2019 (COVID-19) is a new, rapidly spreading pandemic that can lead to a life-threatening disease. Accurate and transparent COVID-19 case reports provide systematic clinical observations supporting researchers designing clinical trials and clinicians delivering health care. The checklist described here is designed to systematically and accurately capture data from case reports and case series for documentation on COVID-19. It is aligned with the CARE guidelines, available from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network.

Long-term survival of a patient with an inoperable thymic neuroendocrine tumor stage IIIa under sole treatment with Viscum album extract: A CARE compliant clinical case report.

RATIONALE: Thymic neuroendocrine tumor (TNET) is very rare and characterized by a tendency to invade adjacent structures, frequent metastasis, resistance to therapy, and a poor prognosis. Viscum album extracts (VAE) have shown immunological, apoptogenic, and cytotoxic properties. PATIENT CONCERNS: A 54-year-old Peruvian man was suffering from constant fatigue, cough, dyspnea, and fever for a couple of months. DIAGNOSES: He was diagnosed with TNET (12.8 cm × 10 cm × 7 cm) stage IIIa, G1. Due to the size and extensive invasiveness (vena cava superior, also obstructing 85% of its lumen, pericardium, and pleura), the TNET was inoperable. INTERVENTIONS: We report the case of this patient who declined chemotherapy and was treated instead with sole subcutaneous VAE 3 times per week for 85 months. No other tumor-specific intervention was applied. OUTCOMES: Quality of life (QoL) improved substantially. The patient returned to work, and the tumor remained stable for 71 months. Thereafter, the tumor progressed, and the patient died 90 months after initial diagnosis. Besides self-limited local skin reactions around the application site, no side effects occurred. LESSONS: This is an exceptionally good course of disease of an inoperable, large, obstructing, and invasive TNET with a reduced baseline condition (Karnofsky index: 50-60) due to pronounced symptoms. Given the considerable reduction of symptoms and improved QoL following the onset of VAE therapy and other reports describing long disease stability and improvement of the QoL using VAE in different cancer types, we presume that the VAE treatment was supportive in this case. As TNETs are rare and few trials are available, future treatments of TNETs using VAE should be carefully documented and published to help determine whether further investigation of the use of VAE in TNET treatment is worthwhile.

Bilateral Asynchronous Renal Cell Carcinoma With Lung Metastases: A Case Report of a Patient Treated Solely With High-dose Intravenous and Subcutaneous Viscum album Extract for a Second Renal Lesion.

BACKGROUND: Bilateral asynchronous renal cell carcinoma (RCC) is infrequent. Immunotherapy is the first-line treatment for advanced RCC not controlled by locoregional therapy. Viscum album extracts (VAE) have been shown to improve quality of life as well as immunological and antineoplastic properties in different types of cancers. CASE REPORT: A 67-year-old man was diagnosed with Fuhrman grade 3/4 RCC, stage pT1bN0M0 in the right kidney. During the subsequent 6 years, he underwent a right nephrectomy and two metastasectomies (lung). Then an RCC lesion of the left kidney was detected. The patient refused a second nephrectomy and was treated solely with high-dose intravenous and subsequent subcutaneous VAE. A central necrotic area and a peritumoral halo were seen on an ultrasound follow-up from month 7. The patient showed no further progression of RCC during the next 2.5 years. CONCLUSION: As far as we are aware of, this is the first report of a patient with metastatic RCC with an RCC lesion of the second kidney treated solely with high-dose intravenous and subcutaneous VAE, associated with 2.5 years of progression-free survival and a good quality of life. The use of VAE in RCC should be carefully documented and published to determine future research.

Long-term survival of a patient with advanced pancreatic cancer under adjunct treatment with Viscum album extracts: A case report.

BACKGROUND: Advanced pancreatic cancer (aPC) has a poor prognosis with limited survival benefit from current standard treatment. Viscum album extracts (VAE) are used by many cancer patients, showing immune-stimulating effects, improved quality of life, and a survival benefit in patients with aPC. CASE SUMMARY: A 59-year-old architect developed epigastric pain. A cystic lesion of the pancreas of 45-mm diameter was detected. In a follow-up magnetic resonance imaging, about one year later, multiple lesions were seen in the corpus and the tail of the pancreas; CA-19-9 was elevated to 58.5 U/mL. A distal pancreatectomy with splenectomy was performed, and a tumor of 7 cm × 5 cm × 3.5 cm was excised. Histologic investigation showed an intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma with invasion of the lymph vessels, perineural invasion, and positive nodes (2/27); surgical margins showed tumor cells, and the tumor was classified as pT3 N1 M0 R1. The patient was treated with radiation of the tumor bed and capecitabine/oxaliplatin followed by gemcitabine and FOLFIRINOX. Seven months after surgery, a liver metastasis was detected and treatment with FOLFIRINOX was started. Four months after detection of the metastasis, the patient opted for additional treatment with VAE. Another month later, the metastasis was treated with radiofrequency ablation (RFA). Eight months later, the hepatic lesion recurred and was again treated with RFA. The continuous VAE treatment was increased in dose, and the patient stayed recurrence-free for the next 39 mo in good health and working full-time (as of the time this case report was written). CONCLUSION: We present the case of a patient with aPC with R1-resection with development of liver metastasis during the course of treatment who showed an overall survival of 63 mo and a relapse-free survival of 39 mo under increasing VAE therapy. The possible synergistic effect on tumor control of RFA treatment and immune-stimulatory effects of VAE should be further investigated.

Chemoimmunotherapy in Advanced Renal Cell Carcinoma: A Case Report of a Long-Term Survivor Adjunctly Treated with Viscum album Extracts.

INTRODUCTION: Metastatic renal cell carcinoma has a poor prognosis. Treatment approaches with immunotherapy show promising results in subpopulations. Viscum album extracts - used as an adjunct to cancer treatment - have cytotoxic, apoptogenic, and immune-stimulating properties and show synergistic effects with chemotherapy agents. CASE REPORT: A 51-year-old man was diagnosed with metastatic renal cell carcinoma of clear cell histology which was classified as pT3a, N1, M1, G3. Nephrectomy was performed, and the patient received chemoimmunotherapy (interferon-α2a, interleukin-2, fluorouracil, isotretinoin). Additionally, he received V. album extracts as intravenous infusions and subcutaneous injections. One year after surgery, the patient was in complete remission, which is ongoing 18 years after the initial diagnosis. DISCUSSION: This case shows an extraordinarily long survival of a metastasized renal cell carcinoma patient under chemoimmunotherapy and fever-inducing V. album extracts. This combined treatment might have synergistically contributed to tumor remission and control. With regard to clinical relevance, further investigations are needed.

Intralesional and subcutaneous application of Viscum album L. (European mistletoe) extract in cervical carcinoma in situ: A CARE compliant case report.

RATIONALE: Carcinoma in situ (CIS) of the uterine cervix is a premalignant condition of squamous epithelium. The standard treatments are excision and ablation procedures; for women with positive margins, hysterectomy is recommended. PATIENT CONCERNS: A 47-year-old Peruvian woman with recurrent candidal vaginitis had been diagnosed with colpocervicitis and squamous metaplasia 8 years ago, which were not treated. DIAGNOSES: The patient was diagnosed with CIS after cervical conization procedure. She refused radical hysterectomy and opted for integrative medicine treatment. INTERVENTIONS: She was treated with intralesional and subcutaneous Viscum album L. extract (VAE) injections. VAE is a widely used herbal cancer treatment with cytotoxic, apoptogenic, and immunological effects, but it has not been investigated in cervical CIS. OUTCOMES: Ending month 5 of treatment, complete remission of cervical CIS was observed. The patient is still in remission after 30 months (until publication). LESSONS: This is the first report on complete remission of cervical CIS after intralesional and subcutaneous injection with VAE. Prospective studies should evaluate to what degree the treatment effect is reproducible.

Long-Term Tumor-Free Survival in a Patient with Stage IV Epithelial Ovarian Cancer Undergoing High-Dose Chemotherapy and Viscum album Extract Treatment: A Case Report.

INTRODUCTION: Epithelial ovarian cancer (EOC) has a poor prognosis in advanced stages. High-dose chemotherapy (HDC) was pursued in the 1990s but was not found to improve survival of patients with EOC in larger studies. Many patients with cancer use Viscum album extracts (VAE). Also called European mistletoe, Viscum album can lead to improved quality of life and reduced chemotherapy side effects and may have synergistic cytotoxic and proliferation-inhibiting effects when used together with chemotherapy. CASE PRESENTATION: A high-grade serous epithelial ovarian carcinoma with peritoneal, adrenal, and hepatic metastases (FIGO Stage IV) was diagnosed in a 50-year-old premenopausal woman. Tumor and metastases were surgically removed in cytoreductive surgery, and the patient received adjuvant chemotherapy, without experiencing side effects from treatment. After a second-look surgery revealed lymph node metastases, HDC and autologous hematopoietic stem cell transplantation were performed. Additionally, the patient opted for treatment with VAE, which she continuously received. The patient remained tumor-free in follow-up examinations and has enjoyed good health for 20 years after initial diagnosis. DISCUSSION: Treatment with VAE in this case might have contributed to the reduction of side effects from HDC and may have acted synergistically with HDC in tumor control. Cases of VAE in EOC should be carefully documented and reported to further illustrate the influence of VAE on this cancer presentation.

Reduction of the frequency of recurrent diverticulitis episodes under treatment with the integrative medicine therapies Carpellum Mali comp. and Kalium aceticum comp.-A case report.

BACKGROUND: Colonic diverticula develop in at least 60% of elderly patients. Less than 25% of these develop diverticulitis. Recurrent episodes are experienced by about 13% of the symptomatic patients. The effect on prevention of recurrent diverticulitis of currently used therapies is controversial. Surgical colon resection is used in some patients in emergency or to prevent future episodes and complications. Carpellum Mali comp. (Juglans regia, Testa; Pirus malus, Carpellum) and Kalium aceticum comp. (Kalium carbonicum, Acetum vini destillatum, Antimonit, Crocus sativus, Spiritus e vino, Corallium rubrum) - preparations of Integrative Anthroposophic Medicine - have been used for at least 60 years to improve chronic abdominal pain and to treat obstipation, irritable bowel syndrome and colitis. CASE PRESENTATION: A 72-year-old retired physician presented in 2013 with a 7-year history of recurrent diverticulitis. During the first 6 years, three to four episodes each year required antibiotic therapy. In 2013 the episodes became more frequent, occurring approximately every 2 months. The patient was concerned about risks from repeated antibiotic treatment and the potential need for surgery. Oral Carpellum Mali comp. and subcutaneous Kalium aceticum comp. treatments were added to the therapy in March. The patient experienced improvement over 4 months without any symptoms. In the following 28 months she had 4 minor diverticulitis episodes, followed by 11-months without any flares; she reported no side effects in the 41-month follow-up period. CONCLUSION: Carpellum Mali comp. and Kalium aceticum comp. seem to have been helpful in the case presented here. Experiences with theses remedies in recurrent diverticulitis should be collected to determine whether it would be meaningful to carry out further investigations.

Complete Remission and Long-term Survival of a Patient with a Diffuse Large B-cell Lymphoma Under Viscum album Extracts After Resistance to R-CHOP: A Case Report.

BACKGROUND: A nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a lymphoproliferative neoplasm with a fair prognosis, but the possibility of a malignant transformation into a diffuse large B-cell lymphoma (DLBCL) is high. DLBCL progresses aggressively. Introduction of rituximab into therapy had led to improved outcomes. The use of Viscum album extracts (VAE) in cancer is established, but their application in lymphoma are rare. CASE PRESENTATION: A 65-year-old patient was diagnosed with DLBCL stage IIa with splenomegaly, transformed from a NLPHL, after a 30-year history of repeatedly enlarged inguinal lymph nodes. The patient initially rejected chemotherapy. After his tumor pain increased, he accepted the consecutive therapies bendamustine plus vincristine plus prednisolone, trofosfamide, and rituximab plus cyclophosphamide plus hydroxydaunorubicin plus vincristine plus prednisone (R-CHOP), inducing only a slight regression of the splenic lesions. VAE was additionally applied to R-CHOP. Five months after termination of chemotherapy - under continued VAE therapy in increasing dosage- regression of paraaortal lesions was found. The patient fully recovered under continuous VAE application and is in ongoing complete remission and in a good state of health 17 years after the initial diagnosis. CONCLUSION: As complete remission of lymphoproliferative disorders after VAE treatment has been previously reported, further investigations of VAE in lymphoma seem highly worthwhile.

A 21-year course of Merkel cell carcinoma with adjuvant Viscum album extract treatment: A case report.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine skin tumor with frequent local recurrence, lymph node involvement, distant metastasis, and a high mortality rate. Viscum album extracts (VAE) are a widely used adjunct in cancer treatment and show cytotoxic and immune-modulating effects. CASE PRESENTATION: A 64-year-old woman was diagnosed with a MCC of the left forearm. In the following course of 21 years, she experienced 4 episodes of lymph node relapse (axillary, submandibular, axillary, clavicular). All lesions were surgically excised. The patient declined chemotherapy and radiation and opted for adjuvant treatment with local subcutaneous VAE injections. Currently-21 years after first diagnosis and 9.5 years after the last relapse-the patient is tumor-free, in good health, and without functional limitations. CONCLUSION: The presented case shows long-time survival in a patient with MCC treated with surgery and VAE injections. The immune system plays a key role in tumorigenesis of MCC. VAE enhances several immune pathways and might therefore contribute to immunologic tumor control in MCC. The role of VAE in MCC should further be investigated.

Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report.

INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred. DISCUSSION: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

CARE guidelines for case reports: explanation and elaboration document.

BACKGROUND: Well-written and transparent case reports (1) reveal early signals of potential benefits, harms, and information on the use of resources; (2) provide information for clinical research and clinical practice guidelines, and (3) inform medical education. High-quality case reports are more likely when authors follow reporting guidelines. During 2011-2012, a group of clinicians, researchers, and journal editors developed recommendations for the accurate reporting of information in case reports that resulted in the CARE (CAse REport) Statement and Checklist. They were presented at the 2013 International Congress on Peer Review and Biomedical Publication, have been endorsed by multiple medical journals, and translated into nine languages. OBJECTIVES: This explanation and elaboration document has the objective to increase the use and dissemination of the CARE Checklist in writing and publishing case reports. ARTICLE DESIGN AND SETTING: Each item from the CARE Checklist is explained and accompanied by published examples. The explanations and examples in this document are designed to support the writing of high-quality case reports by authors and their critical appraisal by editors, peer reviewers, and readers. RESULTS AND CONCLUSION: This article and the 2013 CARE Statement and Checklist, available from the CARE website [www.care-statement.org] and the EQUATOR Network [www.equator-network.org], are resources for improving the completeness and transparency of case reports.

Minor regression and long-time survival (56 months) in a patient with malignant pleural mesothelioma under Viscum album and Helleborus niger extracts-a case report.

Malignant pleural mesothelioma (MPM) is a rare cancer with a dismal prognosis. Viscum album extracts (VAE) have strong immune stimulatory properties, cytotoxic effects, can downregulate cancer genes and inhibit angiogenesis. VAE are often used as an adjunct treatment in cancer patients but have rarely been investigated in MPM. Helleborus niger extracts (HNE) have been used in anticancer therapy since antiquity, and also show tumor specific cytotoxic effects. We present a case of a 64-year old woman with epithelioid MPM of the right chest with node involvement (T2N1M0, stage III). Deciding against the recommended radio-chemotherapy, surgery and pleurodesis, she opted for an integrative treatment approach and was treated with VAE and HNE. After 6 weeks' treatment, the pleural and nodal MPM manifestations were reduced by about 15%. Subsequent tumor growth was slow, and the patient remained in good health, enabling her to remain physically active until shortly before her death 56 months after the initial diagnosis. This is a rare case of an MPM patient not receiving any standard anticancer treatment; it still shows an extraordinary long survival and good performance status. We presume that VAE and HNE might had an impact on this clinically relevant outcome and therefore should be further investigated in MPM.