Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with poor prognosis that can present as HTLV-1-associated bronchioloalveolar disease (HABA). Chemotherapy is recommended for ATL; however, it is not very effective against all types of ATL. Furthermore, there are no effective treatments for smoldering HABA-associated ATL. We present a case in which amplified natural killer cell (ANK) therapy was effective in a woman in her early 80s who was previously diagnosed with ATL-related smoldering HABA and presented with dyspnea and productive cough on exertion. The symptoms were suppressed for approximately 10 months after the first treatment, but then gradually worsened. About a year later, a second treatment was followed by mild side effects. Suppression of ATL cell proliferation by repeated doses of ANK therapy appears to be effective in this patient. The therapeutic effect was high even with long treatment intervals, and the efficacy and safety of repeated treatments have been demonstrated. ANK therapy is expected to be the mainstay of treatment ATL and HABA. ANK therapy has been reported to kill PD-L1 positive tumor cells and some solid tumors with excellent responses have many PD-L1-positive tumor cells. ANK therapy is thought to be effective for ATL because there are many PD-L1-positive tumor cells. Furthermore, administration of activated NK cells may increase tumor-killing activity in those patients with reduced NK activity. While future studies are needed, PD-L1 positive rate and NK activity may be biomarkers for the effectiveness of ANK therapy.
Amplified Natural Killer (ANK) therapy is modified to increase the safety and efficacy of the original (LAK) immunotherapy. It is a method of removing natural killer (NK) cells from the patient's own blood, culturing and amplifying the NK cells, specifically increasing their ability to attack cancer and returning them for treatment. It is generally effective against all cancers. The two cases presented here and the other treated cases show that ANK therapy is very safe and effective against ATL. Further research suggests that ANK therapy, rather than chemotherapy, is likely to be the first-line therapy for ATL. In addition, low activity of NK cells means accumulation of bacterial load. Therefore, ANK therapy with high doses of activated NK cells may be effective not only for ATL and cancer, but also for patients with chronic bacterial and viral infections.
BACKGROUND Gastrointestinal stromal tumor (GIST) constitutes up to 1% of all malignant neoplasms of the gastrointestinal tract, with the stomach and small intestine being the most frequently affected organs. The purpose of this report is to present the first published case of synchronous duodenal and jejunal GISTs. CASE REPORT A 57-years old male patient with type II diabetes complained of asthenia and vertigo, resulting from anemia. On upper digestive endoscopy, a friable lesion was found in the second portion of the duodenum. The biopsy diagnosed GIST and its removal was indicated. During the surgical procedure, a second tumor was found in the jejunum, which was also removed. Anatomopathological examination of this second lesion also revealed GIST with the same cytological features. Digestive reconstruction was performed in Roux-en-Y of the jejunum sectioned distally to the tumor with the open part of the duodenum. The patient evolved without complications, was discharged on the third postoperative day and has been followed up for eleven years without any other treatment and without neoplastic recurrence. Food transit occurs almost exclusively through the duodenum. CONCLUSION This is the first report of two synchronous GISTs of duodenum and jejunum. After removal of both tumors, the Roux-en-Y reconstruction adequately closed the opened duodenum, but food transit persisted physiological through the duodenum.
OBJECTIVE Advances in systemic therapy together with better diagnostic and surgical techniques have contributing to survival improvement of many tumor types. Patients with cancer have an increased risk of suicide and the psychological impact of cancer is due the diagnosis itself, side effects of the therapy and cancer-related symptoms. METHOD The purpose of this study is to present the clinical case of an advanced gastrointestinal stromal tumor patient who committed suicide after 6 years of treatment. RESULT A 49-years-old male with a history positive only for an anxiety-depressive disorder was diagnosed with a locally advanced gastrointestinal stromal tumor. After 6 months of neoadjuvant imatinib, with stable disease, the patients decided to undergo surgery, with the subsequent resumption of adjuvant imatinib. Once the patient experienced disease progression, he preferred a surgical approach, even though he was aware that surgery was not the standard treatment and that a second-line systemic therapy was recommended. When the start of a second line therapy was the only possible treatment option, the patient has resigned himself to the idea that he would never be able to heal from cancer. After few months of second-line therapy he died of suicideSIGNIFICANCE OF RESULTS This case report shows that suicidality in cancer patients is a continuum spectrum from wanting to live, through the decreasing will to live, the readiness to die and then actively ending one’s life. Multidisciplinary teams should focus their attention not only on the disease itself but also on the cancer-related long-term psychological distress. Therefore, patient palliative care on psychological aspects should be improved strengthening psycho-social interventions during the entire cancer treatment history, not only at the end of life.
BACKGROUNDThe cancer stem cell (CSC) hypothesis of tumor genesis suggests that unlike most cancer cells within tumor CSC resist chemotherapy and can regenerate various cell types in tumor thereby causing relapse. Hence drugs that selectively target CSC may offer great promise for cancer therapy especially when combined with chemotherapy. Current treatment options for colorectal cancer (CRC) and other gastrointestinal (GI) tumors rely on combination of surgical resection, cytotoxic and targeted drugs. Recent findings showed that metformin, an ant diabetic drug was associated with a significantly lower risk of CRC (0.63 [0.47 - 0.84]; P = 0.002) in patients with type 2 diabetes. We therefore hypothesize that administration of metformin will reduce CSC.METHODSPatients with CRC and other GI cancers undergoing resection were enrolled. Metformin was administered at 500 mg orally twice daily for up to 14 days and terminated 24 hours, prior to planned surgery. Both tumor and normal tissue was procured. Adverse events (AEs) were graded according to NCI CTCAE Version 3.0. Primary objective was to establish the safety of administering metformin prior to resection. Secondary objective was to evaluate the effects of metformin on the expression of CSC markers by measuring relative mRNA levels of CD133, OCT4 and NANOG by RT-PCR and immunohistochemistry.RESULTSA total of 10 patients (4 Male; 6 Female) received metformin. Grade 3 AEs included anemia, hypoalbuminemia, alanine aminotransferase elevation, abdominal pain and nausea but none of these were related to metformin. No hypoglycemia and lactic acidosis were observed. No unexpected post-operative complications were witnessed. Comparison of markers of CCSC results showed that expression of CD133, OCT4 and NANOG expression were decreased following metformin.CONCLUSIONSOur pilot study showed feasibility of metformin before surgery in GI cancers and indicated impact on CSC. This preliminary data warrants further investigation in a larger randomized placebo-control study to assess these markers and their correlation with survival.
Non-small cell lung cancer (NSCLC) was traditionally associated with a poor prognosis. Between 2010 and 2016, the 5-years overall survival for all stages combined was about 25 percent. However, the recent use of immunotherapy has led to significant improvements in progression free survival (PFS) and overall survival (OS). Immune check point inhibitors enable the host immune system to mount a lethal response against tumor cells. Both PD-1 (nivolumab, pembrolizumab, cemipilimab) and PD-L1 inhibitors (atezolizumab and durvalumab) have been approved by the FDA for use in NSCLC, either as individual agents or in combination with platinum-based chemotherapy, radiation therapy, or other agents. As the future of immunotherapy for lung cancer continues to evolve, with multiple agents approved or in various stages of clinical research, it is imperative that we understand the mechanism of action, clinical activity, ongoing clinical trials, indications for use and toxicity for individual agents in addition to having general, basic knowledge about this new class of cancer therapeutics. In this review, we focus on two of the newer PD-L1 inhibitors, durvalumab and avelumab.
Colorectal carcinoma is the third most common cancer in the US. The liver tends to be the most common site of metastasis. This review provides an in-depth analysis of non-transplant options available in the management of colorectal liver mets.
BACKGROUND:In the last years immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) not supported by a driver mutation. Immunotherapy related adverse events (irAEs) have a unique toxicity profiles distinct from the toxicities of classical chemotherapy treatment relating to their mechanism of action. We analyzed some serious and uncommon life-threatening irAEs, needing a change in the therapeutic strategy.METHOD:Between October 2018 and October 2020, 63 NSCLC patients underwent immunotherapy. Thirty-eight patients underwent first-line Pembrolizumab, 200 mg every 21 days (Group A). Twenty patients were treated in second line with Pembrolizumab 200 mg every 21 days or Nivolumab 240 mg every 14 days or Atezolizumab 800 mg every 14 days (Group B). Five stage III patients treated after radio chemotherapy with Durvalumab 1500 mg every 14 days (Group C).RESULTS:We experienced: a) 2 bowel perforations (3.2%), necessitating Hartmann's resection. Only one of the two patients restored immunotherapy; b) 1 chronic renal insufficiency (1.6%, creatinine up to 8 mg/dL) and 2 severe hypertransaminasemias (3.2%, up to 65 U/L), requiring the immediate and definitive interruption of ICIs; c) 2 pericardial effusions (3.2%), of which one needed subxiphoid pericardiocentesis for cardiac tamponade. Patient restored immunotherapy after resolution of the acute event.CONCLUSIONS:Immunotherapy include monoclonal antibodies reducing the suppression of effector T cells and improving the tumor-specific immune responses. Most common irAEs are evident in mild and reversible form, but sometimes life-threatening irEAs show up. Therefore, further clinical trials needed to increase knowledge of drugs and prevent unexpected irAEs.
Stereotactic body radiotherapy (SBRT) is an emerging treatment option for patients with pancreatic cancer, as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation (CRT). The objective of this review is to present alternative clinical settings in which SBRT may benefit patients with pancreatic cancer. These include palliation of pain, elderly patients who are not surgical candidates, local therapy in oligometastatic cases and salvaging local failures after surgery or external beam radiation. We will review these individually and provide supporting literature for each.
EDITORIAL Olaparib, a PARP inhibitor, was approved in 2019 for use as a first-line maintenance treatment of germline BRCAmutated metastatic pancreatic ductal adenocarcinoma (mPDAC), based on findings from the pivotal POLO trial [1]. This phase III randomized, double-blind controlled trial included 154 metastatic PDAC patients with mutation in germline BRCA1 or BRCA2 who received at least 16 weeks of first line platinum-based chemotherapy, mainly FOLFIRINOX. As maintenance therapy within 4 weeks 8 weeks of completion of chemotherapy, 92 patients were randomized to olaparib 300 mg twice daily while 62 patients were assigned to placebo. The primary endpoint of the study was progression free survival (PFS) which was nearly doubled in olaparib group compared to placebo group (7.4 months and 3.8 months respectively; HR 0.53; P = 0.004). Secondary endpoints were overall survival (OS), second PFS (PFS2), objective response rate (ORR) and the change in scores of global health-related quality of life (QoL). Although the study met its primary endpoint, median OS was not statistically significant (18.9 months in Olaparib arm versus 18.1 months in placebo arm, HR 0.91, 95% CI, 0.56 1.46, p = 0.68). Interestingly, two patients from olaparib group had a complete response at the time of interim analysis and data maturity of 46% [1].
INTRODUCTION:Erb-b2 receptor tyrosine kinase 2 (ERBB2) testing is used to measure the status of ERBB2 gene expression and DNA amplification. Test results have been reported with a discrepancy as high as 20%. The purpose of this study was to improve ERBB2 fluorescence in situ hybridization (FISH) sensitivity by evaluating results generated by median as well as mean calculations.METHODS:We retrospectively identified breast cancer cases at our institution in which ERBB2 FISH testing was performed in-house from June 2018 to May 2020. FISH results were classified using the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines: groups 1 and 5 are FISH positive and negative, respectively, and groups 2-4 are equivocal requiring additional work-up. FISH counting sheets were collected and regrouped by median ERBB2 copy number counts and median ERBB2/CEP17 ratio and compared with the mean ERBB2 and mean ERBB2/CEP17 ratio. Intra-tumor genetic heterogeneity and CEP17 copy number gain (CEP17 ≥3) were assessed to see if they affect the discrepancy between median and mean groups.RESULTS:Seventy-two breast cancer cases were collected and evaluated. Eleven cases (11 of 72 [15%]) had discrepant grouping by mean and median calculations. A significant number of discrepancies were found for CEP17 copy number gain (p = 0.027) but not for ERBB2 (p = 0.411), the ERBB2/CEP17 ratio (p = 0.445), FISH results (p = 0.194), or genetic heterogeneity (p = 0.465). Among the four cases regrouped to median group 1, 2 were from mean group 3 and underwent anti-ERBB2 targeted therapy and 2 were from mean groups 4 and 5 may have benefitted from targeted therapy with more than 30% amplified cells. The median may be better to reflect the monosomy subclone within tumor tissues for the case 387 moved from mean group 5 to median group 2. The 6 cases moved from mean group 5 to median group 4 with CEP17 copy number gain may have had a poor prognosis based on other study result.CONCLUSION:Including the median calculation may increase ERBB2 sensitivity and identification of CEP17 copy number gain. Further clinical studies are necessary to examine the outcome of including median in calculating ERBB2/CEP17 values.
Jehovah's Witnesses undergoing liver or pancreas surgery represent a unique medical and ethical challenge. For hepatic and pancreatic malignancies, resections are currently the only curative treatment. These surgeries pose a risk for significant blood loss, for which blood transfusions are traditionally given. However, blood transfusions are considered unacceptable to many Jehovah's Witnesses patients. As the technology of surgery as well as development of new products continue to evolve, transfusion-less surgery modalities have been utilized for Jehovah's Witnesses. The use of these transfusion-less techniques is not yet standardized for hepatic and pancreatic resections. We aimed to review both oncology and transplant medical literature on pancreatic and hepatic resection to develop guidelines for the management Jehovah's Witnesses patients.
Jean was 33-year-old female diagnosed with metastatic breast cancer in August of 2019. She was altruistic, full of life and eager to participate in clinical research so she could help the patients who came after her. Jean and her mother were a force. They did everything together.
Bladder cancer used to be the only cancer treated by immunotherapy in form of intravesical BCG. Since approval of BCG for Non muscle invasive bladder cancer (NMIBC), there has been significant advancement in our knowledge about immune alteration in cancer and availability of immunotherapeutic agents. Tumor induced cell mediated immunosuppression is identified as a key factor for development and progression of cancer. Immune suppression in bladder cancer is predominantly through Macrophages. Myeloid derived suppressor cell, NK cells, Treg and expression of immune checkpoint receptor inhibitors also contribute to immune suppression. BCG induces innate immune response and its efficacy is limited to NMIBC. Novel immunotherapeutic agents evaluated in bladder cancer are administered locally or systemically to induce innate or adaptive immune response. Systemic administration of antibodies against PD-1/PD-L1 axis are now approved for treatment of locally advanced/metastatic bladder cancer as a first line as well as second line therapy. Pembrolizumab is also approved for BCG unresponsive NMIBC. Since response to immunotherapy are neither uniform nor universal, attempts are made to identify prognostic and predictive biomarkers. Identified biomarkers lack desired specificity and sensitivity. Several immune approaches using innate as well as adaptive mechanism are under evaluation to improve outcome of intravesical BCG or immune check point receptor inhibitors.
COVID-19 has now been declared a global pandemic with evolving incidence rates and fatalities. It is important to identify vulnerable populations who will be impacted most by this pandemic leading to higher mortality rates compared to the general healthy population. Although older patients and patients with co-morbidities fall into this vulnerable group, patients with hematologic and oncologic malignancies on active cytotoxic treatments are at even greater risk as they are both myelosuppressed and immunosuppressed. In addition to following the universal guidelines recommended by the Centers for Disease Control (CDC), it is important to also institute guidelines for cancer centers to help protect this vulnerable population. We review the current data, risks, and recommendations for COVID-19 in cancer patients.
The ability of innate immunity to inhibit metastatic cells is limited, based on Stage IV cancer survival rates. The dysregulation of the immune system through acquired immunity may result in pathological conditions that alter metastatic cells. Immunoglobulin-E (IgE) antibodies developed by the humoral immune system are a significant contributor to maladaptive immunity. Hypersensitivities are maladaptive immune reactions against harmless allergens. Forced allergen-specific immune responses may provide immediate-type allergies that affect the incidence and prevalence of endogenous proteins essential for metastasizing cells. Furthermore, allergies may shift the body’s resource allocation away from metastasizing cells to IgE-primed effector-cell proliferation. Therefore, research efforts need to explore if hyper-allergenic skin creams can be used to starve-out metastatic cells, wherever they are in the body, to determine if maladaptive immunotherapy is a viable treatment for Stage IV cancer.
The cutaneous mastocytosis is characterized by infiltration and proliferation of mast cells in the skin with no evidence of extracutaneous involvement. The clinical findings most frequently found are brownish macules or papules slightly elevated, frequently localized in the limbs, chest and abdomen. Mutations in the c-kit receptor (CD117) are frequent and provide the pathophysiology basis of the disease. These mutations allow autophosphorylation of the c-kit receptor and subsequent degranulation of mast cell precipitated with a variety of stimuli, releasing local or systemic cell mediators capable of causing symptoms. Skin lesions occur in both the systemic and the cutaneous form of the disease, though the latter is more frequently seen in children, while most adults with mastocytosis present signs and symptoms of systemic involvement. Although this clinical pattern, we report a rare case of adult-onset cutaneous mastocytosis in a masculine patient of 32 years old. Clinical presentation featured hyperpigmented macules with brownish coloration diffused through the chest and limbs. Skin and bone marrow biopsies and laboratory testing were made and strengthened the diagnosis of cutaneous mastocytosis, a clinical presentation with little similar case reports.
Objectives: The aim of this study was to measure circulating cytokines (IL17, IL6, IL22, IL23 and TNFα) and to evaluate their role as markers and in prognosis in Tunisian patients with breast cancer. Materials and methods: Our prospective study enrolled 60 untreated patients affected by breast cancer. We evaluated their levels of TNF-α and IL6 within solid-phase, two-site chemoluminescent enzyme immunemetric assay. Seric levels of IL17, IL22 and IL23 were measured by ELISA sandwich technique and results compared by chi-2 square. Results: Our population, all females, have a mean age of 48 years, a localized disease in 75% of cases and metastatic in the resting 25%. The mean cytokines levels for IL6, IL17, TNFα, IL22 and IL23 were respectively 4.8 ± 7.2 pg/ml, 0.27 ± 0.69 pg/ml, 5.9 ± 2.2 pg/ml, 50.8 ± 34.7 pg/ml and 18 ± 30.9 pg/ml. Serum IL6 levels were significantly higher with advanced stages and particularly, metastatic stage IV and in relapsing patients. We observed also higher TNFα levels in advanced stages (III and IV) and IL22 in cases with grade III SBR. For IL23, higher levels were observed in axillary node positive cases and in patients younger than 35 years. IL17 was significantly higher with patients who relapsed. Conclusion: Our results highlight the role of cytokines in the serum as potential prognostic biomarkers in breast cancer patients, which could contribute to tumor growth and progression. Analyzing serum cytokine levels may help to identify patients with poor prognosis who may benefit from more aggressive treatment.
The risk of genitourinary cancers following transplantation is increased following majority of solid organ transplants but is best described following renal transplantation. Increasing average age of the transplant recipient as well as increases in post- transplant survival increases the risk of these malignancies. The risk of Kidney cancer is the highest following most solid organ transplants, whereas prostate cancer risk is lower than the general population in multiple large population-based studies. The etiology of increased risk of cancer following transplant is multifactorial with the predominant influence of immunosuppression and direct toxicity of immunosuppressants, however, the significance of end stage disease particularly in the causation of renal cancer in renal transplant recipients is undeniable. Modifications in immunosuppression regimens as well as changes in the standard treatment principles of some cancers may require changes in the management of some post-transplant malignancies. Standard screening guidelines have not been established but screening for renal tumors in renal transplant recipients is the only widely studied entity. Further work is needed to prepare the urologic oncological community with this once rare population group and standardized recommendations need to be established for screening and for the use of new age cancer therapeutics like immunotherapy.
There is no doubt that the modern scientific medicine helps in sustaining human life, but tends to forget terminal ill experiences unlike other illness is accompanied by several mental and psychological factors. The core criteria to deliver quality of life in terminal illness are to assess its bi-products like mental disharmony, depression, and the psychological issues. The spiritual psychotherapy is a modern humanistic approach that has holistic view on human illness in health and medical sciences. It is an effective coping mechanism to cope with stress, anxiety, depression, and suffering that are frequently experienced by terminally ill patients to delivered quality of life and meaning making policy in the clinical settings. Palliative end-of-life care on the other hand main objective is to improve quality of life of the terminal patients and the family that includes the physical, psychological, and spiritual wellbeing assessments. Considering the helplessness conditions of the terminal patients the spiritual psychotherapy is the urgent needs as it viewed human illness as the complex interplay between the biopsychosocial-spiritual factors. Especially when the patient is in the context of healing impossibility, spirituality plays an important role in meeting the needs of the dying individual’s before the inevitable death strikes. Objective/Purpose The purpose of this analytical review is to ponder on the role of spirituality in meaning-making and a source of hope mainly when cure is not possible in the terminal experiences. It is also to find out how spirituality serves as a coping mechanism in the face of inevitable death and makes life more meaningful to the dying individuals. Method The propose study will use philosophical inquiry on the existing literatures.
