Innovation of the protocol for the application of cryolipolysis: Effects and mechanisms of action.

BACKGROUND: In recent years, aesthetic procedures aiming at body remodeling and have grown exponentially. Cryolipolysis (CLL) has stood out as a noninvasive resource that acts directly on the subcutaneous adipose tissue promoting a significant reduction of adipose tissue through of cooling that could lead to the crystallization cytoplasmic lipids, loss of cellular integrity, apoptosis/necrosis of adipocytes, and local inflammation, producing selective loss of adipose tissue. Thus, the objective of the present study was to evaluate the effects of a specific technique of CLL application on the inflammatory reactions of the target tissue in different post-application times. METHODS: This is a randomized, blind clinical study that evaluated the tissue sample of six patients after 45, 60, and 90 days of an innovative protocol for the application of CLL, with samples collected through abdominoplasty surgeries. The samples were evaluated by immunohistochemical analyses of several markers. RESULTS: A significantly greater increase in fibroblasts was observed at 45 days and greater phagocytic action at 60 days. Regarding the apoptosis process, the expression of caspase 3 and cleaved caspase 3 markers varied at different times, with cleaved caspase 3 being higher at 45 and 90 days after CLL application. CONCLUSION: The protocol of the CLL presented in this study was able to induce inflammatory responses in addition to confirming the selective apoptotic action at the different times studied.

How we approach the perioperative management of patients with chronic lymphocytic leukaemia receiving continuous cancer-directed therapies.

Historically, invasive procedures and surgeries were deferred in patients with haematological malignancies including advanced stage chronic lymphocytic leukaemia (CLL) because of limited life expectancy. However, novel, and often continuous, treatments have markedly improved outcomes in CLL. Some patients may expect years of treatment response and disease control, overcoming the short life expectancy that deters interventionalists. Such patients now often undergo various invasive procedures including major surgery. To inform peri-operative management, we summarize the relevant side effects and drug interactions of continuous CLL therapies, highlight potential surgical risks, and provide recommendations on withholding specific CLL drugs around invasive procedures.

Collision tumor between a spinal schwannoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: case report and review of the literature.

A collision tumor is one where two neoplasms of differing type occur at the same anatomical site. We present a patient suffering from non Hodgkin small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and complaining intense lumbar back pain refractory to medical treatment. Lumbosacral MRI showed an intradural extramedullary lesion in the left L2-L3 foramen with extracanalar development and compression of psoas muscle. CT showed intralesional calcification. The patient underwent resection of the lesion through a paraspinal posterolateral approach (Wiltse approach). The histology was of schwannoma with intralesional calcifications and lymphocitic infiltrates compatible with B-lineage SLL/CLL. After the operation the patient suffer from left psoas muscle motor weakness (3/5 MRC). Because of hematological disease progression, she underwent 6 cycles of chemioterapy (Fludarabine, Cyclophosphamide, Rituximab). At a six-month follow-up no recurrence or residual tumor upon lumbosacral MR imaging was detectable and the left thigh flexion returned normal. To our knowledge, this is the first described case in the literature of collision tumor between a solitary spinal Schwannoma and SLL/CLL.

Segmental cervical instability does not drive the loss of cervical lordosis after laminoplasty in patients with cervical spondylotic myelopathy.

BACKGROUND/CONTEXT: Kyphotic deformity after cervical laminoplasty (CLP) often leads to unfavorable neurological recovery due to insufficient indirect decompression of the spinal cord. Existing literature has described that segmental cervical instability is a contraindication for CLP because it is a potential risk factor for kyphotic changes after surgery; however, this has never been confirmed in any clinical studies. PURPOSE: To confirm whether segmental cervical instability was an independent risk factor for postoperative kyphotic change and to examine whether segmental cervical instability led to poor neurological outcomes after CLP for cervical spondylotic myelopathy (CSM). STUDY DESIGN/SETTING: A retrospective study PATIENT SAMPLE: Patients who underwent CLP for CSM between January 2013 and January 2021 with a follow-up period of ≥1 year were enrolled. OUTCOME MEASURES: Cervical radiographic measurements including C2-C7 lordosis (C2-7 angle), cervical sagittal vertical axis, C7 slope, flexion range of motion (fROM) and extension ROM (eROM) were assessed using neutral and flexion-extension views. Segmental cervical instability was classified into anterolisthesis (AL) of ≥2 mm displacement, retrolisthesis (RL) of ≥2 mm displacement, and translational instability (TI) of ≥3 mm translational motion. The amount of C2-7 angle loss at the follow-up period compared to the preoperative measurements was defined as cervical lordosis loss (CLL). Neurological outcomes were assessed using the recovery rate of the Japanese Orthopedic Association score (JOA-RR). METHODS: CLL was compared among patients with and without segmental cervical instability. Further, multiple linear regression model for CLL was built for the evaluation with adjustment of the reported risks, including cervical sagittal vertical axis, C7 slope, fROM, eROM, and patient age together with AL, RL, and TI, as independent variables. The JOA-RR was also compared between patients with and without segmental cervical instability. RESULTS: A total of 138 patients (mean age, 68.7 years; 65.9% male) were included in the analysis. AL, RL, and TI were found in 12 (8.7%), 33 (23.9%), and 16 (11.6%) patients, respectively. Comparisons among the groups showed that AL led to greater CLL; however, RL and TI did not. Multiple linear regression analysis revealed that greater CLL is significantly associated with greater fROM and smaller eROM (regression coefficient [ß]=0.328, 95% confidence interval: 0.178 to 0.478, p<.001; ß=-0.372, 95% confidence interval: -0.591 to -0.153, p=.001, respectively). However, there were no significant statistical associations in the AL, RL, and TI. Whereas, patients with AL tended to exhibit lower JOA-RR than those without AL (37.8% vs. 52.0%, p=.108). CONCLUSIONS: Segmental cervical instability is not the definitive driver for loss of cervical lordosis after CLP in patients with CSM; thus, is not a contraindication in and of itself. However, it is necessary to consider the indications for CLP, according to individual cases of patients with AL on baseline radiograph, which is a sign of poor neurological recovery.

Extended lymphadenectomy for high-risk prostate cancer in patients with chronic lymphocytic leukemia may not be necessary: a report of two cases.

BACKGROUND: Chronic lymphocytic leukemia is a malignancy with good prognosis. However, the incidence of secondary tumors increases every year after the diagnosis of chronic lymphotcytic leukemia. One of the induced secondary tumors is prostate cancer. For high-risk prostate cancer in particular, the standard therapy is radical prostatectomy and extended lymphadenectomy, which carries high risks of lymphatic leakage and reduced quality of life. Currently, there has been no study reporting the necessity of extended lymphadenectomy for high-risk prostate cancer in patients with chronic lymphocytic leukemia. CASE PRESENTATION: We reported two cases with concomitant high-risk prostate cancer and chronic lymphocytic leukemia. The first patient was a 60-year-old male diagnosed with synchronous prostate cancer and chronic lymphocytic leukemia. The second patient was a 70-year-old male initially presented with chronic lymphocytic leukemia alone but was then diagnosed with high-risk prostate cancer nine years later. Both patients received neoadjuvant androgen deprivation therapy and robot-assisted radical prostatectomy. The first patient underwent extended lymphadenectomy and developed prolonged postoperative lymphatic cyst. Histology showed chronic lymphocytic leukemia infiltration in resected lymph nodes. Serum prostate-specific antigen levels at one and 13 months post-operation were both 0.01 ng/ml. The second patient received positron emission tomography/computed tomography before androgen deprivation therapy, which showed mild fluorodeoxyglucose-avidity in lymph nodes across the entire body. Lymph node biopsy showed only chronic lymphocytic leukemia. The patient experienced no postoperative complication. Serum prostate-specific antigen levels at one and nine months post-operation were both 0.02 ng/ml. CONCLUSIONS: Extended lymphadenectomy may not be necessary for patients with concomitant high-risk prostate cancer and chronic lymphocytic leukemia, but such patients must undergo thorough preoperative assessment and mindful postoperative follow-up. Positron emission tomography/computed tomography may be valuable in detecting nodal metastases. A lymph node biopsy is necessary for patients with an ambiguous positron emission tomography/computed tomography in the metastatic involvement of lymph node.

Rapidly Progressive Intracranial Vasculopathy in Graft Versus Host Disease.

After allogenic hematopoietic stem cell transplantation, cerebrovascular complications are uncommon, occurring in approximately 2%, and typically due to coagulopathy or infection. Graft versus host disease has been rarely reported to affect the central nervous system but these cases typically describe leukoencephalopathy, encephalitis, or perivascular infiltrates or vasculitis with subcortical ischemia or hemorrhage. We report a previously undescribed noninflammatory vasculopathy causing multifocal intracranial arterial occlusions and cerebral infarctions in a man following allogenic hematopoietic stem cell transplantation for chronic lymphocytic leukemia, which we propose to be a central nervous system manifestation of graft versus host disease.

Cardiac Surgery Outcomes in Patients With Chronic Lymphocytic Leukemia.

BACKGROUND: Surgical outcomes of patients with chronic lymphocytic leukemia (CLL) undergoing cardiac surgery are limited. Our objectives were to investigate hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL patients. METHODS: From May 1995 to May 2015, 157 patients with CLL and 55,917 without and older than 47 years underwent elective cardiac surgery at Cleveland Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9.1%) intermediate risk (classes I and II), and 38 (27%) high risk (classes III and IV); 12 (8.5%) were in remission. Mean age of CLL patients was 72 ± 9.0 years, and 18% were women. CLL patients were propensity-score matched to 3 non-CLL patients to compare surgical outcomes. RESULTS: High-risk CLL patients received more blood products than matched non-CLL patients (33/38 [87%] versus 74/114 [65%], p = 0.01), but were less likely to receive cryoprecipitate (0% versus 15/114 [13%], p = .02). Intermediate-risk CLL patients received more platelet units, mean 12 versus 4.6 (p = 0.008). Occurrence of deep sternal wound infection (0% versus 5/471 [1.1%]), septicemia (5/157 [3.2%] versus 14/471 [3.0%]), and hospital mortality (4/157 [2.5%] versus 14/471 [3.0%]) were similar (p > 0.3), independent of prior chemotherapy treatment for CLL. CONCLUSIONS: Although CLL patients did not have higher hospital mortality than non-CLL patients, high-risk CLL patients were more likely to receive blood products. Risks associated with transfusion should be considered when evaluating CLL patients for elective cardiac surgery. Appropriate preoperative management, such as blood product transfusions, and alternative treatment options that decrease blood loss, should be considered for high-risk patients.

Richter Transformation: An Unexpected Diffuse Large B-Cell Lymphoma Within a Fatty Mesenteric Mass in a Patient With Refractory Chronic Lymphocytic Leukemia.

Richter transformation is the development of a high-grade lymphoma from chronic lymphocytic leukemia. This rare disease manifestation is difficult to predict and carries a poor prognosis. We describe the case of a 75-year-old man with refractory chronic lymphocytic leukemia who presented with multiple growing fatty abdominal masses on computed tomography and vague abdominal distension. The patient underwent exploratory laparotomy with mass resection due to the nonspecific imaging findings. A mesenteric mass was found to contain nodules of diffuse large B-cell lymphoma. This case highlights the importance of radiologists to consider the prospect tumor transformation in the differential diagnosis of enlarging abdominal masses.

Transthoracic ultrasonography for the follow-up of a chronic lymphocytic leukemia patient with chemotherapy-induced immunosuppression prior to allogeneic stem cell transplantation. A case report.

In the last years, significant progress has been made in the clinical follow-up of leukemia patients who are especially prone to various infections because of the specific immunosuppressive state following chemotherapy. The follow-up of such patients is of special interest and is based on modern imaging protocols especially computer tomography (CT). Still, CT may not always be effective in the diagnosing of respiratory infections. We report a chronic lymphocytic leukemia patient in which the pleuro-pulmonary complications were successfully diagnosed and followed up using transthoracic ultrasonography.

Rare association of cystic squamous cell carcinoma and small lymphocytic B cell lymphoma: successful surgical approach.

Non-melanoma skin cancer is the most common type of cutaneous neoplasm worldwide. While basal cell carcinoma is the most common tumor, squamous cell carcinoma (SCC) causes higher morbidity and has a risk of metastatic spread, depending on immune status, tumor size, and desmoplastic growth. We reported the case of a 77 year old male patient with retroauricular tumor, which started growing 3 years ago and was excised, buth relapsed three times. The initial diagnosis was infundibular cyst. Delayed Mohs surgery was performed, as was an additional open lymph node biopsy of the patient's right groin, on the occasion of an indolent swelling of the same which developed within 3 months. The first histopathological report confirmed the diagnosis of a cystic squamous cell carcinoma. The histopathologic evaluation of the groin tumor revealed a small lymphocytic B cell lymphoma (BCL). The patient fulfilled the following criteria for high-risk SCC: tumor size ≥2 cm (or 1 cm on the head and 6 mm on the genitals, hands, and feet), tumor thickness ≥4 mm, recurrent tumor, rapid growth. Therefore, lymph node metastasis had to be considered. High-risk SCC has a propensity to metastasize. In cases of primary tumor, Mohs surgery is the most effective treatment, particularly in relapsing tumors. The combination of cystic SCC with a small-sized BCL is very rare. The differential diagnosis and treatment may be challenging. In high-risk SCC, lymph node enlargement warrants histologic evaluation. However, not all suspicious lymph node lesions corroborate as metastatic.

[Synchronous colorectal carcinoma and non-Hodgkin lymphoma - two case reports]. / Synchronní kolorektální karcinom a nehodgkinský lymfom - popis dvou prípadu.

Colorectal carcinoma represents an important cause of morbidity and mortality in adults, and its incidence in the Czech Republic is one of the world´s highest. The basic therapeutic approach is surgery: surgical removal of the affected part of the bowel together with regional lymph nodes dissection. The lymph nodes are routinely examined by means of histopathology. In this paper, we present two patients whose histological examination of mesocolic lymph nodes revealed an infiltration by synchronous malignant B-non-Hodgkin-lymphoma. Mantle cell lymphoma was present in the first case, and small cell lymphoma CLL/SLL in the other. Relevant literature is reviewed. KEY WORDS: synchronous - malignancy - colorectal - lymphoma - lymph node.

Allogeneic Transplantation for Chronic Lymphocytic Leukemia in the Age of Novel Treatment Strategies.

Hematopoietic stem cell transplantation (HSCT) is the only established potentially curative treatment option for chronic lymphocytic leukemia (CLL) to date. However, this approach is associated with high toxicity and significant treatment-related morbidity and mortality; thus, it is suitable for only a minority of high-risk patients, given that most persons with CLL have comorbidities and are of advanced age. Until very recently, international guidelines recommended HSCT for physically fit patients who displayed poor-risk features or had only a short response to immunochemotherapy. In the wake of novel treatment approaches that offer high efficacy and highly durable responses with little toxicity, our approach to HSCT in CLL needs to be re-evaluated. While we wait for data on the long-term efficacy of novel therapies to inform the choice of HSCT or alternative treatment, strategies must be assessed individually for every patient, and treatment must be conducted in the setting of randomized clinical trials whenever possible.

A rare association of chronic lymphocytic leukemia with c-ANCA-positive Wegener's granulomatosis: a case report.

BACKGROUND: Wegener's granulomatosis is a systemic vasculitis of the small- and medium-sized vessels, produced by the action of ANCA, which involves the respiratory tract, kidneys, and eyes, with a potential for lethal evolution in the first year after diagnosis. Its association with chronic lymphocytic leukemia is rarely described in the literature, and it may be difficult to diagnose and to treat this association. CASE PRESENTATION: We present the case of a 73-year-old Caucasian patient, a rare case in which Wegener's granulomatosis is associated in a patient with chronic lymphocytic leukemia, who is admitted in the Infectious Disease Department for fever, diplopia, headache, purulent and hemorrhagic nasal secretions, intense asthenia, and weight loss. The patient had associated eyelid edema; scleritis; chemosis; subconjunctival hemorrhage at the left eye; swelling of the left region of the eyehole, of the base of the nasal pyramid, and of the left zygomatic region; anterior nasal bleeding; pustulous non-itching lesions at the cervical region and posterior thorax; enlarged bilateral axillary lymph nodes; hepatomegaly; and moderate splenomegaly. During the surgical treatment of the pansinusitis, a biopsy from the tissue is taken; the biopsy fragments of the nasal mucosa pleads for Wegener's granulomatosis. The c-ANCA were positive. The patient's evolution was favorable under treatment with meropenem, teicoplanin, fluconazole, transfusions of platelet concentrates, and methylprednisolone. CONCLUSIONS: The real dimension of the association between chronic lymphocytic leukemia and Wegener's granulomatosis is not known; it may be useful to evaluate the vasculitis by testing ANCA routinely in patients with chronic lymphocytic leukemia and by histopathological examinations of the lesions.

Laparoscopic Resection of Gastric Cancer in a Patient with Chronic Lymphocytic Leukemia Accompanied by Neutropenia.

AIM: We report an unusual case of early gastric cancer and T-cell-type chronic lymphocytic leukemia accompanied by severe neutropenia that was successfully treated by laparoscopic gastrectomy. CASE REPORT: A 76-year-old female was referred to our Hospital for resection of a gastric adenoma that was suspicious for malignancy. Routine preoperative laboratory studies showed severe neutropenia and increased atypical lymphocytes in the peripheral blood. Bone marrow biopsy confirmed the diagnosis of T-cell chronic lymphocytic leukemia. One day before surgery, granulocyte colony-stimulating factor was administered. Laparoscopic-assisted distal gastrectomy was performed. The patient's postoperative course was uneventful and she was discharged after 10 days. The histopathological findings revealed well-differentiated adenocarcinoma (pT1a, pN0, and stage IA). CONCLUSION: Laparoscopic gastrectomy may be considered a primary approach in patients with neutropenia because it is associated with lower risk of postoperative infection and a lower mortality rate compared to open resection.

Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease.

PURPOSE: Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues. METHODS: We conducted a clinical trial of allogeneic T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting the B-cell antigen CD19. Patients with B-cell malignancies that had progressed after alloHSCT received a single infusion of CAR T cells. No chemotherapy or other therapies were administered. The T cells were obtained from each recipient's alloHSCT donor. RESULTS: Eight of 20 treated patients obtained remission, which included six complete remissions (CRs) and two partial remissions. The response rate was highest for acute lymphoblastic leukemia, with four of five patients obtaining minimal residual disease-negative CR. Responses also occurred in chronic lymphocytic leukemia and lymphoma. The longest ongoing CR was more than 30 months in a patient with chronic lymphocytic leukemia. New-onset acute graft-versus-host disease after CAR T-cell infusion developed in none of the patients. Toxicities included fever, tachycardia, and hypotension. Peak blood CAR T-cell levels were higher in patients who obtained remissions than in those who did not. Programmed cell death protein-1 expression was significantly elevated on CAR T cells after infusion. Presence of blood B cells before CAR T-cell infusion was associated with higher postinfusion CAR T-cell levels. CONCLUSION: Allogeneic anti-CD19 CAR T cells can effectively treat B-cell malignancies that progress after alloHSCT. The findings point toward a future when antigen-specific T-cell therapies will play a central role in alloHSCT.