Treatment Of Aggressive Forms Research Articles

Large granular lymphocytic leukemia cured by allogeneic stem cell transplant: a case report

BackgroundLarge granular lymphocytic leukemia is a rare lymphocytic neoplasm that can pose a treatment challenge in patients with severe neutropenia in whom conventional therapies fail. We report one of the first cases in which allogeneic stem cell therapy was used as treatment for large granular lymphocytic leukemia.We report and discuss the case of a 42-year-old white Caucasian female who, despite multiple therapies including methotrexate, cyclophosphamide, prednisone, cyclosporine, and pentostatin, continued to show severe neutropenia and recurrent infections. The patient was treated successfully and cured by allogeneic stem cell transplant without any major complications.ConclusionsThe significant importance of this case report is the introduction of a new treatment algorithm for challenging cases of T-cell large granular lymphocytic leukemia in which standard care fails. We hope that this case report will raise awareness of the potential benefits of allogeneic stem cell transplant in the treatment of aggressive forms of T-cell large granular lymphocytic leukemia.

Chapter 16 - Dorsal root entry zone procedure and other surgeries for pain

Pain is a very common symptom that often serves a protective function. It is typically treated medically. When pain becomes chronic and intractable, it no longer serves a protective function and often requires more aggressive forms of treatment. Many types of surgeries can be performed for the management of pain. These surgeries can involve ablation (destruction) or augmentation (stimulation or facilitation) of some part of the nervous system. In many of these surgeries, neurophysiologic intraoperative monitoring (NIOM) is not needed, however, in others neuromonitoring serves a mapping and monitoring purpose. The prototype of pain surgery for this chapter is the dorsal root entry zone (DREZ) procedure. Both mapping and monitoring can help improve lesioning precision and outcomes in this surgery. In this chapter, the DREZ procedures and other surgeries for primarily pain relief in which NIOM is used are discussed. Surgeries, such as spinal stenosis, in which pain relief is important but not the sole purpose, are not discussed here and are covered elsewhere.

Abstract 2797: Changes in the phenotype of macrophages and CD8+ T Cells in the perivascular niche of prostate tumours following androgen deprivation

Abstract Men with intermediate/high-risk, localized prostate cancer usually receive neoadjuvant androgen deprivation therapy (ADT). Although this markedly reduces tumor burden, it may not be curative and over time cancer cells develop resistance to ADT causing the tumor to regrow and spreads to other sites like the bones. Tumors are then termed ‘castration resistant' (CR) and require more aggressive forms of treatment like radical prostatectomy (RP) and chemotherapy. These can have unpleasant side effects so preventing the development of castration resistance and subsequent tumor regrowth/metastasis, would be highly beneficial for patients. A distinct subset of perivascular (PV) tumor-associated macrophages (TAMs) expressing the cell-surface receptor, MRC1, has been shown to be proangiogenic, immunosuppressive and to stimulate tumor regrowth after chemotherapy, irradiation or vascular targeting drugs. In the current study, we have examined the density and phenotype of TAMs in PV vs non-PV areas of localized, human prostate tumors and orthotopic mouse (Myc-CaP) tumors following neoadjuvant ADT or castration respectively. In human tumors, MRC1+ TAMs accumulated at highest density around stromal blood vessels, and were abundant in these sites following ADT. In mice, castration markedly reduced primary tumor growth and changed the distribution and phenotype of TAMs and cytotoxic CD8+ T lymphocytes (CTLs) just prior to the development of CR. In PV areas of tumors in sham-castrated (i.e. control) mice there were significantly more TAMs expressing MRC1 and the broad-spectrum negative checkpoint regulator, VISTA than in non-PV areas. This was accompanied by the preferential accumulation of CTLs around blood vessels (contrasting with the even distribution of CD4+ (helper) cells and CD4+FOXP3+ Tregs across PV and non-PV areas). Following castration, the PV density of MRC1+ and VISTA+ TAMs was markedly increased, along with that of CTLs expressing the cytotoxic protease, granzyme B - a marker of active CTLs. Although these cells may cross the vasculature into tumors in an active state, passing through a PV niche enriched in VISTA+ TAMs would likely suppress their cytotoxic function before they progressed into the tumor mass. An interesting picture is, therefore, emerging of tumor-promoting TAMs accumulating around blood vessels after various forms of treatment, where they regulate a number of important events including the extravasation and function of various immune effectors. Citation Format: Haider Al-janabi, Xuan Pu, Munitta Muthana, Ning Wang, Mateus Crespo, Bora Gurel, Johann De Bono, Janet E. Brown, Claire E. Lewis. Changes in the phenotype of macrophages and CD8+ T Cells in the perivascular niche of prostate tumours following androgen deprivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2797.

Recurrence Rates of Odontogenic Keratocysts Treated with Carnoy’s Compared to Modified Carnoy’s Solution

The odontogenic keratocyst (OKC) composes 5-15% of odontogenic cysts and is known for its locally aggressive behavior and high recurrence rate. It has an unacceptably high recurrence rate of 13-58% when treated surgically with enucleation and curettage (EC) and peripheral ostectomy alone. More aggressive forms of treatment, such as resection, have a lower recurrence rate at the expense of increased morbidity associated with the resultant mandibular bone defect. Carnoy’s solution (CS) was found to improve outcomes and is composed of 60% ethanol, 30% chloroform, 10% glacial acetic acid, and 1 gram of ferric chloride. The FDA banned CS in 2013 for containing chloroform, which was “reasonably anticipated to be a human carcinogen” based on animal studies. This led to substitution with the non-chloroform containing Modified Carnoy’s solution (MC), causing a divide among oral and maxillofacial surgeons (OMSs). A 2016 survey found that 25% of OMSs use CS or MC in conjunction with EC. Of these surgeons, 56% of continue to use CS despite the FDA warning.1 The only study that has investigated the relative effectiveness of the 2 solutions suggested that MC (35% recurrence) is not as effective as CS (10% recurrence) but only involved a single center and combined the results of 3 different surgeons.2 A retrospective chart review study from 2004 to 2019 was conducted on patients treated at UNC with a diagnosis of OKC and who had follow-up of at least 12 months after surgery. Overall, 149 patients were identified who had a diagnosis of OKC treated with billing codes 21046 or 21048 (EC of cyst of maxilla or mandible). All patients were treated by a single surgeon (GHB). Twenty patients were excluded for diagnosis of Gorlin syndrome, 48 for inadequate length of follow-up, and 2 for no use of chemical curettage, resulting in 79 patients who met inclusion criteria. The primary predictor variable was use of CS or MC, which was determined by date of procedure and operative notes. The primary outcome variable was recurrence (yes vs no), determined by pathological analysis of biopsied specimens when radiographic or clinical recurrence was suspected. These data were analyzed using an unpaired test of proportions. For those with a recurrence, the time from treatment to OKC recurrence was collected. Secondary variables included demographics, anatomic location, whether teeth adjacent to the lesion were preserved or extracted, and whether the patient had treatment of a past OKC prior to presentation. We found that 45/79 (57%) patients had OKCs of the mandible, 33/79 (41.8%) of the maxilla, and 1/79 (1.2%) in both. Overall recurrence rate was 11/79 (13.9%). Overall, 40/79 (50.7%) were treated with adjunctive MC, and 39/79 (49.3%) were treated with adjunctive CS. Recurrence rate was 5/40 (12.5%) in the MC group and 6/39 (15.4%) in the CS group. Based on these data, there was no statistically significant difference in recurrence between the 2 groups as evidenced by a P-value of .7115, suggesting that MC is an effective adjunctive to EC for the treatment of OKCs. Based off the high percentage of patients who did not return for 1-year follow-up (28.9%), a future study could seek to enumerate commonalities among patients who were lost to follow-up to determine how this can improve.

Fertility-related considerations in endometriosis

Endometriosis and infertility often present together but the exact cause-effect mechanism of this association is unknown. Though there are several proposed mechanisms regarding the pathophysiology of endometriosis-related infertility, no one theory is universally accepted. Surgical exploration is gold standard for diagnosis but imaging modalities especially specialized ultrasonography and magnetic resonance imaging can highlight disease burden and aid in planning for surgical excision. Overall, medical therapy is ineffective for endometriosis-related infertility; however, surgery may be fertility enhancing in women with minimal stage disease and in women with large endometriomas. Assisted reproductive technology may be required with endometriosis-related infertility. Medically induced superovulation with intrauterine insemination is typically the first line; however, women with advanced disease may need a more aggressive form of treatment with in vitro fertilization.

The local treatment of DCIS should be different than that of early-stage invasive cancer

Surgical methods currently applied in the local treatment of pre-invasive ductal carcinoma are largely the same as those used in early-stage invasive breast cancer. Both conditions are treated either with tumor excision (combined with radiation therapy) or with mastectomy. Comparable proportions of DCIS and early-stage breast cancer patients receive the most aggressive form of treatment. Nearly 30% of the former undergo mastectomy. A question thus presents itself: is this the way it should be? The purpose of DCIS treatment is to prevent its progression to invasive disease or detect a hidden invasive compo­nent. However, in and of itself, DCIS is not a terminal condition and does not directly put life at risk. Indeed, it may be a precursor of invasive cancer, but progression is known to occur in as few as 20–30% of untreated patients. At the same time, it is a quite heterogeneous diagnostic category. Some ductal carcinomas in situ with the lowest degree of malignancy behave more like atypias and show a similar risk of progression, only slightly higher than that for an average 65-year-old woman in the general population. It has even been argued that these DCIS cases are not properly carcinomas at all; labeling them as “cancer” provokes disproportionate fear in patients and compels physicians to take unnecessary and excessive treatment measures. In order to change that, it is first crucial to modify the terminology we use: changes with a very low risk of progression toward invasive carcinoma should be labeled as indolent lesions of epithelial origin (IDLE). To conclude, the local treatment of pre-invasive carcinoma in most cases should differ from that of early-stage invasive cancer. Aggressive methods should be avoided unless specifically required.

Polymeric composite devices for localized treatment of early-stage breast cancer.

For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment.

Abstract 1352: Cytoplasmic galectin-7 has an antiapoptotic function by decreasing p53 nuclear translocation in breast cancer cells

Abstract Resistance to apoptosis induced by anti-cancer drugs is a major obstacle for the treatment of aggressive forms of breast cancer. Galectin-7 was recently shown to be specifically expressed in basal-like and HER-2 positive but not in luminal subtypes of human breast cancer. Overexpression of galectin-7 in breast cancer cells also increases lung and bone metastases. However, the molecular mechanisms used by galectin-7 to increase the dissemination of breast cancer cells remain largely unknown. Although galectins are best known for their ability to bind cell surface receptors, there is increasing evidence that their intracellular forms have important functions in cancer cells. This is particularly true in the control of apoptosis. Up to now, regulation of apoptosis by intracellular galectins has been largely attributed to their ability to translocate to mitochondria, possibly following their interaction with bcl-2. Here, we report that a mutant of galectin-7 that is unable to translocate to mitochondria and nucleus induces resistance of human breast cancer cells to apoptosis induced by etoposide or by hypoxia-mimicking conditions. Surprisingly, this mutant and the wild-type form of galectin-7 bind equally well to bcl-2 in vitro and in vivo. Interestingly, both forms decreases the translocation of p53 to the nucleus and reduce the expression of p21 following treatment with doxorubicin. These results challenges the current paradigm that mitochondrial galectins are important for resistance to apoptosis and call for a greater focus on the role of cytosolic galectins in cancer cells. Our data also indicate that targeting cytosolic galectin-7 could improve the efficacy of anti-cancer drugs for the treatment of aggressive forms of breast cancer. Citation Format: Andrée-Anne Grosset, Donald Gagné, Marilyne Labrie, Maria Vladoiu, Louis Gaboury, Nicolas Doucet, Yves St-Pierre. Cytoplasmic galectin-7 has an antiapoptotic function by decreasing p53 nuclear translocation in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1352. doi:10.1158/1538-7445.AM2014-1352

Emergency embolectomy for embolic occlusion of the middle cerebral artery—review of the literature and two illustrative cases

With the increasing number of endovascular interventions during the last years, the number of procedure-related complications has risen accordingly. Despite sophisticated and effective endovascular treatments for acute thromboembolic events during intervention, vessel occlusion can remain refractory to medical and endovascular treatment. In case of failure of the endovascular revascularisation, microsurgical embolectomy in the anterior circulation can be a last therapeutic option, if case selection is adequate. To date, this rather aggressive form of treatment is still controversial, and there are only few series of reported surgical embolectomy. In the present review, we conducted a Medline (www.pubmed.org) search for reports or studies of microsurgical embolectomies using the keywords (1) middle cerebral artery (MCA) occlusion and (2) embolectomy. The most relevant factors for positive outcome were concluded as such: (1) vessel occlusion time, (2) collateral flow, (3) occlusion site and (4) thromboembolic origin. Additionally, we report on two illustrative cases from our department with acute MCA occlusion treated by emergency microsurgical embolectomy but with very contrary outcomes. Hence, emergency embolectomy in patients with MCA occlusion following endovascular treatment can be quite effective, if endovascular recanalisation options fail. Nevertheless, the decision-making process must be made critically, fast and based on factors such as vessel occlusion time, sufficient collateral flow, occlusion site and thrombus origin.

Pediatric Obesity: Looking into Treatment

Prevalence of pediatric obesity continues to rise worldwide. Increasing the number of health care practitioners as well as pediatricians with expertise in obesity treatment is necessary. Because many obese patients suffer obesity-associated cardiovascular, metabolic and other health complications that could increase the severity of obesity, it is fundamental not only to identify the child prone to obesity as early as possible, but to recognize, treat and monitor obesity-related diseases during adolescence. This short review outlines the treatment of pediatric obesity that may have applications in the primary care setting. It examines current information on eating behavior, sedentary behavior, and details studies of multidisciplinary, behavior-based, obesity treatment programs. We also report the less common and more aggressive forms of treatment, such as medication and bariatric surgery. We emphasize that health care providers have the potential to improve outcomes by performing early identification, helping families create the best possible home environment, and by providing structured guidance to obese children and their families.

Recommendations for Treatment of Child and Adolescent Overweight and Obesity

In this article, we review evidence about the treatment of obesity that may have applications in primary care, community, and tertiary care settings. We examine current information about eating behaviors, physical activity behaviors, and sedentary behaviors that may affect weight in children and adolescents. We also review studies of multidisciplinary behavior-based obesity treatment programs and information about more aggressive forms of treatment. The writing group has drawn from the available evidence to propose a comprehensive 4-step or staged-care approach for weight management that includes the following stages: (1) Prevention Plus; (2) structured weight management; (3) comprehensive multidisciplinary intervention; and (4) tertiary care intervention. We suggest that providers encourage healthy behaviors while using techniques to motivate patients and families, and interventions should be tailored to the individual child and family. Although more intense treatment stages will generally occur outside the typical office setting, offices can implement less intense intervention strategies. We not ony address specific patient behavior goals but also encourage practices to modify office systems to streamline office-based care and to prepare to coordinate with professionals and programs outside the office for more intensive interventions.

Prognostic indices for tumor relapse and tumor mortality in follicular thyroid carcinoma

To establish an objective basis for therapeutic decisions and follow-up programs in patients with follicular thyroid cancer, the authors developed a prognostic scoring system. The prognostic impact of nine clinical, histologic, and therapeutic parameters was quantified retrospectively based on a multivariate analysis covering 149 patients. The relative relapse risk in follicular thyroid cancer (RR) was 6.8-fold increased in the presence of a moderate when compared with a high degree of histologic tumor differentiation. The RR rose with increasing age of the patient at time of tumor diagnosis by a factor of 1.8 per 20 years. The RR was reduced by a factor of 4.3 after the performance of a neck dissection and by a factor of 2.3 after percutaneous radiation therapy of the neck. The relative mortality risk in follicular thyroid cancer (RM) rose in the absence of a tumor capsule by a factor of 10, in the presence of a moderate compared with a high degree of histologic tumor differentiation by a factor of 5.9, in the presence of distant metastases by a factor of 3.2, and with increasing age of the patient at the time of tumor diagnosis by a factor of 2.2 per 20 years. From these data prognostic indices denoting the individual risk for tumor relapse (IRR index) and tumor mortality (IMR index) were calculated. The indices categorize patients into low-risk, medium-risk, or high-risk groups with regard to tumor relapse and tumor-related death. Consequently, the IRR and IMR indices contribute to select patients with follicular thyroid cancer who need an aggressive form of treatment and an intensive follow-up program. The indices may also be used for risk stratification in prospective therapy trials.

Successful resolution of unilateral pulmonary interstitial emphysema in a premature infant by selective bronchial balloon catheterization

Pulmonary interstitial emphysema (PIE) is a common complication in premature infants with respiratory distress syndrome. The development of pulmonary interstitial emphysema leads to marked respiratory embarrassment in an already compromised infant. Although usually bilateral, PIE may be unilateral. Various forms of treatment for unilateral PIE in the premature infant have been described, including selective bronchial intubation, unilateral pneumonectomy, visceral pleurotomy, pure oxygen administration, and high-frequency low-pressure ventilation. A recently reported conservative regimen consisting of downward lateral positioning of the affected lung for several days may not be successful. We describe a premature infant with progressive worsening of unilateral PIE, which was successfully treated by selective bronchial balloon catheterization after failure of conservative management. In this manner, we avoided selective bronchial intubation or other aggressive forms of treatment.

Computed tomography of intracerebral gangliogliomas

CT and clinical findings in 6 histologically proven cases of intracerebral gangliogliomas (out of 14,000 cranial CT examinations are presented. The tumor is most often isodense, with areas of calcification. Even though CT findings are nonspecific, they are suggestive of the benign nature of the tumor. When this histologically confirmed (by biopsy) the more aggressive forms of treatment may be obviated.

Cholangitis complicating congenital hepatic fibrosis.

A patient with cholangitis complicating congenital hepatic fibrosis is presented. In contrast to most other reported cases, many of whom have been treated surgically, this patient had a benign course. The likelihood that this complication of congenital hepatic fibrosis will respond to appropriate conservative therapy suggests that more aggressive forms of treatment should be reserved for those patients who fail to respond to medical management.