A Comprehensive Review of the Diagnosis, Treatment, and Management of Postmastectomy Pain Syndrome.

PURPOSE OF REVIEW: Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy. RECENT FINDINGS: The underlying pathophysiology is likely multifactorial, although exact mechanisms have yet to be elucidated. In this regard, neuralgia of the intercostobrachial nerve is currently implicated as the most common cause of PMPS. Numerous pharmacological options are available in the treatment of PMPS, including gabapentinoids, tricyclic antidepressants, selective serotonin reuptake inhibitors, NMDA receptor antagonists, and nefopam (a non-opioid, non-steroidal benzoxazocine analgesic). Minimally invasive interventional treatment including injection therapy, regional anesthesia, botulinum toxin, and neuromodulation has been demonstrated to have some beneficial effect. A comprehensive update highlighting current perspectives on the treatment of postmastectomy pain syndrome is presented with emphasis on treatments currently available and newer therapeutics currently being evaluated to alleviate this complex and multifactorial condition.

Gut Microbiome Dysbiosis and Depression: a Comprehensive Review.

PURPOSE OF REVIEW: The human gut microbiome is involved in a bi-directional communication pathway with the central nervous system (CNS), termed the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to mediate or modulate various central processes through the vagus nerve. The microbiota-gut-brain axis is involved with the production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. RECENT FINDINGS: Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed in the present investigation include an array of basic science studies that clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to humans. The studies presented in this review demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression.

Current Perspectives on Gut Microbiome Dysbiosis and Depression.

The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

Long-term outcomes of breast-conserving therapy for women with ductal carcinoma in situ.

PURPOSE: Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS: We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS: At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS: With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.

Stem Cell Therapies for Treatment of Discogenic Low Back Pain: a Comprehensive Review.

PURPOSE OF REVIEW: Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases. RECENT FINDINGS: The clinical presentation of DLBP includes increased pain when sitting, coughing, or sneezing, and experiencing relief when standing or ambulating. Dermatomal radiation of pain to the lower extremity and neurological symptoms including numbness, motor weakness, and urinary or fecal incontinence are signs of advanced disease with disc prolapse, nerve root compression, or spinal stenosis. Degenerative disc disease is caused by both a decrease in disc nutrient supply causing decreased oxygen, lowered pH, and lessened ability of the intervertebral disc (IVD) to respond to increased load or injury; moreover, changes in the extracellular matrix composition cause weakening of the tissue and skewing the extracellular matrix's (ECM) harmonious balance between catabolic and anabolic factors for cell turnover in favor of catabolism. Thus, the degeneration of the disc causes a shift from type II to type I collagen expression by NP cells and a decrease in aggrecan synthesis leads to dehydrated matrix cells ultimately with loss of swelling pressure needed for mechanical support. Cell-based therapies such as autologous nucleus pulposus cell re-implantation have in animal models and human trials shown improvements in LBP score, retention of hydration in IVD, and increased disc height. Percutaneously delivered multipotent mesenchymal stem cell (MSC) therapy has been proposed as a potential means to uniquely ameliorate discogenic LBP holistically through three mechanisms: mitigation of primary nociceptive disc pain, slow or reversal of the catabolic metabolism, and restoration of disc tissue. Embryonic stem cells (ESCs) can differentiate into cells of all three germ layers in vitro, but their use is hindered related to ethical concerns, potential for immune rejection after transplantation, disease, and teratoma formation. Another similar approach to treating back pain is transplantation of the nucleus pulposus, which, like stem cell therapy, seeks to address the underlying cause of intervertebral disc degeneration by aiming to reverse the destructive inflammatory process and regenerate the proteoglycans and collagen found in healthy disc tissue. Preliminary animal models and clinical studies have shown mesenchymal stem cell implantation as a potential therapy for IVD regeneration and ECM restoration via a shift towards favorable anabolic balance and reduction of pain.

Effects of Postmastectomy Radiation Therapy on Immediate Tissue Expander and Acellular Dermal Matrix Reconstruction: Results of a Prospective Clinical Trial.

PURPOSE: Postmastectomy radiation therapy (PMRT) delivered to an immediate reconstruction increases the risk of surgical complications. Although acellular dermal matrix (ADM) has been used with immediate tissue expander (TE) reconstruction to improve cosmetic outcomes and minimize capsular contracture, there is a paucity of data on this approach in the setting of PMRT. METHODS AND MATERIALS: Thirty-two patients with stage I to III breast cancer were treated with mastectomy, immediate TE-ADM reconstruction, and PMRT between 2009 and 2012 in a prospective single-arm study. The primary objective was the "success" rate, determined by the number of patients at 2 years after PMRT having an intact final reconstruction, no major complications, and a cosmetic outcome rated by a physician as excellent or good. RESULTS: The median follow-up was 24 months. Final reconstruction status was known in 31 of 32 patients (96.9%; 1 patient left the country) and completed in 29 of 31 patients (93.5%; implant, n = 26; flap, n = 1; both, n = 2; none, n = 2). At 2 years, 6 patients were unevaluable (metastatic disease, n = 3; withdrawn consent, n = 1; left the country, n = 2). Of 26 evaluable patients, the success rate was 65.4% (17 of 26). Lack of success was the result of "fair" cosmesis (n = 2), infection (n = 2), severe capsular contracture (n = 1), major revision (n = 2), and no final reconstruction (n = 2). Most patients had good-to-excellent 2-year overall cosmesis based on patient perception (15; 62.5%) and physician evaluation (19; 79.2%). CONCLUSIONS: To the best of our knowledge, this is the first dedicated prospective trial evaluating long-term cosmetic and complication outcomes in patients treated with immediate TE-ADM reconstruction followed by PMRT. Most patients (65.4%) met the success criteria in this prospective single-arm series. The great majority (93.5%) achieved final reconstruction; most had good-to-excellent overall cosmetic outcomes (79.2%). The results with longer follow-up will be of interest, and further investigation of strategies to optimize reconstruction with PMRT are warranted.

Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy.

PURPOSE/OBJECTIVES: Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT. METHODS: We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. RESULTS: With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4-9 involved nodes = 3.04; >9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age >50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients. CONCLUSION: BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era.