Idiopathic granulomatous mastitis: in search of a therapeutic paradigm

Idiopathic granulomatous mastitis, also known as idiopathic granulomatous lobular mastitis, is a benign breast lesion that represents both a diagnostic and therapeutic dilemma. We report two cases of granulomatous mastitis recently evaluated and managed at our institution. To better understand this rare disease, we analyzed treatment outcomes in reported cases of granulomatous mastitis. One hundred sixteen cases were subsequently analyzed. Primary management strategies included observation (n = 9), steroids (n = 29), partial mastectomy (n = 75), and mastectomy (n = 3). Success rates with each treatment were observation, 56 per cent; steroids, 42 per cent; partial mastectomy, 79 per cent; and mastectomy, 100 per cent. Based on this analysis, we propose a clinically useful algorithm for both workup and management of these challenging cases.     

The Dilemma of Breast Cancer Treatment and Existing Collagen Vascular Disease: A Case of Scleroderma and Review of the Literature

Collagen vascular diseases present a treatment dilemma for patients with breast cancer. Due to the potential for severe, acute, and late complications of radiation therapy, a history of collagen vascular disease (CVD) is a relative contraindication to breast‐conserving treatment. We present a case of early stage breast cancer in a patient with severe scleroderma treated with breast‐conserving surgery without radiation and a brief review of the published literature regarding the therapeutic approach to the patient with CVD and breast cancer.     

HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth. In immunocompetent mice bearing Hepa1-6 HCC tumors, addition of 32-134D to anti-PD1 therapy increased the rate of tumor eradication from 25% to 67%. Treated mice showed no changes in appearance, behavior, body weight, hemoglobin, or hematocrit. Compound 32-134D altered the expression of a large battery of genes encoding proteins that mediate angiogenesis, glycolytic metabolism, and responses to innate and adaptive immunity. This altered gene expression led to significant changes in the tumor immune microenvironment, including a decreased percentage of tumor-associated macrophages and myeloid-derived suppressor cells, which mediate immune evasion, and an increased percentage of CD8⁺ T cells and natural killer cells, which mediate antitumor immunity. Taken together, these preclinical findings suggest that combining 32-134D with immune checkpoint blockade may represent a breakthrough therapy for HCC.     

Self-expandable covered metal tracheal type stent for sealing cervical anastomotic leak after esophagectomy and gastric pull-up: pitfalls and possibilities

From January 2003 to June 2006, 6 patients with leakage of the cervical esophagogastrostomy after esophagectomy and gastric pull-up underwent endoscopic stenting using the self-expandable covered tracheal type device. Anastomotic healing was satisfactory. Stent extraction was performed after an average interval of 91 days. Initial stent migration occurred in 2 patients and post-extraction stenosis developed in 3 patients. Insertion of a self-expandable covered metal tracheal stent represents a safe approach resulting in immediate closure and subsequent healing of cervical anastomotic leakage.     

Use of endoscopic stents to treat anastomotic complications after bariatric surgery

BACKGROUND: Complications after bariatric surgery often require longterm parenteral nutrition to achieve healing. Recently, endoscopic treatments have become available that provide healing while allowing for oral nutrition. The purpose of this study was to present outcomes of the largest series to date treating staple line complications after bariatric surgery with endoscopic covered stents. STUDY DESIGN: A retrospective evaluation was performed of all patients treated for staple line complications after bariatric surgery at a single tertiary care bariatric center. Acute postoperative leaks, chronic gastrocutaneous fistulas, and anastomotic strictures refractory to endoscopic dilation after both gastric bypass and sleeve gastrectomy were included. RESULTS: From January 2006 to June 2007, 19 patients (11 with acute leaks, 2 with chronic fistulas, and 6 with strictures) were treated with a total of 34 endoscopic silicone covered stents (23 polyester, 11 metal). Mean followup was 3.6 months. Immediate symptomatic improvement occurred in 90% (91% of acute leaks, 100% of fistulas, and 84% of strictures). Oral feeding was started in 79% of patients immediately after stenting. Resolution of leak or stricture after stent treatment occurred in 16 of 19 patients (84%). Healing of leak, fistula, and stricture occurred at means of 33 days, 46 days, and 7 days, respectively. Three patients (1 with leak, 1 with fistula, and 1 with stricture) had unsuccessful stent treatment. Migration of the stent occurred in 58% of 34 stents placed. Most migration was minimal, but three stents were removed surgically after distal small bowel migration. There was no mortality. CONCLUSIONS: Treatment of anastomotic complications after bariatric surgery with endoscopic covered stents allows rapid healing while simultaneously allowing for oral nutrition. The primary morbidity is stent migration.