Idiopathic granulomatous mastitis: experience at a New York hospital.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) often mimics breast cancer. Presentation includes pain, palpable mass, suppuration or suspicious imaging. Widely reported in Asia and the Middle East, IGM is diagnosed after excluding specific granulomatous mastitis (SGM). Aetiology remains unknown. Lactation, prolactinaemia, ethnicity, autoimmune disease and Corynebacteria are associated. Treatment is controversial and the prevalence rising. Surgery and non-operative treatments including antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, methotrexate and observation have advocates. METHODS: A retrospective chart review of 63 patients with IGM from 2008 to 2018 was undertaken focusing on birthplace, age, clinical presentation, wound cultures, imaging, treatments and outcomes. RESULTS: Sixty-one of 63 patients were Hispanic; 53 were Mexican-born women aged 23-46. Clinical presentation included pain, painful mass, painless mass, suppuration and abnormal imaging. Some 31/61 ultrasound examinations and 17/33 mammograms were deemed Breast Imaging Reporting and Data System (BI-RADS) score 4 or 5. Management included antibiotics (43), incision and drainage (24), NSAIDs (29), steroids (8), lumpectomy (18) and observation (12). Some 12/20 patients with painless masses resolved with observation, 3 received NSAIDs, 2 received steroids and 3 underwent lumpectomies. Antibiotics resolved 8/43 cases, 5 needed incision and drainage, 26 received NSAIDs, 6 received steroids and 5 underwent lumpectomies. Nineteen patients had indolent disease or recurrence. CONCLUSIONS: Excluding malignancy is critical, treatment challenging and recurrence common in IGM. A preponderance of patients were Mexican-born, similar to other reports from the USA. Over 50% of IGM cases had suspicious BI-RADS scores. Best management remains a challenge and ranges from observation to lumpectomy.

Interacting Genetic Lesions of Melanoma in the Tumor Microenvironment: Defining a Viable Therapy.

Melanoma is the most aggressive form of skin cancer with an estimated 106,110 newly diagnosed cases in the United States of America in 2021 leading to an approximated 7180 melanoma-induced deaths. Cancer typically arises from an accumulation of somatic mutations and can be associated with mutagenic or carcinogenic exposure. A key characteristic of melanoma is the extensive somatic mutation rate of 16.8 mutations/Mb, which is largely attributed to UV exposure. Bearing the highest mutational load, many of them occur in key driver pathways, most commonly the BRAFV600E in the mitogen-activated protein kinase (MAPK) pathway. This driver mutation is targeted clinically with FDA-approved therapies using small molecule inhibitors of oncogenic BRAFV600E and MEK, which has greatly expanded therapeutic intervention following a melanoma diagnosis. Up until 2011, therapeutic options for metastatic melanoma were limited, and treatment typically fell under the spectrum of surgery, radiotherapy, and chemotherapy.Attributed to the extensive mutation rate, as well as having the highest number of neoepitopes, melanoma is deemed to be extremely immunogenic. However, despite this highly immunogenic nature, melanoma is notorious for inducing an immunosuppressive microenvironment which can be relieved by checkpoint inhibitor therapy. The two molecules currently approved clinically are ipilimumab and nivolumab, which target the molecules CTLA-4 and PD-1, respectively.A plethora of immunomodulatory molecules exist, many with redundant functions. Additionally, these molecules are expressed not only by immune cells but also by tumor cells within the tumor microenvironment. Tumor profiling of these cell surface checkpoint molecules is necessary to optimize a clinical response. The presence of immunomodulatory molecules in melanoma, using data from The Cancer Genome Atlas and validation of expression in two model systems, human melanoma tissues and patient-derived melanoma cells, revealed that the expression levels of B and T lymphocyte attenuator (BTLA), TIM1, and CD226, concurrently with the BRAFV600E mutation status, significantly dictated overall survival in melanoma patients. These molecules, along with herpesvirus entry mediator (HVEM) and CD160, two molecules that are a part of the HVEM/BTLA/CD160 axis, had a higher expression in human melanoma tissues when compared to normal skin melanocytes and have unique roles to play in T cell activation. New links are being uncovered between the expression of immunomodulatory molecules and the BRAFV600E genetic lesion in melanoma. Small molecule inhibitors of the MAPK pathway regulate the surface expression of this multifaceted molecule, making BTLA a promising target for immuno-oncology to be targeted in combination with small molecule inhibitors, potentially alleviating T regulatory cell activation and improving patient prognosis.

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.

Amylin, a pancreatic peptide, and amyloid-beta peptides (Aß), a major component of Alzheimer's disease (AD) brain, share similar ß-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aß in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aß1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aß in the serum, the magnitude of which is proportionate to the amount of Aß in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aß than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aß1-42 as well as Aß1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aß from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aß in blood. As naturally occurring amylin may play a role in regulating Aß in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

Negative appendicectomy rate as a quality metric in the management of appendicitis: impact of computed tomography, Alvarado score and the definition of negative appendicectomy.

INTRODUCTION: The negative appendicectomy rate (NAR) is a quality metric in the management of appendicitis. While computed tomography (CT) has been associated with a low NAR, Alvarado scoring produces an acceptable NAR. The definition of negative appendicectomy may affect the NAR. This study examined the impact of CT, Alvarado score and definition on the NAR. METHODS: The charts of 1,306 emergency appendicectomy patients from 1996 to 2010 were reviewed. Three five-year cohorts were created (Cohort A: 1996-2000, Cohort B: 2001-2005, Cohort C: 2006-2010) and the NAR was calculated for each cohort using two definitions of negative appendicectomy: absence of inflammation (NAR-STD) and absence of intramural neutrophils (NAR-STR). NAR-STD was correlated to the CT rate for Cohorts B and C and also to Alvarado score for Cohort C. RESULTS: When the definition of negative appendicectomy was changed, the NAR rose from 9.2% to 15.8% (p=0.0097) for Cohort A, from 2.8% to 8.6% (p=0.0180) for Cohort B (CT rate: 80.6%) and from 3.0% to 6.7% (p=0.0255) for Cohort C (CT rate: 92.4%). The introduction of CT lowered NAR-STD from 1996-2000 (9.2%) to 2001-2010 (2.9%) but increasing the CT rate from 2001-2010 had no impact on the NAR. The positive predictive value for Alvarado score (98.60%) and CT (99.03%) were similar. CONCLUSIONS: The definition of a negative appendicectomy determines the NAR. CT reduces the NAR regardless of definition but routine CT is unnecessary for male patients with positive Alvarado scores. Early/mild appendicitis may resolve without surgery and CT may contribute to unnecessary surgery. Alvarado scoring allows selective use of CT in suspected appendicitis.

Fabrication and evaluation of a near-infrared hyperspectral imaging system.

This paper describes modifications to a hyperspectral imaging microscope that extend its capabilities into the near-infrared (950-1300 nm). The major changes include installing a grating, charge-coupled device camera, and lenses and filters appropriate for infrared wavelengths. Calibration of the system and validation with lead sulfide quantum dots of known emission wavelength is reported. Cells from the breast carcinoma cell line SkBr3 were scanned with lead sulfide quantum dots that emit at 1100 nm as the background and an image which contains the integrated spectral data is presented. We also demonstrate that this instrument is capable of detecting the photoluminescence spectra of single-walled carbon nanotubes dispersed in aqueous solution.

Immunotherapy as an adjuvant therapy in the management of advanced, surgically resected, melanoma.

Metastatic melanoma continues to be one of the most devastating of all cancers. It is a heterogeneous solid tumor whose treatment is challenging and difficult. It afflicts thousands of otherwise healthy patients annually, and clinicians have yet to discover an effective treatment for locally advanced disease. Over the years, much attention has been devoted to the development of an effective adjuvant treatment for patients with resected melanoma who remain at high risk for recurrence. The new advances in the understanding of melanoma's microenvironment and the complexity of its disease process, makes it clear that the treatment approach to this disease needs to be multi-directional. Numerous studies have tested various immunotherapeutic strategies in the treatment of advanced melanoma, in particular. These strategies include melanoma vaccines, interferon-alpha, interleukin-2 (IL-2), and dendritic cell vaccines. The Dr. Wallack's Surgery Research Laboratory has been studying melanoma vaccines for the past three decades. The first generation melanoma vaccine proposed by the Laboratory showed promising results in a subset of patients. Recently, the same Laboratory has produced a second generation melanoma vaccine (DC-Melvac) that consists of five human melanoma cell lines, a recombinant vaccinia virus that encodes for IL-2, as well as dendritic cells that have been programmed to recognize certain melanoma associated antigens. DC-MelVac was recently approved by the Food and Drug Administration for its use in Phase I clinical trials. These trials are expected to be underway in the near future. The ensuing review discusses many of the immunotherapeutic strategies that have been studied in the treatment of melanoma, including DC-MelVac.

Intracolonic use of vancomycin for treatment of clostridium difficile colitis in a patient with a diverted colon: report of a case.

Clostridium difficile-associated pseudomembranous colitis (PMC) is a common affliction of postoperative patients. Risk factors include antibiotic therapy, recent surgery, and hospitalization (1,2,3). We present a case of PMC in a diverted colon and its treatment using vancomycin enemas.

Overview analysis of adjuvant therapies for melanoma--a special reference to results from vaccinia melanoma oncolysate adjuvant therapy trials.

A phase III, randomized, double-blind, multi-institutional vaccinia melanoma oncolysate (VMO) trial was performed for patients with stage III (AJCC) melanoma. When compared with the control vaccinia virus (V) therapy, VMO therapy did not show clinical efficacy in the final analysis of data from this trial. However, the data did allude to significant therapeutic efficacy with VMO therapy if it had been compared with an observation arm. Therefore, a comparative overview statistical analysis was performed to identify the therapeutic efficacy of VMO. This review compares VMO results with data from the treatment and observation arms of other prominent randomized anti-melanoma biologic trials (i.e., ECOG EST 1684; SWOG, IFN-gamma (J. Natl. Cancer Inst. 87 (1995) 1710); WHO IFN-alfa-2a (ASCO 14 (1995) 410); Mayo IFN-alfa-2a (J. Clin. Oncol. 13 (1995) 2776); French IFN-alfa-2a (ASCO 15 (1996) 437). The analysis was carried out comparing the disease-free interval (DFI) and overall survival (OS). The analysis shows that the VMO results are fairly comparable to the results of the treatment arms from the ECOG and Mayo trials at the 5-year mark; percent DFI 0.37, 0.37, and 0.4, percent OS 0.48, 0.46, 0.47, respectively. In some cases, VMO DFI is superior to the observation arms from other studies; ECOG, Mayo, and WHO; 0.37 versus 0.26, 0.3, 0.27 (4 years), respectively. These comparative results suggest that the vaccinia arm is not a true observation arm in the VMO trial, and the VMO could have shown an enhanced efficacy had the trial included a no-treatment observation control arm.

Ectopic supernumerary kidney, a cause of para-aortic mass: case report and review.

Ectopic supernumerary kidney is a rare congenital urinary tract abnormality. Because of the scarcity of published cases and atypical presenting symptomatology this entity frequently causes a diagnostic as well as therapeutic dilemma. We report a case of an unusually symptomatic supernumerary kidney that presented as back pain. Noncontrast CT scan showed a suspicious left-sided para-aortic mass, which prompted a percutaneous biopsy. Intravenous contrast CT scan revealed an anatomically and functionally free supernumerary kidney. The approach to diagnosis as well as management of supernumerary kidneys is discussed herein.

Balloon blunt-tip trocar for laparoscopic cholecystectomy: improvement over the traditional Hasson and Veress needle methods.

BACKGROUND AND PURPOSE: Laparoscopic cholecystectomy (LC) is a routine procedure for most general surgeons, yet the technical aspects of gaining access to the peritoneal cavity continue to be quite diverse. We describe a prospective review of 180 LCs using three access techniques: open balloon blunt-tip trocar (BBTT), open Hasson (HA), and closed Veress needle (VN). We favor the BBTT because it is designed to avoid all sharp instrumentation and offers superior seal and mobility, as well as expeditious and easy abdominal access. PATIENTS AND METHODS: The techniques and devices were evaluated prospectively with regard to simplicity of access, leakage of carbon dioxide, access time, and complications. All patients underwent LC by one of two Board-certified surgeons. RESULTS: The mean time to insertion of the laparoscope for the BBTT (3.5 +/- 0.99 minutes) was significantly less than the insertion time for the VN technique (5.2 +/- 0.9 minutes, P < 0.05). The insertion time for the BBTT was also less than for the standard HA approach (4.25 +/- 1.0 minutes; P < 0.05). There were no visceral or vascular injuries noted, but CO2 leakage and subcutaneous insufflation of gas experienced in the standard HA and VN groups resulted in lengthened operative times. One patient in the BBTT group experienced a postoperative port-site herniation, which was repaired primarily without consequence. CONCLUSION: The BBTT is an established, safe alternative to blind access for LC. Our technique is simple and rapid and avoids most of the technical difficulties encountered by other open access devices. We believe this method provides surgeons with an option that is efficient and easier to perform than most other conventional open-access laparoscopic techniques.

Pacemaker leads: a simple atraumatic method for replacing pacemaker electrodes.

Early dislodgment or malfunction of pacemaker leads can result in significant morbidity and therefore must be corrected promptly. We describe a method of changing pacemaker leads that is atraumatic, maintains central venous access, and eliminates the need for venipuncture. Our technique is simple, highly reproducible, and can be performed with standard operating room instruments.

Recurrent malignant chondroid syringoma of the foot: a case report and review of the literature.

Malignant chondroid syringoma, or mixed tumor of the skin, salivary gland type, is an uncommon neoplasm believed to originate in sweat glands. This neoplasm occurs mostly in women and is typically seen in the extremities and torso. A case of recurrent malignant chondroid syringoma of the right foot in a man aged 34 years is described with a review of pertinent literature. The surgically excised neoplasm was evaluated by routine histology, immunohistochemistry, and transmission electron microscopy. The malignant chondroid syringoma showed microscopic dermal satellite tumor nodules. Immunohistochemical staining was positive for keratin and S100 and negative for actin and p53. Ki-67 showed <10% positive staining. Ultrastructurally, the neoplasm was composed of epithelial cells with tonofilaments, cell junctions, and electron-dense amorphous keratin-like substance in the intercellular spaces. No evidence of myoepithelial differentiation was noted. Given the tumoral size, acral location, and histologic findings, the neoplasm was classified as a malignant chondroid syringoma. After reviewing the literature, it became apparent that wide surgical excision, adjuvant radiation therapy as well as patient education are critical in facilitating long-term survival.

Pedunculated malignant melanoma.

BACKGROUND: The pedunculated melanoma is an unusual variant of nodular melanoma that presents a challenge in staging and management. OBJECTIVE: We discuss the clinical and histopathologic characteristics of a case of pedunculated melanoma and present a brief review of the literature. METHODS: Routine stain with hematoxylin and eosin was performed on tissue specimens. RESULTS: The pedunculated melanoma was excised. Sentinel lymph node dissection was performed and was negative for the presence of melanoma. CONCLUSIONS: Pedunculated melanoma is a rare type of melanoma. Conventional staging methods for melanoma may not be reliable in this type of tumor. Complete workup, possibly including sentinel lymph node dissection, should be performed in all patients with pedunculated melanomas.

Palliative treatment of recurrent obstructing gastric cancer. A case report of successful treatment with three self-expanding metallic stents.

Patients with advanced or recurrent gastric cancer affecting the upper and lower gastrointestinal tract usually experience obstructive symptoms, causing a severe compromise in their quality of life. Surgery may not be feasible because of the patient's precarious medical condition and multilevel tumor infiltration. When faced with these circumstances, surgeons have few options. Parenteral nutrition and comfort measures are utilized when surgical bypass is not a tenable option. We herein describe a unique case of multilevel upper and lower gastrointestinal obstruction secondary to recurrent gastric cancer. The patient was treated palliatively through a combined surgical, radiological, and endoscopic approach by implanting a series of self-expanding metallic stents. To our knowledge, there are no previous reports of successful management of simultaneous strictures of the upper and lower gastrointestinal tract using this technique.

A Brunner's gland adenoma as a cause of anemia.

Benign tumors of the small bowel are rare. They present with many different manifestations depending on the size and location, and also cause a variety of symptoms that are often nonspecific. These include abdominal pain, dyspepsia, nausea, vomiting, and gastrointestinal bleeding that may be melena or hematemesis. Most of the time patients are asymptomatic and the lesions are discovered as an incidental finding. When bleeding occurs, and it may be severe in certain situations, the patient may develop signs of anemia, such as dyspnea, fatigue, and even high-output cardiac failure. The authors present a patient who was evaluated for melena and who was found to have a duodenal polyp that proved to be a Brunner's gland adenoma on pathology.

Colon cancer cell vaccine prepared with replication-deficient vaccinia viruses encoding B7.1 and interleukin-2 induce antitumor response in syngeneic mice.

A replication-deficient recombinant vaccinia virus, NYVAC, was developed by deleting 18 open reading frames in the vaccinia virus genome. Recombinant NYVAC, encoding the murine T cell co-stimulatory gene B7.1 (CD 80) (NYVAC-B7.1) and the murine interleukin-2 gene (NYVAC-IL-2), were prepared and the expression of B7.1 and the secretion of IL-2 were respectively confirmed in vitro. The use of these viruses to prepare a potent tumor cell vaccine was studied in a syngeneic murine CC-36 colon adenocarcinoma model. Mice were immunized on days 1 and 8 with 10(6) irradiated CC-36 cells that were infected with 10(7) plaque-forming units of either NYVAC-B7.1, NYVAC-IL-2 or a control virus, NYVAC-HR, which encodes a vaccinia virus host-range gene. These mice were then challenged with 10(8) viable CC-36 tumor cells on day 15. All mice (10/10) in a group that had received no vaccination and all mice (20/20) in a group that had received a control vaccine of CC-36/NYVAC-HR developed tumor 4-weeks after tumor cell challenge. Interestingly, only 16/20 mice in a group that had received CC-36/ NYVAC-B7.1 showed the development of tumor after the same interval. The protection against tumor development and the reduction in tumor burden (as mean tumor diameter, 4 weeks after tumor challenge) were significant in this group when compared to groups that were either unvaccinated or vaccinated with CC-36/NYVAC-HR (mean tumor diameter = 6.51+/-3.2 mm compared to 26.5+/-0.9 mm or 26.2+/-1.8 mm respectively) (P = < 0.05). The protection against tumor in a group of mice that received CC-36/ NYVAC-IL-2 vaccination was similar to that in the unvaccinated group or the group receiving a CC-36/NYVAC-HR control vaccination. However, in a survival experiment, mice that received either CC36/NYVAC-B7.1 or CC-36/ NYVAC-IL-2 vaccination on the day of tumor transplantation survived significantly longer than mice that had not been vaccinated (median survival 60+ days, 60+ days or 23.5 days respectively) (P = < 0.05). Interestingly, when a therapeutic tumor vaccination was performed on day 4 after tumor transplantation, mice that had been vaccinated with either CC36/NYVAC-B7.1 or CC-36/NYVAC-IL-2 did not show an improved survival when compared to mice in the control that had not been vaccinated (median survival 28 days compared to 26 days or 25 days respectively). However, mice that had received a therapeutic vaccination with CC-36 cells infected with both NYVAC-B7.1 and NYVAC-IL-2, 4 days after tumor transplantation, survived significantly longer than control mice that had not received any vaccination (median survival 29.5 days compared to 25 days respectively) (P<0.05). These results suggest that a replication-deficient recombinant NYVAC encoding the B7.1 gene and NYVAC encoding the IL-2 gene can be used to produce an effective vaccinia-virus-augmented tumor cell vaccine.

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial.

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.