Periglandular Tissue Research Articles

From modified radical mastectomy to infra-radical mastectomy: a phase I study for surgical de-escalation focusing on pathological analyses.

Despite that breast conservative therapy became the standard of care in breast cancer, modified radical mastectomy, a large mutilating surgery, is still required for an important number of patients. In order to improve the quality of life and the psychological aspects of a surgery involving the femininity of woman, we developed a new less invasive procedure called infra-radical mastectomy. It aims to save the neckline of patients by the maintenance of the peripheral skin-fatty flap that constitutes the base for implantation of the breast. This phase I study analyzed the feasibility of this procedure using outcome of anatomo-pathological analyses as primary endpoint. Between March 2015 and July 2017, all women with operable breast cancer without signs of lymph node invasion were invited to participate in the study in the 2 participating institutions. After a water-assisted dissection of the peri-glandular space, an enucleation of the breast was performed by a cold knife which represents the infra-radical mastectomy. A peri-glandular re-excision (PGR) of the skin and the fat tissue surrounding the gland was then achieved to obtain an MRM. This PGR underwent a careful pathological examination (10 samples per patient). Moreover, the tissue volume and the skin surface of the PGR were quantified. A total of 53 patients (median age: 60 years) were prospectively recruited. The pathological analysis of peri-glandular biopsies revealed none residual invasive carcinoma, 1% of biopsies contained focal ductal carcinoma in situ (DCIS) and 0.4% atypical hyperplasia corresponding to 4 and 2 patients respectively. These 4 patients with residual DCIS were preoperatively diagnosed with extensive DCIS. On average after an infra-radical mastectomy, 37% of the volume and 53% of the skin surface of a complete modified radical mastectomy were sparred. The evaluation of biopsies from peri-glandular tissue suggests that infra-radical mastectomy should be further evaluated except for patients diagnosed with extensive DCIS which must be excluded of this infra-radical approach. Additional work is needed to evaluate cosmetic outcome and impact on quality of life, the need of radiotherapy and the oncological long-term outcome.

Meibography guided intraductal meibomian gland probing using real-time infrared video feed

PurposeTo evaluate use of infrared meibography video to visualise meibomian gland probing and correlate probe findings of intraductal space with meibography images.MethodsVideos were reviewed and probe findings recorded of 996...

Abstract P3-13-22: Should modified radical mastectomy be modified? A phase 1 study to evaluate infraradical mastectomy for invasive breast cancer

Abstract Background: Surgical procedures in breast cancer have become less aggressive. However, around one in three patients must undergo modified radical mastectomy (MRM). We evaluated if infraradical mastectomy (IFM), which preserves the skin and fat tissues surrounding the breast, is safe. IFM has the potential to preserve neck opening and by the way femininity of patients. Aesthetic results obtained after breast reconstruction are also expected to be improved. Objective: The primary objective of this phase 1 trial is to evaluate the feasibility and safety of IFM. Methods: Patients were recruited in two specialized breast clinics. We performed enucleation with a cold knife to the mammary gland after a water-assisted dissection of the periglandular space using a dedicated tool. In a second step we removed the peripheral skin and fat tissue which surrounded the gland to obtain a classical MRM. Fat tissue removed in the second step underwent a careful pathological examination (10 biopsies) in order to evaluate residual invasive or in situ breast cancer and atypical hyperplasia. We also evaluated which is the percentage of tissue and skin removed in the second step with regard to the global surgical specimen because that could be left in the future if the procedure is declared safe. Results: A total of 35 patients (43 to 80 years old) were prospectively recruited from March 2015 to March 2016. The distribution of tumor type was: pTis 2.9%, pT1 45.7%, pT2 45.7% and pT3 5.7%. Pathological analysis of the periglandular tissue removed in the second step revealed: 0% invasive carcinoma, 1% focal ductal carcinoma in situ (DCIS), and 0% atypical hyperplasia. On average, the weight of an IFM was 37% lower compared to the weight of a MRM. Skin resection was reduced by 48% with IFM. No serious adverse event was observed. Conclusions: Preliminary results are promising. Our phase 1 trial suggests that the procedure is safe concerning premalignant or malignant disease left after IFM. Moreover, a high quantity of skin and fat tissue is saved by IFM. We are now recruiting a second cohort of patients in order to confirm these results. In addition, we will also quantify the amount of mammary glands left around IFM compared to MRM by performing additional biopsies and quantitative evaluation by pathologists. Presurgical selection criteria have been modified for the second cohort in order to avoid residual DCIS left after IFM. After this second cohort, we plan to begin a large prospective randomized phase 3 trial with long-term disease-free survival and aesthetic results as the primary endpoints. Citation Format: Coibion M, Lifrange E, Jossa V, Mutijima E, Crevecoeur A, Olivier F, Di Bella J, Jerusalem G. Should modified radical mastectomy be modified? A phase 1 study to evaluate infraradical mastectomy for invasive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-22.

Compression Dressing Using Dental Impression Compound for Conservative Management of Sialocele.

A Sialocele or salivary pseudocyst is due to extravasation of saliva into periglandular tissue due to disruption of gland parenchyma. Various techniques of management have been described in literature; both conservative and surgical management have been documented. We report a simple economical and efficient method to deal with sailocele presenting after neck dissection.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome.

A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.

Migratory sialocele after fine needle aspiration of the parotid gland

Sialocele is a subcutaneous collection which contains saliva. This collection is mainly developing at the area of parotid gland and it is evolving after trauma in this region or after a surgical procedure. During these procedures, a disruption of a duct or injury of the parenchyma promotes extravasation of the saliva and the formation of this collection in glandular or periglandular tissues [1]. This condition usually is a self-limited phenomenon and conservative measures are efficient in most of the times. Rarely, interventional measures like drainage of the collection and botulinum toxin injection or surgical management are needed [2, 3]. In this report, a case of a patient who developed a migrating sialocele after fine needle aspiration (FNA) for a Warthin tumor of the parotid gland is presented. This male patient 60-year old had a progressive bulge in his both parotid glands for approximately the last 10 years. The patient presented in our department with a painful swelling of his left gland after a diagnostic FNA 48 h before. This bulge was movable and the parotid duct in the affected side was normal and salivary flow had normal physical aspects without debris or purulent discharge. Imaging studies were performed. Ultrasound of the region revealed lesions in both of the glands. In the left gland, the lesion seems to be collection or abscess (Fig. 1). Moreover, a computed tomography (CT) of the cervix revealed a 3-cm tumor in the right parotid gland and two tumors in the left parotid gland approximately 1.0 and 1.3 cm in diameter (Fig. 2). CT and FNA results both confirmed that these tumors were Warthin tumors of the parotid gland type 2B. The patient was hospitalized and antibiotic therapy was administered. The fourth day after the FNA, this reddish bulge of the patient which located in the preauricular region in the left side of the patient moved distally to the cervix. The migration of this red bulge was continued and in approximately 6 h the bulge was located in the left sternocostal space. After this position, the bulge was progressively diminished. The presumptive diagnosis of this bulge in the left parotid gland site was initially the abscess from the previously performed FNA. But the rapid migration and disappearing of the bulge with complete loss of the symptoms and signs of inflammation just in few hours made the diagnosis of a sialocele as the most appropriate one. It seems that FNA generated an injury in Warthin tumor or the healthy part of the parotid gland and produced the collection of the saliva.

Massive facial edema and airway obstruction secondary to acute postoperative sialadenitis or "anesthesia mumps": a case report

IntroductionA case of massive facial edema and airway obstruction secondary to an acute sialadenitis is described that occurred a few hours after a neurosurgical procedure performed in the prone position. Literature on this topic is reviewed.Case presentationA 73-year-old Caucasian woman underwent a right parieto-occipital craniotomy to remove a meningioma. The procedure was performed in the prone position and lasted for 7 hours. One hour after the end of surgery, left submandibular gland swelling was clearly visible and in a few hours, she developed massive facial edema. Imaging (computed tomography and magnetic resonance) showed inflammatory swelling of the submandibular and parotid glands and of the periglandular tissues, undilated excretory ducts, and complete obliteration of the pharynx lumen (pharyngeal mucosa adhered to the endotracheal tube). Analgesics, corticosteroids, and antibiotics were administered. Edema regressed from the 4th postoperative day and the endotracheal tube could be removed on the 7th postoperative day. The patient was discharged from the surgical intensive care unit on the 14th postoperative day and from hospital on the 28th postoperative day.ConclusionThis is the first case report in which acute postoperative sialadenitis caused complete upper airway obstruction: only the presence of a tracheal tube avoided the need for an emergency tracheostomy. Since edema evolves insidiously, we recommend caution when removing the endotracheal tube in patients who are acutely developing postoperative sialadenitis.

Ultrastructural Findings In Patients with Allergic Rhinitis

RATIONALE: The symptoms of allergic rhinitis are considered to be a result of accumulation and activation of inflammatory cells. Furthermore, some neuropeptides like Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) play an additional role in pathophysiology of allergic rhinitis.METHODS: Tissue samples from 38 human turbinates of patients with perennial rhinitis were taken during nasal surgery and preserved in phosphate-buffered glutaraldehyde. Ultrathin sections were cut and electron microscopy was performed. Additionally, samples were dehydrated and embedded in Araldit. Primary antibodies against CGRP and Substance P were applied and an immunocytochemical staining technique using a gold labeled antibody was carried out. Immunostained structures were photodocumented by using a transmission electron microscope.RESULTS: In the nasal mucosa an extensive edema and inflammatory cells like lymphocytes, plasma cells, eosinophiles and macrophages was found. The capillaries showed an activated endothelium. Immunoreactive nerve fibers were detected perivascular and in the periglandular tissue around the acini and ducts. Neuroglandular synapses with dense core vesicles and positive immunoreactions to CGRP and SP could be observed.CONCLUSIONS: Using electron microscopical techniques nerval structures near the submucosal glands could be demonstrated. Immunoreactions to the vasoactive neuropeptides CGRP and SP were detected in periglandular and perivascular nerves. These findings demonstrate the direct nerval influence on nasal mucosa in allergic rhinitis. CGRP and SP may induce vascular permeability and glandular secretion. These findings further elucidate pathomorphological mechanisms in allergic rhinitis. RATIONALE: The symptoms of allergic rhinitis are considered to be a result of accumulation and activation of inflammatory cells. Furthermore, some neuropeptides like Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) play an additional role in pathophysiology of allergic rhinitis. METHODS: Tissue samples from 38 human turbinates of patients with perennial rhinitis were taken during nasal surgery and preserved in phosphate-buffered glutaraldehyde. Ultrathin sections were cut and electron microscopy was performed. Additionally, samples were dehydrated and embedded in Araldit. Primary antibodies against CGRP and Substance P were applied and an immunocytochemical staining technique using a gold labeled antibody was carried out. Immunostained structures were photodocumented by using a transmission electron microscope. RESULTS: In the nasal mucosa an extensive edema and inflammatory cells like lymphocytes, plasma cells, eosinophiles and macrophages was found. The capillaries showed an activated endothelium. Immunoreactive nerve fibers were detected perivascular and in the periglandular tissue around the acini and ducts. Neuroglandular synapses with dense core vesicles and positive immunoreactions to CGRP and SP could be observed. CONCLUSIONS: Using electron microscopical techniques nerval structures near the submucosal glands could be demonstrated. Immunoreactions to the vasoactive neuropeptides CGRP and SP were detected in periglandular and perivascular nerves. These findings demonstrate the direct nerval influence on nasal mucosa in allergic rhinitis. CGRP and SP may induce vascular permeability and glandular secretion. These findings further elucidate pathomorphological mechanisms in allergic rhinitis.

Immunoelectron microscopic findings in patients with allergic rhinitis

In middle Europe the prevalence of allergic rhinitis is up to 15 % to 25 %. Allergic rhinitis is characterised by an inflammation of the nasal mucosa induced by different allergens. The patients suffer from symptoms like sneezing, rhinorrhea and nasal airway obstruction caused by morphological changes of the nasal mucosa. This symptomatology is considered to be a result of accumulation and activation of inflammatory cells. Further some neuropeptides like Calcitonin Gene Related Peptide (CGRP) and Substance P (SP) play an additional role in pathophysiology of allergic rhinitis. Tissue samples from 28 human turbinates of patients with perennial rhinitis were taken during nasal surgery and preserved in phosphate-buffered glutaraldehyde or paraformaldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. After polymerization an immunocytochemical staining-technique using a gold-labeled antibody was carried out. Immunostained structures were photodocumented by using a transmission electron microscope. In the lamina propria mucosae an extensive edema and several inflammatory cells like lymphocytes, plasma cells, eosinophiles and macrophages was found. The capillaries showed an activated endothelium. Immunoreactive nerve fibers were found in the periglandular tissue around the acini, ducts and in the glandular connective tissue. Neuroglandular synapses with dense core vesicles and positive immunoreactions to CGRP and SP could be detected. Neuropeptidergic axons were often observed near to plasma cells. In the edematous nasal mucosa an infiltration with different inflammatory cells was found. Using electron microscopical techniques nerve structures near the submucosal glands could be demonstrated. Immunoreactions to the neuropeptides CGRP and SP were detected in the periglandular nerves and in neuroglandular synapses. These findings demonstrate the direct nerve control of glandular functions in allergic rhinitis. CGRP is generally known to have a vasodilatatory effect and to stimulate the secretion of nasal seromucous glands. In addition, SP as a short-acting vasodilatator may induce vascular permeability and glandular secretion. These immunoelectron microscopical findings further elucidate pathomorphological mechanisms in allergic rhinitis.

Basic classical, peptidergic and nitrergic innervation pattern of human nasal glands--a histochemical and immunohistochemical study

Seromucous glands are important components of the human nasal mucosa. The innervation patterns are relevant for understanding the control of the different physiological and pathophysiological glandular functions. Beside classic neurotransmitters some neuropeptides seem to influence the glandular secretion. Tissue samples of 35 human inferior turbinates were taken during nasal surgery and preserved. Serial cryosections or paraffin sections were cut and incubated with antibodies either to Tyrosinhydroxilase or to Vasoactive Intestinal Peptide (VIP), Calcitonin Gene-Related Peptide (CGRP) and endothelial or brain Nitric Oxide Synthase (eNOS or bNOS). AChE- and NADPH-diaphorase-histochemistry were performed. Immunoreactive nerve fibers were found in the periglandular tissue around the acini, ducts and in the periglandular connective tissue. The density of positive immunoreactive structures depended on the different antibodies. VIP was found in contact to acinus cells, CGRP in the connective tissue around glandular cells. Particular immunoreactions to VIP and CGRP-antibodies could be detected near the glandular duct system. The eNOS-reactions were found in small capillaries near the acinus cells. Immunohistochemical and histochemical methods allow a detailed marking of nerval structures in nasal mucosa. The localization of neurons with different neurotransmitters and neuropeptides in the periglandular tissue confirms the direct nerval control of the diverse glandular functions. The detection of bNOS- and NADPH-d-positive structures around glandular cells and eNOS in the endothelium of periglandular capillaries suggests that NO takes an additional part in the regulation of nasal glands.

Electron microscopy studies of innervation of nasal mucosa glands in humans

Seromucous glands are one of the main components of human nasal mucosa. The innervation pattern is important to understand the control of the different physiological glandular functions. In addition to light-microscopical findings electronmicroscopic investigations were performed to get more detailed information on the innervation of nasal glands. Tissue samples of 16 human inferior turbinates were taken during nasal surgery and preserved in Unicryl or 3.5% phosphate-buffered glutaraldehyde. After fixation ultrathin sections were cut. Electron microscopical structures were photodocumented by using a transmission-electron microscope (EM 902 A Zeiss). Few axons were found in the periglandular tissue. No myo- or glandular-neural tight junctions could be identified. Unmyelinated nerve fibers showed typical components such as neurofilaments, neurotubules and mitochondria in their cytoplasm. An additional control of the glandular secretion by the vascular tone of the fenestrated capillary vessels will be discussed. Based on these ultramorphological findings further immunoelectron microscopical investigations will follow to demonstrate the various neurotransmitters and their distribution in periglandular axons.

Characterisation of inflammatory cells in benign prostatic hyperplasia

Inflammation is a common finding in benign prostatic hyperplasia (BPH) and may be classified as acute, chronic active or chronic inactive prostatitis. The aim of the present study was to localise the different types of inflammatory cells in prostatic lesions to determine the sequence of events in the cellular reaction. We have carried out immunohistological characterisation of the inflammatory cells, using CD45RO and CD3 antibodies to detect T-lymphocytes, CD20 antibodies to detect B-lymphocytes, CD68 to detect macrophages, kappa and lambda immunoglobulin light chains, and antibodies against prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP). Macrophages accumulated in the lumen and glandular epithelial layers of damaged prostatic glands and were found in the periglandular cuff of inflammatory cells in acute and chronic active prostatitis. Lymphocytes also accumulated in large numbers in the glandular epithelial layers and around the glands, indicating an association with macrophages. B-lymphocytes were scanty, if at all present, in acute and chronic active prostatitis, but were prominent within well-organised follicle centres in chronic active prostatitis. Cells positive for light chains were few and scattered in prostatic tissue. PSA and PSAP activity was lost in recently damaged prostatic glandular epithelium and reappeared only in regenerating secretory epithelium, indicating leakage as a result of damage. We suggest that the initial response to prostatic injury is cellular, and probably related to leakage into the periglandular tissues of PSA, PSAP and other antigenic molecules normally present in prostatic secretion. Macrophages respond, followed by recruitment of T-lymphocytes which participate in the inflammatory response and accumulate around the damaged glands. B-cell activity appears to be a late event.

Thermolytic salivation, substance P and kinins in rats.

In the heat, rats produce a large flow of saliva that they spread on their fur. We have tested whether substance P (SP) is involved in this response by using RP 67580, a NK1 tachykinin receptor antagonist, in normal and in kininogen-deficient rats. In anaesthetized rats, the sialogogic effect of SP (1 and 5 micrograms.kg-1 iv) was inhibited by RP 67580 (50 to 2500 micrograms.kg-1 iv). SP (5 micrograms.kg-1 iv) did not modify the vascular permeability to 125I-labelled albumin in submaxillary glands but increased this permeability in periglandular soft tissues and in the ears. This effect was suppressed by RP 67580 (50 to 2500 micrograms.kg-1 ip). Unanaesthetized normal male Wistar rats were exposed to ambient temperatures of 26 degrees C (thermoneutral range) or 36 degrees C for one hour. After this time period, a loss of body weight was observed. The thermolytic water loss reached 2% of body weight. This body weight loss was reduced by atropine (3 mg.kg-1 ip) or RP 67580 (50 to 2500 micrograms.kg-1 ip). The submaxillary glands were swollen and accumulated labelled albumin. This accumulation was reduced by atropine but was not affected by RP 67580. An extravasation of labelled albumin occurred in periglandular tissues. This accumulation was not modified by atropine which induced a large oedema of the soft tissues. Protein extravasation was suppressed by RP 67580 (2500 micrograms.kg-1) which did not modify or increased the volume of the oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocervicosis of the urinary bladder. A report of six cases of a benign müllerian lesion that may mimic adenocarcinoma.

Six tumor-like glandular lesions characterized by a prominent component of endocervical-type epithelium involved the wall of the urinary bladder in women of reproductive age (31 to 44 years; mean, 37). All of the lesions posed problems in histologic diagnosis; indeed, a diagnosis of adenocarcinoma was initially rendered in three cases. Five patients presented with bladder symptoms, including--alone or in combination--suprapubic pain, dysuria, frequency, and hematuria. There was catamenial exacerbation of the symptoms in one case. The sixth patient--the only one with documented pelvic endometriosis--presented with dysmenorrhea, dyspareunia, and lower abdominal tenderness. In each patient, a mass that ranged from 2 to 5 cm in maximum dimension was typically located in the posterior wall or posterior dome of the urinary bladder. A partial cystectomy (five cases) or transurethral resection (one case) was performed. In one patient, extravesical pelvic soft tissue was involved, precluding complete resection of the lesion. Microscopic examination revealed extensive involvement of the bladder wall by irregularly disposed, benign-appearing, or mildly atypical endocervical-type glands, some of which were cystically dilated. Other findings included occasional ciliated cells, typically interspersed with the endocervical-type cells (four cases), a minor component of endometrioid glands (three cases), and glands lined by nonspecific cuboidal or flattened cells with eosinophilic cytoplasm (all cases). Some of the glands were surrounded only by the smooth muscle of the muscularis propria, but in other areas, the periglandular tissue was fibrous or edematous. In three cases, rare glands were surrounded by thin rims of endometriotic stroma. Gland rupture resulted in stromal extravasation of mucin in all cases and was a prominent feature in one. All patients had uneventful postoperative follow-up periods ranging from 1.5 to 14 years. The findings indicate that these bladder lesions are müllerian in nature and represent examples of endocervicosis, the mucinous analogue of endometriosis. Awareness of the lesion, which with one possible exception is hitherto undescribed in the bladder, and attention to its typical histologic features should facilitate its crucial distinction from adenocarcinoma.

Undifferentiated Tumours of Salivary Glands: Immunocytochemical Investigations and Differential Diagnosis of 22 Cases

22 undifferentiated tumours of the Salivary Gland Register (University of Hamburg) were studied by conventional light microscopical and immunocytochemical methods to elucidate the heterogeneity of this tumour group. The following observations were made in this collective: 18 tumours displayed one or more markers for the epithelial character and were classified as carcinomas. 10 carcinomas were considered as primary ones and 8 were considered as secondary ones (metastatic or invasive "per continuitatem"). Primary carcinomas were subclassified as poorly differentiated variants of a distinctive type of salivary gland tumours, as follows: 6 cases of carcinoma in pleomorphic adenoma, and one case each of mucoepidermoid tumour, adenocarcinoma, salivary duct carcinoma and epidermoid carcinoma. Secondary carcinomas were subclassified as follows: 3 epidermoid carcinomas, 3 nasopharyngeal carcinomas and 2 bronchial carcinomas. One tumour positive for S-100 protein and NSE (Neuron-specific enolase) was classified as a metastatic melanoma. Another tumour positive for vimentin and actin was classified as a rhabdomyosarcoma of the periglandular tissue. Two tumours lacked any markers studied here and were regarded as a malignant paraganglioma and an undifferentiated lymphoma, respectively. The differential diagnosis of the undifferentiated tumours of salivary glands and the special problems of this tumour group are discussed.