Comparison of manual and automated digital image analysis systems for quantification of cellular protein expression.

OBJECTIVE: Quantifying protein expression in immunohistochemically stained histological slides is an important tool for oncologic research. The use of computer-aided evaluation of IHC-stained slides significantly contributes to objectify measurements. Manual digital image analysis (mDIA) requires a user-dependent annotation of the region of interest (ROI). Others have built-in machine learning algorithms with automated digital image analysis (aDIA) and can detect the ROIs automatically. We aimed to investigate the agreement between the results obtained by aDIA and those derived from mDIA systems. METHODS: We quantified chromogenic intensity (CI) and calculated the positive index (PI) in cohorts of tissue microarrays (TMA) using mDIA and aDIA. To consider the different distributions of staining within cellular sub-compartments and different tumor architecture our study encompassed nuclear and cytoplasmatic stainings in adenocarcinomas and squamous cell carcinomas. RESULTS: Within all cohorts, we were able to show a high correlation between mDIA and aDIA for the CI (p<0.001) along with high agreement for the PI. Moreover, we were able to show that the cell detections of the programs were comparable as well and both proved to be reliable when compared to manual counting. CONCLUSION: mDIA and aDIA show a high correlation in acquired IHC data. Both proved to be suitable to stratify patients for evaluation with clinical data. As both produce the same level of information, aDIA might be preferable as it is time-saving, can easily be reproduced, and enables regular and efficient output in large studies in a reasonable time period.

Retrospective analysis of time-related three-dimensional iliac bone graft resorption following sinus lift and vertical augmentation in the maxilla.

The atrophic maxilla frequently requires bone grafting using an onlay graft (OG) or sinus lifting (SL) before implant rehabilitation. The resorption of bone grafts is influenced by the time until implantation, quality of donor bone, and grafting technique. The aim of this study was to investigate the impact of both grafting techniques on the time-related resorption of autologous iliac bone graft. Forty-three patients underwent either onlay grafting or a sinus lift at 73 sites in the maxilla. Graft height was measured by cone beam computed tomography after augmentation and during follow-up for up to 12 months prior to implant insertion. The effect of time and technique on graft resorption was evaluated retrospectively. The reduction in bone graft height was greater for OG than SL over the investigated time intervals (OG = 51%, SL = 28%; P = 0.002). Each technique followed a specific course of resorption, which was independent of the initial graft height and could be calculated by a non-linear regression model. Iliac bone graft undergoes rapid resorption when used as an OG prior to implant insertion. For SL, this resorption is reasonably lower. This is especially crucial to determine the optimal time for implant insertion after graft healing to improve implant survival.

Salivary gland scintigraphy in patients suffering from severe keratoconjunctivitis sicca. Evaluation of the viability of submandibular glands before and after transfer into the temporal fossa.

UNLABELLED: Low tear production or elevated tear evaporation can lead to severe keratoconjunctivitis sicca. In patients with this disease, the transfer of an autologous submandibular gland into the temporal fossa is currently the most common surgical lacrimal gland substituting procedure. AIM: We compared the pre- and postoperative viability of transferred submandibular glands. PATIENTS, METHODS: Altogether 16 submandibular glands had been transferred in 12 patients. The graft's viability was evaluated before and 0.5-1, 1-6 and 8-12 months after transplantation by dynamic salivary gland scintigraphies after application of 40-50 MBq 99mTc-pertechnetate. Quantitative analysis was performed by calculation and comparison of the glandula submandibularis-to-background-ratio (SBR) and the transplant-to-background-ratio (TBR). The scintigraphic results were correlated with the clinical follow-up. RESULTS: All grafts remained viable during clinical follow-up. Salivary gland scintigraphy yielded 15 true positive results and 1 false-negative result. Comparison of presurgical SBR and postsurgical TBR showed good correlation with the clinical course. In 10 patients at least one transplant-reduction was necessary due to excessive epiphora occurring averagely 8 months after transplantation. CONCLUSION: Our results show that salivary gland scintigraphy very exactly reflects the morphological and biochemical postsurgical changes in a transferred submandibular gland. Thus, it is a reliable tool to exactly and objectively evaluate the viability of the grafts in the postsurgical course.

Impact of zoledronic acid on control of metastatic spinal cord compression.

BACKGROUND: Zoledronic acid was demonstrated to reduce the rate of skeletal-related events, a hypernym including various outcomes, in patients with bone metastases. In contrast to other studies, this matched-pair analysis focused solely on the impact of zoledronic acid on metastatic spinal cord compression (MSCC). PATIENTS AND METHODS: Data from 98 patients with MSCC receiving radiotherapy plus zoledronic acid were matched 1:2 to 196 patients receiving radiotherapy alone for ten potential prognostic factors. Both groups were compared for local control of MSCC within the irradiated region, overall control of MSCC (local and distant MSCC control), and survival. RESULTS: The 1-year local control rates were 90% after radiotherapy plus zoledronic acid and 81%, after radiotherapy alone (p = 0.042). The 1-year overall control rates were 87% and 75%, respectively (p = 0.016), and the 1-year survival rates were 60% and 52%, respectively (p = 0.17). Results were significant in the Cox proportional hazards model regarding local control (p = 0.024) and overall control (p = 0.008). CONCLUSION: According to the results of this study, zoledronic acid was associated with improved control of MSCC in irradiated patients.

Cisplatin superior to carboplatin in adjuvant radiochemotherapy for locally advanced cancers of the oropharynx and oral cavity.

BACKGROUND AND PURPOSE: The optimal radiochemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN) is controversial. In most cases, platin-based chemotherapy regimens are used. However, uncertainty exists whether cisplatin or carboplatin is the better choice. This retrospective study compared radiochemotherapy with either cisplatin or carboplatin in patients with locally advanced SCC of the oropharynx and oral cavity. PATIENTS AND METHODS: Concurrent chemotherapy consisted of two courses of cisplatin (20 mg/m(2) on days 1-5 and days 29 - 33; n = 65) or two courses of carboplatin (AUC 1.5 on days 1-5 and days 29 - 33; n = 41). Both regimens were retrospectively compared for locoregional control (LRC), overall survival (OS), and toxicity. Thirteen additional potential prognostic factors were evaluated including age, gender, ECOG performance status, tumor site, histologic grade, T/N category, AJCC stage, year of treatment, extent of resection, interval between surgery and RT, completion of chemotherapy, and radiotherapy breaks. RESULTS: The 3-year LRC rates were 85% in the cisplatin group and 62% in the carboplatin group, respectively (p = 0.004). The 3-year OS rates were 78% and 51%, respectively (p = 0.001). Acute toxicity (mucositis, skin toxicity, nausea/vomiting, renal toxicity, hematologic toxicity) and late toxicity (xerostomia, neck fibrosis, skin toxicity, lymph edema) rates were not significantly different between the two groups. On multivariate analysis, better LRC was significantly associated with cisplatin (p < 0.001), an ECOG performance status of 0-1 (p = 0.001), and an interval between surgery and RT of ≤ 6 weeks (p = 0.001). Improved OS was significantly associated with cisplatin (p < 0.001) and completion of chemotherapy (p = 0.002). CONCLUSION: For adjuvant radiochemotherapy of patients with locally advanced cancer of the oropharynx and oral cavity, cisplatin appears preferable to carboplatin as it resulted in better outcomes without increased toxicity.

Including the platysma muscle in a cervicofacial skin rotation flap to enhance blood supply for reconstruction of vast orbital and cheek defects: anatomical considerations and surgical technique.

The surgical technique introduced in this work describes a modification of the rotation skin flap that includes the platysma muscle in order to improve the blood supply of the flap. This modified rotation flap enables sufficient reconstruction of extended regions following ablative surgery of the head and neck. The anatomy and clinical application of a bilayer cervicofacial skin-platysma rotation flap is described in 6 patients. Flap design ensures sufficient blood perfusion mainly via the occipital artery, the superficial cervical artery and the transverse cervical artery; venous drainage is achieved by the external jugular vein and by randomised vascularisation. The surgical procedures led to sufficient and successful reconstruction of the orbital and cheek region. Further oncological management, such as neck dissection and total parotidectomy could be performed through the flap approach because of the adequate exposure of neck structures. Due to the sensory supply reaching the flap dorsally, sensibility in the reconstructed region could be regained in all patients. This modified skin-platysma rotation flap represents an appropriate surgical technique for safe and simple closure of vast orbital and cheek defects with enhanced blood supply, which enables the extended mobilization required after ablative surgery of the orofacial region.

Laminin-5 immunocytochemistry: a new tool for identifying dysplastic cells in oral brush biopsies.

BACKGROUND: The brush biopsy technique is not only a seminal technique but also a critically discussed method for detection of oral pre-cancerous stages and manifest carcinomas. The gamma2 chain of laminin-5 and its proteolytic fragments comprise an invasion factor for many carcinomas. OBJECTIVES: The aim of this study was to determine whether the immunocytochemical presentation of the laminin gamma2 chain identifies pre-invasive or invasive squamous cells in brush biopsies. METHODS: The value-based identification of atypical epithelia was analysed in 93 consecutive brush biopsies with histopathological diagnoses: standardized haematoxylin and eosin staining; standardized immunocytochemistry: monoclonal antibodies against laminin gamma2 chain: D4B5, 4G1, detection using ChemMate and Autostainer. RESULTS: Conventional cytology did not result in any false-positive cases, i.e. atypical cells in normal, inflamed or benignly hyperproliferative mucosa (specificity, 100%), whereas immunocytochemistry revealed one false-positive case (specificity, 98%). In brush biopsies of oral squamous cell carcinomas, the following immunocytochemical patterns were possible: (1) staining of the cytoplasm, (2) banded markings between clumped carcinoma cells and (3) positive hazes surrounding atypical cells. Bacterial colonies appeared as false-positive results. Four of 27 carcinomas and one of three recurrences were not cytologically identified (sensitivity of conventional cytology, 79%). Three of the five carcinomas not identified by cytology were immunocytochemically stained with laminin gamma2 chain antibody (sensitivity of laminin gamma2 chain immunocytochemistry, 93%). The positive predictive value was 100% for conventional cytology and 97% for laminin gamma2 chain immunocytochemistry. The negative predictive value attained was 92% for conventional cytology and 97% for laminin gamma2 chain immunocytochemistry. CONCLUSIONS: The high sensitivity level observed for method-enhanced brush cytology suggests that this technique be used as an initial diagnostic step.

High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies.

Tumour-invasion like wound healing is characterised by the formation of an extracellular matrix with a high tenascin-C content. The tenascin-C molecule undergoes alternative splicing. Analysis using antibody BC2 indicates that especially the high-molecular tenascin-C (hm tn-C) variants are typically tumour-associated, while distribution in normal tissue is restrictive. This study investigated whether hm tn-C is a suitable indicator of atypical cells with invasive potential in oral brush biopsies. One hundred fifty nine consecutive oral brush biopsies with histopathological diagnoses were analysed for the identification of atypical cells. A standardised haematoxylin and eosin staining plus standardised immunocytochemistry using the monoclonal anti-hm tn-C antibody was performed. The bound hm tn-C antibodies were detected with the streptavidine/alkaline phosphatase technique in the autostainer. Conventional cytology produced four false-positives when identifying atypical cells in brush biopsies of inflammatory/benign hyperproliferative mucosa (specificity 96%), while 10 in 52 carcinomas and three of eight recurrences were not identified (sensitivity 78%). Ten of these 13 non-identified tumours could be marked when adding the hm tn-C assay (increasing specificity to 99%). Combining the two assays also reduced the false-positive outcomes from four to one (increasing sensitivity to 95%). The positive and negative predictive values were 92 and 88% for conventional cytology vs 98 and 97% for the dual assay. (1) A 95%-sensitivity proves hm tn-C assisted conventional cytology to be a suitable means of identifying atypical cells in oral brush biopsies. (2) The positive (98%) and negative (97%) predictive values obtained approximate hm tn-C assisted conventional cytology to laminin-5 (100/97%).

The value of FDG-PET and bone scintigraphy with SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible.

OBJECTIVE: To appraise the value of FDG-PET and bone scintigraphy using SPECT in the primary diagnosis and follow-up of patients with chronic osteomyelitis of the mandible (COM). METHODS: In a prospective study the pattern of tracer uptake was investigated using 2 diagnostic methods in 42 patients. Results were compared with histology and radiographs as well as clinical and laboratory parameters. RESULTS: The use of FDG-PET in the primary diagnosis of COM resulted in a sensitivity of 64% and a specificity of 77.7%. The sensitivity of SPECT was 84% and the specificity 33.3%. During the follow-up period of these patients the sensitivity of SPECT increased to 93.7%, while the specificity decreased (6.6%). The sensitivity and specificity of FDG-PET for this follow-up group were 62.5 and 80%, respectively. CONCLUSION: Because of its high sensitivity, SPECT is vastly superior to other diagnostic methods in initiating treatment. In the follow-up period it might be replaced by FDG-PET, which reflects the disease course better and indicates the time of clinical remission.

Exposure of implants using a modified multiple-flap transposition vestibuloplasty.

AIM: To introduce a minimally invasive operation to improve the condition of the soft tissues around the implants in an atrophied mandible, at the same time, as uncovering the implants. PATIENTS AND METHOD: A multiple-flap transposition vestibuloplasty was done in 11 patients after the insertion of four implants in the interforaminal region of an atrophied mandible. Improvement in soft tissues and successful exposure of implants and attached gingiva were evaluated during a follow-up period of 55 months. All the patients were operated on local anaesthesia as outpatients. RESULTS: Adequate exposure of implants and an area of attached gingiva 4-9 mm wide were attained. There was no bleeding on probing or local infection. CONCLUSION: The transposition multiple-flap vestibuloplasty is a simple and minimally invasive method of improving the condition of soft tissue after insertion of implants. It does not limit the patients' routine activities and avoids staged operations.

[Incorporation of multiple foreign bodies due to borderline personality disorder]. / Inkorporation multipler Fremdkörper bei Borderlinepersönlichkeitsstörung. Literaturübersicht und Fallbeschreibung.

BACKGROUND: Autoaggressive behaviour is one of the pathognomonic characteristics in patients with borderline personality disorder. Clinical symptoms of such behaviour can be the self-induced incorporation of foreign bodies. In the head and neck area, this form of autoaggressivity causes primary or secondary infectious complications with different clinical manifestations. Below follows a description of diagnosis, therapy and follow-up of such a case, comparing our own findings with the corresponding literature. CASE REPORT: A 24-year-old woman with manifest borderline personality disorder was referred to the Department of Maxillofacial Surgery after developing a swelling in the infra-auricular region. After antibiotic therapy failed to reduce inflammatory symptoms, local revision was performed including excision of two metallic foreign bodies. Comprehensive radiological evaluation identified multiple foreign bodies in the head and neck region and lower arms. A total of 76 metallic foreign bodies was removed surgically. During early surgical follow-up and subsequent psychiatric treatment, the patient incorporated new foreign bodies. DISCUSSION: The case reported represents a pattern of foreign body incorporation which is unusual based on review of the literature but characteristic for patients with borderline personality disorder. Diagnostics and therapy require an individual concept which only can be implemented in close co-operation with psychiatrists. Secondary clinical benefit derived from surgical diagnostics and therapy as well as the possibility of autoaggressive relapse have to be taken into consideration.

Re-distribution of tenascin-C in the parotid acinar cells. An early marker of radiation-induced damage of salivary glands?

PURPOSE: In order to investigate the early changes in the expression of tenascin-C, following irradiation and the associated functional impairment of salivary glands. MATERIALS AND METHODS: Fifteen rabbits were used for the study. Five provided control parotid gland tissue and a further 10 rabbits were scintigraphically examined prior to and 24 h after 15/30 Gy. Glands were studied histologically using HE-staining and tenascin-C antibodies. RESULTS: Reduction in the salivary ejection fraction (SEF) was observed in all irradiated glands. Simultaneously, a marked re-distribution of tenascin-C expression was noticed. Reactivity detected in the intercalated, secretory ducts and perineurinal regions prior to radiation was noticed intracellularly after 24 h. Furthermore, nerves showed tenascin-C expression in the Schwann cells, but no longer perineurinally. Myofibroblasts were also observed in the stroma. CONCLUSION: This study proves the ability to predict functional disorders of salivary function as early as 24 h after radiation and provides evidence of the participation of tenascin-C in the pathological process of radiation-induced damage in salivary glands.

[Intra- and postoperative monitoring of transplanted flaps. Measurement of the partial pressure of oxygen in tissue]. / Intra- und postoperatives Monitoring von Lappentransplantaten. Messung des Gewebesauerstoffpartialdrucks.

BACKGROUND: According to Schmelzeisen et al. (1996), the failure rate for microvascular free flaps is 5%. While surface tissue oxygenation can be assessed clinically, if necessary by a puncture, the oxygen supply to deeper areas mostly cannot be checked. We therefore wished to find whether measurement of tissue pO(2) would prove to be an objective and practical technique that could be used for continuous and accurate intra- and postoperative evaluation of flap perfusion. MATERIAL AND METHODS: A Clark-type microcatheter was used intra- and postoperatively to monitor tissue pO(2) in 5 pedicled pectoralis major flaps and 32 free revascularized flaps (9 jejunal flaps, 5 latissimus dorsi flaps, 6 radial forearm flaps and 12 scapular flaps). RESULTS: The mean values for tissue pO(2) were significantly lower in pedicle grafts than in free revascularized flaps. Within in each flap group the pO(2) values measured did not vary significantly over an observation period of up to 77.2 h after transplantation. CONCLUSIONS: Continuous measurement of tissue pO(2) by means of a Clark-type microcatheter combined with clinical examination constitutes a reliable method of monitoring tissue oxygenation in pedicle grafts and free revascularized flaps during the intra- and postoperative phases. Analysis of small and of wide fluctuations in pO(2) values may help in the diagnosis of early arterial and venous obstructions in flaps and may in the future result in new insights into the tissue oxygenation in surgical flaps allowing some alleviation of the problems currently experienced in clinical monitoring.

[Perioperative use of medical hypnosis. Therapy options for anaesthetists and surgeons]. / Perioperativer Einsatz von medizinischer Hypnose. Therapieoption für Anästhesisten und Chirurgen.

BACKGROUND: Surgical treatment of patients under local anaesthesia is quite commonly restricted by limited compliance from the patient. An alternative to treatment under pharmacological sedation or general anaesthesia could be the application of medical hypnosis. With this method, both suggestive and autosuggestive procedures are used for anxiolysis, relaxation, sedation and analgesia of the patient. PATIENTS AND METHODS: During a 1-year period of first clinical application, a total of 207 surgical procedures on a non-selected collective of 174 patients were carried out under combined local anaesthesia and medical hypnosis. RESULTS: Medical hypnosis proved to be a standardisable and reliable method by which remarkable improvements in treatment conditions for both patient and surgeons were achievable. CONCLUSION: Medical hypnosis is not considered to be a substitute for conscious sedation or general anaesthesia but a therapeutic option equally interesting for anaesthesists and surgeons.

[Evaluation of intraoperative standardized hypnosis with the State-Trait Anxiety Inventory]. / Evaluation des intraoperativen Einsatzes standardisierter Hypnose mit State-Trait-Angst-Inventar.

BACKGROUND: Surgical treatment under local anesthesia is commonly restricted by limited compliance of patients. Hypnosis may represent an alternative to sedation or general anesthesia. As the procedure demonstrated promising prospects during 1-year experience, the observed hypnosis-induced effects are now being evaluated in clinical studies. PATIENTS AND METHOD: The prospective study included 50 patients scheduled for dental surgery. All procedures were performed under standardized surgical conditions. The experimental group (n=25) received supplementary standardized tape hypnosis, whereas the control group received standard treatment (only local anesthesia). Individual and situative anxiety levels were determined by the State-Trait Anxiety Inventory (STAI). RESULTS: After simultaneous increase of preoperative state anxiety, anxiety levels in the hypnosis group showed a significant intraoperative reduction to baseline level, whereas intraoperative anxiety of the control group (n=25) remained unchanged. CONCLUSIONS: Hypnosis reduces intraoperative anxiety of oral and maxillofacial patients significantly. Further clinical studies on the use of hypnosis are considered useful.

Early immunohistochemical and functional markers indicating radiation damage of the parotid gland.

In order to evaluate the correlation between functional impairment and changes in the expression pattern of immunohistochemical antibodies in the early phase of radiation-induced dysfunction of salivary glands, eight rabbits were scintigraphically examined prior to and 24 h after irradiation with 15 Gy. The parotid glands were studied using HE-staining, Ki-67, alpha-smooth muscle actin (ASMA) and tenascin-C antibodies at every scintigraphic examination. The results demonstrated a significant alteration in the 99mTc-pertechnetate uptake in all irradiated glands. HE-staining showed no relevant impairment of salivary gland tissue in this early phase. Immunohistochemically, we observed a marked re-distribution of ASMA and tenascin-C as well as a reduction of the proliferating rate of acinar cells. This immunohistochemical change correlated with the functional impairment manifested scintigraphically. This study proves the possibility to assess disorders of salivary gland function with immunohistological antibodies as early as 24 h after irradiation and yields the prerequisites to prove the effects of radioprotective agents on salivary gland tissues.

[Long-term follow-up after autologous submandibular gland transplantation in scarring keratoconjunctivitis with absolute dry eyes]. / Mehrjahresverlauf nach Autotransplantation der Unterkieferspeicheldrüse bei vernarbender Keratokonjunktivitis mit absolutem Tränenmangel.

INTRODUCTION: An autologous submandibular gland can be transplanted to the temporal fossa and following microvascular anastomosis to the temporal artery and vein and implantation of the secretory duct into the superotemporal conjunctival fornix to provide continuous substitute lubrication. Here we report our experiences with this procedure. PATIENTS AND METHODS: In a prospective, controlled clinical cohort study, we investigated the development of the Schirmer- test, fluorescein-break up time (F-BUT), degree of discomfort, use of pharmaceutical tear substitutes, visual acuity, Rose Bengal staining and conjunctival hyperemia in 14 eyes with a successful submandibular gland transplant and 11 dry eyes without salivary lubrication. RESULTS: Over a mean postoperative period of 3.3 years the transplantation group showed significant improvements of the Schirmer-Test, FBUT, use of pharmaceutical tear substitutes, discomfort and Rose Bengal staining up to the last follow-up when compared to the preoperative and control groups. CONCLUSION: Transplantation of an autologous submandibular gland can improve the lubrication and discomfort of absolute tear deficiency on a long term basis, but the salivary tear film only partially stabilises the ocular surface. The procedure is however able to provide symptomatic relief in extreme cases of absolute dry eyes.

Subcutaneous fat layer in different donor regions used for harvesting microvascular soft tissue flaps in slender and adipose patients.

The aim of this study is to provide valid data concerning the thickness of the subcutaneous fat layer in seven donor regions which are most commonly used for soft tissue replacement in the head and neck region. Furthermore the study focuses on differences in thickness of this layer depending on the nutritional status and sex. In 100 volunteers the thickness of the subcutaneous fat layer was evaluated using ultrasound in seven potential donor regions: radial and ulnar forearm, lateral upper arm, scapular and parascapular region, abdominal/supra-umbilical region and the lateral calf. Volunteers were divided into 4 groups: male and female, slender (body mass index [BMI] < 25) and adipose (BMI > 30). Data obtained was compared and differences were proven to be statistically significant (Student's t-test, P<0.05). The largest thickness was found in the supra-umbilical region followed by the lateral upper arm whereas the ulnar forearm region had the smallest thickness. Depending on the BMI the supra-umbilical and the lateral upper arm regions showed the most wide variation. Depending on sex the most noticeable variation in thickness of the subcutaneous layer was seen in the lateral calf region with a significant larger tissue layer in females.

Scintigraphic evaluation of lacrimal glands using a rabbit experimental model.

The aim of this study was to establish an experimental model to evaluate functional changes in lacrimal gland parenchyma using gamma scintigraphy. Although the lacrimal glands of the rabbit have frequently been used for ophthalmological research, scintigraphic evaluation of these glands has received far less attention and we could not find any reports concerning this topic in the literature. Ten rabbits were used for the study; in 4 of them, the orbital region was dissected to provide the topographic anatomy of the lacrimal glands. Four rabbits underwent a static scintigraphy after excision of a unilateral lacrimal gland. Changes in the pattern of tracer uptake indicated the exact position of the gland on the scintiscan. One rabbit served as a control, and another one was used to prove the surgical accessibility of the gland. Using a frontal projection of the head the (99m)TcO(-)(4) uptake of the rabbit lacrimal glands could be identified and evaluated in the upper lateral region of the scintiscan. In conclusion, the lacrimal glands of the rabbit provide an appropriate experimental model to study quantitative disturbances of lacrimal secretion using scintigraphy and enable the assignment of functional impairment to morphological changes of the lacrimal parenchyma.