Macrophage polarisation changes within the time between diagnostic biopsy and tumour resection in oral squamous cell carcinomas--an immunohistochemical study.

BACKGROUND: The prognosis of solid malignancies has been shown to depend on immunological parameters, such as macrophage polarisation (M1/M2). Recently, it was reported that preoperative oral surgery leads to a worsening of oral squamous cell carcinomas (OSCC) prognosis. Diagnostic incision biopsies are oral surgery procedures that might lead to healing-associated M2 macrophage polarisation with a potential negative influence on tumour biology. No studies have compared macrophage polarisation in OSCC biopsies and tumour specimens. METHODS: Preoperative diagnostic incision biopsies (n=25) and tumour resection specimens (n=34) of T1/T2 OSCC were processed for immunohistochemistry to detect CD68-, CD11c-, CD163- and MRC1-positive cells. Samples were digitised using whole-slide imaging, and the expression of macrophage markers was quantitatively analysed. RESULTS: Carcinoma tissues obtained during OSCC tumour resections showed a significantly (P<0.05) increased CD163 cell count (M2 macrophages) compared with tissues obtained during preoperative incision biopsies. Additionally, the CD163/CD68 ratio (an indicator of M2 polarisation) was significantly (P<0.05) higher in tumour resection specimens than in biopsies. CONCLUSIONS: This study revealed for the first time an increase in M2 polarisation in samples obtained during OSCC tumour resection surgery compared with preoperative incision biopsies. The biopsy-induced tissue trauma might explain the observed shift in macrophage polarisation towards the tumour-promoting M2 type and could lead to accelerated tumour progression.

Perioperative factors that influence the outcome of microsurgical reconstructions in craniomaxillofacial surgery.

Microsurgical tissue transfer is a well-established way of reconstructing the head and neck, but there are still many postoperative complications that require revision. The aim of this study was to clarify perioperative factors and characteristics of patients that influence the success of the flap and the need for revision. We retrospectively studied 368 patients who were treated with microsurgical free tissue transfer in the head and neck area at the Department of Oral and Maxillofacial Surgery at the University Medical Centre, Erlangen, between 2004 and 2009. Investigations concentrated on patients' characteristics and operative factors. Free scapular or parascapular flaps (n=161, 44%) and radial forearm flaps (n=119, 32%) were predominantly used for the reconstruction of major defects in the mandible and the floor of the mouth. In 39 patients (11%) revision was required, which resulted in a success rate of 96%. There was a significant association between preoperative American Society of Anesthesiologists (ASA) grade and postoperative survival of the flap (p=0.04). Patients previously treated by irradiation required significantly more revisions than those not so treated (p=0.04). The use of vein grafts was also significantly associated with the need for revision (p=0.02). The ASA grade influenced the success rate but was not associated with the number of revisions. These factors must be taken into consideration when intervention is planned to reduce the number of postoperative complications and interventions further.

Oral findings associated with primary hyperoxaluria type I.

In the present paper we report the oral findings of a patient who was diagnosed with hyperoxaluria. Hyperoxalurias can basically be classified as primary and secondary, with the first being inborn errors of metabolism and the second a result of excessive oxalate intake. Primary hyperoxalurias form a rare group of metabolic diseases that are inherited in the autosomal recessive fashion. The affected genes code for specific hepatic enzymes that are involved in glyoxylate metabolism and their deficiency results in overproduction of oxalate. Two different types are described: Primary hyperoxaluria type I results from a deficiency of peroxisomal enzyme alanine-glyoxylate aminotransferase and the more rare type II from a deficiency of cytosolic enzyme D-glycerate dehydrogenase. Since oxalate is primarily excreted through the kidneys, abnormally high concentration of oxalate in the urine occurs. This can in turn result in recurrent kidney stones and parenchymal renal damage and end-stage renal disease (ESRD). Inability to further excrete oxalate through the kidneys leads to its deposition in various organs (oxalosis). Several oral findings have been described in patients with oxalosis, most important of whose are bone resorption in the jaws, external root resorption and rapidly progressive dental mobility, as well as dental pain associated with deposition of oxalate in the dentine and the pulp.

Msx-1 is suppressed in bisphosphonate-exposed jaw bone analysis of bone turnover-related cell signalling after bisphosphonate treatment.

OBJECTIVES: Bone-destructive disease treatments include bisphosphonates and antibodies against receptor activator for nuclear factor κB ligand (aRANKL). Osteonecrosis of the jaw (ONJ) is a side-effect. Aetiopathology models failed to explain their restriction to the jaw. The osteoproliferative transcription factor Msx-1 is expressed constitutively only in mature jaw bone. Msx-1 expression might be impaired in bisphosphonate-related ONJ. This study compared the expression of Msx-1, Bone Morphogenetic Protein (BMP)-2 and RANKL, in ONJ-affected and healthy jaw bone. MATERIAL AND METHODS: An automated immunohistochemistry-based alkaline phosphatase-anti-alkaline phosphatase method was used on ONJ-affected and healthy jaw bone samples (n = 20 each): cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed to quantitatively compare Msx-1, BMP-2, RANKL and GAPDH mRNA levels. RESULTS: Labelling indices were significantly lower for Msx-1 (P < 0.03) and RANKL (P < 0.003) and significantly higher (P < 0.02) for BMP-2 in ONJ compared with healthy bone. Expression was sevenfold lower (P < 0.03) for Msx-1, 22-fold lower (P < 0.001) for RANKL and eightfold higher (P < 0.02) for BMP-2 in ONJ bone. CONCLUSIONS: Msx-1, RANKL suppression and BMP-2 induction were consistent with the bisphosphonate-associated osteopetrosis and impaired bone remodelling in BP- and aRANKL-induced ONJ. Msx-1 suppression suggested a possible explanation of the exclusivity of ONJ in jaw bone. Functional analyses of Msx-1- RANKL interaction during bone remodelling should be performed in the future.

Evaluation of substitutes for bone: comparison of microradiographic and histological assessments.

We created defects of standard size in the frontal bones of adult pigs and filled them with four different materials. On six occasions (at 1, 2, 4, 8, 12, and 26 weeks), samples were harvested, and evaluated by computing microradiographic images. We examined the specimens histologically as controls. After insertion of anorganic materials, microradiographic evaluation was easy and precise, and there were no significant differences between them and the histological controls (p=0.2). A quantitative evaluation of chemically sterilised bone by computer was not possible for more than 4 weeks.

Expression of interleukin 1-beta, transforming growth factor beta-1, and vascular endothelial growth factor in soft tissue over the implant before uncovering.

BACKGROUND: Overexpression of inflammatory cytokines interleukin 1-beta (IL-1beta), transforming growth factor beta-1 (TGF-beta1), and vascular endothelial growth factor (VEGF) may cause healing impairment following implant insertion, jeopardizing success especially in patients previously irradiated. Limited data is available regarding expression pattern of inflammatory cytokines in peri-implant soft tissue caused by the surgical intervention itself. STUDY DESIGN: This study examined 21 patients receiving dental implants. Biopsies of peri-implant tissue were harvested at re-entry 4 months after initial surgery. Eight patients underwent probing of untreated mucosa. Three groups were created (group 1: regular peri-implant mucosa; group 2: patients with irradiated peri-implant mucosa, radiation treatment due to oral squamous cell cancer; group 3: control). Immunohistochemical staining was performed for TGFss1, IL-1ss, and VEGF. RESULTS: Following the placement of dental implants (group 1 vs group 3) a significant increase (P > .05) in TGF-beta1, IL-1beta, and VEGF expression in the peri-implant mucosa was demonstrated. No alteration of this distinct pattern was found for previously irradiated tissue (group 1 vs. group 2). CONCLUSIONS: The study highlights the fundamental involvement of TGF-beta1, IL-1beta, and VEGF during the regeneration of peri-implant soft tissue structures. The use of extended interim solutions may be one clinical implication of these prolonged tissue remodeling processes.