The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes.

Hyperglycemia mediated oxidative stress and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) are considered important for diabetic retinopathy onset and progression. Melatonin is a pineal hormone that regulates circadian and seasonal rhythms and most likely is involved in regulating glucose metabolism. We aimed to evaluate the potential benefit of melatonin supplementation to the pre-diabetic retina by assessing melatonin effects on lipid peroxidation (thiobarbituric acid reactive substances, TBARS), protein oxidation (advanced oxidation protein products, AOPP) and concentrations of inducible nitric oxide synthase (iNOS), VEGF and MMP9 in the retina of rats with pre-diabetes. Pre-diabetes was induced by streptozotocin (45 mg/kg, i.p.) following nicotinamide injection (110 mg/kg, i.p.). Beside mild hyperglycemia, lower serum insulin, increased fructosamine and lower HDL cholesterol, the present study demonstrated decreased serum melatonin in pre-diabetic rats, as well as, increased concentration of retinal TBARS, AOPP, iNOS, VEGF, and MMP9. Oral supplementation with melatonin (85 µg/animal/day) caused melatonin and HDL cholesterol levels to rise in treated rats and reduced levels of fasting serum glucose and fructosamine. It also affected serum insulin and quantitative insulin sensitivity check index (QUICKI) in treated groups but had no significant effect on non-fasting glucose. Finally, supplementation with melatonin reduced concentrations of TBARS, AOPP, iNOS, VEGF, and MMP9 in significant level, thereby exerting an overall positive effect on oxidative stress and pro-angiogenic signaling in the pre-diabetic retina. Thus, oral melatonin might be considered in an early treatment or in the prevention of retinal changes associated with pre-diabetes.

Expression of CD34 and CD146 vascular markers contributes to the immunological function of the human palatine tonsil.

The fundamental function of the palatine tonsil is the immune response to airborne and foodborne pathogenic agents. Small blood vessels have an important role in the provision of a special microenvironment in which the immune response occurs. In this study, we investigated the expression of vascular markers CD34 and CD146 and basal lamina marker - type IV collagen - in the small blood vessels of the human palatine tonsil in the context of their role in the immunological function of the tonsil. The tonsils were collected after tonsillectomy from ten patients with chronic tonsillitis, aged 18-28 years. Five-µm-thick paraffin sections were routinely stained with haematoxylin and eosin, while the studied markers (CD34, CD146 and type IV collagen) were detected immunohistochemically using LSAB2/HRP method. CD34 was expressed equally in the capillaries within and below the crypt epithelium, in lymphoid follicles and in high endothelial venules localized para- and interfollicularly. CD146 molecule was expressed on the luminal surface of endothelial cells in the capillaries of the crypt epithelium, while its expression in high endothelial venules was seen on the luminal and lateral surfaces of the cuboidal endothelial cells. In contrast to the basal lamina of intraepithelial capillaries, where collagen IV-immunopositivity is mostly seen as a continuing line, the basal lamina of high endothelial venules was seen as a two- or three-layered structure beneath the cuboidal endothelial cells. The specifics of expression of CD34, CD146, and type IV collagen confirm the morphofunctional specialization of endothelium in crypt epithelium capillaries, and also in endothelium of high endothelial venules, which is directly associated with the role of these vessels in the immune function of the tonsil.

Tensor fascia lata flap is a workhorse for defects after inguinal lymph node block dissection.

Introduction: Enlarged inguinal lymph nodes very often present a site of metastatic disease. Inguinal lymph node block dissection is a demanding procedure, which usually requires at least one of reconstructive modalities. Among different reconstruction options we selected the tensor fascia lata (TFL) musculocutaneous flap. Objective: The paper aims at presenting a series of inguinal block dissections, followed by immediate reconstruction, using the TFL flap, and evaluation of tumor type, flap dimension, complication rate and the duration of hospital stay. Methods: We present a consecutive case series of 25 conducted block dissections. The defects were reconstructed using TFL flap, because of the extent and site of the tissue defects, reliability of the flap, and potentially primarily infected exulcerated tumors. Results: The reconstruction was successful in all cases, the incidence of surgical complications was 16%, no further complications, such as lymphedema or gait disturbances, were noted. Primary skin tumors were predominant (13 cases), followed by genitalia tumors (four cases). The male sex was more frequently affected (14 vs. 11 cases). Conclusion: Having in mind that TFL presents as a flap of adjustable size, length, shape, and volume, with negligible donor site morbidity, and after comparing of our results to those of other authors, we advise broader use of TFL flap. As a reliable flap, not too difficult to harvest, with a low complication rate, it must be taken into consideration regarding the benefits for the patient, and, on the other hand, the surgery cost and duration.

Primary reconstruction of neck defect after excision of metastatic melanoma of unknown primary site with regional pectoral myocutaneous flap.

Introduction: Metastatic melanoma of unknown primary (MMUP) is already a well described oncologic phenomenon in the literature, whereas tissue defects' reconstructions on the neck region always present a challenge for the reconstructive surgeon. Two cases of giant metastatic, skin infiltrative neck tumor masses are presented. In both cases MMUP was diagnosed. Both intraoperative tissue defects were reconstructed using pectoralis major (PM) regional flap. Outline of cases: The first patient was admitted with giant tumor mass on the right side of the neck. The fast growing mass appeared two months prior to the admission. Thorough examination showed no signs of primary tumor. Removal surgery was performed and the defect was reconstructed using the PM musculocutaneous flap. The second patient was admitted with large tumor mass on the left side of the neck. Thorough examination displayed no signs of any primary tumor. After the excision, the tumor mass and subsequent neck dissection, reconstruction followed, using the pedicled PM muscle flap and partial thickness skin transplants. There were no major complications in either case. The histopathological examinations presented metastatic melanoma diagnoses. Conclusion: Clinical outcome of MMUP described in literature is rather variable. Different studies have shown that prognosis in patients with MMUP is better than that in patients with diagnosed primary melanoma with metastatic disease. Therefore, the best initial course of action in those cases would be surgery, according to oncological principles, if possible. Neck defects' reconstructions should fulfill both functional and esthetic demands. Due to the reliability and low cost of the procedure, PM regional flap presents a very good and trustworthy reconstruction modality.

Reconstruction of full thickness abdominal wall defect following tumor resection: a case report.

INTRODUCTION: Reconstruction of a full thickness abdominal wall defect is a demanding procedure for general and also for plastic surgeons, requiring vigorous planning and reconstruction of three layers. CASE OUTLINE: We present a case of a 70-year-old patient with a huge abdominal wall tumor with 40 years evolution. Surgery was performed under general anesthesia. Full thickness abdominal defect appeared after the tumor resection. Reconstruction followed in the same act. The defect was reconstructed using a combination of techniques, including omental flap, fascia lata graft, local skin flaps and skin grafts. After surgery no major complications were noted, only a partial skin flap loss, which was repaired using partial thickness skin grafts. The final result was described by the patient as very good, without hernia formation. CONCLUSION: Omenthoplasty, abdominal wall reconstruction in combination with free fascia lata graft and skin grafts can be one of good options for the reconstruction of full thickness abdominal wall defects.

Second look procedure for large burn defect by banana peel pericranial flap based on one artery.

INTRODUCTION: Scalp and calvarial defects may result from trauma, thermal or electrical burns, resection of benign or malignant tumors, infections or radionecrosis. Reconstruction of large scalp defects is a demanding procedure. The reconstructive "ladder" are applicable to scalp and calvarial defects reconstruction. CASE OUTLINE: A 68-year-old female was admitted to our clinic due to the nine-day old scalp burn wound, incurred under unclear circumstances. Third degree burn wound affected the left frontal-parietal, temporal and part of the occipital region with carbonification of the whole left ear lobe.The treatment was carried out in two stages. Radical full thickness necrectomy of the scalp was performed, the defect margins were curetted to the active bleeding, and the ear lobe was amputated.The defect sized 23 x 15 cm was reconstructed using the"banana peel"transposition galea-cutaneous flap from the remainder of the scalp, which was based only on the right occipital artery.Two months after the surgery the appearance was satisfactory, and all wounds were healed. CONCLUSION: Designing of large-scale flaps is very hazardous, especially in elderly people. Scalp reconstruction based on one artery has to be planned in detail and performed when the possibility of complication is reduced to minimum. Our case report underlines possible reconstruction as delayed procedure even with the exposed bone (second look procedure), as well as the reconstruction of half scalp with the local flap based on one pericranial artery.

Appearance of interstitial cells of Cajal in the human midgut.

Several subtypes of the interstitial cells of Cajal (ICC) form networks that play a role in gastrointestinal motor control. ICC express c-kit and depend on signaling via Kit receptors for development and phenotype maintenance. At 7-8 weeks of development, c-kit-immunoreactive (c-kit-IR) cells are present in the human oesophagus, stomach and proximal duodenum wall. In the remaining small and large bowel, c-kit-IR cells appear later. The object of the present study is to determine the timing of the appearance of c-kit-IR ICC in the parts of the digestive tube originating from the midgut (distal duodenum, jejunum, ileum and proximal colon). Specimens were obtained from eight human embryos and 11 fetuses at 7-12 weeks of gestational age. The specimens were exposed to anti-c-kit antibodies to investigate ICC differentiation. The differentiation of enteric neurons and smooth muscle cells was immunohistochemically examined by using anti-PGP9,5 and anti-desmin antibodies, respectively. In the distal duodenum, jejunum and ileum, c-kit-IR cells emerged at week 9 at the level of the myenteric plexus in the form of a thin row of cells encircling the inception of the ganglia. These cells were multipolar or spindle-shaped with two long processes and corresponded to the ICC of the myenteric plexus. In the proximal colon, c-kit-IR cells emerged at week 9-10 in the form of two parallel belts of cells extending at the submucosal plexus and the myenteric plexus levels. We conclude that ICC develop following two different patterns in the human midgut.