Expression of Notch pathway components (Numb, Itch, and Siah-1) in colorectal tumors: A clinicopathological study.

BACKGROUND: The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs, including the colon. Accordingly, studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression. Although Numb, Itch, and seven in absentia homolog-1 (Siah-1) have been shown to contribute to the regulation of Notch signaling, their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date. AIM: To evaluate Numb, Itch, and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior. METHODS: Expression of Notch-1, Numb, Itch, and Siah-1 was investigated in 50 colorectal carcinomas, 30 adenomas, and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analyses. RESULTS: In contrast to Notch-1, which is expressed at higher levels in tumor tissues and adenomas, expression of Numb, Itch, and Siah-1 was stronger and more frequent in normal mucosa (P < 0.01). There was a positive correlation between Notch-1 expression and high histological grade, the presence of lymph node metastasis, and advanced-stage tumors, whereas expression of Numb, Itch, and Siah-1 was absent or reduced in tumors with these clinicopathological parameters (P < 0.05). In survival analysis, expression of Notch was related to poor prognosis but that of Numb, Itch, and Siah-1 correlated with improved survival (P < 0.05). Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis (P < 0.05). CONCLUSION: Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma (CRC) progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.

Focal pyloric hypertrophy in adults: a diagnostic pitfall-a case report and review of the literature.

Adult hypertrophic pyloric stenosis in the form of focal pyloric hypertrophy is an uncommon but a well-established lesion. In most cases, clinical findings suggest malignancy, and despite advances in imaging techniques, preoperative diagnosis is difficult. Herein, an example of focal pyloric hypertrophy is presented with a review of the literature to emphasize the clinicopathological characteristics of this lesion. In a 43-year-old man with abdominal discomfort, endoscopy showed a 1.5 cm nodular lesion near the pylorus that necessitated surgery to exclude malignancy. Pathological examination allowed the diagnosis of focal pyloric hypertrophy. The present case and the review revealed that focal pyloric hypertrophy is a male dominant lesion in middle-aged patients. The clinical diagnosis is problematic, and its initial diagnosis depends on a high clinical suspicion in patients with upper gastrointestinal system complaints irrespective of the duration of the symptoms. It is not known whether it is a separate entity from the diffuse form. Although both are similar in a clinical point of view, etiopathogenetic studies are required to clarify their differences completely. Moreover, the rare occurrence of focal pyloric hypertrophy and the lack of diagnostic clinical findings do not exclude its consideration in the differential diagnosis, especially in patients with gastric outlet obstruction.

PUVA Induced Bullous Pemphigoid in a Patient with Mycosis Fungoides.

Background. Bullous pemphigoid is an autoimmune subepidermal blistering skin disease in which autoantibodies are directed against components of the basement membrane. The disease primarily affects the elderly people and in most of the patients inducing factors cannot be identified. Herein, we report a case of BP that occurred in a patient who was receiving PUVA therapy for the treatment of mycosis fungoides. Main Observation. A 26-year-old woman with mycosis fungoides developed blisters while receiving PUVA therapy. On physical examination tense bullae on the normal skin, remnants of blisters, and erosions were observed on her breasts, the chest wall, and the upper abdomen. Histopathological investigations revealed subepidermal blisters with eosinophilic infiltration and in direct immunofluorescence examination linear deposition of IgG along the basement membrane zone was observed. The diagnosis of bullous pemphigoid was also confirmed by ELISA and BIOCHIP mosaic-based indirect immunofluorescence test. Conclusions. PUVA therapy is an extremely rare physical factor capable of inducing bullous pemphigoid. So the development of blistering lesions during PUVA therapy may be suggestive sign of a bullous disease such as bullous pemphigoid and it should be excluded with proper clinical and laboratory approaches immediately after withdrawal of PUVA therapy.

Comparing the effects of pedicle torsion on axial or perforator flaps; improving the perforator flap resistance to pedicle torsion with delay phenomenon.

BACKGROUND: The torsion of the flap's pedicle is one of the most common conditions causing vascular compromise. We aimed to compare the resistance to torsion of axial flap pedicle and perforator pedicle patterns. In the second part of the study, we investigated whether the delay phenomenon is an effective method for improving perforator flap resistance to pedicle torsion. METHODS: In the first phase, 90 male Wistar rats were randomly divided into two groups: perforator and axial. Bilateral groin flaps were elevated in the axial group and bilateral posterior thigh perforator-based flaps were elevated in the perforator group. Viable flap areas were compared at 90, 180, 270, 360, and 720 degrees of pedicle rotation. Microangiographic and histopathological studies were performed. RESULT: As a result, necrosis was seen following earlier rotation in the perforator group and viable flap areas were also lower. In the second phase, after delay procedure, the perforator flaps were exposed to 270, 360, and 720 degrees of pedicle rotation. With the delay procedure, no significant difference in viable flap areas was observed. CONCLUSION: In conclusion, the resistance to torsion of the axial flap pedicle pattern was greater than that of the perforator pedicle pattern, and the delay procedure was not an effective method for improving flap resistance to torsion.

An aggressive aneurysmal bone cyst of the proximal humerus and related complications in a pediatric patient.

Clinical behavior of aneurysmal bone cyst (ABC) in younger patients can be more aggressive than that in older children and adults. Angular deformity and shortening can occur due to growth plate destruction or tumor resection. A 11-year-old boy who had been operated twice in another center for an ABC located in the left proximal humerus presented to the author's institution with complaints of pain, deformity and shortening of the left arm. Plain radiographs revealed left proximal humerus nonunion with a large defect. Reconstruction with nonvascularized fibular autograft was applied and left upper extremity was immobilized in a velpou bandage. At the third-month follow-up, graft incorporation was observed in the distal part; however, proximal part did not show adequate healing on radiographs. Additional immobilization in a sling for 3 months was advised to the patient and his family. However, they were lost to follow-up and readmitted to the author's institution at the 12th month postoperatively. Radiographs showed failure of the fibular graft fixation and nonunion of the humerus. Autogenic bone grafts, either vascularized or nonvascularized are the best treatment method for the large defects after tumor curettage or resection. Nonvascularized grafts are technically much easier to use than vascularized grafts and provide excellent structural bone support at the recipient side. However, they may take several months to be fully incorporated. In addition, good therapeutic outcomes require patience and collaboration with the patient and parents. Most importantly, the patient should be monitored closely.

The effect of erythropoietin on anastomotic healing of irradiated rats.

AIM: The aim of the present study is to evaluate the possible protective effects of erythropoietin (EPO) on anastomotic wound healing after preoperative radiotherapy according to its pleiotropic mechanism of action. METHODS: Thirty-two male Wistar albino rats were randomized into four groups containing eight rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group, radiation plus standard resection plus anastomosis; ANAS+EPO group, standard resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard resection plus anastomosis plus EPO. All animals were sacrificed by cardiac puncture, and anastomotic healing was measured by bursting pressure, hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens. RESULTS: OHP levels in the RT+ANAS + EPO group were significantly increased compared with other groups (p < .05). In contrast, MPO activity in the RT+ANAS+EPO group was significantly decreased compared with other groups (p < .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO groups (p < .05). Group comparisons demonstrated that bursting pressure was significantly higher in EPO treated rats (p < .05). The histopathology results revealed that EPO treatment improves anastomotic wound healing though decreased necrosis and inflammatory cell infiltration and increased fibroblast activity. CONCLUSION: The findings of the present study indicate that EPO contributes to wound healing and the strength of colon anastomosis following radiation due to its antioxidant and anti-inflammatory effects, but further studies are needed to explore the significance of these effects.

Importance of TNF-related apoptosis-inducing ligand in pathogenesis of interstitial cystitis.

INTRODUCTION: Although interstitial cystitis is an inflammatory disease, its etiopathogenesis is not clearly understood. The objective of the present study is to investigate the distribution of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in bladder biopsy samples of patients diagnosed with interstitial cystitis and the role of TRAIL in the pathogenesis of interstitial cystitis. MATERIALS AND METHODS: TRAIL and its receptors were stained immunohistochemically in bladder biopsy samples of 27 patients diagnosed with interstitial cystitis, and the samples were evaluated independently by two pathologists and were scored in terms of expression intensity and distribution. RESULTS: An evaluation of the results of the statistical analysis showed that the TRAIL-R4 receptor was immunohistochemically stained with a higher score than TRAIL-R1, TRAIL-R2, TRAIL-R3 receptors and TRAIL, with a statistically significant difference (P < 0.05). CONCLUSION: These findings indicate that TRAIL-R4 is the predominant receptor in the interstitial cystitis inflammation.