Which part of the blood in the knee joint is responsible for its detrimental effects? (An experimental study on the knee joint in rabbits).

AIM: This study aims to determine the potential causative elements which are responsible for the cartilage damage in case of frequent intra-articular bleeding and to evaluate the effects of intra-articular free iron and chelation of iron in the knee joint. METHODS: Thirty-five New Zealand rabbits were randomly divided into five groups according to substances injected into their knee joints. Plasma (group I) and cellular components (group II) of the blood harvested from the rabbits, iron (ferric hydroxide sucrose) (group III), iron&chelator (group IV) and only chelator (deferoxamine mesylate) (group V) were injected into their right knees three times a week for 12 weeks. The joint surface was examined histologically according to the classification system modified from Colombo et al. The changes in the synovial tissue were evaluated according to the scoring system modified from Madhok et al. RESULTS: Cartilage and synovial abnormality scores were significantly higher in all study groups when compared to their own controls (p < 0.0001). Cartilage scores of groups I and V were significantly lower when compared to groups III and IV (p = 0.002 for group I and p = 0.003 for group V). Synovial abnormality score of group I was significantly lower than scores of groups III and IV (p = 0.001); and of group V lower than groups III and IV (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: All substances tested in this study caused a certain amount of damage in the cartilage tissue and led to synovial abnormalities. Both iron and iron&chelator caused more damage in the cartilage and led to more advanced synovial changes when compared to the plasma component of blood and chelator itself. Influence of iron and iron&chelators were found to be similar showing that chelation was inadequate in antagonizing the detrimental effects of iron.

Evaluation of the role of Epstein-Barr virus in cases of nodal or extranodal T- and NK-cell lymphoma using eber in situ hybridization.

Various racial and geographic differences have been observed in studies questioning the role of Epstein-Barr virus (EBV) infection in the etiology of T- and NK-cell lymphomas. The aim of this study was to evaluate the relationship of EBV with nodal or extranodal (skin excluded) T- and NK-cell lymphoma subtypes encountered in our geographic area. Sixty-two cases of peripheral T-cell lymphoma were included in the study. EBV-encoded early RNA (EBER) was detected by in situ hybridization. The distributions of T- and NK-cell lymphoma subtypes were as follows: 32 peripheral T-cell lymphomas, unspecified (PTCL, NOS), 13 anaplastic large-cell lymphomas (ALCL), 8 angioimmunoblastic T-cell lymphomas (AITCL), 4 extranodal NK/T-cell lymphomas, nasal type (NKTCL), 3 enteropathy-type T-cell lymphomas (ETTCL), 1 hepatosplenic T-cell lymphoma (HSTCL), and 1 subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Using a cut-off value of >25% of EBER-positive neoplastic lymphoid cells, EBV was positive in 22.6% of all cases. According to subtype, the neoplastic cells of 31.3% of PTCL, NOS and 100% of extranodal NKTCL, nasal type were EBER positive, whereas some cases of ALCL, AITCL, and ETTCL presented EBER-positive non­neoplastic cells, and all cells of HSTCL and SPTCL were EBV negative. Extranodal NKTCL, nasal type, presented the strongest association with EBV, followed by PTCL, NOS.

Clinical and morphological characteristics of osteoid osteoma and osteoblastoma: a retrospective single-center analysis of 204 patients.

Osteoid osteoma and osteoblastoma are histologically similar, benign bone-forming tumors. In this retrospective study, we aimed to evaluate the natural history; clinical, pathologic, and radiologic findings; and treatment results in 204 patients between 1959 and 2006 in a single institution. According to the World Health Organization's definition, tumors ≤1 cm in diameter were classified as osteoid osteoma, and those ≥2 cm, as osteoblastoma. For tumors between 1 cm and 2 cm, other criteria, such as the bone involved, the site, the presence of a nidus, and presence of peripheral sclerosis, were used for diagnosis. There were 131 patients with osteoid osteoma (93 male, 38 female) and 73 patients with osteoblastoma (40 male, 33 female). The mean age in the osteoid osteoma and osteoblastoma groups was 16.4 ± 7 and 19.6 ± 9.9 years, respectively. The osteoid osteoma cases were mostly localized in the extremities, whereas the osteoblastoma cases involved the vertebral column and sacrum. The nidus size varied between 0.2 and 1.5 cm in osteoid osteoma cases, and the tumor size range was 1.3-10 cm in the osteoblastoma cases. The pain was encountered in 89% of osteoid osteoma and 45% of osteoblastoma patients. Histopathology was similar in both cases. The treatment of choice was conservative surgery for both diagnoses. In conclusion, osteoblastoma is clinically and radiologically more aggressive than osteoid osteoma.

The Association of the Epidermal Growth Factor Receptor (EGFR) Immunoexpression With Prognostic Parameters in Adenocarcinoma Patients Receiving Neoadjuvant Treatment.

The epidermal growth factor receptor (EGFR) expression is considered to play an essential role in the pathogenesis of colorectal adenocarcinoma. This study assessed the expression and predictive/prognostic value of EGFR expression in pre-op biopsy and post-op resection specimens in patients receiving neoadjuvant radiotherapy/neoadjuvant chemoradiotherapy (NRT/NCRT). Thirty-four consecutive patients were included in this study. The association between the prognostic features and EGFR immunohistochemical expression was analyzed in pre- (n=34) and post-treatment (n=22) tissue samples in cases with available tissue blocks. Of 34, 23 (67.6%) were men. The median age was 60.50 ± 10.69 (range, 31-84) years. EGFR expression was detected in 88.2% of biopsy specimens and in 91.2% of surgical specimens. There was only slight agreement between pre-op and post-op EGFR expression scores (kappa value 0.11). There was no significant correlation between pre-op and post-op EGFR expression scores (p>0.05). Although pre-op EGFR positivity and higher pre-op EGFR scores seemed to indicate a worse prognosis, this association between pre-op EGFR expression and overall survival (OS) or disease-specific survival (DSS) did not reach statistical significance (p>0.05). The only case with a post-op EGFR score of three who died of the disease experienced local recurrence and had distant metastasis. In conclusion, EGFR positivity in pre-op biopsy samples seems to be associated with shorter survival, and increased EGFR expression in post-treatment resection specimens predicts aggressive behavior in patients with rectal adenocarcinoma who received NRT/NCRT. However, due to the molecular heterogeneity, EGFR expression status should be evaluated in resection specimens rather than in pre-op biopsy samples for optimal prognosis prediction.

An autoimmune disease refractory to immunosuppressive regimens: celiac disease diagnosed long after liver transplantation.

CD is defined as T-lymphocyte-mediated gluten sensitivity. Although CD is known to affect the small intestine, it is nonetheless a multisystem disorder. Liver involvement in CD may vary from isolated hypertransaminasemia to cirrhosis. Because CD is an inappropriate immune response to gluten proteins, strict gluten-free diet is the principal therapy, along with management of liver dysfunction. In patients who fail to respond to a gluten-free diet, immunosuppressive drugs may improve intestinal inflammatory activity in untreated CD. The present case report is of a 25-yr-old woman with diarrhea lasting several weeks. The patient had received a liver transplant 13 yr earlier, and presented with cryptogenic cirrhosis diagnosed as CD. This appears to be the first case of its kind in which a pediatric long-term liver transplant patient presents with diarrhea eventually diagnosed as CD whose diet included gluten, and who was treated by an immunosuppressive drug regimen. Because of the normalization of CD-related antibodies in the post-transplantation period without gluten restriction, CD should be part of a list of diagnostic possibilities in liver transplant patients presenting with diarrhea of unknown etiology.

Revisiting the Role of Esophageal Mucosal Dilated Intercellular Spaces in the Diagnosis and Pathophysiology of Heartburn.

Background/Aims: Dilated intercellular spaces (DISs) facilitate the diffusion of noxious agents into the deep layers of the esophageal epithelium. The role of DIS in heartburn pathogenesis is still controversial. Therefore, we aim to reinvestigate DIS in an extensively evaluated group of patients and healthy controls (HCs). Methods: We classified 149 subjects into the following groups: 15 HC, 58 mild erosive reflux disease (ERD), 17 severe ERD, 25 nonerosive reflux disease (NERD), 15 reflux hypersensitivity (RH), and 19 functional heartburn (FH). A total of 100 length measurements were performed for each patient's biopsy. Results: The overall intercellular spaces (ISs) value of gastroesophageal reflux disease (GERD) patients was higher than that of HC (P = 0.020). In phenotypes, mild ERD (vs HC [P = 0.036], NERD [P = 0.004], RH [P = 0.014]) and severe ERD (vs HC [P = 0.002], NERD [P < 0.001], RH [P = 0.001], FH [P = 0.004]) showed significantly higher IS. There was no significant difference between the HC, NERD, RH, and FH groups. The 1.12 µm DIS cutoff value had 63.5% sensitivity and 66.7% specificity in the diagnosis of GERD. There was a weak correlation (r = 0.302) between the IS value and acid exposure time, and a weak correlation (r = -0.359) between the IS value and baseline impedance. A strong correlation was shown between acid exposure time and baseline impedance (r = -0.783). Conclusions: Since the IS length measurement had better discrimination power only in erosive groups, it is not feasible to use in daily routine to discriminate other nonerosive phenotypes and FH. The role of DIS in heartburn in nonerosive patients should be reconsidered.

What has changed in the last 25 years in osteosarcoma treatment? A single center experience.

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor in the extremities. The main purpose of this study was to determine clinical features, prognostic factors, and treatment results of patients with osteosarcoma at our center. METHODS: We retrospectively analyzed the medical records of children with osteosarcoma between the years 1994-2020. RESULTS: 79 patients were identified (54.4% male, 45.6% female). The most common primary site was the femur (62%). Twenty-six of them (32.9%) had lung metastasis at diagnosis. The patients were treated between 1995- 2013 according to the Mayo Pilot II Study protocol, while the others were treated with the EURAMOS protocol between the years 2013-2020. Sixty-nine patients underwent limb salvage surgery as a local treatment, whereas seven underwent amputation. The median follow-up time was 53 months (2.5-265 months). The event-free survival (EFS) and overall survival (OS) rates at 5 years were 52.1% and 61.5%. The 5-year EFS and OS rates were 69.4% and 80% in females; 37.1% and 45.5% in males (p=0.008/p=0.001). The 5-year EFS and OS rates of the patients without metastasis were 63.2% and 66.3%; with metastasis 28.8% and 51.8% (p=0.002/p=0.05). For good-responders, the 5-year EFS and OS rates were 80.2% and 89.1%; while for poor-responders, 35% and 46.7% (p=0.001). Mifamurtide was used in addition to chemotherapy as of the year 2016 (n=16). The 5-year EFS and OS rates were 78.8% and 91.7%, respectively for the mifamurtide group; 55.1% and 45.9%, respectively for the non-mifamurtide group (p=0.015, p=0.027). CONCLUSIONS: Metastasis at diagnosis and poor response to preoperative chemotherapy were the most important predictors of survival. Females had a better outcome than males. In our study group, the mifamurtide group`s survival rates were significantly higher. Further large studies are needed to validate the efficacy of mifamurtide.

Effects of hyaluronic acid and chondroitin sulfate on acute radiation proctitis in rats.

BACKGROUND: This study was designed to investigate the prophylactic and therapeutic effects of hyaluronic acid and chondroitin sulfate combination (HA/CS) on a model of acute radiation proctitis. METHODS: Rats were divided into five groups: SHAM; irradiation (IR) + saline (1 mL for 5th and 10th day); IR + HA/CS (1 mL for 5th and 10th day). A single fraction of 17.5 Gy was delivered to each rat. HA/CS was administered rectally each day after irradiation. Each rat was observed daily for signs of proctitis. Irradiated rats were euthanized on days 5 and 10. The mucosal changes were evaluated macroscopically and pathologically. RESULTS: According to the clinical findings, five rats in the irradiation + saline group showed grade 3-4 symptoms on the 10th day. No significant difference in the macroscopic finding scores on the 5th day was observed between the irradiation + saline and irradiation + HA/CS groups. In the pathological examination, radiation-induced mucosal damage was the most prominent finding 10 days after irradiation in saline-treated rats. On the 10th day, the irradiation + HA/CS group showed mild inflammation and slight crypt changes, which corresponded to grade 1-2 pathological findings. CONCLUSION: We think that HA/CS used in radiation cystitis can be beneficial for radiation proctitis.

Does bile reflux reduce Helicobacter pylori gastritis?

BACKGROUND: Chronic abdominal pain is a frequent childhood complaint. This study aims to determine the relationship between bile reflux, which is increasing with the growth in packaged food consumption resulting from the changing food industry, and Helicobacter pylori gastritis. METHODS: In this retrospective study, 804 cases where there was an endoscopic examination for abdominal pain were included. We recorded the patients` age, sex, and macroscopic and microscopic endoscopic findings. Patients with chronic diseases were excluded. RESULTS: Our study included 804 cases. Of patients, 61.8% were female and 38.2% were male. The mean age was 11.56±4.14 years. The Helicobacter pylori gastritis rate was found to be 22.3% among all patients. Bile reflux was seen in 192 (23.9%) patients. Only 27 (14.1%) of the 192 patients had Helicobacter pylori positivity (p=0.002). CONCLUSIONS: Helicobacter pylori gastritis is less common among patients with bile reflux. In another study conducted in our outpatient clinic before the 2000s, the frequency of Helicobacter pylori gastritis was found to be 40%, but after 2000 this rate decreased to 22.3% due to bile reflux caused by the changing food industry. This result may be explained by the bactericidal effects of bile acids.

Effect of interval between neoadjuvant chemoradiotherapy and surgery on disease recurrence and survival in rectal cancer: long-term results of a randomized clinical trial.

BACKGROUND: The optimal timing of surgery following chemoradiotherapy (CRT) is controversial. This trial aimed to assess disease recurrence and survival rates between patients with locally advanced rectal adenocarcinoma (LARC) who underwent total mesorectal excision (TME) after a waiting interval of 8 weeks or less (classic interval; CI) versus more than 8 weeks (long interval; LI) following preoperative CRT. METHODS: This was a phase III, single-centre, randomized clinical trial. Patients with LARC situated within 12 cm of the anal verge (T3-T4 or N+ disease) were randomized to undergo TME within or after 8 weeks after CRT. RESULTS: Between January 2006 and January 2017, 350 patients were randomized, 175 to each group. As of February 2022, the median follow-up time was 80 (6-174) months. Among the 322 included patients (CI, 159; LI, 163) the cumulative incidence of locoregional recurrence at 5 years was 10.1 per cent in the CI group and 6.9 per cent in the LI group (P = 0.143). The cumulative incidence of distant metastasis at 5 years was 30.8 per cent in the CI group and 18.6 per cent in the LI group (sub-HR = 1.78; 95 per cent c.i. 1.14 to 2.78, P = 0.010). The disease-free survival (DFS) in each group was 59.7 and 69.9 per cent respectively (P = 0.157), and overall survival (OS) rates at 5 years were 73.6 versus 77.9 per cent (P = 0.476). CONCLUSION: Incidence of distant metastasis decreased with an interval between CRT and surgery exceeding 8 weeks, but this did not impact on DFS or OS. REGISTRATION NUMBER: NCT03287843 (http://www.clinicaltrials.gov).

How Does It Feel to Be a Pathologist in Turkey? Results of a Survey on Job Satisfaction and Perception of Pathology.

OBJECTIVE: Job satisfaction affects productivity and professional performance in many aspects; however, there is limited data regarding pathologists' job satisfaction. Hence, in this study, we aimed to evaluate surgical pathologists' job satisfaction in Turkey. MATERIALS AND METHODS: We conducted a 59-item web-based survey questioning respondents' institutional background, history of training, continuing education status/research activities, physical conditions, professional well-being, and job satisfaction level. Likert-type and open/ close ended questions were asked and scored. The participants were also asked to complete the Minnesota Satisfaction Questionnaire-Short Form. RESULTS: Of the 321 respondents, 75% were female, the median age was 41 years (range 28-71 years), experience as a pathologist ranged between 0.12 and 44 years (mean 11.4±9.16 years). Academic pathologists, senior pathologists with ≥20 years of experience, and pathologists working at large institutions and living in developed cities expressed better physical conditions, higher satisfaction with working conditions and, therefore, higher overall job satisfaction (p < 0.05). 98% agreed that pathologists have a critical impact on patient management; however, the majority ( > 80%) thought that patients barely know what pathologists do and other physicians rarely understand the difficulty and limitations in pathology practice. 82% were happy to have chosen pathology but 45% reported to experience the feeling of being "burnt out". CONCLUSIONS: Our findings suggest that younger pathologists are less satisfied with their jobs and a surgical pathologist's job satisfaction increases with the physical and technical quality of the pathology laboratory/institution, and years of experience. Pathologists seem to be aware of their important role in patient management although they think that pathology remains "invisible" to many physicians and patients.

Gastroesophageal reflux with children requiring adenotonsillectomy.

BACKGROUND: Our aim is to determine the incidence of reflux in children older than 3 years requiring adenotonsillectomy and relationship between GER and diagnostic tests. METHODS: Forty-four patients, who were listed for adenoidectomy/tonsillectomy at Pediatric Ear Nose Throat department due to severe hypertrophy, were evaluated for accompanying GER (Group 1). GER was diagnosed as having at least one positive GER test result (including esophagitis or pH monitoring). Twenty children without reflux symptoms were used as healthy control group (Group 2) and LPR was held. RESULTS: Reflux was detected in 32 children requiring adenotonsillectomy (72.7%). LPR score was negative in all patients in Group 2. There was no correlation between pH monitoring and histopathological evaluation of esophagus. There was a correlation between the LPR score and histological esophagitis in the proximal esophagus. CONCLUSIONS: GER was high in patients with adenotonsillary hypertrophy. LPR score and the history of patients are as effective as invasive techniques like pH monitorization and endoscopy in determining GER disease.

The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience.

Panitumumab and cetuximab are monoclonal antibodies known to be effective in metastatic colorectal cancer (mCRC). Although the survival benefits when combined with chemotherapy have been determined, there are no studies comparing the two agents with chemotherapy in the second-line treatment. In this study, we aimed to compare the efficacy of cetuximab vs panitumumab in patients who previously received chemotherapy. Who progressed after first-line treatment for K-ras wild type mCRC were analyzed. The efficacy of cetuximab vs panitumumab on overall survival (OS) and progression-free survival (PFS) when combined with FOLFIRI regimen was compared retrospectively. Median PFS was 6.9 months in the cetuximab group and 4.7 months in the panitumumab group. Median OS cetuximab and panitumumab groups were 18.4 and 12.2 months, respectively. In the second-line treatment of K-ras wild type mCRC, both PFS and OS were found to be longer in patients receiving cetuximab than in patients receiving panitumumab, but no statistically significant difference was found.

Secondary osteosarcoma arising in fibrous dysplasia, case report.

Malignant transformation of fibrous dysplasia is very rare. The frequency is increased in polyostotic forms, in McCune-Albright and Mazabraud's syndromes and previously irradiated cases. Pain, which is rapidly becoming worse over a short period unrelated to trauma is the most alarming symptom. Early radiological features of sarcomatous transformation are moth-eaten or cystic areas of osteolysis, cortical destruction and gradual formation of a soft tissue mass. The prognosis is unfavorable as most of the cases are in an advanced stage in the time of diagnosis. We present an unusual case of unsuspected secondary osteosarcoma arising in a previously unirradiated, monostotic fibrous dysplasia. A 46-year-old woman was admitted with hip pain, which worsened after a minor trauma occurred 1 year ago. Plain graphies of left femur showed a well-delineated lesion with endosteal scalloping and areas having a ground-glass appearance. The MRI revealed minimal contrast enhancement but no heterogenous signal intensity, cortical destruction, periost reaction or accompanying soft tissue component was noted. The lesion was initially curetted. But being diagnosed as osteosarcoma histologically, classical osteosarcoma protocol pre and postoperative chemotherapy was applied. Resected femur showed areas of fibrous dysplasia admixed with osteosarcoma having fibroblastic, chondroblastic and osteoblastic areas that were focally invading the soft tissue. Tumor viability was estimated as 95%. The clinical course worsened rapidly after the operation. She did not respond to postoperative chemotherapy and lost with pulmonary metastases less than a years' time after the operation. The case is presented to increase awareness on the possibility of malignant transformation in an otherwise unsuspected fibrous dysplasia.

Dedifferentiated chondrosarcoma of the thumb: a case report.

Dedifferentiated chondrosarcoma (DDCS) comprises approximately 10% of all chondrosarcomas and has the worst outcome with 5-year survival of 10%. The preferred localizations are femur, humerus and pelvis. We report a case of DDCS that arose in proximal phalanx of left-hand thumb of a 66-year-old man. He was admitted with a 2-month history of pain and swelling in his thumb. He had experienced a fracture 15 years ago in the same localization with a history of suspected preexisting enchondroma. Plain radiographs showed an expansive osteolytic lesion with milimetric calcifications while magnetic resonance imaging revealed intraosseous focal globular hyperintense spots consistent with chondroid areas as well as a surrounding soft tissue mass with intermediate signal intensity. In biopsy specimen we observed a low-grade chondrosarcoma next to a spindle cell sarcoma with an abrupt transition. He was treated with amputation and died of the disease within 9 months following the surgery. The presence of dedifferented chondrosarcoma in bones of hands was not previously reported. The presented case was provided with the macroscopic and microscopic features observed in amputation specimen in comparison with radiological findings.

Gastrointestinal findings in 26 adults with common variable immunodeficiency: The fickle nature of the disease manifests in gastrointestinal biopsies.

BACKGROUND/AIMS: The aim of the present study was to demonstrate the histopathological findings in gastrointestinal (GI) biopsies in adults with common variable immunodeficiency (CVID). MATERIALS AND METHODS: A total of 172 GI biopsies of 26 patients with CVID obtained over a 16-year period were reevaluated. Findings were analyzed using descriptive analyzes and χ2 test. RESULTS: Female-to-male ratio was 1.36. The median age at diagnosis was 36±13.94 (16-72) years. Chronic esophagitis was noted in 3 patients. The absence of plasma cells in the stomach, duodenum, and colon was observed in 16, 14, and 9 patients, respectively. Divergent results for the presence of plasma cells in concurrent stomach and duodenum samples were found in 11 (44%) patients. Nodular lymphoid hyperplasia (NLH) was notable in the duodenum (56%). The mean number of eosinophils in one high-power field was significantly higher in duodenal biopsies with NLH (27.21 vs. 14.37, p=0.002). Active inflammation was more prominent in the colon (91%) than in the stomach (65%) and duodenum (60%). Helicobacter pylori infection was found in 57.6%, including a case with persistent infection by the coccoid form. Celiac-like villous blunting and increased intraepithelial lymphocytes were seen in 40% and 24%, respectively. In addition, 23% had giardiasis associated with acute duodenitis and duodenal NLH (p<0.05). CONCLUSION: CVID gastroenteropathy is a challenging entity, and due to the heterogeneity in the presence and distribution of plasma cells throughout the GI tract and diverse disease course, multiple concurrent biopsies may be needed for tissue diagnosis. Duodenal CVID may present with villous alterations and giardiasis, and NLH appears to be an important clue in the duodenum. The association between duodenal NLH and eosinophil infiltration deserves further investigation.

Perianal fibroadenoma, case report.

Extramammary fibroadenomas, occurring in the anogenital region, are rare lesions thought to be arising from "mammary-like anogenital sweet glands" described by van der Putte. We present a 42-year-old woman with a slow-growing, 4-cm, well-circumscribed but nonencapsulated mass in perianal region. The cut surface of the lesion was bulging, gray-white, and slightly lobulated. Microscopically, it was identical to mammary fibroadenoma and composed of concurrent glandular and stromal elements. Low columnar or cuboidal cells with focal, apical cytoplasmic snouts lined the glands, whereas the underlying layer had myoepithelial cell features, expressing smooth muscle actin and S-100. Epithelial component was immunoreactive for human milk fat globulin I. Progesterone receptor positivity was 80%, whereas the estrogen receptor expression was 60%. Gross cystic disease fluid protein and human milk fat globulin II were negative. The case is presented to increase the awareness on mammary-like glands of anogenital region, which may give rise to not only fibroadenomas but also fibrocystic disease, phyllodes tumor, carcinoma in situ, invasive carcinoma and lactating adenoma, hidrocystoma, hidradenoma papilliferum, intraductal papilloma, and sclerosing adenosis, although very rare.

How does it feel to be a pathology resident? Results of a survey on experiences and job satisfaction during pathology residency.

Residents' career choices and professional motivation can be affected from perception of their role and recognition within a medical team as well as their educational and workplace experiences. To evaluate pathology trainees' perceptions of their pathology residency, we conducted a 42-item survey via a web-based link questioning respondents' personal and institutional background, workplace, training conditions, and job satisfaction level. For the 208 residents from different European countries who responded, personal expectations in terms of quality of life (53%) and scientific excitement (52%) were the most common reasons why they chose and enjoy pathology. Sixty-six percent were satisfied about their relationship with other people working in their department, although excessive time spent on gross examination appeared less satisfactory. A set residency training program (core curriculum), a set annual scientific curriculum, and a residency program director existed in the program of 58, 60, and 69% respondents, respectively. Most respondents (76%) considered that pathologists have a direct and high impact on patient management, but only 32% agreed that pathologists cooperate with clinicians/surgeons adequately. Most (95%) found that patients barely know what pathologists do. Only 22% considered pathology and pathologists to be adequately positioned in their country's health care system. Almost 84% were happy to have chosen pathology, describing it as "puzzle solving," "a different fascinating world," and "challenging while being crucial for patient management." More than two thirds (72%) considered pathology and pathologists to face a bright future. However, a noticeable number of respondents commented on the need for better physical working conditions, a better organized training program, more interaction with experienced pathologists, and deeper knowledge on molecular pathology.

Immunohistochemical detection of CD 95 (Fas) & Fas ligand (Fas-L) in plasma cells of multiple myeloma and its correlation with survival.

Multiple myeloma (MM) is a malignant disease resulting from an uncontrolled proliferation of a neoplastic plasma cell clone in the bone marrow, which might also be induced by the loss of control on apoptosis. Fas ligand (Fas-L), a member of the tumor necrosis factor family, induces apoptosis mediated via its transmembrane death receptor Fas (Apo-1/CD95) antigen. In the present study, immunostaining was performed on the initial diagnostic bone marrow biopsies of 36 MM patients (1 stage I, 5 stage II, 30 stage III), to evaluate the distribution of Fas receptor and Fas-L on malignant plasma cells. Both Fas and Fas-L were positive in 13 cases and negative in 3, whereas 10 cases were Fas-negative, Fas-L-positive and 10 were Fas-positive, Fas-L-negative. Although no association was found between the expression of Fas receptor or Fas-L and overall survival, Fas-L positivity was significantly associated with a shorter event-free survival (p = 0.0335). In this study, it has been shown that the expression of Fas-L, in malignant plasma cells of myeloma patients significantly shortens the event-free survival, indicating that the defect in apoptosis might be associated with disease progression in MM.

p21 and p27 immunoexpression in gastric well differentiated endocrine tumors (ECL-cell carcinoids).

AIM: To investigate the expression of cyclin-dependent kinase inhibitors p21 and p27 in gastric well differentiated endocrine tumors (GWDET) (ECL-cell carcinoids). METHODS: The expressions of p21 and p27 were examined immunhistochemically in endoscopic biopsy specimens from 16 patients matching the diagnostic criteria of GWDET. Percentage of positive nuclear staining either weak or strong was noted. The association of immunoexpressions with age, gender, tumor localization, multifocality and accompanying chronic atrophic gastritis, neuroendocrine cell hyperplasia (NEH), neuroendocrine dysplasia (NED), intestinal metaplasia (IM), Ki-67 proliferation index and clinical outcome were also evaluated. RESULTS: All cases expressed p27 with a mean expression score of 43.6%, while 31.3% of the cases showed any p21 expression. p21 and p27 immunoexpressions were significantly correlated with each other (P < 0.01), and the p21-expressing group had higher p27 expression scores (68% vs 22%). p21 and p27 expressions were lower in women, in non-atrophic mucosa and cases whose tumors were located somewhere other than fundus without submucosal extension. On contrary, p21 and p27 expressions were higher in males and the patients with submucosal extension and atrophic gastritis. Cases presenting lower p27 scores had solitary tumors showing neither NEH-NED nor IM. Despite, cases with lower p21 expression presented multifocal tumors accompanied by NEH-NED. However, no correlation of p21 and p27 expressions was found with age and Ki-67 expression. CONCLUSION: p27 is widely expressed in GWDETs, while p21 expression is sparse and observed in two thirds of the cases. Loss of p21 and p27 expressions may be correlated with different carcinoid tumor subtypes; however, more studies are needed to assess the role of these prospective markers in gastrointestinal endocrine tumors.