Urinary bladder cancer in Jordanian adults: A histopathological and epidemiological study from a tertiary care center in Amman.

The aim of this retrospective study was to analyze urinary bladder cancer cases that were diagnosed in Jordan University Hospital, Amman according to age, gender, grade and muscle invasion.There were 212(85.1%) male and 37(14.9%) female patients. Of them, 115(46.2%) patients were aged <65 years (range: 25-64 years), 128(51.4%) were aged 65-84 years, and 6(2.4%) were aged > 85 years. Analysis of transitional cell carcinoma cases revealed that 143(59.3%) of the cases were of low grade, while 98(40.7%) were of high grade. Of these cases, 199(82.6%) were superficial, whereas 42(17.4%) were muscle invasive at initial diagnosis. Of the high-grade tumour cases, 57 (58.2%) and 5(5.1%) were found in the age groups 65-84 and >84 years, respectively. Both the grade and the muscle-invasion status were not significantly associated with patient gender. Our study showed significant demographic changes in urinary bladder cancer in comparison to a previous study from northern Jordan.

Characterization of BCL-X L , MCL-1, and BAX Protein Expression in Response to Neoadjuvant Chemotherapy in Breast Cancer.

The use of chemotherapy has improved the overall treatment of breast cancer, which is frequently administered in the form of neoadjuvant chemotherapy (NAC). Apoptosis is an established cell stress response to NAC in preclinical models; however, there is limited understanding of its role in clinical cancer, specifically, its contribution to favorable pathologic responses in breast cancer therapy. Here, we aimed to characterize the change in protein expression of 3 apoptosis-associated biomarkers, namely, BCL-X L , MCL-1, and BAX in breast cancer in response to NAC. For this, we utilized a set of 68 matched invasive breast cancer FFPE samples that were collected before (pre) and after (post) the exposure to NAC therapy that were characterized by incomplete pathologic response. Immunohistochemistry (IHC) analysis suggested that most of the samples show a decrease in the protein expression of all 3 markers following exposure to NAC as 90%, 69%, and 76% of the matched samples exhibited a decrease in expression for BCL-X L , MCL-1, and BAX, respectively. The median H-score of BCL-X L post-NAC was 150/300 compared with 225/300 pre-NAC ( P value <0.0001). The median H-score of MCL-1 declined from 200 pre-NAC to 160 post-NAC ( P value <0.0001). The median H-score of BAX protein expression decreased from 260 pre-NAC to 190 post-NAC ( P value <0.0001). There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.

Melatonin mitigates cisplatin-induced cognitive impairment in rats and improves hippocampal dendritic spine density.

Cisplatin-induced cognitive impairment (chemobrain) affects a considerable percentage of cancer patients and has no established pharmacological treatment. Chemobrain can be associated with neuroinflammation and oxidative stress. Melatonin, a pineal hormone, is known to have antioxidant, anti-inflammatory and neuroprotective potential. In this study, we investigated cisplatin-induced cognitive impairment in rats and whether melatonin can improve or reverse this impairment. Behavioral testing involved measuring working memory using the novel location recognition test (NLRT) under conditions of cisplatin or cisplatin + melatonin treatment, followed by the collection of rats' brains. The brains were subsequently stained with Golgi-Cox stain and then the hippocampus area CA3 of each one was examined, and dendritic spine density was calculated. Treatment with cisplatin resulted in deficits in the rats' performance in the NLRT (P < 0.05). These deficits were prevented by the coadministration of melatonin (P < 0.05). Cisplatin also reduced the density of dendritic spines in the hippocampus (P < 0.0001), specifically CA3 area, while the coadministration of melatonin significantly reversed this reduction (P < 0.001). This study showed that melatonin can ameliorate cisplatin-induced spatial memory deficits and dendritic spines density abnormalities in rats. Given that melatonin is a safe and wildly used supplement, it is feasible to explore its use as a palliative intervention in cancer treatment.

A successfully treated gastric mucormycosis in an immunocompetent patient: Case report and literature review.

Mucormycosis is an opportunistic fungal infection that usually affects patients with diabetes mellitus or immunosuppression. The fungus invades the nearby blood vessels leading to thrombosis and necrosis of the organs involved. Although Mucorales can invade any organ in the body, the gastrointestinal system is an uncommon site for infection. Mucormycosis is a fatal infection, and prompt intervention is required to ensure survival. In this report, we present a case of a 46-year-old man with history of valve replacement surgery on warfarin, who admitted with abdominal pain and life-threatening gastrointestinal bleeding. Esophagogastroduodenoscopy revealed an active gastric ulcer bleeding, and the diagnosis of mucormycosis infection was confirmed with direct microscopy and histopathological evaluation from a tissue biopsy. Typically, antifungal therapy alone is inadequate to control mucormycosis infection and surgical intervention is often required. Our patient was successfully treated using antifungal therapy alone. This report presents a rare case of gastrointestinal mucormycosis in setting of valve replacement and was successfully treated with antifungal therapy.

NOXA expression is downregulated in human breast cancer undergoing incomplete pathological response and senescence after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is a frequently utilized approach to treat locally advanced breast cancer, but, unfortunately, a subset of tumors fails to undergo complete pathological response. Apoptosis and therapy-induced senescence (TIS) are both cell stress mechanisms but their exact role in mediating the pathological response to NAC is not fully elucidated. We investigated the change in expression of PAMIP1, the gene encoding for the pro-apoptotic protein, NOXA, following NAC in two breast cancer gene datasets, and the change in NOXA protein expression in response to NAC in 55 matched patient samples (pre- and post-NAC). PAMIP1 expression significantly declined in post-NAC in the two sets, and in our cohort, 75% of the samples exhibited a downregulation in NOXA post-NAC. Matched samples that showed a decline in NOXA post-NAC were examined for TIS based on a signature of downregulated expression of Lamin-B1 and Ki-67 and increased p16INK4a, and the majority exhibited a decrease in Lamin B1 (66%) and Ki-67 (80%), and increased p16INK4a (49%). Since our cohort consisted of patients that did not develop complete pathological response, such findings have clinical implications on the role of TIS and NOXA downregulation in mediating suboptimal responses to the currently established NAC.

Primary ovarian adenocarcinoma presenting with rubeotic glaucoma and vitritis: A case report.

Ovarian adenocarcinoma is an unusual cause of head or brain metastasis and seeding to the eye ball is extremely rare. A high index of suspicion and a careful ophthalmic examination can guide the patient work up. In this particular case, rubeotic glaucoma and vitritis antedated the diagnosis of ovarian malignancy.

The Expression of the Senescence-Associated Biomarker Lamin B1 in Human Breast Cancer.

Senescence is a major response to cancer chemotherapy and has been linked to unfavorable therapy outcomes. Lamin B1 is a component of the nuclear lamina that plays a pivotal role in chromatin stability. Downregulation of lamin B1 represents an established biomarker for cellular senescence. However, the protein expression level of lamin B1 in malignant tissue, particularly of the breast, has not been previously described. In this work, we investigated lamin B1 protein expression in normal breast epithelium, malignant breast tissue (including adjacent non-malignant tissue) and in malignant tissue exposed to neoadjuvant chemotherapy (NAC) using immunohistochemistry (IHC) in three patient groups (n = 15, n = 87, and n = 43, respectively). Our results indicate that lamin B1 mean positive expression was 93% in normal breast epithelium and 88% in malignant breast cells, but significantly decreased (mean: 55%, p < 0.001) in malignant breast tissue after exposure to NAC, suggestive of senescence induction. No significant association between lamin B1 expression and other clinicopathological characteristics or survival of breast cancer patients was recorded. To our knowledge, this is the first report that established the baseline protein expression level of lamin B1 in normal and malignant breast tissue, and its reduction following exposure to chemotherapy. In conclusion, lamin B1 downregulation can be used reliably as a component of multiple biomarker batteries to identify therapy-induced senescence (TIS) in clinical cancer.

Age of the donor affects the nature of in vitro cultured human dental pulp stem cells.

OBJECTIVES: The dental pulp stem cells (DPSCs) of six donors (three young donors aged < 19 years and three adult donors aged > 25 and < 30 years) were characterized for their stem cell marker expression and differentiation potential to study the effect of donor age on DPSCs in vitro. METHODS: DPSCs were cultured in αMEM supplemented with 20% fetal calf serum (conventional conditions) or on fibronectin-coated flasks with neurobasal medium supplemented with B27, bFGF and EGF (alternative conditions). DPSCs were characterized by immunofluorescence staining to detect the neural crest/mesenchymal stem cells markers P75 and CD146, respectively. The differentiation potential was tested by the induction of DPSCs into osteogenic, adipogenic and glial lineages and then by detecting the corresponding markers osteocalcin, lipidtox and S100ß, respectively. RESULTS: The DPSCs of the young donors expressed CD146 only under the conventional conditions and expressed P75 regardless of the culture conditions. However, the DPSCs of adult donors expressed CD146 only under the alternative conditions and expressed P75 only under conventional conditions. Only the DPSCs of the young donors differentiated into the glial linage. The DPSCs of the adult donors differentiated more efficiently into the adipogenic linage. Osteogenic differentiation was comparable. CONCLUSION: Donor age affects the expression of stem cell markers and differentiation potential of DPSCs. Moreover, the effect of culture conditions on DPSCs is age dependent.

An Uncommon Recurrent Metastasis of Ovarian Immature Teratoma to the Small Bowel.

Immature ovarian teratomas are rare ovarian germ cell tumors associated with a variable potential of distant metastasis. The acquisition of mature phenotypes upon post-treatment recurrence of immature teratomas has been previously described. In this study, we report, for the first time, a rare case of a recurrent ovarian immature teratoma with mature deposits in the small bowel. An incidental pelvi-abdominal mass was identified in a 30-year-old pregnant patient during antenatal ultrasonography. The mass, which was resected through salpingo-oopherectomy, was histopathologically characterized as an immature teratoma of grade 2 and treated with 3 cycles of chemotherapy. After 3 years of completing treatment, the patient suffered from severe anemia which was investigated by capsule endoscopy that identified a bleeding source in the ileum. Imaging studies revealed an intrabdominal mass that was resected laparoscopically. The pathological assessment of the mass identified a submucosal/intramuscular teratoma with mature elements indicative of a recurrent metastasis of immature teratoma associated with post-chemotherapy retroconversion. The secondary mass was then managed with adjuvant chemotherapy.

Differential Expression of Androgen Receptor in Type I and Type II Endometrial Carcinomas: A Clinicopathological Analysis and Correlation with Outcome.

OBJECTIVES: Endometrial carcinomas (EC) are the most common gynecological malignancies and are conventionally divided into type I and type II due to diagnostic and prognostic considerations. Female hormone expression in EC is extensively studied; however, data about androgen receptor (AR) expression in EC are sparse. We aimed to study AR expression in different types of EC at our institute and whether it had an impact on patient outcomes. METHODS: A retrospective analysis of EC cases diagnosed and treated from 2010-2019. AR immunohistochemical expression was tested in 52 EC cases (type I = 40; type II = 12). Histological typing was verified according to conventional diagnostic criteria. Only primary EC were included without neoadjuvant therapy. Histologic score was calculated as: stain intensity (graded 0-3) × positive cells percentage (graded 0-4). Level of expression was scored from 0 to 12. RESULTS: The mean age of the selected patients was 60.3 years (range = 31-88 ± 12.6). Recurrence was detected in 11 (21.2%) patients. The outcome was 40 patients were alive without disease, eight alive with disease, three dead of disease, and one dead of other causes. About 62.5% of type I-EC and 25.0% of type II-EC were AR positive. AR expression was analyzed against different clinicopathological parameters including: type (p = 0.005), histotype (p = 0.044); grade (p = 0.035); age group (p = 0.207); menopause (p = 0.086); estrogen receptor (ER) expression (p = 0.284); atypical complex hyperplasia (p = 0.594); tumor stage (p = 0.994); tumor recurrence (p = 0.530); node status (p = 0.110); and outcome (p = 0.202). CONCLUSION: AR expression was higher in type I EC, endometrial endometrioid carcinoma histotype, and with a lower grade. AR expression was not significantly correlated with age, stage, ER, atypical hyperplasia, recurrence, node status, or outcome. Results agree with recent literature that AR expression is associated with better-differentiated EC and may be a potential hormonal therapeutic tool.

The usefulness of histopathology examples in teaching practical histology for medical students: A CONSORT-compliant randomized crossover trial.

BACKGROUND: Teaching histology as an image-intensive discipline is a major challenge to medical teachers. We compared knowledge retention and student preference after performing comparison-based and traditional methods of teaching practical histology. METHODS: We performed a crossover randomized controlled trial. Eighty nine first-year and 37 second-year medical students were randomly assigned to comparison-based or traditional classes in which PowerPoint slides were used. Each teaching approach was then switched to another group for a second tissue set. Quantitative assessment was performed using multiple-choice questions and a questionnaire. RESULTS: The first-year students' overall examination scores were significantly higher in the comparison-based approach compared to the traditional approach for both tissue sets, with a large effect size. Interestingly, even for the second-year students, a significantly higher overall score for one set of tissue samples was observed in the comparison-based approach compared to the traditional approach. The students' responses to all the elements in the questionnaire were significantly in favor of the comparison-based approach. CONCLUSION: Our findings indicate that the simple implementation of a few histopathology examples can yield a tremendous improvement in first-year medical students' understanding, enjoyment, and engagement in practical histology classes.

Characteristics and Histological Types of Lupus Nephritis in a Jordanian Tertiary Medical Center.

OBJECTIVES: Few reports of lupus nephritis (LN) from Jordan and the Middle East exist. This study assessed the demographic, clinical, and basic laboratory characteristics of Jordanian patients with LN and correlations with the histological class of LN. METHODS: This was a retrospective study of all patients who underwent kidney biopsy between 2007 and 2018 at a tertiary medical center in Jordan. Patients' demographic, clinical, laboratory, and pathological data were reviewed. RESULTS: In total, 79 patients were included in this study [mean age, 29.95 ± 12.16 years; 11 men (13.9%), 68 women (86.1%)]. Asymptomatic proteinuria and hematuria were the most common presentations in LN patients at biopsy (59.5%). The study revealed a significant difference in frequency of nephritic syndrome (p= 0.01) between sexes (10.3% female vs. 45.5% male). Class IV was the most common pathological class of LN [37 (46.8%)], followed by class V [15 (19%)] and class III [10 (12.7%)]. Post hoc analysis of the associations between laboratory values and histopathological patterns revealed a significant correlation between class IV lupus and renal failure (p= 0.018) and class IV lupus and anti-DNA antibodies p= 0.030). End-stage renal disease (ESRD) occurred in 25% of lupus nephritis cases. There was an increased likelihood of ESRD among men than women (45% vs. 22%). Overall mortality was 10%. CONCLUSION: Although some clinical and laboratory findings correlate with histological types of LN, clinical and laboratory parameters of Jordanian patients with LN are not predictive of the histological type, although differences with regional studies were noted.

C1q nephropathy among children with nephrotic syndrome: Ten-year experience from a pediatric nephrology unit.

Abu-Shahin N, Al-Khader A, Qattan D, Akl K. C1q nephropathy among children with nephrotic syndrome: Ten-year experience from a pediatric nephrology unit. Turk J Pediatr 2018; 60: 14-21. C1q nephropathy (C1qN) is a rare glomerulopathy mostly seen in children, and presents with nephrotic syndrome (NS). Diagnosis depends on immunoflourescence or immunohistochemical C1q mesangial deposition, excluding other immune-mediated diseases. We retrospectively investigated C1qN incidence, clinicopathological features, and outcome among pediatric NS in our institution.Clinical data, microscopic slides and corresponding tissue blocks of pediatric renal biopsies were retrieved. According to diagnostic criteria for C1qN, 53 pediatric NS renal biopsies were selected for Anti-C1qA IHC stain microscopic examination. Clinicopathological features and follow up data were recorded. C1qN incidence was 9.4% among pediatric NS biopsies. Mesangial proliferation was the most common histopathological pattern. Steroid dependency with frequent relapses was the most frequent outcome, with a second line immunosuppressant added, yet without impact on progression. Small sample size hinders coherent conclusions; nevertheless, it indicates that C1qN is a rare cause of pediatric NS. C1qN may require second line immunosupressants more often than non-C1q NS.

Capillary Hemangioma as an Unusual Cause of Doughnut Sign on Bone Scan.

ABSTRACTS: A 28-year-old woman presented with a mass in her right leg, which, on plain radiograph, appeared as a lytic lesion in the mid-shaft of the tibia with cortical thinning but without periosteal reaction. Tc-MDP 3-phase bone scan demonstrated intense uptake in the periphery of the mass with a photopenic center, the so-called doughnut sign. Histopathology revealed a capillary hemangioma. This case demonstrates that the doughnut sign on bone scan can be caused by capillary hemangioma in addition to other reported bone pathologies, including aneurysmal bone cyst, giant cell tumor, and telangiectatic osteosarcoma.

Leiomyoma of Urinary Bladder Presenting with Febrile Urinary Tract Infection: A Case Report.

INTRODUCTION: Leiomyomas of urinary bladder constitute only about 0.43% of all bladder tumors. Only about 250 cases were reported in English literature. This is the first reported case of bladder leiomyoma to present with febrile urinary tract infection. CASE PRESENTATION: We report a case of a 37- year old male who presented with febrile urinary tract infection. Imaging showed a bladder lesion. This lesion was managed by transurethral resection. Pathologic diagnosis was bladder leiomyoma. DISCUSSION: Although bladder leiomyomas are benign, they can cause serious sequelae, including serious urinary tract infections as the case we present here shows. This is why it is important to early diagnose and treat this condition. CONCLUSION: This case highlights the importance of early introduction of imaging in patients presenting with severe urinary tract infections. Failure to diagnose this lesion as the underlying cause of infection may have easily led to recurrence of similar severe life-threatening infections.

Medical students' perceptions of pathology and a proposed curricular integration with histology: a future vision of curricular change / Percepciones de los estudiantes de medicina sobre patología y una propuesta de integración curricular con histología: una visión futura de cambio curricular

Students' perceptions and feedback have a significant impact on academic progress. The aim of this study was to determine the perceptions of medical students regarding the cumulative effects of the first year general histology course and the sophomore pathology introductory course, in addition to their perceptions regarding the curricular integration of histology and pathology. In this cross-sectional study, a questionnaire was given to second-year and third-year medical students in the middle of second semester. The questionnaire comprised several items on students' attitudes toward anatomic pathology, their feedback on the first year general histology and the sophomore pathology courses, and their perceptions regarding the integration of histology and pathology courses. A five-point Likert scale was used. Data were analyzed using Statistical Package for the Social Science (SPSS) v 20 software. Two hundreds and fourteen of the 236 questionnaires distributed were analyzed (response rate = 90.7 %). More than 51 % of the respondents reported that they couldn't identify the normal tissue counterpart of most practical pathology cases. Only 31.3 % thought their practical histology knowledge was beneficial for them in practical pathology. More than 87 % agreed or strongly agreed that pathology cases need to be copresented with normal tissue examples. A significant proportion of the respondents (60.7 %) were with merging histology and pathology in integrated courses. Pathology was of career choices for only 15.4 % of the participants. The curricular integration of histology and pathology in the first year needs to be tested, and much effort is needed to increase students' affinity for anatomic pathology.

Las percepciones y comentarios de los estudiantes tienen un impacto significativo en el progreso académico. El objetivo de este estudio fue determinar las percepciones de los estudiantes de medicina con respecto a los efectos acumulativos del curso de Histología general de primer año y del curso introductorio de Patología de segundo año, además de sus percepciones con respecto a la integración curricular de Histología y Patología. En este estudio transversal, se entregó un cuestionario a estudiantes de medicina de segundo y tercer año, a mediados del segundo semestre. Asimismo, el cuestionario comprendió varios aspectos referente a la actitud de los estudiantes hacia Patología Anatómica, sus comentarios sobre la Histología general en el primer año y los cursos de Patología de segundo año. Además se incorporaron las percepciones de los estudiantes con respecto a la integración de los cursos de Histología y Patología. Se utilizó una escala de Likert de cinco puntos. Los datos se analizaron utilizando el paquete Statistical Package for Social Science (SPSS) v 20. Se analizaron 214 de los 236 cuestionarios distribuidos (tasa de respuesta = 90,7 %). Más del 51 % de los encuestados indicaron estar de acuerdo o totalmente de acuerdo, en que no lograron identificar el tejido normal, en la mayoría de los casos de Patología práctica. Solo el 31,3 % observó que su conocimiento de Histología práctica era beneficioso para ellos durante la Patología práctica. Más del 87 % estuvo de acuerdo o muy de acuerdo en que los casos de Patología deben ser analizados con muestras de tejido normal. Un grupo importante de los encuestados (60,7 %) consideraba incorporar la Histología y la Patología en cursos integrados. Patología fue de elección en la carrera para el 15,4 % de los participantes. La integración curricular de Histología y Patología en el primer año, debe ser evaluada con el propósito de incrementar la afinidad de los estudiantes con la Patología Anatómica.

Differential expression, diagnostic and prognostic significance of stathmin-1 and CD147 in various uterine smooth muscle tumors / Expresión diferencial, diagnóstico y significado de pronóstico de stathmin-1 y CD147 en diferentes tumores del músculo liso uterino

SUMMARY: Uterine smooth muscle tumors (USMT) are common, behavior-distinct gynecological tumors; including: leiomyoma (ULM), leiomyosarcoma (ULMS), and smooth muscle tumors of undetermined malignant potential (STUMP). Pre-operative distinction is difficult, thus diagnosis relies on histopathology. Immunohistochemistry (IHC) had been used to help in distinction. We studied two markers (stathmin-1 and CD147) to demonstrate whether they have diagnostic/ prognostic assist. Sixty seven USMT are studied. Age, follow up, and recurrence/metastasis data were collected. Representative slides were stained and Histologic score (HS) calculated as stain intensity (SI) X percentage of positive tumor cells (PP). Results were grouped as low expression (LE) and high expression (HE); then correlated to tumor types, and risk of recurrence/ metastasis. Statistical analysis (P < 0.05); Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were calculated. Stathmin-1 HS (p= 0.000) and HE (p=0.002) were different among groups. Same as for CD147 HS and HE (both p=0.000), with a gradient increase from LM to STUMP to ULMS. Sensitivity, specificity, positive and negative predictive values and confidence intervals in diagnosing ULMS were as following: For stathmin-1 HS: 92 %; 20 %; 42 %; and 80 % (CI= 44-96 %). For Stathmin-1 HE: 80 %; 66 %; 60 %; and 84 % (CI=66-94 %). For CD147 HS: 85 %; 22 %; 41 %; and 69 %. For CD147 HE: 58 %; 49 %; 42 %; and 65 % (CI= 45-80 %), respectively. Recurrence / metastasis were documented in 6 cases (4 ULMS; 2 STUMP) with follow up ranging from 6 months to 102 months. 5 tumors had stathmin-1 HE (p=0.099); 2 had CD147 HE (p=0.393) in the primary tumors. STMN1 and CD147 are helpful diagnostic tests for USMT sub-typing, especially for ULMS. Gradient increase of expression from LM, to STUMP, to ULMS may indicate a role in malignant transformation in USMT, and in increased risk of recurrences/metastasis.

RESUMEN: Los tumores del músculo liso uterino (USMT, por sus siglas en inglés) son tumores ginecológicos comunes y de comportamiento distinto; incluyendo: leiomioma (ULM), leiomiosarcoma (ULMS) y tumores de músculo liso de potencial maligno indeterminado (STUMP). La distinción preoperatoria es difícil, por lo que el diagnóstico se basa en la histopatología. La inmunohistoquímica (IHQ) se había utilizado para ayudar en la distinción. Estudiamos dos marcadores (stathmin-1 y CD147) para demostrar si había efecto diagnóstico / pronóstico. Se estudiaron 67 USMT. Se recopilaron los datos de edad, seguimiento y recurrencia / metástasis. Las muestras representativas se tiñeron y la puntuación histológica (HS) se calculó como la intensidad de la tinción (IS) x porcentaje de células tumorales positivas (PP). Los resultados se agruparon como expresión baja (EB) y expresión alta (EA); luego se correlacionaeon con los tipos de tumores y el riesgo de recurrencia / metástasis. Análisis estadístico (P <0,05); se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS. Stathmin-1 HS (p = 0,000) y HE (p = 0,002) fueron diferentes entre los grupos. Igual que para CD147 HS y HE (ambos p = 0,000), con un aumento de gradiente de LM a STUMP a ULMS. La sensibilidad, la especificidad, los valores predictivos positivos y negativos y los intervalos de confianza en el diagnóstico de ULMS fueron los siguientes: Para stathmin-1 HS: 92 %; 20 %; 42 %; y 80 % (IC = 44-96 %). Para Stathmin-1 HE: 80 %; 66 %; 60 %; y 84 % (IC = 66-94 %). Para CD147 HS: 85 %; 22 %; 41 %; y el 69 %. Para CD147 HE: 58 %; 49 %; 42 %; y 65 % (IC = 45-80 %), respectivamente. La recurrencia / metástasis se documentaron en 6 casos (4 ULMS; 2 STUMP) con un seguimiento que osciló entre 6 meses y 102 meses. Cinco tumores tenían stathmin-1 HE (p = 0,099); dos tenían CD147 HE (p = 0,393) en los tumores primarios. STMN1 y CD147 son pruebas de diagnóstico útiles para la subclasificación de USMT, especialmente para ULMS. El aumento en el gradiente de la expresión de LM, a STUMP, a ULMS puede indicar un papel en la transformación maligna en USMT y en un mayor riesgo de recurrencias / metástasis.

Phase I trial of intraperitoneal pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer.

PURPOSE: This phase I trial evaluated intraperitoneal (i.p.) pemetrexed, cisplatin, and paclitaxel in optimally debulked ovarian cancer. EXPERIMENTAL DESIGN: Dose escalation of day 1 i.p. pemetrexed accrued three patients to each of five dose levels (60-1,000 mg/m(2)), along with day 2 i.p. cisplatin (75 mg/m(2)) and day 8 i.p. paclitaxel (60 mg/m(2)). The goals were to determine maximum tolerated dose (MTD), 18-month progression-free survival (PFS), and pharmacokinetics of i.p. pemetrexed. RESULTS: Cycles, given every 21 days, had an 80% 6-cycle completion rate. There was minimal grade III toxicity in the first 4 dose levels and remarkably an almost complete absence of peripheral neuropathy and alopecia. At the highest dose level, two of three patients experienced ≥ grade III and dose-limiting toxicity (DLT; hematologic, infection, gastrointestinal). There was a pharmacokinetic advantage for i.p. pemetrexed with an intraperitoneal:plasma area under the concentration-time curve ratio of 13-fold. Neither analysis of pharmacokinetic nor homocysteine levels explains the unexpected severity of toxicity in those two patients. On the basis of plasma C(24h) levels, the 42 cycles at ≥ 500 mg/m(2) i.p. pemetrexed without DLT, the MTD appears to be 500 mg/m(2). Median PFS is 30.1 months; 18-month PFS is 78.6% (median follow-up 22.4 months). CONCLUSIONS: This i.p.-only regimen in front-line ovarian cancer is feasible with PFS in line with recent literature. We suggest phase II trials of this regimen in this population with i.p. pemetrexed at 500 mg/m(2). The favorable toxicity profile at doses <1,000 mg/m(2), which needs to be confirmed, appears to compare well with standard combination i.v./i.p. platinum/taxane chemotherapy in this disease.