The efficacy of the levonorgestrel intrauterine system versus oral megestrol acetate in treating atypical endometrial hyperplasia: a superior randomized controlled trial.

OBJECTIVE: To compare the efficacy of the levonorgestrel intrauterine system (LNG-IUS) versus megestrol acetate (MA) in inducing complete regression among women with atypical endometrial hyperplasia (AEH) who declined hysterectomy. METHODS: In this single-center, open-label randomized controlled trial, we included 148 women with AEH who declined hysterectomy. We randomized participants to receive either daily oral MA 160 mg (n=74) or apply LNG-IUS (n=74) and scheduled their follow-up by endometrial sampling at 3, 6, 9, 12, 18, and 24 months. The success rate and duration until complete regression were the primary outcomes. RESULTS: The mean duration until complete regression was 5.52 months (95% confidence interval [CI]=4.85-6.18) for the LNG-IUS group versus 6.87 months (95% CI=6.09-7.64) for the megestrol group (log-rank test p-value=0.011). The cumulative regression rate after 12 months was 91.9% with the LNG-IUS versus 77% with MA (p=0.026). Weight gain in the MA group vs LNG-IUS group after one year (4.7±4 kg vs. 2.7±2.6 kg, 95% CI=0.89-3.12; p=0.001) and after two years of therapy (7.8±5.1 kg vs. 4.1±2.9 kg, 95% CI=2.29-5.06; p<0.001). CONCLUSION: Compared to MA, the LNG-IUS was more efficacious in treating AEH in women who declined hysterectomy, especially those with moderate/severe obesity, with fewer adverse effects and less weight gain. Extending therapy to 12 months for persistent cases would improve regression rates with reasonable safety. Alternate hysteroscopic and office sampling seemed convenient for follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04385667.

PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study.

BACKGROUND: It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression. PATIENTS AND METHODS: Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters. RESULTS: Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients. CONCLUSIONS: We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression.

Protein Expression of NEK2, JMJD4, and REST in Clear Cell Renal Cell Carcinoma (ccRCC): Clinical, Pathological, and Prognostic Findings.

Background & Objective: Cells of renal cell carcinoma (RCC) are resistant to the most currently used chemotherapeutic agents and targeted therapies; hence, we evaluated the expression of NEK2, JMJD4, and REST in cases of clear cell renal cell carcinoma (ccRCC) and benign adjacent tissues of kidney to detect associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates. Methods: We collected 200 samples including tumoral and adjacent non-neoplastic tissues related to 100 ccRCC patients. All samples were evaluated for the expression of NEK2, JMJD4, and REST, and the patients were followed up for about 5 years. Tumor recurrence and survival data were documented and analyzed. Results: NEK2 and JMJD4 expression showed increase in ccRCC tissues (P=0.002 and 0.006), while REST was downregulated (P<0.001). The elevated expression of NEK2 was positively related ro the tumor size (P=0.015), higher grades (P=0.002), higher stages (P=0.013), distant spread (P=0.004), tumor recurrence, shorter progression-free survival (PFS) rate, and overall survival (OS) rate (P<0.001). Likewise, the high expression of JMJD4 showed positive correlation with the tumor size (P=0.047), higher grades (P=0.003), higher stages (P=0.043), distant spread (P=0.001), tumor recurrence, shorter PFS rate, and OS rate (P<0.001). Conversely, low expression of REST demonstrated positive relationship with the tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates (P<0.001). Conclusion: Overexpression of NEK2 and JMJD4 and downregulation of REST may be noted in malignant renal tissues compared to benign renal tissues and may be correlated with unfavorable pathological findings, poor clinical parameters, and poor patient outcomes.

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Risk factors and outcomes of occurrence of anastomotic leakage and reoperations for its management after colorectal surgery

Background: Anastomotic leakage (AL) is still the most annoying postsurgery complication after colorectal resection due to its serious complications up to death. Limited data were available regarding differences in AL incidence, management, and consequences for different types of colorectal resection. The aim of the present work was to evaluate differences in incidence of AL, incidence of postoperative complications, and length of hospital stay in a large number of patients who underwent elective colorectal resection for management of colorectal lesions. In addition to detect when and what type of reoperation for management of AL occur after colorectal resection. Patients: All 250 included patients underwent elective surgeries for colorectal resection with performance of primary anastomosis for management of colorectal neoplastic and non-neoplastic diseases in the period between May 2016 and July 31, 2021. We followed the patients for 90 days; we registered the follow-up findings. Results: the rates of AL occurrence were variable after the different procedures. The lowest rate of AL occurrence was found in patients who underwent right hemicolectomy, then in patients who underwent sigmoidectomy, left hemicolectomy, transversectomy and anterior resection (p= 0.004). A stoma was frequently performed during reoperation (79.5%) which was significantly different between different procedures: 65.5% in right hemicolectomy, 75.0% in transversectomy, 85.7% in left hemicolectomy, and 93.0% in sigmoid resection (p< 0.001). Conclusion Rates, types, time of occurrence and severity of AL vary according to the type of colectomy performed and selective construction of stoma during AL reoperation is currently safely applied with comparable mortality rates for patients who did and who did not have a stoma after reoperation. (AU)

Expression of epithelial-mesenchymal transition biomarkers: Discoidin domain receptor 2, Snail-1, and Ovol-2 as predictors of clinical outcome in patients with epithelial ovarian carcinoma.

Context: Discoidin domain receptor 2 (DDR-2), which belongs to the receptor tyrosine kinase family, Snail-1, which is a member of zinc-finger transcription factor family, and Ovol-2, which is a member of Ovol family, are incriminated in epithelial-mesenchymal transition (EMT) during cancer progression. Aim: In the current study, we aim to clarify the extent to which EMT biomarkers, DDR-2, Snail-1, and Ovol-2 expression, are involved in the progression of EOC aiming at identification of novel markers for predicting the prognosis of EOC patients. Settings and Design: This was a prospective cohort that was performed in the Faculty of Medicine, Zagazig University. Materials and Methods: We evaluated DDR-2, Snail-1, and Ovol-2 expression in 60 patients of EOC using immunohistochemistry. We followed our patients for about 36 months and analyzed the relationship between markers expression and the prognosis of patients. Statistical Analysis Used: SPSS program (Statistical Package for the Social Sciences). Results: High expression of both DDR-2 and Snail-1 was related to higher grade (P = 0.006) and advanced FIGO stage of the tumor (P < 0.001). Ovol-2 high expression was associated with lower grade of the tumor (P = 0.002) and early stage of the tumor (P < 0.001). High Ovol-2 and low DDR2 and Snail-1 expression were strongly correlated with better response to therapy (P = 0.003 and 0.005, respectively) and increased 3-year survival rates (P < 0.001). Conclusion: DDR-2 and Snail-1 are markers of poor prognosis in EOC while Ovol-2 is a marker of good prognosis.

Antimullerian Hormone Levels and Association with Abortion and Preterm Delivery in Patients with Polycystic Ovary Syndrome Who Conceived with Assisted Reproductive Techniques.

Background: Pregnant PCOS patients were found to suffer from many adverse outcomes of pregnancy. Prediction of the fate of pregnancy and labor in PCOS patients was highly needed. There were recently discovered roles of serum AMH in those patients who were seeking for pregnancy and who were conceiving with assisted reproductive techniques. Aim: To analyze the predictive roles of measuring serum levels of AMH in patients with PCOS who became pregnant spontaneously or used assisted reproductive techniques regarding abortion and preterm delivery. Patients and Study Design: A total of 100 females with PCOS were included in the study and they underwent assisted reproductive techniques were included in the study and underwent measurement of AMH levels regularly. Results: We found that a total of 70 patients had a term delivery, and 30 patients had a preterm delivery. We found no statistically significant differences between both groups regarding their age or body mass index (BMI). We showed that serum AMH levels were higher in the group of PCOS patients who had preterm delivery than in the group of patients with term delivery (p < .0.001). Conclusions: High serum AMH levels were found to be associated with higher risks of occurrence of preterm labor in patients with PCOS who underwent assisted reproductive techniques. Our results gave a clue to clinicians for better management of the pregnancy process in these patients.

The prognostic roles of PYCR2 and ZBTB18 expression in tissues of colorectal carcinoma and non-neoplastic tissues: an immunohistochemical study

Background: It is important to detect novel biomarkers responsible for the progression and spread of colorectal cancer (CRC) to better evaluate the prognosis of the patients, provide better management, and foster the development of therapeutic targets. In humans, pyrroline-5-carboxylate reductase 2 (PYCR2) is encoded on chromosome 1q42.12, and its metabolic activity has been linked to oncogenesis in many cancers. Zinc finger and broad-complex, tramtrack, and bric-à-brac (BTB) domain-containing protein 18 (ZBTB18), a zinc finger transcriptional repressor, has been found to have a tumor-suppressor role and to be methylated in CRCs. To date, the prognostic roles of PYCR2 and ZBTB18 in CRC patients have not been thoroughly studied. Objective: To evaluate the tissue protein expression of PYCR2 and ZBTB18 in CRC and adjacent non-neoplastic intestinal tissues, to detect their roles in CRC carcinogenesis, progression and metastases. Patients and methods: After applying the inclusion criteria, 60 CRC patients were included in the study. Tissue samples from the tumor and the adjacent non-neoplastic tissues were stained with PYCR2 and ZBTB18. The patients were followed up for about 30 months (range: 10 to 36 months). We performed a correlation regarding the expression of the markers, and clinicopathological and prognostic parameters. Results Upregulation of PYCR2 and downregulation of ZBTB18 were found to be higher in CRC tissue than in the adjacent non-neoplastic colonic mucosa (p = 0.026 and p < 0.001 respectively). High expression of PYCR2 and low expression of ZBTB18 were positively correlated with large tumor size, higher tumor grade, advanced tumor stage, presence of spread to lymph nodes, and presence of distant metastases (p < 0.001). High PYCR2 and low ZBTB18 expressions were significantly associated with poor response to therapy (p = 0.008 and 0.0.17 respectively), as well as high incidence of progression and recurrence (p = 0.005), and unfavorable overall survival (OS) rates (p = 0.001). Conclusion: High expression of PYCR2 and low expression of ZBTB18 were independent predictors of CRC, progression, poor prognosis and unfavorable patient OS and progression-free survival (PFS) rates. (AU)

Surgical roles in the management of metachronus para-aortic lymph node recurrence and synchronous para-aortic lymph node metastasis in colorectal cancer patients

Background: The relative rarity of synchronous para-aortic lymph node (PALN) metastasis (SPM) and metachronous PALN recurrence (MPR) in colorectal carcinoma (CRC) patients leads to a limited number of studies on patient management, and no treatment guidelines have been established to date. Objective: To assess the prognostic, predictive roles, and long-term outcomes of different management strategies for isolated MPR and SPM in CRC patients to establish the best one. Materials and Methods: We included 35 CRC patients with isolated MPR and 25 patients with isolated SPM who underwent curative R0 resection. We performed PALN dissection (PALND) in 15 cases in MPR group and in 10 cases in the SPM group; all remaining patients in both groups underwent chemoradiotherapy (CRT) without further surgical intervention. During the study period of about 5 years, we compared the patients who underwent PALND and those who underwent CRT. Results: The overall survival and recurrence-free survival rates were significantly longer in patients who underwent PALND (p = 0.049 and 0.036 respectively). (AU)

Clinical significance of cytokeratin 19 and OCT4 as survival markers in non-metastatic and metastatic breast cancer patients.

Introduction: Cytokeratin 19 (CK19) is highly expressed in epithelial tumours such as breast cancer (BC). Octamer-binding transcription factor 4 (OCT4), a transcription factor of the POU (Pit-Oct-UNC) family, plays a criti-cal role in the self-renewal and maintenance of pluripotency of embryonic stem cells; therefore, it has been used as a promising CSC marker. Material and methods: CK19 was assessed in peripheral blood using flow-cytometric analysis while OCT4 was evaluated in breast tissue samples by immunohistochemistry from 70 patients (non-metastatic BC, meta-static BC, and non-malignant breast tumours). Results: CK19 and OCT4 were significantly associated with BC patients compared to control (p < 0.001). CK19 was detected in 38 patients with BC (62.2%); meanwhile, OCT4 was positive in 37 BC patients (60.6%). CK19 was positively associated with grade (p = 0.002), HER2 (p = 0.009), metastasis (p = 0.026), molecular subtypes and LN (p < 0.001), and stage (p = 0.001) while OCT4 expression was positively associated with BMI (p < 0.023), aggressive molecular subtype (p < 0.019), ER expression (p = 0.025), presence of LN metastases (p < 0.017), and distant metastasis (p < 0.018). A non-significant relation was found between the expression of CK19 and OCT (p = 0.291). The positive expression of CK19 and OCT4 was significantly and inversely associated with both 3-year OS and 3-year PFS. Conclusions: CK19 and OCT4 are associated with BC, so they can be considered as prognostic and predictive markers for poor OS and PFS in non-metastatic as well as metastatic BC patients.

Prognostic Roles of ZNF703 and SMAD4 Expression in Patients with Papillary Thyroid Cancer and Association with Nodal Metastasis.

It is important to detect novel predictive biomarkers of cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) to help the surgeons in making early decision of performing central lymph node dissection and aggressive management strategies in selected high-risk patients, thus improving their prognosis. Zinc finger protein 703 (ZNF703) is a member of the neutrophil extracellular trap (NET) transcription factors family which has roles in proliferation and invasion of cancer cells. SMAD4 is a protein that has a role in cellular processes including cell proliferation, invasion, and metastasis through many genes' transcription. In this study, we aimed to assess the expression of ZNF703 and SMAD4 in PTC and evaluated the correlation between its expression, clinicopathological features of PTC cases, and prognostic parameters of patients to evaluate their roles in PTC progression. This is a retrospective study which included 40 cases with PTC. For immunohistochemistry, tissues stained their paraffin blocks with ZNF703 and SMAD4. We followed patients to detect disease progression and recurrence. Positive ZNF703 expression and negative SMAD4 expression were associated with higher incidence of CLNM, advanced stage and large tumor size, higher incidence of disease progression, recurrence, unfavorable PFS, and unfavorable OS rates. The higher ZNF703 expression and the lower SMAD4 expression were significantly increased in PTC patients with cervical LNM compared with those without. ZNF703 over expression and downregulation SMAD4 expression was significantly increased in PTC patients. Elevated expression of ZNF703 in tumor tissue with CLNM can be considered a predictive factor for the development of metastasis.

A comparison between different management surgical approaches in the treatment of splenic flexure colon cancer

Background: There are many surgical approaches which described extent of resection of the colon for adequate surgicalmanagement of splenic flexure cancer, but up till now there is no established surgical procedure, this is because the presence of double lymphatic drainage of themesenteric vessels. Segmental resection of the colon for the management of splenic flexure cancer was a recently accepted surgical procedure. Objective: In the present study, we aimed to compare three surgical management techniques to clarify the best management approach of Egyptian patients with splenic flexure cancer regarding operative, clinical, and oncological outcomes: segmental resection, and extended left or right hemicolectomy,. Materials and Methods In the present study, we included 90 patients with splenic flexure cancer. Cases were divided into 3 groups. Each group included 30 patients in order to compare three surgical techniques: segmental resection, extended left hemicolectomy, and extended right hemicolectomy. Results: We have found no statistically significant differences between the three included groups regarding operative findings, postoperative complications, local recurrence, distant recurrence, disease progression, recurrence-free survival rate, progression-free survival rate, and overall survival rate. The operative time was longer, and the number of lymph nodes was higher in the extended right hemicolectomy group (p<0.001). Conclusion: We have shown that segmental resection of the splenic flexure is surgically and clinically suitable for the adequate management of operable cases of carcinoma of the splenic flexure. (AU)

Choosing the Appropriate Individualized Adjuvant Chemotherapy in Stage III Colon Cancer Patients Under and Over 70 Years.

BACKGROUND: Colon cancer is one of the leading causes of cancer-related deaths worldwide. The increased incidence of comorbid diseases in elderly patients above 70 leads to the need of less aggressive strategies to be used in the adjuvant setting of stage III colon cancer. METHOD: Our prospective cohort study was performed in the period from April 2017 to March 2020. Seventy-five patients with newly diagnosed stage III colon cancer received adjuvant chemotherapy after surgery. Patients who either received adjuvant chemotherapy less than 3 months due to intolerability or toxicity from medications or who have more than one type of cancers or metastatic disease from the start were excluded from the study. Patients' clinicopathological characteristics in relation to oxaliplatin- and non-oxaliplatin-based chemotherapeutic regimens were analyzed with survival assessment. RESULTS: In our study, patients above 70 had better overall survival (OS) in the non-oxaliplatin chemotherapy group (p-value = 0.032) in contrast to OS in patients under 70 which was better in the oxaliplatin group (p-value < 0.001). By comparing the OS between the two age groups, the OS was better in patients < 70 years (p-value = 0.001). Additionally, we found that the DFS in patients above 70 was better in oxaliplatin-based regimens than in the non-oxaliplatin group (p-value = 0.011) with better survival rates (81.8% vs 15.7%), and markedly high DFS in patients under 70 for oxaliplatin based regimens (p-value < 0.001), with survival rates (31.1% vs 0%). By comparing the DFS between the two age groups, the DFS was better in patients < 70 years (p-value < 0.001). The disease recurrence was in favor of the non-oxaliplatin group with significant p-value = 0.003, while mortality occurred more in the oxaliplatin group (p-value < 0.001). CONCLUSIONS: The appropriate selection of a personalized strategy for treatment of stage III colon cancer plays an important role in the outcome of the disease. Our findings supported the use of oxaliplatin-based chemotherapy as a standard treatment option in the adjuvant management of stage III colon cancer patients in all age groups. The benefit of non-oxaliplatin-based chemotherapy was limited to patients above 70 which might be an effective option for elderly patients.

Value of fertility-sparing surgery for young females with epithelial ovarian cancer: a comparative study / Valor de la cirugía de preservación de la fertilidad en mujeres jóvenes con cáncer de ovario epitelial: un estudio comparativo

Resumen OBJETIVO: Comparar la cirugía radical con la cirugía conservadora de la fertilidad en mujeres con cáncer de ovario epitelial en estadio 1A-C con respecto a la tasa de recurrencia y las tasas de supervivencia. Además, evaluar los desenlaces reproductivos y obstétricos para las mujeres con cáncer de ovario epitelial en estadio I tratadas con una conducta conservadora de la fertilidad. PACIENTES Y MÉTODOS: Estudio prospectivo efectuado en pacientes con cáncer de ovario epitelial, estadio I, con edad ≤ 40 años. A las pacientes del grupo de preservación de la fertilidad se les practicó salpingooforectomía del lado del ovario afectado y una biopsia por incisión o escisión en cuña del ovario contralateral. A las pacientes del grupo de cirugía radical se les practicó la histerectomía total y salpingooforectomía bilateral. Para evaluar los desenlaces reproductivos y oncológicos se dio seguimiento a todas las pacientes durante cinco años. RESULTADOS: Se estudiaron 60 pacientes; las del grupo de cirugía de preservación de la fertilidad eran significativamente más jóvenes (30 ± 4 en comparación con 35 ± 5) (p < 0.001), el tamaño de sus tumores era más pequeño 3.4 ± 1.3 en comparación con 6.0 ± 2,6 (p < 0.001), de menor grado (p < 0.001). = 0.011), estadio más precoz (p < 0.001) y con más histología mucinosa que las pacientes del grupo de cirugía radical. No hubo diferencias estadísticamente significativas entre ambos grupos en cuanto a la recurrencia tumoral o las tasas de supervivencia. De 25 pacientes operadas para preservación de la fertilidad 18 de 25 intentaron quedar embarazadas. Se registraron 15 de 18 embarazos, incluidos 13 nacidos vivos, 1 aborto espontáneo y 1 muerte fetal intrauterina. CONCLUSIÓN: La cirugía conservadora de la fertilidad podría ser una alternativa adecuada a la cirugía radical para mujeres jóvenes con cáncer epitelial de ovario en estadio I.

Abstract OBJECTIVE: In the current study, we aimed to compare between radical surgery and fertility saving surgery in females with stage 1A-C EOC regarding recurrence rate and patients survival rates in addition to evaluating reproductive and obstetric outcomes for stage I EOC females who were managed by fertility saving surgery. PATIENTS AND METHODS: We prospectively identified 60 patients diagnosed with stage I EOC aged ≤ 40 years. Patients in the fertility-preservation group underwent salpingo-oophorectomy on the side of the affected ovary in addition to incisional biopsy or wedge excision of the ovary on the other side. Patients in the radical surgery group underwent total hysterectomy and bilateral salpingo-oophorectomy. We followed up all patients for 5 years to assess their reproductive and oncological outcomes. RESULTS: Patients in the fertility preservation surgery group were significantly younger (30 ± 4 versus 35 ± 5) (p < 0.001), their tumor sizes were smaller 3.4 ± 1.3 versus 6.0 ± 2.6 (p < 0.001), of lower grade (p = 0.011), earlier stage (p < 0.001) and has more mucinous histology than patients in the radical surgery group. There were no statistically significant differences between both groups regarding tumor recurrence or survival rates. Of 25 patients underwent fertility preservation surgery, 18/25 (72%) tried to get pregnant. 15/18 (83%) pregnancies were recorded, including 13 live births, 1 miscarriage, and 1 intrauterine fetal death. CONCLUSION: Fertility sparing surgery could be adequate alternative to radical surgery for young females with stage I EOC.

Forkhead box M1 over-expression and dachshund homolog 1 down-regulation as novel biomarkers for progression of endometrial carcinoma in Egyptian patients.

INTRODUCTION: Forkhead box M1 (FOXM1) is considered as a novel anti-cancer target, because it has many essential functions such as mitosis regulation, cell cycle transition, and other carcinogenesis signaling pathways. Dachshund homolog 1 (DACH1) is a member of the Sno/Ski co-repressor family. MATERIAL AND METHODS: Expression of DACH1 has been detected in many cancers. Patients and pathologic specimens: 50 patients with endometrial cancer (EC) were included in the study: ten specimens of normal endometrium and twenty specimens of endometrial hyperplasia. All samples underwent processing to investigate FOXM1 and DACH1 expression using immunohistochemistry. RESULTS: FOXM1 expression was detected in EC tissues more than normal endometrium and endometrial hyperplasia tissues (p = 0.001) and 0.01. Increased FOXM1 expression was positively associated with larger tumor size (p = 0.002), high grade (p = 0.004), myometrial invasion, presence of lymph node metastases, higher Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.001), and worse progression-free survival (PFS) and overall survival (OS) rates. The expression of DACH1 was lower in EC cells than normal endometrium and endometrial hyperplasia tissues (p = 0.071) and 0.252. Low DACH1 expression was associated with high grade (p = 0.001), presence of lymph node metastases (p = 0.49), higher FIGO stage (p = 0.022), and unfavorable PFS and OS rates (p = 0.037). We found an inverse association between expression of FOXM1 and DACH1 in EC tissues and in non-neoplastic endometrial tissues (p = 0.007). CONCLUSIONS: FOXM1 over-expression and DACH1 down-regulation in EC were related to poor clinical and pathological parameters and unfavorable prognosis.

Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma.

Background there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues. AIM: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients. PATIENTS AND METHODS: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60). RESULTS: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001). In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.

The Diagnostic and Prognostic Roles of Combined Expression of Novel Biomarkers in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: An Immunohistochemical Study.

BACKGROUND & OBJECTIVE: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry. METHODS: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values. RESULTS: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (P <0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (P=0.038 and P=0.019, respectively). CONCLUSION: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Evaluating the value of Amphiregulin, Phosphatase and Tensin Homologue (PTEN) and P21 Expression for Anti-EGFR Treatment in Metastatic Colorectal Carcinoma.

BACKGROUND: Despite the significant progress in target therapy for the treatment of metastatic colorectal carcinoma (mCRC), the overall survival isn't satisfactory. METHODS: We assessed the expression of Amphiregulin, PTEN, and P21 in sections from 23 paraffin blocks prepared from 23 patients with left-sided mCRC using immunohistochemistry (IHC). The relationship between their level of expressions, clinicopathological parameters, response to anti-EGFR, and prognosis were analyzed. RESULTS: High Amphiregulin, PTEN and low P21 expression levels were associated with low tumor grade (p= 0.038 and 0.025 respectively), better response to anti-EGFR treatment (p <0.001), and favorable outcome {progression-free survival (PFS) and overall survival (OS)} (p <0.05). There was a direct relation between Amphiregulin and PTEN expressions (phi coefficient=+0.840), while there was an inverse relation between P21expression and both Amphiregulin (phi coefficient= -0.840) and PTEN expressions (phi coefficient = -1.000), which was statistically significant (P <0.001). CONCLUSION: High Amphiregulin and PTEN expression levels and low P21 expression levels were associated with better response to anti-EGFR therapy and improved survival outcome. They might be considered predictive markers of response to anti-EGFR therapy in mCRC.

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The validity, reliability, and reviewer acceptance of VI-RADS in assessing muscle invasion by bladder cancer: a multicenter prospective study.

OBJECTIVE: To assess diagnostic validity and reliability of VI-RADS in predicting muscle invasion by bladder cancer (BCa) and evaluate reviewer acceptance of VI-RADS for clinical routine. METHODS: A prospective multicenter study enrolled 331 patients with suspected/untreated BCa who underwent preoperative multiparametric MRI examination (mp-MRI) of the urinary bladder. Four experienced radiologists independently evaluated all mp-MRI using VI-RADS. The diagnostic validity of VI-RADS for predicting muscle invasion by BCa was calculated using histopathology of the first transurethral resection bladder tumor (TURBT) and second TURBT as the reference standards. The kappa statistics (κ) were applied to assess the interreader agreement (IRA). Reviewer acceptance was evaluated with questionnaires. RESULTS: The risk of muscle invasion in VI-RADS 2, 3, 4, and 5 after the first and second TURBT was 21.8%, 45.8%, 69.6%, and 96.4% and 24.4%, 58.3%, 87%, and 99.2%, respectively. The overall diagnostic validity of VI-RADS was high. The optimal cut-off value for predicting muscle invasion after first TURBT was > VI-RADS 3 (sensitivity = 84.1% and specificity = 92.3%), and after second TURBT was > VI-RADS 2 (sensitivity = 89.9% and specificity = 90.1%). VI-RADS categorization showed a very good IRA (κ = 0.93). Reviewers fully agreed with the statement, "The application of structured reporting of bladder tumor should be encouraged" (score = 20). CONCLUSIONS: VI-RADS showed high diagnostic validity and reliability for predicting muscle invasion by BCa, especially VI-RADS 4 and 5. However, VI-RADS 2 and 3 require further modifications to enhance their diagnostic validity. VI-RADS is highly encouraged to be used in daily practice. KEY POINTS: • VI-RADS showed high diagnostic validity and reliability in predicting BCa muscle invasion, especially VI-RADS 4 and 5. • In VI-RADS 2 and 3, we observed a notable percentage of BCa with muscle invasion and this would require further modifications to enhance the diagnostic validity for these scores. • Overall VI-RADS is well-accepted by radiologists who recommend it for daily practice.

Prognostic Significance of VEGF and HIF-1 α in Hepatocellular Carcinoma Patients Receiving Sorafenib Versus Metformin Sorafenib Combination.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem. HCC burden has been increasing in Egypt in the past 10 years. Most HCC cases are diagnosed at an advanced stage with limited treatment options. Sorafenib is the standard therapy for advanced HCC, but the effectiveness is not satisfied. Metformin may decrease the risk of HCC development in diabetic patients, reduces tumor invasion, and augments sensitivity to sorafenib; however, safety and efficacy of combined treatment are still unclear. As HCC is characterized by high vascularity, and vascular endothelial growth factor (VEGF) plays an important role in vascularization, many studies questioned if VEGF and HIF-1 α could offer information about HCC response to sorafenib. We conducted this study to assess the benefits from adding metformin to HCC treatment, and appraise the role of VEGF and HIF-1 α in HCC prognosis. METHOD: This was a prospective, randomized study in which 80 advanced measurable patients consecutively treated with sorafenib plus metformin (arm A) or sorafenib alone (arm B), prognostic value of plasma, and tissue levels of VEGF and HIF-1 α were evaluated. RESULTS: We enrolled 61 men and 19 women with a median age of 60 years (range 49-68 years). Fifty-seven patients had Child-Pugh A while 23 had early B, the most common etiology of liver disease was hepatitis C (86%). Sixty percent of patients were diabetic. No significant difference was detected between arm A and arm B regarding response to treatment (p = 0.5), time to disease progression (p = 0.3), or overall survival (p = 0.6). Low VEGF and HIF-1 α plasma levels were significantly associated with better treatment response (p < 0.001 for both), and higher OS (p < 0.001). Patients with high expressions of VEGF and HIF in HCC tissue had significantly poor treatment outcome (p < 0.001, p = 0.03, respectively), and poor OS (p < 0.001, p < 0.001, respectively). CONCLUSIONS: No superior efficacy of adding metformin to sorafenib in HCC treatment. VEGF and HIF-1 α had promising prognostic value in HCC.