A phase 2 study of dasatinib in recurrent clear cell carcinoma of the ovary, fallopian tube, peritoneum or endometrium: NRG oncology/gynecologic oncology group study 0283.

OBJECTIVE: Gynecologic cancers are traditionally managed according to their presumed site of origin, without regard to the underlying histologic subtype. Clear cell histology is associated with chemotherapy refractoriness and poor survival. Mutations in SWI/SNF chromatin remodeling complex member ARID1A, which encodes for BAF250a protein, are common in clear cell and endometriosis-associated endometrioid carcinomas. High-throughput cell-based drug screening predicted activity of dasatinib, a tyrosine kinase inhibitor, in ARID1A-mutant clear cell carcinoma. METHODS: We conducted a phase 2 clinical trial of dasatinib 140 mg once daily by mouth in patients with recurrent or persistent ovarian and endometrial clear cell carcinoma. Patients with measurable disease were enrolled and then assigned to biomarker-defined populations based on BAF250a immunohistochemistry. The translational endpoints included broad next-generation sequencing to assess concordance of protein expression and treatment outcomes. RESULTS: Twenty-eight patients, 15 of whom had tumors with retained BAF250a and 13 with loss of BAF250a were evaluable for treatment response and safety. The most common grade 3 adverse events were anemia, fatigue, dyspnea, hyponatremia, pleural effusion, and vomiting. One patient had a partial response, eight (28%) had stable disease, and 15 (53.6%) had disease progression. Twenty-three patients had next-generation sequencing results; 13 had a pathogenic ARID1A alteration. PIK3CA mutations were more prevalent in ARID1A-mutant tumors, while TP53 mutations were more prevalent in ARID1A wild-type tumors. CONCLUSIONS: Dasatinib was not an effective single-agent treatment for recurrent or persistent ovarian and endometrial clear cell carcinoma. Studies are urgently needed for this rare gynecologic subtype.

A multi-ethnic analysis of immune-related gene expression signatures in patients with ovarian clear cell carcinoma.

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and the UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation, and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1, and CTLA4 expression, and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

[Clear Cell Carcinoma of Cervix in a 12-Year-Old Girl: A Case Report].

The 12-year-old patient was admitted to the hospital on September 19, 2019 for "vaginal bleeding for 2 + months and pelvic mass to be diagnosed". The patient and her family explicitly denied any previous history of diethylstilbestrol exposure. After admission, relevant examinations were conducted and hysteroscopic exploration was performed under general anesthesia. During the procedure, cervical neoplasms were extracted and pathology results indicated cervical cancer. Then, extensive transabdominal hysterectomy+bilateral salpingectomy+bilateral ovarian transposition+pelvic lymph node dissection+para-aortic lymph node sampling were performed. Postoperative pathology analysis of the removed tissue showed that clear cell carcinoma of cervix (CCAC) had infiltrated into 1/3 of the cervical stroma and there was downward involvement of the vaginal wall; the cancer metastasized to the left obturator lymph node and the left internal and external iliac lymph nodes. Immunohistochemical staining of the removed tissue showed the following results: cytokeratin 7 (+), cytokeratin 20 (-), Napsin-A (+), cell adhesion molecule CD15 (+), heatocyte nuclear factor-1 ß (+), Sal-like protein 4 (-), tumor suppressor gene P16 protein (+), estrogen receptor (+), progesterone receptor (-), tumor suppressor gene P53 protein (focal positive), tumor suppressor gene WT-1 protein (-) and Ki67 antigen (about 40% positive). The patient was diagnosed with CCAC stage ⅢC1p. Four cycles of postoperative systemic chemotherapy (fluorouracil+cisplatin) and 25 times of three-dimensional afterloading radiotherapy were performed. The patient did follow-up visits and did not show obvious signs of recurrence. The clinical manifestations of this disease are basically the same as those of cervical squamous cell carcinoma, and if the patient is younger, it can be easily misdiagnosed as dysfunctional uterine bleeding, indicating the need for differential diagnosis.

Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End Results Cohort Study, 2000-2013.

BACKGROUND: We sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model. RESULTS: In all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS-81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359-0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage. CONCLUSIONS: Adjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS.

Identification of molecular characteristics of FUT8 and alteration of core fucosylation in kidney renal clear cell cancer.

BACKGROUND: Kidney renal clear cell cancer (KIRC) is a type of urological cancer that occurs worldwide. Core fucosylation (CF), as the most common post-translational modification, is involved in the tumorigenesis. METHODS: The alterations of CF-related genes were summarized in pan-cancer. The "ConsensusClusterPlus" package was utilized to identify two CF-related KIRC subtypes. The "ssgsea" function was chosen to estimate the CF score, signaling pathways and cell deaths. Multiple algorithms were applied to assess immune responses. The "oncoPredict" was utilized to estimate the drug sensitivity. The IHC and subgroup analysis was performed to reveal the molecular features of FUT8. Single-cell RNA sequencing (scRNA-seq) data were scrutinized to evaluate the CF state. RESULTS: In pan-cancer, there was a noticeable alteration in the expression of CF-related genes. In KIRC, two CF-related subtypes (i.e., C1, C2) were obtained. In comparison to C2, C1 exhibited a higher CF score and correlated with poorer overall survival. Additionally, the TME of C2 demonstrated increased activity in neutrophils, macrophages, myeloid dendritic cells, and B cells, alongside a higher presence of silent mast cells, NK cells, and endothelial cells. Compared to normal samples, higher expression of FUT8 is observed in KIRC. The mutation of SETD2 was more frequent in low-FUT8 samples while the mutation of DNAH9 was more frequent in high-FUT8 samples. scRNA-seq analyses revealed that the CF score was predominantly higher in endothelial cells and fibroblast cells. CONCLUSIONS: Two CF-related subtypes with distinct prognosis and TME were identified in KIRC. FUT8 exhibited elevated expression in KIRC samples.

AI predictive modeling of survival outcomes for renal cancer patients undergoing targeted therapy.

Renal clear cell cancer (RCC) is a complex disease that is challenging to predict patient outcomes. Despite improvements with targeted therapy, personalized treatment planning is still needed. Artificial intelligence (AI) can help address this challenge by developing predictive models that accurately forecast patient survival periods. With AI-powered decision support, clinicians can provide patients with tailored treatment plans, enhancing treatment efficacy and quality of life. The study analyzed 267 patients with renal clear cell carcinoma, focusing on 26 who received targeted drug therapy. The data was refined by excluding 8 patients without enhanced CT scans. The research team categorized patients into two groups based on their expected lifespan: Group 1 (over 3 years) and Group 2 (under 3 years). The UPerNet algorithm was used to extract features from CT tumor markers, validating their effectiveness. These features were then used to develop an AI-based predictive model trained on the dataset. The developed AI model demonstrated remarkable accuracy, achieving a rate of 93.66% in Group 1 and 94.14% in Group 2. In conclusion, our study demonstrates the potential of AI technology in predicting the survival time of RCC patients undergoing targeted drug therapy. The established prediction model exhibits high predictive accuracy and stability, serving as a valuable tool for clinicians to facilitate the development of more personalized treatment plans for patients. This study highlights the importance of integrating AI technology in clinical decision-making, enabling patients to receive more effective and targeted treatment plans that enhance their overall quality of life.

Descending Colon Metastasis of Renal Cell Carcinoma: An Unusual Site of Metastasis.

Renal cell carcinoma (RCC) has a high metastatic potential. While metastasis to common sites like the lungs, liver, bones, and brain is well-documented, metastasis to the colon, particularly the descending colon, remains an uncommon occurrence. When RCC does metastasize to the gastrointestinal tract, it commonly spreads to the small bowel and stomach. There are few cases reported in literature involving RCC metastasis to the colon. The commonly affected areas within the colon include the rectosigmoid colon, splenic flexure, and transverse colon. We describe an 87-year-old male with a history of stage III RCC diagnosed three years ago, followed by left-sided nephroureterectomy, partial adrenalectomy, and perinephric lymph node dissection. He presented to the emergency department (ED) with melena and generalized abdominal pain for one week. Stool occult blood was positive. Computed tomography (CT) of the abdomen was significant for stable postsurgical changes related to prior left nephrectomy and colonic mass at the proximal descending colon. A colonoscopy revealed a necrotic appearing friable mass in the descending colon. The pathology of the mass revealed proliferated atypical cells positive for paired box 8 (PAX8), a cluster of differentiation 10 (CD10), RCC, and pan-cytokeratin and negative for caudal-type homeobox 2 (CDX2), thyroid transcription factor-1 (TTF-1), and a cluster of differentiation 68 (CD68), consistent with metastatic RCC.

Metastatic Clear Cell Carcinoma of Unknown Primary Origin in an Elderly Female Patient With Paraneoplastic Hypercalcemia.

Metastatic clear cell carcinoma (mCCC) is a rare histological subtype of cancer with ovarian and renal origins most common primary sites. Cancer of unknown primary origin (CUP) is a rare type of cancer in the United States and the most common histologic subtypes are adenocarcinoma, squamous cell cancer, and neuroendocrine cancer. We are presenting a rare case of an 86-year-old female patient with mCCC of unknown origin, biopsy and staining showed renal and ovarian in the differential of primary cancer type. However, the patient did not survive the aggressive nature of mCCC and was unable to get any trials of chemotherapy. Primary sites of adenocarcinoma of unknown origin are most common in the breast, lung, pancreas, prostate, colon, and liver. In most cases, empiric chemotherapy with platinum-based agents is the standard of care but needs more data to manage CUP, making it difficult to identify the primary site.

Risk factors for omental metastasis and the effect of omentectomy on survival in type 2 endometrial cancer patients.

To investigate the risk factors for occult omental metastasis and the effect of omentectomy on the survival of type 2 endometrial cancer (EC) patients. This study enrolled patients who were diagnosed with high-risk (grade 3, serous, clear cell, undifferentiated, carcinosarcoma, or mixed type) EC between 2000 and 2021 and underwent surgery in our center. Data from 482 patients were analyzed retrospectively. Omentectomy was performed in 405 (84.0%) patients. Omental metastases were detected in 61 (12.7%) patients. Eighteen (29.5%) of these metastases were occult. Adnexal involvement, malignant cytology, and peritoneal spread were independent risk factors for omental metastasis. The 5-year overall survival (OS) rate was 59.5% in patients who underwent omentectomy and 64.7% in those who did not (P = 0.558). In patients with and without omental metastases, the overall 5-year OS rates were 34.9% and 63.5%, respectively (P < 0.001). The 5-year OS rates of patients with a normal omentum, gross tumors, and occult metastases were 63.5%, 26.9%, and 52.5%, respectively (P < 0.001). Omental metastases is not uncommon in type II endometrial cancer; approximately one third of patients have occult metastases. Factors - positive cytology, adnexal involvement, and peritoneal involvement are associated with higher probability of omental metastases.

Case Report: Successful immune checkpoint inhibitor-based rechallenge in a patient with advanced renal clear cell cancer.

With the rapidly evolving of immune checkpoint inhibitors (ICIs), it has shown remarkable clinical benefits in treating various cancers. However, immune-related adverse events (irAEs) remain a significant challenge in the management of patients undergoing immunotherapy. There are limited data about immunotherapy re-challenge in patients with renal clear cell cancer who had irAE in the initial ICI therapy. In this study, we reported the case of a patient with advanced renal clear cell cancer who developed serious irAEs but also achieved a partial remission of tumor after ICI combined with pazopanib in the first-line treatment. After intravenous methylprednisolone therapy for two weeks, the patient fully recovered from treatment-related toxicities. After a multidisciplinary treatment (MDT) discussion and a communication with the patient, the decision was made to undergo a new fully humanized programmed death 1 (PD-1) agent, zimberelimab, combined with pazopanib for immune restart therapy. After two cycles of treatment, the patient demonstrated a partial response (PR), and the disease remained in continuous remission without any irAE at our last follow-up after 14 months' treatment. Re-challenging with immunotherapy after irAEs is an emerging strategy that offers the potential for additional clinical benefits to previously responding patients. However, careful patient selection and monitoring are essential to maximize the safety and efficacy of this approach.

Liposomal DQ in Combination with Copper Inhibits ARID1A Mutant Ovarian Cancer Growth.

Therapeutic strategies for ARID1A-mutant ovarian cancers are limited. Higher basal reactive oxygen species (ROS) and lower basal glutathione (GSH) empower the aggressive proliferation ability and strong metastatic property of OCCCs, indicated by the increased marker of epithelial-mesenchymal transition (EMT) and serving the immunosuppressive microenvironment. However, the aberrant redox homeostasis also empowers the sensitivity of DQ-Lipo/Cu in a mutant cell line. DQ, a carbamodithioic acid derivative, generates dithiocarbamate (DDC) in response to ROS, and the chelation of Cu and DDC further generates ROS and provides a ROS cascade. Besides, quinone methide (QM) released by DQ targets the vulnerability of GSH; this effect, plus the increase of ROS, destroys the redox homeostasis and causes cancer cell death. Also importantly, the formed Cu(DDC)2 is a potent cytotoxic anti-cancer drug that successfully induces immunogenic cell death (ICD). The synergistic effect of EMT regulation and ICD will contribute to managing cancer metastasis and possible drug resistance. In summary, our DQ-Lipo/Cu shows promising inhibitory effects in cancer proliferation, EMT markers, and "heat" the immune response.

Etiologies, Gross Appearance, Histopathological Patterns, Prognosis, and Best Treatments for Subtypes of Renal Carcinoma: An Educational Review.

Of all primary renal neoplasms, 80-85% are renal cell carcinomas (RCCs), which develop in the renal cortex. There are more than 10 histological and molecular subtypes of the disease, the most frequent of which is clear cell RCC, which also causes most cancer-related deaths. Other renal neoplasms, including urothelial carcinoma, Wilms' tumor, and renal sarcoma, each affect a particular age group and have specific gross and histological features. Due to the genetic susceptibility of each of these malignancies, early mutation discovery is necessary for the early detection of a tumor. Furthermore, it is crucial to avoid environmental factors leading to each type. This study provides relatively detailed and essential information regarding each subtype of renal carcinoma.

Prognostic Characteristics and Immune Effects of N6-Methyladenosine and 5-Methylcytosine-Related Regulatory Factors in Clear Cell Renal Cell Carcinoma.

In recent years, methylation modification regulators have been found to have essential roles in various tumor mechanisms. However, the relationships between N6-methyladenosine (m6A) and 5-methylcytosine (m5C) regulators and clear cell renal cell carcinoma (ccRCC) remain unknown. This study investigated these relationships using the data from The Cancer Genome Atlas database. We calculated risk scores using a Lasso regression analysis and divided the patient samples into two risk groups (tumor vs. normal tissues). Furthermore, we used univariate and multivariate Cox analyses to determine independent prognostic indicators and explore correlations between the regulatory factors and immune infiltrating cell characteristics. Finally, quantitative reverse transcriptase-polymerase chain reaction (PCR) and The Human Protein Atlas were used to verify signature-related gene expression in clinical samples. We identified expression differences in 35 regulatory factors between the tumor and normal tissue groups. Next, we constructed a five-gene risk score signature (NOP2 nucleolar protein [NOP2], methyltransferase 14, N6-adenosine-methyltransferase subunit [METTL14], NOP2/Sun RNA methyltransferase 5 [NSUN5], heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1], and zinc finger CCCH-type containing 13 [ZC3H13]) using the screening criteria (p < 0.01), and then divided the cases into high- and low-risk groups based on their median risk score. We also screened for independent prognostic factors related to age, tumor grade, and risk score. Furthermore, we constructed a Norman diagram prognostic model by combining two clinicopathological characteristics, which demonstrated good prediction efficiency with prognostic markers. Then, we used a single-sample gene set enrichment analysis and the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method to evaluate the tumor microenvironment of the regulatory factor prognostic characteristics. Moreover, we evaluated five risk subgroups with different genetic signatures for personalized prognoses. Finally, we analyzed the immunotherapy and immune infiltration response and demonstrated that the high-risk group was more sensitive to immunotherapy than the low-risk group. The PCR results showed that NSUN5 and HNRNPA2B1 expression was higher in tumor tissues than in normal tissues. In conclusion, we identified five m6A and m5C regulatory factors that might be promising biomarkers for future research.

Primary Laparoscopic Surgery Does Not Affect the Prognosis of Early-Stage Ovarian Clear Cell Cancer.

PURPOSE: Minimally invasive surgery (MIS) is performed frequently in early-stage ovarian cancer patients, especially in ovarian clear cell carcinoma (OCCC). The aim of this study was to investigate whether primary laparoscopic surgery influences prognosis in patients with early-stage OCCC. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I  OCCC were retrospectively reviewed in two hospitals between April 2010 and August 2020. Clinical data were abstracted, and patients were followed up until February 2021. Patients were divided into open surgery (laparotomy) and laparoscopy groups, and the Kaplan-Meier method was applied to compare progression-free survival (PFS) and overall survival (OS) between the groups. Statistical differences were determined by the Log rank test. RESULTS: Eighty-nine patients were included in the study; 20 (22.5%) and 69 (77.5%) patients underwent laparoscopic and open surgery, respectively. The patients' characteristics were well-balanced except that patients in the laparoscopy group tended to have smaller tumors and lower frequency of omentectomy and lymphadenectomy compared with the open surgery group. The median follow-up duration was 42.6 and 36.5 months in the laparoscopy and open surgery groups, respectively. Nine (10.1%) patients developed recurrence, and 4 (4.5%) died of the disease; all in the open surgery group. The estimated 2-year PFS rates were 100.0% and 90.1%, and the estimated 5-year OS rates were 100.0% and 91.9% in the laparoscopy and open surgery groups, respectively. No significant survival differences were found between the groups. CONCLUSION: Survival was not compromised when primary laparoscopic surgery was performed in early-stage OCCC patients. A well-designed randomized controlled trial is warranted.

Therapeutic Role of Retroperitoneal Lymphadenectomy in 170 Patients With Ovarian Clear Cell Cancer.

INTRODUCTION: We evaluated the therapeutic role of retroperitoneal lymphadenectomy in patients with ovarian clear cell cancer (OCCC). MATERIALS AND METHODS: We retrospectively reviewed 170 OCCC patients diagnosed at two hospitals in China between April 2010 and August 2020. Clinical data were abstracted, and patients were followed until February 2021. Patients were divided into retroperitoneal lymphadenectomy and no lymphadenectomy groups. The Kaplan-Meier method was used to compare progression-free (PFS) and overall survival (OS) between the two groups. Statistical differences were determined by the log-rank test. The COX proportional hazards regression model was applied to identify predictors of tumor recurrence. RESULTS: The median age was 52 years; 90 (52.9%) and 80 (47.1%) patients were diagnosed as early and advanced stage, respectively. Clinically positive and negative nodes was found in 40 (23.5%) and 119 (70.0%) patients, respectively. Of all the 170 patients, 124 (72.9%) patients underwent retroperitoneal lymphadenectomy, while 46 (27.1%) did not. The estimated 2-year PFS and 5-year OS rates were 71.4% and 65.9% in the lymphadenectomy group, and 72.0% and 73.7% in no lymphadenectomy group (p = 0.566 and 0.669, respectively). There was also no difference in survival between the two groups when subgroup analysis was performed stratified by early and advanced stage, or in patients with clinically negative nodes. Multivariate analysis showed that retroperitoneal lymphadenectomy were not an independent predictor of tumor recurrence. CONCLUSION: Retroperitoneal lymphadenectomy provided no survival benefit in patients diagnosed with OCCC. A prospective clinical trial is needed to confirm the present results.

Primary Clear Cell Carcinoma of the Pancreas: A Systematic Review.

Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of the molecular drive behind these neoplasms, leading to tangible therapeutic evolution and promising prognostic implications. However, pancreatic cancer remains a highly lethal disease. With recent discoveries, modern medicine has been able to delineate histopathologic subtypes of pancreatic cancer in hopes of improved diagnosis and treatment to improve survival. A once vague entity, clear cell adenocarcinoma of the pancreas, in particular, has been better characterized on a histopathological and molecular level over the past two decades. With novel technological support, this disease has become less inconspicuous, and more researchers have reported its occurrence. Its diagnosis relies heavily on a mix of histological and immunohistochemical clues such as a clear cell cytoplasm and positivity for cytokeratins and other markers. However, new molecular markers, such as hepatocyte nuclear factor 1 beta, have been associated with this entity and may aid in further diagnostic and therapeutic strategies. This review article aims to portray how the identification and description of clear cell adenocarcinoma of the pancreas have evolved over the past few decades and how this may impact future treatment strategies.

Cesarean Section: A Potential and Forgotten Risk for Abdominal Wall Endometriosis.

Cesarean section endometriosis (CSE) can be caused by the iatrogenic deposition of endometrial cells, glands, and stroma during any time of the surgical procedure. It can be asymptomatic or, more frequently, resulting in chronic pain. Our article intends to provide more clinical information on CSE symptomatology, diagnosis, and preventive methods available in the literature, and discuss the malignancy transformation risk. We performed a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We included all types of study designs and selected only English articles from 2016 and forward. A total of 268 patients with abdominal wall endometriosis (AWE) were included in the final review; 260 women had CSE and eight women had endometriosis related to another gynecologic procedure. Attention for suggestive symptoms during anamnesis and the presence of abdominal nodules close to the cesarean scar should raise suspicions of scar endometriosis. In addition, abdominal ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and fine-needle aspiration (FNA) biopsy can be helpful to differentiate from other conditions such as incisional hernias, suture granulomas, or malignant tumors. However, the final diagnosis and treatment is still the complete excision of the tumor. Therefore, additional studies on pathophysiology would help with new preventive methods and less invasive therapeutic options.

An exploratory analysis about cycles of adjuvant chemotherapy and outcomes by substage for stage I ovarian clear cell carcinoma: a single institution retrospective study.

This retrospective cohort study was designed to explore the prognostic impact of adjuvant chemotherapy and tumor substage on stage I ovarian clear cell carcinoma (OCCC). Data of 102 patients with stage I OCCC who underwent surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from February 1999 to December 2018 was retrospectively analyzed. Prognostic factors were evaluated using the Cox Regression Model. The disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method and compared between different groups with the log-rank test. P < 0.05 was considered statistically significant. The median follow-up duration was 40.5 months. Thirty-one (30.4%) patients were at stage IA, and 17 (16.7%), 5 (24.5%) and 17 (16.7%) patients were at stage IC1, IC2 and IC3 respectively. The 5-year and 10-year DFS rates of the entire cohort were 82.8% and 78.8% respectively, and the 5-year OS was 97.9%. Patients at stages ICI (intraoperatively ruptured tumor) and IA had similar DFS (P=0.538, OR=0.024), and that of patients at stages IC2 (tumor ruptured preoperatively or tumor on ovarian surface) or IC3 (ascites or peritoneal washings with positive cytology) was significantly lower (72.6% vs. 95.1%, P=0.039, OR=5.051). The 5-year DFS of patients receiving four (83.9%) and more than four (81.7%) cycles adjuvant chemotherapy were similar. Furthermore, univariate analysis showed that age, tumor size and CA199 levels were significantly correlated with DFS, although none of these variables were identified as independent prognostic factors in the multivariate analysis. In summary, our results suggest that patients with stage I OCCC have overall good prognosis. However, tumor surface involvement or positive cytology can worsen prognosis, and the prognosis may not be improved by more than four cycles chemotherapy following surgery. The remarkable increased CA199 may be a potential indicator of poor prognosis in stage I OCCC.