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Background: BRCA1 and BRCA2 have been identified as high-penetrance breast cancer predisposition genes, but they only account for a small fraction of the inherited component of breast cancer. To explain the remaining cases, a polygenic model with a large number of low- to moderate-penetrance genes have been proposed; one of these, is the CHEK2 gene (Checkpoint Kinase 2). The objective of this study was to determine the role of the CHEK2 gene, specifically the c.1100delC mutation in familial breast cancer susceptibility in Colombian patients. Methods: We screened 131 high-risk breast and/or ovarian cancer patients (negative for mutations in BRCA1 and BRCA2) and 131 controls for the germline mutation CHEK2 c.1100delC by allele-specific PCR. Results: None of the cases or controls showed the CHEK2 c.1100delC mutation, neither as a homozygote nor as a heterozygote. Conclusions: Our results suggest that the CHEK2 c.1100delC mutation is not a risk factor for genetic susceptibility to familial breast or ovarian cancer in the Colombian population. The absence of the CHEK2 c .1100delC mutation in our population show the importance of considering ethnic background before offering a genetic test.

Breast and endometrial cancer are the most common types of female cancers, but the incidence of both of these malignancies in a single patient is a rare event. Multiple primary malignancy has been increasingly reported over the past decade, and double primary cancer is considered as the most common type. In this study, we present a 53-year-old woman with synchronous primary malignancy of breast and endometrium. This patient had a history of breast and endometrial cancer in her family. Mammography and chest CT of the patient revealed a mass in the right breast and left supraclavicular region. However, the patient did not want to initiate treatment. Subsequently, the patient returned with a chief complaint of persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient revealed a huge soft tissue mass in the pelvic cavity. She underwent hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded the full thickness of uterine wall. Since this type of malignancy is rare and several risk factors are associated with it, it is worth being considered by clinicians when making decisions about screening or strategy for prevention.

Metastases are responsible for most cancer-related deaths. The kinetics of tumor relapse is highly heterogeneous, ranging from recurrences shortly after diagnosis to years or even decades after the initial treatment. This subclinical period is known as tumor dormancy, in which residual disease remains in an undetectable state before finally appearing as an overtly proliferative metastasis. Despite recent advances in our understanding of the molecular mechanisms leading to tumor dormancy, it is still a poorly understood phase of cancer progression, which limits opportunities for the design of successful therapeutic interventions. The influence of the tumor microenvironment at the metastatic site and anti-metastatic immune responses have been shown to play a crucial role in the onset and maintenance of metastatic dormancy. However, there is still a significant gap in our understanding of how dormant cells remain viable in a quiescent state for long periods of time. Here, we review the latest experimental evidence shedding light on the biological processes that enable dormant tumor cells to endure the multiple stresses encountered at the metastatic site.

Breast and endometrial cancer are the most common types of female cancers, but the incidence of both of these malignancies in a single patient is a rare event. Multiple primary malignancy has been increasingly reported over the past decade, and double primary cancer is considered as the most common type. In this study, we present a 53-year-old woman with synchronous primary malignancy of breast and endometrium. This patient had a history of breast and endometrial cancer in her family. Mammography and chest CT of the patient revealed a mass in the right breast and left supraclavicular region. However, the patient did not want to initiate treatment. Subsequently, the patient returned with a chief complaint of persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient revealed a huge soft tissue mass in the pelvic cavity. She underwent hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded the full thickness of uterine wall. Since this type of malignancy is rare and several risk factors are associated with it, it is worth being considered by clinicians when making decisions about screening or strategy for prevention.

Breast and endometrial cancer are the most common types of female cancers, but the incidence of both of these malignancies in a single patient is a rare event. Multiple primary malignancy has been increasingly reported over the past decade, and double primary cancer is considered as the most common type. In this study, we present a 53-year-old woman with synchronous primary malignancy of breast and endometrium. This patient had a history of breast and endometrial cancer in her family. Mammography and chest CT of the patient revealed a mass in the right breast and left supraclavicular region. However, the patient did not want to initiate treatment. Subsequently, the patient returned with a chief complaint of persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient revealed a huge soft tissue mass in the pelvic cavity. She underwent hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded the full thickness of uterine wall. Since this type of malignancy is rare and several risk factors are associated with it, it is worth being considered by clinicians when making decisions about screening or strategy for prevention.

Age is the most important risk factor for the occurrence of cancer, and a declining mortality from heart disease and other non-cancer causes leaves an older population that is at high risk of developing cancer. Choosing the optimal treatment for older cancer patients may be a challenge. Firstly, older age and associated factors such as comorbidities, functional limitations, and cognitive impairment are risk factors for adverse effects of cancer treatment. Secondly, older patients are often excluded from clinical trials, and current clinical guidelines rarely address how to manage cancer in patients who have comorbidities or functional limitations. The importance of incorporating frailty assessment into the preoperative evaluation of older surgical patients has received increasing attention over the last 10 years. Furthermore, studies that include endpoints such as functional status, cognitive status, and quality of life beyond the standard endpoints, i.e. postoperative morbidity and mortality, are starting to emerge. This review looks at recent evidence regarding geriatric assessment and frailty in older surgical cancer patients and provides a summary of newer studies in colorectal, liver, pancreatic, and gynecological cancer and renal and central nervous system tumors.

We currently have the knowledge and experience to prevent much of human papillomavirus (HPV)-related disease burden globally. In many countries where prophylactic HPV vaccination programs have been adopted as highly effective public health programs with good vaccine coverage, we are already seeing, in real-world settings, reduction of vaccine-related HPV-type infections, genital warts and cervical pre-cancers with potential reductions in vulvar, vaginal and anal pre-cancers. Moreover, we are seeing a change in cervical screening paradigms, as HPV-based screening programs now have strong evidence to support their use as more sensitive ways to detect underlying cervical abnormalities, as compared with conventional cervical cytology. This article describes the impact of prophylactic vaccination on these outcomes and in settings where these vaccines have been implemented in national immunisation programs. Given the successes seen to date and the availability of essential tools, there has been a global push to ensure that every woman has access to effective cervical screening and every girl has the opportunity for primary prevention through vaccination. A gender-neutral approach by offering vaccination to young boys has also been adopted by some countries and is worthy of consideration given that HPV-related cancers also affect males. Furthermore, vaccination of young boys has the advantage of reducing the risk of HPV transmission to sexual partners, lowering the infectious pool of HPV in the general population and ultimately HPV-related diseases for both genders. Therefore, it is appropriate that all countries consider and promote national guidelines and programs to prevent HPV-related diseases.

High-risk human papillomaviruses (hrHPV) are responsible for anogenital and oropharyngeal cancers, which together account for at least 5% of cancers worldwide. Industrialised nations have benefitted from highly effective screening for the prevention of cervical cancer in recent decades, yet this vital intervention remains inaccessible to millions of women in low- and middle-income countries (LMICs), who bear the greatest burden of HPV disease. While there is an urgent need to increase investment in basic health infrastructure and rollout of prophylactic vaccination, there are now unprecedented opportunities to exploit recent scientific and technological advances in screening and treatment of pre-invasive hrHPV lesions and to adapt them for delivery at scale in resource-limited settings. In addition, non-surgical approaches to the treatment of cervical intraepithelial neoplasia and other hrHPV lesions are showing encouraging results in clinical trials of therapeutic vaccines and antiviral agents. Finally, the use of next-generation sequencing to characterise the vaginal microbial environment is beginning to shed light on host factors that may influence the natural history of HPV infections. In this article, we focus on recent advances in these areas and discuss their potential for impact on HPV disease.

Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas.

Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.

The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment.

Introduction : Hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming a standard therapy in the treatment of peritoneal carcinomatosis (PC). Compared to systemic chemotherapy, HIPEC improves survival in patients with PC. This therapy has high morbidity rates (up to 41%). In vitro it has been demonstrated that hyperthermia has a toxic effect on malign cells. However, hyperthermia also affects normal tissue. To my knowledge, any additional effect of hyperthermia combined with chemotherapy has never been demonstrated in a clinical setting. In this study, the effects of hyperthermia on outcome and survival were analyzed. Methods : Patients with PC from any origin who were treated with HIPEC were included in this retrospective, non-randomized study. Data on patient characteristics, tumor characteristics, features of the surgery and postoperative complications were extracted from patient files. Models predicting time to removal of nasogastric tube (TRNT), post-operative major complications, the occurrence of anastomotic leaks and post-operative survival were built, using negative binomial regression, logistic regression or Cox proportional hazards regression as appropriate. Results: 138 patients treated with HIPEC were included. Maximal temperature during the operation was not statistically significantly associated with anastomotic leaks or post-operative major complications. Maximal temperature during the operation was negatively associated with post-operative survival (P=0.01). Conclusion : The results suggest that hyperthermia may negatively affect survival in patients who are treated with HIPEC for PC of various origins. This study has the classical limitations of a retrospective study. Therefore, randomized trials are required to confirm the results.

Uterine leiomyomas (fibroids) are the most prevalent medical problem of the female reproductive tract, but there are few non-surgical treatment options. Although many advances in the understanding of the molecular components of these tumors have occurred over the past five years, an effective pharmaceutical approach remains elusive. Further, there is currently no clinical method to distinguish a benign uterine leiomyoma from a malignant leiomyosarcoma prior to treatment, a pressing need given concerns about the use of the power morcellator for minimally invasive surgery. This paper reviews current studies regarding the molecular biology of uterine fibroids, discusses non-surgical approaches and suggests new cutting-edge therapeutic and diagnostic approaches.

In this paper we report two interesting cases of metastatic ovarian cancer. The first case is a patient who developed rectal and breast metastases mimicking an inflammatory breast cancer. In the second case, subclinical breast and axillary lymph node metastases were revealed by PET/CT. Metastases in the breast originating from solid tumors are extremely rare. The ovarian primitive is the fourth most common origin. The occurrence of breast metastasis is associated with an advanced disease and a poor prognosis. Their incidence is increasing since they are found more often due to better imaging techniques and to better treatment that, accordingly, improve patients’ survival. Thus, unusual sites of metastases are more and more reported. Indeed, some authors reported the occurrence of colorectal metastases from ovarian cancer. However, they remain much less frequent.

In this paper we report two interesting cases of metastatic ovarian cancer. The first case is a patient who developed rectal and breast metastases mimicking an inflammatory breast cancer. In the second case, subclinical breast and axillary lymph node metastases were revealed by PET/CT. Metastases in the breast originating from solid tumors are extremely rare. The ovarian primitive is the fourth most common origin. The occurrence of breast metastasis is associated with an advanced disease and a poor prognosis. Their incidence is increasing since they are found more often due to better imaging techniques and to better treatment that, accordingly, improve patients’ survival. Thus, unusual sites of metastases are more and more reported. Indeed, some authors reported the occurrence of colorectal metastases from ovarian cancer. However, they remain much less frequent.

Sustained estrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. Unexpectedly, physiological level of estrogen together with a novel IKKα inhibitor BAY11-7082 could effectively induce cell apoptosis in ER-positive breast cancer cells, suggesting combining estrogen with IKKα inhibition may be beneficial for breast cancer patients. This opinion article touches upon the dual role estrogen played in inducing cancer cell death and asks whether use of estrogen in combination with IKKα-targeted therapy would be possible reconsider the newly identified crosstalk between ER and NFκB pathway which can be utilized to switch the effects of estrogen on cell death.

Estrogen has profound effects on growth, differentiation and function in male and female reproductive systems, and it is important for bone density, brain function and cholesterol mobilization. Despite beneficial estrogen functions, sustained estrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. This opinion article touches upon the dual role estrogen played in cancer and asks whether the use of estrogen in combination with other targeted therapy would be possible, considering the newly identified crosstalk pathway which can switch the effects of estrogen.

Introduction : Hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming a standard therapy in the treatment of peritoneal carcinomatosis (PC). Compared to systemic chemotherapy, HIPEC improves survival in patients with PC. This therapy has high morbidity rates (up to 41%). In vitro it has been demonstrated that hyperthermia has a toxic effect on malign cells. However, hyperthermia also affects normal tissue. To my knowledge, any additional effect of hyperthermia combined with chemotherapy has never been demonstrated in a clinical setting. In this study, the effects of hyperthermia on outcome and survival were analyzed. Methods : Patients with PC from any origin who were treated with HIPEC were included in this retrospective, non-randomized study. Data on patient characteristics, tumor characteristics, features of the surgery and postoperative complications were extracted from patient files. Models predicting time to removal of nasogastric tube (TRNT), post-operative major complications, the occurrence of anastomotic leaks and post-operative survival were built, using negative binomial regression, logistic regression or Cox proportional hazards regression as appropriate. Results: 138 patients treated with HIPEC were included. Maximal temperature during the operation was not statistically significantly associated with anastomotic leaks or post-operative major complications. Maximal temperature during the operation was negatively associated with post-operative survival (P=0.01). Conclusion : The results suggest that hyperthermia may negatively affect survival in patients who are treated with HIPEC for PC of various origins. This study has the classical limitations of a retrospective study. Therefore, randomized trials are required to confirm the results.

Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo is critical but challenging. Intravital microscopy (IVM) of subcutaneous tumors provides dynamic, continuous, long-term imaging at high resolution. Although popular, subcutaneous tumor models are often criticized for being ectopic and lacking orthotopic tissue microenvironments critical for proper development. Similar IVM of orthotopic and especially spontaneous tumors is seldom possible. Here, we generate and characterize tumor models in mice for breast, lung, prostate and ovarian cancer by co-engrafting tumor spheroids with orthotopic tissue in dorsal skin window chambers for IVM. We use tumor cells and tissue, both genetically engineered to express distinct fluorescent proteins, in order to distinguish neoplastic cells from engrafted tissue. IVM of this new, two-colored model reveals classic tumor morphology with red tumor cell nests surrounded by green stromal elements. The co-implanted tissue forms the supportive stroma and vasculature of these tumors. Tumor growth and angiogenesis are more robust when tumor cells are co-implanted with orthotopic tissue versus other tissues, or in the skin alone. The orthotopic tissue promotes tumor cell mitosis over apoptosis. With time, tumor cells can adapt to new environments and ultimately even grow better in the non-orthotopic tissue over the original orthotopic tissue. These models offer a significant advance by recreating an orthotopic microenvironment in an ectopic location that is still easy to image by IVM. These “ectopic-orthotopic” models provide an exceptional way to study tumor and stroma cells in cancer, and directly show the critical importance of microenvironment in the development of multiple tumors.

A 17-year-old woman had undergone exploratory laparotomy because of a huge cystic pelviabdominal mass equivalent of 36 weeks' gestation. A closed system drainage maneuver was applied via using a laparoscopic trocar to drain a revealed large left paraovarian cyst. This maneuver was found to be a simple and effective method to safely aspirate giant paraovarian cysts; thus allowing their total excision.

Tumor models are needed to study cancer. Noninvasive imaging of tumors under native conditions in vivo is critical but challenging. Intravital microscopy (IVM) of subcutaneous tumors provides dynamic, continuous, long-term imaging at high resolution. Although popular, subcutaneous tumor models are often criticized for being ectopic and lacking orthotopic tissue microenvironments critical for proper development. Similar IVM of orthotopic and especially spontaneous tumors is seldom possible. Here, we generate and characterize tumor models in mice for breast, lung, prostate and ovarian cancer by co-engrafting tumor spheroids with orthotopic tissue in dorsal skin window chambers for IVM. We use tumor cells and tissue, both genetically engineered to express distinct fluorescent proteins, in order to distinguish neoplastic cells from engrafted tissue. IVM of this new, two-colored model reveals classic tumor morphology with red tumor cell nests surrounded by green stromal elements. The co-implanted tissue forms the supportive stroma and vasculature of these tumors. Tumor growth and angiogenesis are more robust when tumor cells are co-implanted with orthotopic tissue versus other tissues, or in the skin alone. The orthotopic tissue promotes tumor cell mitosis over apoptosis. With time, tumor cells can adapt to new environments and ultimately even grow better in the non-orthotopic tissue over the original orthotopic tissue. These models offer a significant advance by recreating an orthotopic microenvironment in an ectopic location that is still easy to image by IVM. These “ectopic-orthotopic” models provide an exceptional way to study tumor and stroma cells in cancer, and directly show the critical importance of microenvironment in the development of multiple tumors.

Surgery remains a main part of the treatment of most solid tumors. Paradoxically, rapid disease progression may be a consequence of surgery in patients presenting with a dysregulated inflammatory response, and increased angiogenesis consequent to a suppressed antitumoral immune response. Physicians taking care of cancer patients should be aware of the important findings that indicate that analgesic techniques could play a role in these phenomena.

A 17-year-old woman had undergone exploratory laparotomy because of a huge cystic pelviabdominal mass equivalent of 36 weeks' gestation. A closed system drainage maneuver was applied via using a laparoscopic trocar to drain a revealed large left paraovarian cyst. This maneuver was found to be a simple and effective method to safely aspirate giant paraovarian cysts; thus allowing their total excision.