Search

Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research. [ABSTRACT FROM AUTHOR]

Background: There is little information on which to base the prognostic counselling as to whether an antenatally diagnosed fetal abdominal cyst will grow or shrink, or need surgery. This study aims to provide contemporary data on prenatally diagnosed fetal abdominal cysts in relation to their course and postnatal outcomes. Methods: Fetal abdominal cysts diagnosed over 11 years in a single centre were identified. The gestational age at diagnosis and cyst characteristics at each examination were recorded (size, location, echogenity, septation and vascularity) and follow-up data from postnatal visits were collected. Results: Eighty abdominal cysts were identified antenatally at 28 + 4 weeks (range 11 + 0--38 + 3). Most (87%) were isolated and the majority were pelvic (52%), simple (87.5%) and avascular (100%). Antenatally, 29% resolved spontaneously; 29% reduced in size; 9% were stable and 33% increased in size. Forty-one percent of cysts under 20 mm diameter increased in size, while only 20% of cysts with a diameter of over 40 mm increased in size. The majority of cysts were ovarian in origin (n = 45, 56%), followed by intestinal (n = 15, 18%), choledochal (n = 3, 4%), liver (n = 2, 3%) and renal/adrenal origins (n = 2, 3%), respectively. In 16% (n = 13), the antenatal diagnosis was not obvious. Seventy-five percent of the cysts that persisted postnatally required surgical intervention. Conclusion: Most antenatally diagnosed fetal abdominal cysts were ovarian in origin. Though most disappeared antenatally, nearly three quarters required surgical intervention when present after birth. Cysts of intestinal origin are more difficult to diagnose antenatally and often require surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrioid endometrial cancer is typically estrogen-positive and associated with obesity. Indeed, circulating estrogens are strongly and linearly related to adiposity and increased BMI, which have been identified as the most important risk factors for endometrioid endometrial cancer. However, the relationship between excess body weight and endometrial cancer is more complex, and, besides the unopposed estrogens, involves multiple mechanisms, including hyperinsulinemia, altered adipokines, inflammation, and oxidative stress associated with obesity. We investigated the association between classical tumor prognostic factors (i.e., tumor size (T), and nodal (N) and metastatic (M) status) and the levels of leptin, proinflammatory cytokines, and oxidative stress, together with BMI, among type I (endometrioid) and type II endometrial cancer patients. We found that BMI, leptin, IL-6, and reactive oxygen species correlated with T, N, and M status in type I, but not in type II endometrial cancers. This could open new therapeutic perspectives based on the specific pathogenetic mechanisms involved. Endometrioid endometrial cancer is associated with increased BMI and obesity through multiple pathogenetic mechanisms involving hyperestrogenism, hyperinsulinemia, altered adipokine secretion, inflammation, and oxidative stress. In the present study, we aimed to investigate the correlation between BMI, leptin, the proinflammatory cytokines IL-6 and TNFα, reactive oxygen species (ROS), and the traditional prognostic factors T, G, N and M status among type I endometrioid and type II endometrial cancer patients. We enrolled 305 consecutive endometrial cancer patients prospectively. We found that BMI, leptin, and IL-6 significantly correlated with T status, N status, and M status among endometrioid type I endometrial cancer patients. Among type II endometrial cancer patients, BMI and leptin did not correlate with any of the prognostic parameters, whereas there was a positive correlation between IL-6 and the presence of distant metastases. In the multivariate regression analysis, BMI, leptin, and IL-6 were independent predictive variables of T, N, and M status in endometrioid type I endometrial cancer patients. Our study demonstrates that weight gain, adiposity-related adipokines, inflammation, and oxidative stress correlate with the prognostic factors of endometrioid endometrial cancer. Knowledge of the role of obesity-related biological pathways and mediators in the pathogenesis and prognosis of endometrioid endometrial malignancies may offer new perspectives on combined therapeutic strategies that have not been explored to date, both in the advanced disease and in the adjuvant setting. [ABSTRACT FROM AUTHOR]

Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures. [ABSTRACT FROM AUTHOR]

Since chronic inflammation is associated with ovarian cancer growth and progression, some clinical studies have assessed the association between the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ovarian cancer. The purpose of this study was to assess the dynamic behavior of the NLR during the course of neoadjuvant chemotherapy (NACT) in patients with high grade serous (HGS) advanced epithelial ovarian cancer and assess its correlation with clinical response, progression free survival (PFS) and changes in other inflammatory indexes. We performed a prospective observational study on 161 patients who underwent NACT at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, between 2009 and 2019. NLR was evaluated before starting and after three cycles of NACT. Based on response after three cycles of NACT, patients were divided into two groups: responsive and non-responsive. The primary endpoint was to assess the predictive role of NLR by comparing the responsive and non-responsive patients at baseline and after three cycles of NACT. Secondary endpoints were (a) to correlate NLR with other inflammation markers (CRP, fibrinogen, ferritin, IL-6), albumin, and modified Glasgow Prognostic Score (mGPS) with NLR at baseline and after NACT; (b) to assess the association between NLR and PFS. We found that the NLR value at baseline was not associated with response to NACT, while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response. Moreover, we found that patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in patients with HGS advanced ovarian cancer. This allows for the early identification of non-responsive patients who will need treatment remodeling. [ABSTRACT FROM AUTHOR]

During its evolution, cancer induces changes in patients' energy metabolism that strongly affect the overall clinical state and are responsible for cancer-related cachexia syndrome. To better understand the mechanisms underlying cachexia and its metabolic derangements, research efforts should focus on the events that are driven by the immune system activation during the evolution of neoplastic disease and on the phenomena of "resistance" and "tolerance" typically involved in the human body response against stress, pathogens, or cancer. Indeed, in the case where resistance is not able to eliminate the cancer, tolerance mechanisms can utilize the symptoms of cachexia (anemia, anorexia, and fatigue) to counteract unregulated cancer growth. These notions are also sustained by the evidence that cancer cachexia may be reversible if the resistance and tolerance phases are supported by appropriate antineoplastic treatments. Accordingly, there is no doubt that anticachectic therapies have an irreplaceable role in cases of reversible cancer cachexia where, if harmoniously associated with effective antineoplastic therapies, they can contribute to preserve the quality of life and improve prognosis. Such anticachectic treatments should be based on targeting the complex immunological, inflammatory, and metabolic pathways involved in the complex pathogenesis of cachexia. Meanwhile, the role of the anticachectic therapies is very different in the stage of irreversible cachexia when the available antineoplastic treatments are not able to control the disease and the resistance mechanisms fail with the prevalence of the tolerance phenomena. At this stage, they can be useful only to improve the quality of life, allowing the patient and their family to get a better awareness of the final phases of life, thereby opening to the best spiritual remodulation of the final event, death. [ABSTRACT FROM AUTHOR]

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients. [ABSTRACT FROM AUTHOR]

Bartholin gland adenocarcinoma (BGA) is extremely rare and is characterized by high rates of lymph-node recurrence and distant metastases. No effective palliative treatments are available for metastatic BGA; therefore, advanced BGA remains a challenge for gynecologic oncologists. Considering the rarity of this disease and the lack of a standardized approach, the present study aims to discuss the available literature on current therapies for BGA and to describe an emblematic case treated with a novel tailored approach. A postmenopausal woman with advanced BGA was referred to our department for an adequate evaluation, staging and treatment. Notably, we used PET/CT as a fundamental imaging technique for staging and follow-up. The patient underwent primary surgery followed by standard chemotherapy and pelvic radiotherapy. Three months later, she relapsed, with the appearance of multiple metastatic sites. Considering the evident chemoresistance to standard chemotherapy and the absence of valid therapeutic alternatives for this rare cancer, she was treated with a combination of repeated minimally invasive surgical procedures for all the resectable metastatic lesions and innovative approaches comprising, firstly, chemoimmunotherapy with Nivolumab combined with metronomic vinorelbine, which resulted in a clinical response for approximately 7 months. Upon disease progression, we used a targeted systemic approach based on the whole genomic profile of the primary tumor, which showed PTEN loss, which is predictive of a benefit from an mTOR inhibitor, and a CCND1 amplification, which predicts sensitivity to CDK4/6 inhibitors. Therefore, she received Everolimus, resulting in a significant metabolic response that lasted 12 months. Thereafter, upon further progression of the disease, the patient started Palbociclib treatment, which is currently ongoing, with evidence of a metabolic response. The patient has survived for 54 months from diagnosis, with a good performance status. In conclusion, the present paper confirms the lack of efficacy of conventional therapeutic regimens in the context of advanced, recurrent or metastatic adenocarcinomas of the Bartholin gland. The case report shows how a personalized multidisciplinary approach based on repeated minimally invasive surgery and tailored anticancer treatment based on whole-genome sequencing analysis could be effective and associated with prolonged survival in this rare gynecological cancer. [ABSTRACT FROM AUTHOR]

Background: The majority of simple renal cysts diagnosed postnatally are asymptomatic and rarely require treatment unless they become symptomatic or complex. We hypothesised that prenatally-detected simple renal cysts would have a similar harmless outcome.Aims: To establish the natural history and postnatal outcome of prenatally-diagnosed simple renal cysts.Study Design: Single-centre retrospective case-series review (12-year period).Subjects: All patients with prenatally-diagnosed simple renal cysts (defined as a solitary, non-septated, non-communicating cyst in an otherwise normal kidney).Outcome Measures: Prenatal and postnatal changes to cyst size, persistence, resolution or modification of diagnosis. Data is presented as the proportion of patients or median (range).Results: 30 cysts were detected (2 bilateral, 26 unilateral) in 28 fetuses (median gestational age of 23 [20-36] weeks). Median maximum diameter was 15 (4-35) mm at initial diagnosis and 17.5 (4-100) mm across all prenatal scans. On follow-up scans diagnosis was modified in 16 (53%) to: multicystic dysplastic kidney (MCDK), dilated duplex kidney, hydronephrosis, urinoma, renal agenesis and adrenal mass. 12 (40%) cysts resolved. 2 (7%) asymptomatic cysts persisted at one year postnatally. Cyst maximum diameter in the modified diagnosis group (21.5 [10-100] mm) was significantly larger than the simple cyst group (12 [4-20] mm) (P = 0.03).Conclusions: Our study revealed the challenges of prenatal ultrasound imaging, with modified diagnoses in over half the cases. Kidneys with solitary cysts could evolve into multicystic kidneys or involute completely, which suggests a true alteration in morphology rather than sonographic error. Persistent simple cysts in an otherwise normal kidney, however, resolved spontaneously or remained asymptomatic. Prenatally-detected simple cysts should be monitored with serial imaging. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility and safety of total laparoscopic hysterectomy (TLH) for uteri ≥ 1.5 kg. Methods: We prospectively evaluated all elective TLHs (with or without adnexectomy) performed for fibromatous uteri between August 2009 and August 2019 in the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and the Department of Gynecologic Oncology, Businco Hospital, Azienda Ospedaliera Brotzu, Cagliari. Patients with large myomatous uteri (uterine weight ≥ 1.5 kg on pathology reports) were included in the analysis. We examined all procedures and collected data about intra- and post-operative short-term and long-term complications, intraoperative blood loss, operative time, hospital stay, and time to achieve well-being. Results: Seventy-eight patients were included. The median weight was 2,000 g (range 1,500–11,000 g), estimated blood loss was 100 mL (range 10–700 mL), operating time was 135 min (range 60–300 min), and hospital stay was 2 days (range 2–5 days). Conversion to laparotomy occurred in 4 patients (5.1%) with uterine weight ranging from 3 to 5.5 kg, due to severe adherence syndrome or inadequate visualization. As for intraoperative complications, 1 patient (who had the largest removed uterus weighing 11,000 g) experienced an intraoperative ureteral injury (grade III). No major postoperative complications occurred. Conclusions: This study provides the largest case series of TLH for fibromatous uteri > 1.5 kg and includes some of the largest uteri reported to date in the literature (weighing 5,320, 5,720, and 11,000 g, respectively). The study reaffirms the feasibility and safety of a minimally invasive hysterectomy even in the case of abnormally large uteri. [ABSTRACT FROM AUTHOR]

Background: Complications after laparoscopic gynecological surgery may increase patients' morbidity and mortality; therefore, their timely diagnosis and early treatment would help clinicians to avoid life-threatening situations. We aimed to evaluate the predictive role of fibrinogen for diagnosing complications after laparoscopic gynecologic surgery for benign and malignant conditions. Patients and methods: All patients who underwent elective laparoscopic gynecologic surgery between June 2013 and December 2017 at the Department of Gynecologic Oncology, Azienda Ospedaliera Brotzu, Cagliari, were prospectively included. Post-operative complications were assessed and graded according to the Clavien-Dindo classification. Fibrinogen and white blood cell level were determined preoperatively, on the first post-operative day and at the appearance of symptoms indicative of an irregular post-operative course or at the time of re-hospitalization for persistent symptoms. The postoperative changes (calculated from the first postoperative day) were correlated with the occurrence and severity of complications and their predictive role was assessed. Results: We enrolled 1016 patients: 36% underwent surgery for benign pathologies (mainly voluminous fibromatous uteri and severe deep endometriosis) and 64% for gynecologic malignancies. The overall complication rate was of 3.45%, the rate of major postoperative complications was 2.85%. A postoperative fibrinogen increase ≥ 20% had a high diagnostic accuracy to identify postoperative complications early (AUC 0.931, sensitivity 89%, and specificity 99%). The magnitude of postoperative fibrinogen change was associated with complication severity. Conclusions: Our findings demonstrated that fibrinogen increase can enable the early detection of postoperative complications after laparoscopic gynecological surgery. Further prospective and multi-center studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]