How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?

BACKGROUND: Aim of this study was to rate the misdiagnosis of histological type between preoperative endometrial biopsy and final postoperative pathology focusing on non-endometrioid endometrial cancer (NEEC). Secondary objective is to assess the concordance between intraoperative assessment and final pathology in a subgroup of patients. METHODS: A multicenter retrospective study was conducted in patients with histological diagnosis of endometrial cancer who underwent surgical staging between 2011 and 2016. The concordance rate and the Kappa Cohen coefficient were calculated to assess the correlation concerning the histological type between endometrial biopsy and final pathology, and between intraoperative assessment and final pathology in a subgroup of patients. RESULTS: Two hundred ninety-five patients were enrolled, 226 were endometrioid carcinomas and 61 NEEC at final pathology. The concordance rate between pre-operative and final pathology for NEEC and the Kappa Cohen coefficient were 81.4% and 0.41 (CI 95% 0.3059-0.5122), respectively. 26 out of 61 (42.6%) NEEC were preoperatively misdiagnosed. The frozen section was performed in a subgroup of 86 patients (29.15%): the concordance rate between frozen section and final pathology for NEEC was 80% and the Kappa Cohen coefficient was 0.28 (CI 95% 0.212-0.347). CONCLUSIONS: Preoperative pathological histotype assessment predicts final pathology with a moderate grade of accuracy and the identification of NEEC could be challenging. Efforts should be directed toward molecular characterization of diagnostic samples in order to improve diagnostic accuracy and guide therapeutic decisions.

Angiogenesis and molecular markers in advanced epithelial ovarian cancer: a retrospective study.

OBJECTIVE: The role of molecular markers in ovarian cancer is still a matter of debate. Angiogenesis is a necessary condition for tumor growth. Hypoxia induces angiogenesis, and cyclooxygenase-2 (COX-2), p53 and HER2 are involved in cancer proliferation and angiogenesis regulation. The aims of this study were to evaluate the relationship between intratumoral microvessel density (IMD) and the expression of molecular markers that affect angiogenesis (COX-2, p53 and HER2) in advanced epithelial ovarian cancer (EOC), to analyze their prognostic and predictive value and their association with clinicopathological features, such as serum hemoglobin level at diagnosis (Hb). METHODS: Immunohistochemical staining with CD34 (for IMD), COX-2, p53 and HER2 antibodies was performed in 113 patients with advanced EOC who had undergone primary surgery. Clinicopathological data were collected and statistical analyses were performed. RESULTS: Neither IMD, COX-2 nor HER2 had any predictive or prognostic value in EOC. A relationship that approached statistical significance was found between p53 expression and a complete response to treatment (p=0.05). p53 expression and tumor grade were inversely associated (p=0.012). Hb<12g/dl had predictive value (p=0.02). CONCLUSIONS: In our series IMD, COX-2 and HER2 had neither prognostic nor predictive value in advanced EOC. p53 and Hb may be predictive factors. The results and clinical usefulness of immunohistochemistry are controversial. Further evaluations are required to determine whether the serum levels of molecular markers correlate with the results of immunohistochemical assays and whether they offer any prognostic and/or predictive value. Targeted therapy remains the ultimate goal of these studies.

Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases.

BACKGROUND: The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. METHODS: A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. RESULTS: Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. CONCLUSIONS: Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.

Analysis of vitamin D receptor expression and clinical correlations in patients with ovarian cancer.

OBJECTIVE: Although the antiproliferative and differentiating properties of vitamin D have been demonstrated, its effects on cancer cells are variable. Little is known about vitamin D receptor (VDR) levels in patients with ovarian cancer. In this population we sought to determine correlations between VDR expression, clinical parameters and treatment outcome. METHODS: We analyzed VDR content in platelets of healthy women and of a cohort of patients with ovarian tumors and we evaluated possible correlations with clinical parameters, tumor characterization (stage, histology, nuclear grading, ascites), response to therapy and survival. Moreover receptor expression was evaluated immunohistochemically on tissue samples. RESULTS: VDR levels were markedly lower in healthy women when compared with the pathological group. In the latter a significant increase in receptor expression was observed in malignancies compared with benign cases. No correlation existed between VDR expression and clinicopathological parameters, although we observed an advantage on survival if patients had a higher level of VDR expression in platelets. A cytoplasmic localization of the protein was observed by immunohistochemistry in ovarian cancer cells. CONCLUSIONS: Vitamin D receptor status measured in platelets differs significantly between healthy and pathological groups, increasing with malignancy, and there is a trend towards longer overall survival for tumors showing higher VDR levels. These data suggest that platelet VDR content could be used as a pathological marker. The meaning of this increased VDR expression in platelets needs further investigation and it is possibly linked to an inflammatory response.

Prevalence of atrophic gastritis in dyspeptic patients in Piedmont. A survey using the GastroPanel test.

BACKGROUND: Chronic atrophic gastritis (CAG) is a precursor of the intestinal type of gastric cancer, the second leading cause of cancer-related death worldwide. GastroPanel is a recently marketed serological kit for the non-invasive diagnosis of CAG, defined by some authors "even more reliable than biopsy histology". The goal of this study was 1) to evaluate the agreement between the serum gastric profile provided by GastroPanel (PGI, PGII, G-17, AbHp) and histology over CAG diagnosis, and 2) to evaluate the prevalence of CAG by means of GastroPanel in a Northern Italian dyspeptic population. METHODS: Basal blood samples for GastroPanel parameters evaluation (Biohit Plc, Finland) were collected after an overnight fast from 1387 dyspeptic patients (age range: 18-80 years; F 704). Gastroscopy with two biopsies each of the antrum and corpus was offered to a group of the first 400 consecutive patients (age 18-80 years, F 214) to compare the results of histology and GastroPanel in CAG. RESULTS: Agreement between GastroPanel and histology for corpus-prevalent CAG was 94%, with a sensitivity and specificity of 80% and 96%, respectively. In our series of 1387 dyspeptic patients, the prevalence of corpus-prevalent CAG, of antral-prevalent CAG and of multifocal CAG (antrum+ corpus) was 10.7%, 3.6% and 2.4%, respectively. Out of the 34 patients with multifocal atrophic gastritis, 12% were under 30 years of age. CONCLUSIONS: GastroPanel is a reliable non-invasive test for diagnosis of CAG and deserves consideration for current use in clinical practice as a valuable diagnostic tool.

Low-dose vaginal estrogens or vaginal moisturizer in breast cancer survivors with urogenital atrophy: a preliminary study.

The study aim is to evaluate the efficacy and safety of two low-dose vaginal estrogen treatments (ETs) and of a non-hormonal vaginal moisturizer in postmenopausal breast cancer survivors with urogenital atrophy. Eighteen patients receiving estriol cream 0.25 mg (n = 10) or estradiol tablets 12.5 microg (n = 8) twice/week for 12 weeks were evaluated and compared with eight patients treated with polycarbophil-based moisturizer 2.5 g twice/week. Severity of vaginal atrophy was assessed using subjective [Vaginal Symptoms Score (VSS), Profile of Female Sexual Function (PFSF)] and objective [Vaginal Health Index (VHI), Karyopycnotic Index (KI)] evaluations, while safety by measuring endometrial thickness and serum sex hormones levels. After 4 weeks, VSS and VHI were significantly improved by both vaginal ETs, with further improvement after 12 weeks. PFSF improved significantly only in estriol group (p = 0.02). Safety measurements did not significantly change. Vaginal moisturizer improved VSS at week 4 (p = 0.01), but score returned to pre-treatment values at week 12; no significant modification of VHI, KI, PFSF was recorded. Both low-dose vaginal ET are effective for relieving urogenital atrophy, while non-hormonal moisturizer only provides transient benefit. The increase of serum estrogens levels during treatment with vaginal estrogen at these dosages is minimal.

Intratumoral microvessel density in advanced epithelial ovarian cancer and its use as a prognostic variable.

BACKGROUND: The aim of this retrospective study was to assess whether the intratumoral microvessel density (IMD) in primary tumour specimens had any impact on the clinical outcome of patients with advanced epithelial ovarian cancer treated in two Italian departments of gynaecological oncology. MATERIALS AND METHODS: The study was conducted on 101 patients who underwent initial surgery followed by platinum-based chemotherapy (37) or paclitaxel/platinum-based chemotherapy (64) for International Federation of Gynecology and Obstetrics (FIGO) stage III-IV epithelial ovarian cancer. The median follow-up of survivors from initial surgery was 65 months (range, 27 to 132 months). Paraffin-embedded sections of primary tumour specimens were analysed for IMD by immunohistochemistry using anti-CD34 antibodies. RESULTS: Progression-free survival and overall survival were significantly better in patients with IMD > or =40 microvessels/field compared with those with lower IMD (p = 0.0105 and p = 0.0065, respectively). Cox model showed that IMD was the strongest independent prognostic variable for both progression-free survival (p = 0.0267) and overall survival (p = 0.0189). CONCLUSION: An elevated IMD was associated with a significantly better progression-free survival and overall survival in patients with stage III-IV epithelial ovarian cancer who underwent initial surgery followed by chemotherapy, mainly consisting of a paclitaxel/platinum-based regimen.

Endometriosis-associated Ovarian Cancer: A Distinct Clinical Entity?

AIM: The aim of the study was to evaluate the incidence of endometriosis-associated ovarian cancer (EAOC) and compare clinicopathological characteristics and overall survival (OS) between patients with EAOC and those with ovarian cancer not associated with endometriosis. PATIENTS AND METHODS: We identified EAOC among 203 patients with invasive epithelial ovarian cancer who underwent complete surgery at our Institution from January 2004 to March 2014. RESULTS: EAOC was present in 45 patients. EAOC was significantly more frequently diagnosed at an earlier stage of disease (p=0.038). At a median follow-up time of 32 months, OS among patients with EAOC was significantly longer (p=0.039). However, stratifying by stage, the OS advantage of EAOC was not significant. At multivariate analysis, only stage was an independent prognostic factor for OS (hazard ratio=5.7; 95% confidence interval=1.8-18.6; p=0.003). CONCLUSION: EAOC incidence was 22.2%. EAOC appears to be diagnosed at an earlier stage and confers a better OS. However, stratifying by stage, the advantage in survival of EAOC disappears.

Aggressive clinical course of primary invasive vaginal carcinoma associated with type 61 HPV: a case report.

Primary invasive vaginal cancer is one of the rarest malignant processes in the female genital tract. The etiology has not been identified, but the strongest association is with HPV infection and subtypes 16 and 18 have the highest oncogenic potential. We present the case of a young woman diagnosed with metastatic squamous cell carcinoma of the vagina associated with HPV type 61, a non-oncogenic HPV type. We report the propensity of a primary vaginal neoplasm to spread to lymphatic vessels early and the unresponsive aggressive behavior to multimodal therapy.

Prospective evaluation of accuracy of liver biopsy findings in the identification of chemotherapy-associated liver injuries.

OBJECTIVE To evaluate the accuracy of liver biopsy findings in preoperative assessment of chemotherapy-associated liver injuries (CALIs). DESIGN Prospective study. SETTING Tertiary care referral hospital. PATIENTS From July 1, 2007, to January 31, 2011, all patients with colorectal metastases receiving preoperative oxaliplatin- and/or irinotecan-based chemotherapy (≥4 cycles) were considered for the present study. Patients underwent parenchymal biopsy before liver resection. Blinded CALI evaluation was performed on biopsy and resection specimens. INTERVENTION Liver resection. MAIN OUTCOME MEASURES Sensitivity, specificity, and accuracy of liver biopsy in CALI evaluation. RESULTS We included 100 patients. At specimen analysis, grade 2 or 3 steatosis was diagnosed in 30 patients; grade 2 or 3 sinusoidal dilatation, in 28; grade 2 hepatocellular ballooning, in 3; grade 2 or 3 lobular inflammation, in 25; and steatohepatitis in 19. Obesity was associated with grade 3 steatosis (20.8% vs 5.3%; odds ratio [OR], 4.74 [P = .03]) and steatohepatitis (33.3% vs 14.5%; OR, 2.96 [P = .04]). Oxaliplatin administration was associated with higher sinusoidal dilatation grade (P = .049). Mortality (2 cases) was increased among patients with steatohepatitis (10.5% vs 0; OR, 13.67 [P = .04]). Biopsy findings correctly predicted steatosis (sensitivity, 88.9%; accuracy, 93.0%) but had low sensitivity and accuracy for sinusoidal dilatation (21.4% and 63.0%, respectively), hepatocellular ballooning (16.0% and 69.0%, respectively), lobular inflammation (20.0% and 78.0%, respectively), and steatohepatitis (21.1% and 79.0%, respectively). Biopsy accuracy did not improve regarding specific chemotherapy regimens or prolonged treatments. CONCLUSIONS Liver biopsy cannot be considered a reliable tool in assessing CALIs except for steatosis. The procedure should not be recommended during preoperative workup.

Syringoid eccrine carcinoma: Case report of a rare tumor occasionally detected in the vulva.

► Syringoid eccrine carcinoma (SEC) is a rare tumor. ► There are no published reports describing diagnosis of this tumor on the vulva. ► We report a case of a 58-year-old female with a SEC of left labia majora.

COX-2 expression in human breast carcinomas: correlation with clinicopathological features and prognostic molecular markers.

OBJECTIVE: COX-2 is implicated in carcinogenesis and tumour progression in many cancers, including breast cancer. Recently, it has been reported that human breast carcinomas aberrantly express COX-2, and that raised tissue levels of COX-2 may have prognostic value. Patients expressing high levels of COX-2 can develop local recurrence, and have reduced disease-free and disease-related overall survival. The aim of this study was to investigate COX-2 expression in human ductal and lobular breast cancers and its possible association with clinicopathological features and prognostic molecular markers. RESEARCH DESIGN AND METHODS: Cytoplasmic COX-2 expression was detected by means of immunohistochemistry in a series of 91 breast carcinomas with ductal (n = 60) and lobular (n = 31) patterns. COX-2 expression was investigated by multivariate analyses and compared with clinicopathological features. RESULTS AND CONCLUSIONS: COX-2 immune positivity and percentage of positive cells correlated significantly with the size, grading, extent of primary tumour and vascular invasion of carcinoma but not with biological parameters (estrogen receptor, progesterone receptor and human EGF receptor 2). The findings of the present study suggest that COX-2 overexpression in lobular and ductal breast cancers, which correlates with traditional clinico-pathological parameters, may be considered as a negative prognostic marker.

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer.

OBJECTIVE: The primary aim of this study was to evaluate the prognostic and predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian cancer; second aim was to perform a preliminary investigation of intratumoral microvessel density (IMD). METHODS: The influence on survival and response to treatment of several clinico-pathological features, including Hb, was analyzed in 72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of 25 of the 72 patients to compare three different endothelial markers: anti-FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary analysis of the prognostic and predictive value of IMD, and its relationship with Hb and other clinico-pathological features, was performed. RESULTS: Hb >or= 12 g/dl was significantly associated with a better overall survival in univariate analysis (P = 0.0181) and was the only independent prognostic variable in multivariate analysis (P = 0.0160). Hb was directly related to progression-free survival (P = 0.0240) and complete response to treatment (P = 0.016). In the preliminary investigation of IMD, mean microvessel count did not show any significant difference among the three endothelial markers used, but anti-CD34 revealed a more consistent staining reaction. The relationship between IMD and complete response to treatment was found near to statistical significance (P = 0.05); Hb and IMD were inversely related (r = -0.47; P = 0.045). CONCLUSIONS: Hb has a prognostic and predictive value in advanced ovarian cancer. In our preliminary study, which was performed on a limited number of patients, we found anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible predictive factor of complete response to treatment, and IMD and Hb to be inversely related.