Red Cell Distribution Width as a Predictor of Survival in Patients with Hepatocellular Carcinoma.

Background and Objectives. Hepatocellular carcinoma (HCC) and the intrahepatic biliary tract cancers are estimated to rank sixth for incidence among solid cancers worldwide, and third for mortality rates. A critical issue remains the need for accurate biomarkers for risk stratification and overall prognosis. The aim of this study was to investigate the ability of a biomarker of heterogeneity of the size of red blood cells, the red cell distribution width (RDW), to predict survival in patients with HCC. Materials and Methods. A consecutive series of patients with a histologic diagnosis of HCC were included into this study irrespective of their age, stage of the disease, and treatment administered, and followed-up for a period of three years. Demographic, anthropometric [age, sex, body mass index (BMI)], and clinical data (Charlson Comorbidity Index, Child-Pugh score, etc.), along with laboratory tests were retrieved from clinical records. Results. One-hundred and four patients were included in this study. Among them, 54 (69%) were deceased at the end of the follow-up. Higher RDW values, but not other hematological and biochemical parameters, were significantly associated with mortality in both univariate and multivariate analysis. The optimal RDW cut-off value identified with the Youden test for survival was 14.7%, with 65% sensitivity and 74% specificity (AUC = 0.718, 95% CI 0.622-0.802, p < 0.001). Kaplan-Meier survival curves showed significantly lower survival with higher RDW values (HR = 3.5204; 95% CI 1.9680-6.2975, p < 0.0001) with a mean survival of 30.9 ± 9.67 months for patients with RDW ≤ 14.7% and 22.3 ± 11.4 months for patients with RDW > 14.7%. Conclusions. The results of our study showed that RDW can perform better than other blood-based biomarkers in independently predicting prognosis in patients with HCC.

The importance of the multidisciplinary team in the decision-making process of patients undergoing neoadjuvant chemotherapy for breast cancer.

BACKGROUND AND OBJECTIVES: Recent literature suggests that rates of breast conservation surgery (BCS) are lower than expected in patients submitted to neoadjuvant chemotherapy (NAC) for breast cancer. The aim of this study was to underscore the role of the multidisciplinary team (MDT) in the decision-making process of patients who underwent breast surgery after NAC. METHODS: We conducted a retrospective study on patients with breast cancer treated according to an algorithm developed at the Breast Unit of Northern Sardinia between January 2019 and May 2023. Data collected included demographics, tumor characteristics, upfront treatment (surgery or NAC), type of primary surgery (BCS or mastectomy [Ma]) and patients' adherence to the treatment proposed by the MDT. RESULTS: Overall, 1061 women were treated during the study period, of whom 164 received NAC (Group A) and 897 upfront surgery (Group B). In group A, conversion from BCS ineligibility to BCS eligibility was observed in 47 patients (40.1%). Final surgery in patients who became BCS-eligible after NAC was BCS in 42 cases (89.3%) and Ma in 5 (10.6%). Rates of patients' adherence to the treatment proposed by the MDT were significantly better in the Group A (p = 0.02). CONCLUSIONS: Our results suggest that the MDT has a pivotal role in increasing the rates of breast conservation in women submitted to NAC.

Antibody-Drug Conjugates in HR+ Breast Cancer: Where Are We Now and Where Are We Heading?

Hormone receptor-positive (HR+) breast cancer (BC) accounts for about 60-70% of all diagnosed BCs, and endocrine therapy has long been the hallmark of systemic treatment for this tumor subtype. However, the therapeutic paradigm of luminal BC has been overcome due to recent evidence of antibody-drug conjugate (ADC) activity (such as trastuzumab deruxtecan and sacituzumab govitecan) in pretreated metastatic HR+ BC patients. Therefore, nowadays, the identification of patients who can benefit more from this approach represents a new challenge, as does the management of new toxicities and the integration of these drugs into the therapeutic algorithm of HR+ metastatic BC patients.

Rising age-specific rates of immediate breast reconstruction after mastectomy: Report from an Italian Breast Unit.

BACKGROUND AND OBJECTIVES: Immediate breast reconstruction (IBR) represents a fundamental part in the management of patients receiving mastectomy. In recent years, there has been an increasing trend in the use of IBR in all age groups. The study aims were to evaluate the age-specific trend of IBR, and to discuss its effects in work organization at an Italian Breast Unit. METHODS: We searched for women diagnosed with breast cancer between 2010 and 2019, focusing on IBR rates in patients who received mastectomy. Age-specific trends were assessed using the Cochrane-Armitage test. Differences in operative times and hospital stay between women undergoing mastectomy + IBR (Ma + IBR) or mastectomy alone (Ma) were evaluated by Student's t test or χ2 test. RESULTS: Among 1915 patients, 62.4% underwent breast conserving surgery (BCS), and 37.6% mastectomy. Overall, rates of Ma + IBR increased from 32% in 2010 to 58% in 2019 (p < 0.001). Although rates of IBR rose in all age groups, the trend was significantly increased among patients aged 50-59 (p < 0.001), 60-69 (p < 0.0001), and 70-79 (p < 0.05). CONCLUSIONS: Rates of Ma + IBR have increased over years, especially among older women. Ma + IBR resulted in longer operative times and hospital stay than Ma alone. These findings imply that, in the near future, resources should be implemented to improve and strengthen the surgical activity of Breast Units, to support the increasing use of IBR in women of all age groups.

Genetic Characterization of Echinococcus granulosus sensu stricto Isolated from Human Cysts from Sardinia, Italy.

This study involved 20 patients affected by cystic echinococcosis (CE) who were referred to different hospitals of Sardinia (Italy) from 2017 to 2022. By means of a multidisciplinary approach, diagnosis was confirmed for CE in 18 patients and for different aetiologies in two subjects. Moreover, serology was positive for 15 subjects. Since multiple CE cysts were found in five patients, a total of 27 lesions were collected; however, only one for each patient was investigated for genetic characterization of E. granulosus s.s. DNA isolates. Our results included 15 fertile cysts that underwent DNA extraction and amplification by three different PCRs targeting nuclear (calreticulin) and mitochondrial genes (cox1 and nad5). DNA was sequenced, and by neighbour-joining phylogenetic trees we determined 10 G1 and five G3 genotypes previously reported in Sardinia. These sequences were used to construct a network, along with those circulating in Mediterranean areas. The haplotype network calculated on cox1 evidenced seven different haplotypes of the 15 isolates, with SAR2 the most represented, carried by seven cysts, and SAR17 never described in the Mediterranean area. Meanwhile, the nad5 sequences showed the most common haplotype as nd5SAR7, as well as two new haplotypes not previously described, nd5SAR13, isolated from a Sardinian patient, and nd5SAR14, isolated from a Romanian patient.

Advances in pharmacotherapies that target the cell cycle for treatment of breast cancer: where are we at today?

INTRODUCTION: Advances in pharmacotherapies that target cell cycle in breast cancer have transformed the therapeutic armamentarium of breast oncology leading to the approval of CDK4/6 inhibitors plus endocrine therapy as the upfront treatment in the HR+/HER2- metastatic setting. The current challenge is to evaluate the efficacy of these drugs in the early setting. The current challenge is to evaluate the efficacy of these drugs in the early setting. Research is also making progress for other breast cancer subtypes (triple negative and HER 2+ breast cancer). AREAS COVERED: The aim of this review is to summarize the recent therapeutic updates regarding the efficacy of CDK4/6 inhibitors in the metastatic and early setting for the treatment of HR+/HER2- breast cancer. The review also presents data regarding the clinical role of CDK4/6 inhibitors in HER2+, triple negative breast cancer, and on therapeutic sequences in resistant tumors. A comprehensive search for the literature was conducted using MEDLINE, ASCO, ESMO, and SABCS databases. EXPERT OPINION: The therapeutic paradigm of breast cancer involving CDK4/6 inhibitors presents some still open discussion points. Further evidence regarding the best treatment strategy in HR+ HER2- metastatic breast cancer and the efficacy of CDK 4/6is in the early stage will be necessary in the next future. Predictive biomarkers of response or resistance need to be validated.

Breast-conserving therapy leads to better survival outcomes compared to mastectomy in patients with early breast cancer: evidences from the recent literature.

Classical studies comparing breast-conserving therapy (BCT) and mastectomy (Mx) focused on the non-inferiority of BCT in terms of survival outcomes. However, recent large retrospective studies have provided evidence that BCT could confer a survival advantage over Mx. The prognostic benefit of BCT was observed in all molecular subgroups, including triple negative breast cancer, and also in young patients affected from the disease, who are often submitted to Mx irrespective of tumor size. This new concept, regarding the prognostic importance related to the type of surgical treatment of breast cancer, is of particular relevance in current times. In fact, in the last two decades there has been a rise in Mx rates in BCT-eligible women, as well as a rise in bilateral mastectomy in patients with unilateral breast cancer. This phenomenon occurs despite lack of scientific evidence supporting the necessity of a more extensive surgery, and is primarily a patient-driven trend. The results of recent studies, demonstrating that BCT achieves better overall survival than Mx, should be incorporated in the multidisciplinary decision-making process. Patients with early breast cancer for whom either BCT or Mx are surgical options, should be properly informed that the prognosis of their disease is largely dependent from the biological behaviour of the tumor, and that Mx should not be considered equal to BCT in terms of survival. The present review underscored that BCT, when feasible, should be considered the option of choice also due to its advantage in survival outcomes.

Deciphering clinical significance of BCL11A isoforms and protein expression roles in triple-negative breast cancer subtype.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive clinical tumor, accounting for about 25% of breast cancer (BC) related deaths. Chemotherapy is the only therapeutic option to treat TNBC, hence a detailed understanding of the biology and its categorization is required. To investigate the clinical relevance of BCL11A in TNBC subtype, we focused on gene and protein expression and its mutational status in a large cohort of this molecular subtype. METHODS: Gene expression profiling of BCL11A and its isoforms (BCL11A-XL, BCL11A-L and BCL11A-S) has been determined in Luminal A, Luminal B, HER2-enriched and TNBC subtypes. BCL11A protein expression has been analyzed by immunohistochemistry (IHC) and its mutational status by Sanger sequencing. RESULTS: In our study, BCL11A was significantly overexpressed in TNBC both at transcriptional and translational levels compared to other BC molecular subtypes. A total of 404 TNBCs were selected and examined showing a high prevalence of BCL11A-XL (37.3%) and BCL11A-L (31.4%) isoform expression in TNBC, associated with a 26% of BCL11A protein expression levels. BCL11A protein expression predicts scarce LIV (HR = 0.52; 95% CI, 0.29-0.92, P = 0.03) and AR downregulation (HR = 0.37; 95% CI, 0.16-0.88; P = 0.02), as well as a higher proliferative index in TNBC cells. BCL11A-L expression is associated with more aggressive TNBC histological types, such as medullary and metaplastic carcinoma. CONCLUSION: Our finding showed that BCL11A protein expression acts as an unfavorable prognostic factor in TNBC patients, especially in non luminal TNBCs subgroups. These results may yield a better treatment strategy by providing a new parameter for TNBC classification.

Edmonton Symptom Assessment Scale may reduce medical visits in patients undergoing chemotherapy for breast cancer.

BACKGROUND: Adjuvant chemotherapy is recommended in high-risk breast cancer. However, no universally accepted guidelines exist on pre-chemotherapy assessment. In particular, the number and frequency of medical visits vary according to each institution's policy. We hypothesised that the Edmonton Symptom Assessment Scale (ESAS) may have a favourable impact on the pre-treatment assessment in candidates for adjuvant chemotherapy. AIM: To investigate whether the ESAS can be used to safely reduce the number of medical visits in women with breast cancer undergoing adjuvant chemotherapy. METHODS: In a retrospectively prospective matched-pair analysis, 100 patients who completed the ESAS questionnaire before administration of adjuvant chemotherapy (ESAS Group) were compared with 100 patients who underwent chemotherapy according to the traditional modality, without ESAS (no-ESAS Group). Patients of the ESAS Group received additional visits before treatment if their ESAS score was > 3. The primary endpoint was the total number of medical visits during the entire duration of the chemotherapy period. The secondary endpoints were the occurrence of severe complications (grade 3-4) and the number of unplanned visits during the chemotherapy period. RESULTS: The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group (age P = 0.880; breast cancer stage P = 0.56; cancer histology P = 0.415; tumour size P = 0.258; lymph node status P = 0.883; immunohistochemical classification P = 0.754; type of surgery P = 0.157), except for premenopausal status (P = 0.015). The study variables did not statistically differ between patients of the ESAS Group and no-ESAS Group regarding age, cancer stage, histology, tumour size, lymph node status, immunohistochemical classification, and type of surgery. Unplanned visits during the entire duration of chemotherapy were 8 in the ESAS Group and 18 in the no-ESAS Group visits (P = 0.035). Grade 3-4 toxicity did not differ between the study groups (P = 0.652). Forty-eight patients of the ESAS Group received additional visits due to an ESAS score > 3. The mean number of medical visits was 4.38 ± 0.51 in the ESAS Group and 16.18 ± 1.82 in the no-ESAS group (P < 0.001). With multivariate analysis, women of the ESAS group were more likely to undergo additional visits for an ESAS score > 3 if they were aged 60 or older, received a mastectomy, or had tumour stage II/III. CONCLUSION: The ESAS score may safely reduce the number of medical visits in candidates for adjuvant chemotherapy for early breast cancer. Our results suggest that the ESAS score may be used for selecting a group of breast cancer patients for whom it is safe to reduce the number of medical visits in the setting of adjuvant chemotherapy. This may translate into several advantages, such as a more rational utilization of human resources and a possible reduction of coronavirus pandemic infection risk in oncologic patients.

Tailoring antiHer2 treatment strategies in breast cancer and beyond.

Precision medicine advances are opening new opportunities in the treatment of Her2 driven cancers. Her2 signaling activation was found in around 20% of breast cancers about 3 decades ago and define an aggressive subtype of the disease. Nowadays antiHer2 targeted approach is standard of care in both metastatic and early-stage Her2 -positive breast cancer and has changed the general course of the disease. However, the challenge of personalizing cancer treatments through de-escalation and escalation strategies is still open, especially in the early setting of the disease. New evidences are emerging on the role of Her2 dysregulation in the carcinogenesis of solid tumors other than breast cancer. Recently reported clinical trials of antiHer2 targeted therapies have shown promising results in a variety of tumors, especially gastrointestinal and lung cancers. In this review we report challenges and opportunities of tailored antiHer2 treatments in breast cancers and beyond based on the results of recent clinical trials.

How the COVID-19 pandemic has affected the colorectal cancer screening in Italy: A minireview.

The coronavirus disease 2019 (COVID-19) pandemic has caused detrimental effects on many aspects of healthcare practice. Screening programs for the commonest malignancies, namely colorectal cancer (CRC), breast cancer and cervical cancer have been discontinued or interrupted since the beginning of restriction measures aimed to limit transmission of the new coronavirus infection. Robust evidence exists in favour of the role of screening campaigns in reducing mortality from CRC. In fact, the majority of pre-malignant lesions of the colon and rectum can be diagnosed with colonoscopy and treated by endoscopic or surgical resection. Besides, colonoscopy screening allows the diagnosis of CRCs in their pre-clinical stage. Italy was one of the first European countries where a high level of COVID-19 infections and deaths was observed, and one of the first where lockdowns and strict measures were adopted to reduce the risk of COVID-19 diffusion among the population. A systematic review of the literature was performed, including the PubMed, Scopus, Web of Sciences, and Reference Citation Analysis databases, with the aim of critically evaluating the impact of the COVID-19 pandemic on CRC screening in Italy. We found that reduction of CRC screening activity surpassed 50% in most endoscopic units, with almost 600000 fewer CRC screening exams conducted in the first 5 mo of 2020 vs the same period of 2019. While the consequences of the discontinuation of endoscopy screening for the prognosis and mortality of CRC will be evident in the next few years, recent data confirm that CRC is currently treated at a more advanced stage than in the pre-COVID-19 era. Since delays in CRC prevention and early diagnosis may translate to increased CRC-specific mortality, world healthcare systems should adopt strategies to maintain the regularity of CRC screening during subsequent peaks of the COVID-19 pandemic, or future events that might hamper screening programs.

The Increasing Role of CT-Guided Cryoablation for the Treatment of Liver Cancer: A Single-Center Report.

Purpose: Cryoablation (CrA) is a minimally invasive treatment that can be used in primary and metastatic liver cancer. The purpose of this study was to assess the effectiveness of CrA in patients with hepatocellular carcinoma (HCC) and liver metastases. Methods: We retrospectively evaluated the patients who had CrA for HCC or liver metastases between 2015 and 2020. Technical success, complete ablation, CrA-related complications, local tumor progression, local recurrences, and distant metastases were evaluated in the study population. In patients with HCC, the median survival was also estimated. Results: Sixty-four liver tumors in 49 patients were treated with CrA (50 metastases and 14 HCC). The mean tumor diameter was 2.15 cm. The mean follow-up was 19.8 months. Technical success was achieved in the whole study population. Complete tumor ablation was observed after one month in 92% of lesions treated with CrA (79% and 96% in the HCC Group and metastases Group, respectively, p < 0.001). Local tumor progression occurred in 12.5 of lesions, with no difference between the study groups (p = 0.105). Sixteen patients (33%) developed local recurrence (45% and 29% in the HCC Group and metastases Group, respectively, p = 0.477). Seven patients (14%) developed distant metastases in the follow-up period. Ten patients (20.8%) underwent redo CrA for local recurrence or incomplete tumor ablation. Minor complications were observed in 14% of patients. In patients with HCC, the median survival was 22 months. Conclusions: CrA can be safely used for treatment of HCC and liver metastases not amenable of surgical resection. Further studies are necessary to better define the role of CrA in the multidisciplinary treatment of liver malignancies.

Jejunal adenocarcinoma after biliopancreatic diversion. Report of a case.

The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro's technique. The patient developed a marked distension of the biliopancreatic limb caused by a jejunal mass, evolving towards the so called "duodenal blowout". Emergency jejunal resection of the biliopancreatic limb, with creation of a new end-to-side jejunal-ileal anastomosis was necessary. The histological examination resulted in a moderately-differentiated ulcerated adenocarcinoma, with reactive lymph nodes and tumor-free resection margins. Tumors of the gastrointestinal system can arise following malabsorptive operations for morbid obesity, and they may be difficult to diagnose, since the symptoms are often attributed to the anatomical-functional changes resulting from this type of surgery. The case reported herein suggests that there is a need for surveillance in patients complaining of digestive symptoms after malabsorptive bariatric surgery.

Inflammatory Indexes as Predictive Biomarkers of Postoperative Complications in Oncological Thoracic Surgery.

The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = -0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.

Comparison and evaluation of analytic and diagnostic performances of four commercial kits for the detection of antibodies against Echinococcus granulosus and multilocularis in human sera.

Cystic echinococcosis (CE) is a disease caused by Echinococcus granulosus sensu lato (s.l.), an ubiquitous worldwide zoonotic agent affecting humans and animals. Diagnosis of CE in humans is usually performed by imagine techniques along with immunoassays. The aim of our study was to evaluate and compare four commercial diagnostic kits, based on the detection of IgG antibodies against E. granulosus and E. multilocularis. The study was performed on a total of 259 sera: the positive (n = 74) and the negative (n = 185) group. The following analytic and diagnostic performances of the four kits were evaluated: operator skills, specificity, sensitivity, repeatability, reproducibility, accuracy, positive and negative predictive values. Based on the parameters evaluated, all four tests demonstrated excellent quality and proved to be reliable diagnostic tools to support the clinical evaluation of human patients suspected of having CE. The four commercial assays, in our hands, presented altogether, a range of performances from good to excellent, being immunoblotting (IB) the most reliable, used as gold standard, followed by the immunochromatographic test (ICT) and finally the two enzyme linked immunosorbent assay (ELISAs).

Current management of incidental gallbladder cancer: A review.

Early-stage gallbladder cancer (GBC) is mostly discovered incidentally by the pathologist after cholecystectomy for a presumed benign disease. It is the most common malignancy of the biliary tract with a variable incidence rate all over the World. The majority of patients with GBC remain asymptomatic for a long time and diagnosis is usually late when the disease is at an advanced stage. Radical surgery consisting in resection of the gallbladder liver bed and regional lymph nodes seems to be the best treatment option for incidental GBC. However, recurrence rates after salvage surgery are still high and the addition of neoadjuvant/adjuvant chemotherapy may improve outcomes. The aim of the present review is to evaluate current literature for advances in management of incidental GBC, with particular focus on staging techniques and surgical options.

Red Blood Cell Distribution Width (RDW) Correlates to the Anatomical Location of Colorectal Cancer. Implications for Clinical Use.

PURPOSE: The pathological, clinical, and therapeutic features of colorectal cancer (CRC) depend on its anatomical localization. We investigated possible associations between the red blood cell distribution width (RDW) and CRC localization. METHODS: Two-hundred eighty-eight consecutive patients with CRC were retrospectively studied. Demographic, clinical, pathological and laboratory data were retrieved from clinical records and reports. RESULTS: Median RDW values were significantly higher in patients with right-sided CRC when compared to those with CRC in other localizations (16.2, IQR: 14.5-20.0 vs 13.8, IQR: 13.0-16.1, p < 0.0001). Anisocytosis was statistically associated to haemoglobin (Hb), mean haemoglobin concentration (MHC), and mean corpuscular volume (MCV) values in all the patient groups examined. A cut-off value of 14.3% was associated with right-sided localization with sensitivity and specificity of 76.3% and 64.2%, respectively (AUC 0.71). CONCLUSION: Median RDW values were significantly higher in right-sided CRC when compared to other tumour locations, and may represent an additional marker for differential diagnosis.