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.

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.

Vascular resection for locally advanced pancreatic ductal adenocarcinoma: analysis of long-term outcomes from a single-centre series.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Radical surgery is the best option for cure and, nowadays, it is performed by many surgeons also in cases of vascular infiltration. Whether this aggressive approach to a locally advanced PDAC produces a survival benefit is under debate. Most data in the literature come from retrospective comparative studies; therefore, it is still unclear if such an extensive surgery for an advanced cancer is justified. METHODS: A retrospective review of patients with PDAC treated at our institution over a 12-year period was performed. Data concerning patients' characteristics, operative details, postoperative course, and long-term survival were retrieved from prospective databases and analysed. Factors associated with poor survival were assessed via Cox regression analysis. RESULTS: A total of 173 patients with PDAC were included in the analysis, 41 subjects underwent pancreatectomy with vascular resection for locally advanced disease, and in 132 patients, only a pancreatic resection was undertaken. Demographics, major comorbidities, and tumour characteristics were similar between the two groups. Length of surgery (P=0.0006), intraoperative blood transfusions (P<0.0001), and overall complications (P<0.0001) were significantly higher in the vascular resection group. Length of hospital stay (P=0.684) and 90-day mortality (P=0.575) were comparable between groups. Overall median survival (P= 0.717) and survival rates at 1, 3, and 5 years (P=0.964, P=0.500, and P=0.445, respectively) did not differ significantly between groups. Age ≥70 years and postoperative complications were independent predictors of lower survival. CONCLUSIONS: Our study confirms that pancreatectomy with vascular resection for a locally advanced PDAC is a complex operation associated with a significant longer operating time that may increase morbidity; however, in selected patients, R0 margins can be obtained with an acceptable long-term survival rate. Older patients are less likely to benefit from surgery.

Laparoscopic versus Open Transverse-Incision Approach for Right Hemicolectomy: A Systematic Review and Meta-Analysis.

Background and Objectives: There is general agreement on the benefits of laparoscopy for treatment of rectal and left colon cancers, whereas findings regarding the comparison of laparoscopic and open right colonic resections are discordant. The aim of this systematic review and meta-analysis was to assess the outcomes and advantages of laparoscopic versus transverse-incision open surgery for management of right colon cancer. Materials and Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Comparative studies evaluating the results of laparoscopic and transverse-incision open right hemicolectomies were analyzed. The measured outcomes were mean operative time, time to feeding, duration of hospital stay, and number of lymph nodes harvested. Results: A total of 5 studies including 318 patients met the inclusion criteria. Meta-analysis revealed no differences in time to resume oral feeding, hospital stay, and number of lymph nodes harvested in between groups, but mean length of surgery was significantly longer in the laparoscopic group. Conclusion: These data confirm that the preferred approach to right hemicolectomy is yet unclear. Laparoscopy has a longer operative time than transverse-incision open surgery, and no significant short-term benefits were observed for the studied parameters. Well-designed randomized control trials (RCTs) might help to identify the differences between these two techniques for the surgical treatment of right colon cancer.

Combined Microwave Ablation and Osteosynthesis for Long Bone Metastases.

Background and Objectives: The purpose of this study was to evaluate the feasibility, safety and efficacy of microwave ablation (MWA) in combination with open surgery nail positioning for the treatment of fractures or impending fractures of long bone metastases. Material and Methods: Eleven patients (four men, seven women) with painful bone metastases of the humerus, femur or tibia with non-displaced fractures (one case) or impending fractures (10 cases) underwent open MWA in combination with osteosynthesis by locked nail positioning. Pain intensity was measured using a VAS score before and after treatment. CT or MRI were acquired at one month before and 1, 3, 6, 12 and 18 months after treatment. Results: All procedures were successfully completed without major complications. The level of pain was significantly reduced one month after treatment. For the patients with humerus metastases, the complete recovery of arm use took 8 weeks, while for the patients with femoral metastases the complete recovery of walking capacity took 11 weeks. The VAS score ranged from 7 (4-9) before treatment to 1.5 (0-2.5) after treatment. During a mid-term follow-up of 18 months (range 4-29 months), none of the patients showed tumor relapse or new fractures in the treated site. Two patients died due to tumor disease progression. Conclusion: Results of this preliminary study suggest that combined MWA and surgical osteosynthesis with locked nails is a safe and effective treatment for pathological fractures or malignant impending fractures of long bone metastases of the humerus, femur and tibia. Further analyses with larger cohorts are warranted to confirm these findings.

The emerging role of pectoral nerve block (PECS block) in breast surgery: A case-matched analysis.

To evaluate the benefits of pectoral nerve block (PECS block) in breast cancer surgery, we compared outcomes of 100 patients receiving PECS vs 107 without PECS. Intraoperative use of fentanyl (P < .001) acetaminophen (P = .02), morphine (P < .01), and nonsteroidal anti-inflammatory drugs (NSAIDS) (P < .01) was lower in the PECS group. Occurrence of postoperative nausea and vomiting (PONV) was lower in the PECS group (P = .04). On postoperative day 1, the use of acetaminophen (P = .23), morphine (P = .83), and NSAIDS (P = .4) did not differ. Twenty-one patients received surgery with PECS block plus sedation alone. PECS block can reduce intraoperative use of opioids and analgesic drugs, and is associated with reduced occurrence of PONV. Selected patients can receive breast-conserving surgery with PECS plus sedation, avoiding general anesthesia.

The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. METHODS: The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. RESULTS: Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan-Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000-1.0001, p = 0.029) in multivariate Cox regression analysis. CONCLUSIONS: The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in breast cancer: a Sardinian preliminary case-control study.

Two common polymorphisms in the MTHFR gene, C677T and A1298C, are associated with reduced enzyme activity and may be associated with breast cancer susceptibility. We performed a case-control study to investigate the association between the two SNPs in the MTHFR gene and risk of breast cancer. In total, 58 breast cancer patients and 58 unaffected controls were enrolled in the study. Polymerase chain reaction/restriction fragment length polymorphism technique (PCR-RFLP) was conducted to determine the genotypes. No significant differences were found in the genotypes of the two polymorphisms of the MTHFR gene between cases and controls. The OR and 95% CI for the 677CC, 677CT and 677TT genotypes were 1.00, 0.95 (0.39-2.31) and 0.87 (0.27-2.80), respectively; those of the 1298AA, 1298AC and 1298CC genotypes were 1.00, 0.59 (0.26-1.36) and 0.78 (1.32-4.66) respectively. Furthermore, it has been shown in patients with breast cancer a risk of presenting with an aggressive biophenotype about twice or three times higher in the presence of the C677T and A1298C polymorphisms, respectively. Finally, the A1298Cpolymorphism is significantly associated with increased recurrence risk of lymph node-positive breast cancer. Our study has not shown a significant association between MTHFR gene polymorphisms and breast cancer risk. However, it highlighted the key-role played by the presence of mutant alleles for both polymorphisms in increasing the risk of developing more aggressive phenotypes; moreover, specifically in A1298C, it might also lead to a higher risk of developing lymph node metastasis.

CT-guided percutaneous screw fixation plus cementoplasty in the treatment of painful bone metastases with fractures or a high risk of pathological fracture.

OBJECTIVE: To evaluate the feasibility and effectiveness of computed tomography (CT)-guided percutaneous screw fixation plus cementoplasty (PSFPC), for either treatment of painful metastatic fractures or prevention of pathological fractures, in patients who are not candidates for surgical stabilization. MATERIALS AND METHODS: Twenty-seven patients with 34 metastatic bone lesions underwent CT-guided PSFPC. Bone metastases were located in the vertebral column, femur, and pelvis. The primary end point was the evaluation of feasibility and complications of the procedure, in addition to the length of hospital stay. Pain severity was estimated before treatment and 1 and 6 months after the procedure using the visual analog scale (VAS). Functional outcome was assessed by improved patient walking ability. RESULTS: All sessions were completed and well tolerated. There were no complications related to either incorrect positioning of the screws during bone fixation or leakage of cement. All patients were able to walk within 6 h after the procedure and the average length of hospital stay was 2 days. The mean VAS score decreased from 7.1 (range, 4-9) before treatment to 1.6 (range, 0-6), 1 month after treatment, and to 1.4 (range 0-6) 6 months after treatment. Neither loosening of the screws nor additional bone fractures occurred during a median follow-up of 6 months. CONCLUSIONS: Our results suggest that PSFPC might be a safe and effective procedure that allows the stabilization of the fracture and the prevention of pathological fractures with significant pain relief and good recovery of walking ability, although further studies are required to confirm this preliminary experience.

Pancreatic head excavation for tissue diagnosis may reduce unnecessary pancreaticoduodenectomies in the setting of chronic pancreatitis.

BACKGROUND: The necessity to obtain a tissue diagnosis of cancer prior to pancreatic surgery still remains an open debate. In fact, a non-negligible percentage of patients undergoing pancreaticoduodenectomy (PD) for suspected cancer has a benign lesion at final histology. We describe an approach for patients with diagnostic uncertainty between cancer and chronic pancreatitis, with the aim of minimizing the incidence of PD for suspicious malignancy finally diagnosed as benign disease. METHODS: Eighty-eight patients (85.4%) with a clinicoradiological picture highly suggestive for malignancy received formal PD (group 1). Fifteen patients (14.6%) in whom preoperative diagnosis was uncertain between pancreatic cancer and chronic pancreatitis underwent pancreatic head excavation (PHEX) for intraoperative tissue diagnosis (group 2): those diagnosed as having cancer received PD, whereas those with chronic pancreatitis received pancreaticojejunostomy (PJ). RESULTS: No patient received PD for benign disease. All patients in group 1 had adenocarcinoma on final histology. Eight patients of group 2 (53.3%) received PD after intraoperative diagnosis of cancer, whereas 7 (46.7%) received PJ because no malignancy was found at introperative frozen sections. No signs of cancer were encountered in patients receiving PHEX and PJ after a median follow-up of 42 months. Overall survival did not differ between patients receiving PD for cancer in the group 1 and those receiving PD for cancer after PHEX in the group 2 (P=0.509). CONCLUSION: Although the described technique has been used in a very selected group of patients, our results suggest that PHEX for tissue diagnosis may reduce rates of unnecessary PD, when the preoperative diagnosis is uncertain between cancer and chronic pancreatitis.

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.

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.

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.

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.

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.

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.