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.

MTHFR, XRCC1 and OGG1 genetic polymorphisms in breast cancer: a case-control study in a population from North Sardinia.

BACKGROUND: Despite conflicting results, considerable evidence suggests the association between single nucleotide polymorphisms in MTHFR, XRCC1 and OGG1 genes and, risk of developing breast cancer. Here a case-control study is reported, including 135 breat cancer patients and 112 healthy women, all representative of Northern Sardinian population. METHODS: Polymerase chain reaction/restriction fragment length polymorphism method was used to determine the genotypes of five polymorphisms: MTHFR C677T (rs1801133) and A1298C (rs1801131), XRCC1 Arg194Trp (rs1799782) and Arg399Gln (rs25487) and OGG1 Ser326Cys (rs1052133). Allelic, genotypic and haplotype association analyses with disease risk and clinicopathological parameters were performed. RESULTS: A nominally significant association with breast cancer risk was observed for MTHFR C677T polymorphism heterozygous genotype in the codominant model (OR: 0.57, 95% CI: 0.32-1.00, p = 0.049) and for Cys/Cys genotype of the OGG1 Ser326Cys polymorphism in the recessive model (OR: 0.23, 95% CI: 0.05-1.11, p = 0.0465). No significant differences were found at genotype-level for A1298C polymorphism of the MTHFR gene and Arg194Trp and Arg399Gln of the XRCC1 gene. Furthermore, the OGG1 and XRCC1 rs25487 polymorphisms were nominally associated with PgR, Her2 status and with sporadic breast cancer, respectively. CONCLUSIONS: Based on genetic characteristics of individuals included in this study, results suggest that MTHFR CT and OGG1 Cys/Cys genotypes have a protective effect that may have an influence on breast cancer risk in a representative Northern Sardinian population.

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.

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.

Synergizing Immunotherapy and Antibody-Drug Conjugates: New Horizons in Breast Cancer Therapy.

The advent of immunotherapy and antibody-drug conjugates (ADCs) have revolutionized breast cancer treatment, offering new hope to patients. However, challenges, such as resistance and limited efficacy in certain cases, remain. Recently, the combination of these therapies has emerged as a promising approach to address these challenges. ADCs play a crucial role by delivering cytotoxic agents directly to breast cancer cells, minimizing damage to healthy tissue and enhancing the tumor-killing effect. Concurrently, immunotherapies harness the body's immune system to recognize and eliminate cancer cells. This integration offers potential to overcome resistance mechanisms and significantly improve therapeutic outcomes. This review explores the rationale behind combining immunotherapies with ADCs, recent advances in this field, and the potential implications for breast cancer treatment.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials. Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer-free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall's τ and R2 ≥ 0.70 were considered as indicators of a clinically relevant surrogacy. Findings: Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49-65). After a median follow-up of 10.3 years (IQR 6.4-14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall's τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI. Interpretation: Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials. Funding: This analysis was supported by the Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and by Italian Ministry of Health-5 × 1000 funds (years 2021-2022).

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.

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.

Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies.

Background: Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant. However, this classification is largely based on expert opinion and no proper evidence exists to date to support its possible prognostic and clinical impact. Methods: This analysis included individual patient-level data from 4 adjuvant phase III randomized trials by the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. The impact of endocrine resistance/sensitivity classification on overall survival (mOS, defined as time between date of distant relapse and death) was assessed in both univariate and multivariate Cox proportional hazards models. Findings: Between November 1992 and July 2012, 9058 patients were randomized in 4 trials, of whom 6612 had HR+/HER2- BC. Median follow-up was 9.1 years (interquartile range [IQR] 5.6-15.0). In the whole cohort, disease-free survival and OS were 90.4% and 96.6% at 5 years, and 79.1% and 89.4% at 10 years, respectively. The estimated hazard of recurrence raised constantly during the first 15 years from diagnosis, being more pronounced during the first 2 years and less pronounced after year 7. Among the 493 patients with a distant relapse as first disease-free survival event and available date on ET completion, 72 (14.6%), 207 (42.0%) and 214 (43.4%) were classified as having 1ER, 2ER and ES, respectively. Median follow-up from diagnosis of a distant relapse was 3.8 years (IQR 1.6-7.5). Patients with 1ER were significantly more likely to be younger, to have N2/N3 nodal status, grade 3 tumours and to develop visceral metastases. Site of first distant relapse was significantly different between the 3 groups (p = 0.005). In patients with 1ER, 2ER and ES breast cancer, median mOS was 27.2, 38.4 and 43.2 months, respectively (p = 0.03). As compared to patients with ES disease, a higher risk of death was observed in those with 1 ER (adjusted Hazard Ratio [aHR] 1.54; 95% CI 1.03-2.30) and 2ER (aHR 1.17; 95% CI 0.87-1.56) (p = 0.11). Interpretation: This large analysis with long-term follow-up provides evidence on the prognostic and clinical impact of the currently adopted endocrine resistance/sensitivity classification in patients with HR+/HER2- advanced BC. This classification may be considered a valid tool to guide clinical decision-making and to design future ET trials in the metastatic setting. Funding: AIRC.

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.

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.

Impact on breast cancer susceptibility and clinicopathological traits of common genetic polymorphisms in TP53, MDM2 and ATM genes in Sardinian women.

Common variants of genes involved in DNA damage correction [tumor protein p53 (TP53), murine double 2 homolog oncoprotein (MDM2) and ataxia-telengiectasia mutated (ATM)] may serve a role in cancer predisposition. The purpose of the present study was to investigate the association of five variants in these genes with breast cancer risk and clinicopathological traits in a cohort of 261 women from northern Sardinia. Polymorphic variants in TP53 (rs17878362, rs1042522 and rs1625895), MDM2 (rs2279744) and ATM (rs1799757) were determined by PCR and TaqMan single nucleotide polymorphism assay in patients with breast cancer (n=136) and healthy controls (n=125). Association with clinicopathological (e.g., age at diagnosis, lymph node involvement, clinical stage) and lifestyle factors (e.g., smoking status, alcohol intake, contraceptive use) was also evaluated. TP53 rs17878362 and rs1625895 polymorphisms were associated with decreased risk of BC diagnosis in patients older than 50 years (codominant and recessive models) and post-menopause (recessive model). Furthermore, there was a significant association between lymph node status (positive vs. negative) and ATM rs1799757-delT in dominant and additive models and between MDM2 rs2279744-allele and use of oral contraceptives. This analysis suggested that TP53 rs17878362 and rs1625895 may affect age of onset of breast cancer and ATM rs1799757 and MDM2 rs2279744 may be associated with lymph node status and prolonged use of oral contraceptives, respectively.

Meta-analysis of trials comparing minimally-invasive and open liver resections for hepatocellular carcinoma.

BACKGROUND: Recent literature suggests that minimally-invasive hepatectomy (MIH) for hepatocellular carcinoma (HCC) is associated with better perioperative results and similar oncologic outcomes compared to open hepatectomy (OH). However, previous reports have been limited by small sample size and single-institution design. METHODS: To overcome these limitations, we performed a meta-analysis of studies comparing MIH and OH in patients with HCC using a random-effects model. RESULTS: Nine eligible studies were identified that included 227 patients undergoing MIH and 363 undergoing OH. Patients were similar respect to age, gender, rates of cirrhosis, hepatitis C infection, tumour size, and American Society of Anesthesiology classification. The MIH group had lower rates of hepatitis B infection. There were no differences in type of resection (anatomic or non-anatomic), use of Pringle's maneuver, and operative time. Patients undergoing MIH had less blood loss [difference -217 mL; 95% confidence interval (CI), -314 to -121], lower rates of transfusion [odds ratio (OR), 0.38; 95% CI, 0.24 to 0.59], shorter postoperative stay (difference -5 days; 95% CI, -7.84 to -2.25), lower rates of positive margins (OR, 0.30; 95% CI, 0.12 to 0.69) and perioperative complications (OR, 0.45; 95% CI, 0.31 to 0.66). Survival outcomes were similar in the two groups. CONCLUSIONS: Although patient selection might have influenced some of the observed outcomes, MIH was associated with decreased blood loss, transfusions, rates of positive resection margins, overall and specific morbidity, and hospital stay. Survival outcomes did not differ between MIH and OH, although further studies are needed to evaluate the impact of MIH on long-term results.

Surgical treatment of hepatocellular carcinoma in the era of COVID-19 pandemic: A comprehensive review of current recommendations.

The new coronavirus disease 2019 (COVID-19) pandemic has resulted in a global health emergency that has also caused profound changes in the treatment of cancer. The management of hepatocellular carcinoma (HCC) across the world has been modified according to the scarcity of care resources that have been diverted mostly to face the surge of hospitalized COVID-19 patients. Oncological and hepatobiliary societies have drafted recommendations regarding the adaptation of guidelines for the management of HCC to the current healthcare situation. This review focuses on specific recommendations for the surgical treatment of HCC (i.e., hepatic resection and liver transplantation), which still represents the best chance of cure for patients with very early and early HCC. While surgery should be pursued for very selected patients in institutions where standards of care are maintained, alternative or bridging methods, mostly thermoablation and transarterial therapies, can be used until surgery can be performed. The prognosis of patients with HCC largely depends on both the characteristics of the tumour and the stage of underlying liver disease. Risk stratification plays a pivotal role in determining the most appropriate treatment for each case and needs to balance the chance of cure and the risk of COVID-19 infection during hospitalization. Current recommendations have been critically reviewed to provide a reference for best practices in the clinical setting, with adaptation based on pandemic trends and categorization according to COVID-19 prevalence.

Current role of hepatopancreatoduodenectomy for the management of gallbladder cancer and extrahepatic cholangiocarcinoma: A systematic review.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is the simultaneous combination of hepatic resection, pancreaticoduodenectomy, and resection of the entire extrahepatic biliary system. HPD is not a universally accepted due to high mortality and morbidity rates, as well as to controversial survival benefits. AIM: To evaluate the current role of HPD for curative treatment of gallbladder cancer (GC) or extrahepatic cholangiocarcinoma (ECC) invading both the hepatic hilum and the intrapancreatic common bile duct. METHODS: A systematic literature search using the PubMed, Web of Science, and Scopus databases was performed to identify studies reporting on HPD, using the following keywords: 'Hepatopancreaticoduodenectomy', 'hepatopancreatoduodenectomy', 'hepatopancreatectomy', 'pancreaticoduodenectomy', 'hepatectomy', 'hepatic resection', 'liver resection', 'Whipple procedure', 'bile duct cancer', 'gallbladder cancer', and 'cholangiocarcinoma'. RESULTS: This updated systematic review, focusing on 13 papers published between 2015 and 2020, found that rates of morbidity for HPD have remained high, ranging between 37.0% and 97.4%, while liver failure and pancreatic fistula are the most serious complications. However, perioperative mortality for HPD has decreased compared to initial experiences, and varies between 0% and 26%, although in selected center it is well below 10%. Long term survival outcomes can be achieved in selected patients with R0 resection, although 5-year survival is better for ECC than GC. CONCLUSION: The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct, provided that it is performed in centers with high experience in hepatobiliary-pancreatic surgery. Extensive use of preoperative portal vein embolization, and preoperative biliary drainage in patients with obstructive jaundice, represent strategies for decreasing the occurrence and severity of postoperative complications. It is advisable to develop internationally-accepted protocols for patient selection, preoperative assessment, operative technique, and perioperative care, in order to better define which patients would benefit from HPD.

Exploring metastatic breast cancer treatment changes during COVID-19 pandemic.

The emergency caused by COVID-19 pandemic has imposed a sudden reorganization of the healthcare structures and has created consequences in cancer patients management. General clinical recommendations for cancer patients were released, even if limited clinical cancer-specific data were available. A number of critical issues have come out during COVID-19 pandemic in the management of patients with metastatic breast cancer (MBC). To explore the changes in the treatment of patients with MBC during COVID-19 pandemic, we promoted a survey to the oncologists operating in the Italian breast units. The results of this survey show that Italian oncologists have tried to ensure continuity of care for patients with MBC. De-escalation of cancer treatments, especially monotherapy administration, and greater use of oral anticancer drugs are the main changes that emerge from this survey. Some subgroups of patients, especially the elderly and endocrine-responsive patients, have been undertreated during the COVID-19 pandemic.

De-escalating cancer treatments during COVID 19 pandemic: Is metronomic chemotherapy a reasonable option?

COVID 19 pandemic represents an emergency for public health services and containment measures to reduce the risk of infection have been promptly activated worldwide. The healthcare systems reorganization has had a major impact on the management of cancer patients who are considered at high risk of infection. Recommendations and guidelines on how to manage cancer patients during COVID 19 pandemic have been published. Oral administration of chemotherapy is recommended to limit the access of cancer patients to hospital facilities and in some cases to guarantee the continuum of care. Low-dose metronomic administration of chemotherapy with different drugs and schedules has emerged in the last years as a possible alternative to conventional chemotherapy, due to its promising tumor control rates and excellent safety profiles. Moreover, given that many metronomic schedules use the oral route administration, it could represent a therapeutic strategy to ensure continuum of cancer care during COVID 19 pandemic. In this review we have selected all the clinical studies that have used the metronomic strategy, especially with oral drugs, in order to identify the subgroups of cancer patients who can benefit most from a metronomic approach even during COVID 19 pandemic.

The Impact on Survival and Morbidity of Portal-Mesenteric Resection During Pancreaticoduodenectomy for Pancreatic Head Adenocarcinoma: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: The literature is conflicting regarding oncological outcome and morbidity associated to portal-mesenteric resection during pancreaticoduodenectomy (PD) in patients with pancreatic head adenocarcinoma (PHAC). Methods: A meta-analysis of studies comparing PD plus venous resection (PD+VR) and standard PD exclusively in patients with adenocarcinoma of the pancreatic head was conducted. Results: Twenty-three cohort studies were identified, which included 6037 patients, of which 28.6% underwent PD+VR and 71.4% underwent standard PD. Patients who received PD+VR had lower 1-year overall survival (OS) (odds radio OR 0.79, 95% CI 0.67-0.92, p = 0.003), 3-year OS (OR 0.72, 95% CI 0.59-0.87, p = 0.0006), and 5-year OS (OR 0.57, 95% CI 0.39-0.83, p = 0.003). Patients in the PD+VR group were more likely to have a larger tumor size (MD 3.87, 95% CI 1.75 to 5.99, p = 0.0003), positive lymph nodes (OR 1.24, 95% CI 1.06-1.45, p = 0.007), and R1 resection (OR 1.74, 95% CI 1.37-2.20, p < 0.0001). Thirty-day mortality was higher in the PD+VR group (OR 1.93, 95% CI 1.28-2.91, p = 0.002), while no differences between groups were observed in rates of total complications (OR 1.07, 95% CI, 0.81-1.41, p = 0.65). Conclusions: Although PD+VR has significantly increased the resection rate in patients with PHAC, it has inferior survival outcomes and higher 30-day mortality when compared with standard PD, whereas postoperative morbidity rates are similar. Further research is needed to evaluate the role of PD+VR in the context of multimodality treatment of PHAC.