3D Printed Devices for the Separation of Blood Plasma from Capillary Samples.

Sample preparation is a critical requirement for many clinical tests and diagnostic procedures, but it is difficult to perform on a lab-on-a-chip platform. The analytical side of microfluidic technologies has been gradually catching up with laboratory methods in terms of sensitivity, selectivity, and reliability. There is a growing need for the development of sample preparation modules that can either be connected or embedded into such devices and extract blood plasma in a fast, safe, and automated way. Achieving this functionality is an important step towards creating commercially viable products that can one day become part of everyday life. In this study, a range of simple, yet effective, 3D printed sample preparation devices was developed. The devices rely on snap-fit mechanisms and "resin-bonding" methods to fasten two layers and integrate a plasma separation membrane in between. The devices have excellent usability, with only one step required for their operation without any waiting time for the user, and could extract an average of 56.88% of the total available plasma from 50 µL capillary blood samples in 87 s without inducing any haemolysis. The manufacturing process is quick and straightforward, requiring only low-cost equipment and minimal training. The devices can either be used as a stand-alone device or integrated into an existing lab-on-a-chip system to provide blood filtration capabilities.

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.

Open Hemorrhoidectomy With Ligasure™ Under Local or Spinal Anesthesia: A Comparative Study.

BACKGROUND: There is increasing evidence that many anorectal surgical procedures may be performed under local anesthesia. The aim of the present study was to evaluate the safety and efficacy of local anesthesia in the outpatient clinic vs spinal anesthesia in the operating room for open hemorrhoidectomy. METHODS: Sixty-two patients with grade III or IV hemorrhoids underwent open hemorrhoidectomy with LigaSure™ between 2018 and 2020. Of them, 32 procedures were performed in the operating room under spinal anesthesia with hyperbaric bupivacaine and other 30 procedures were undertaken in the outpatient clinic under local anesthesia with ropivacaine. RESULTS: There were no significant differences regarding age, gender, American Society of Anesthesiologists class, and Goligher's grade in between groups. No significant differences were observed in postoperative pain score (P = .85), perioperative complications (P = .51), and reoperation rate (P = .96). No recurrences and no differences in patients' satisfaction degree (P = .76) were documented at long-term follow-up in both study groups. DISCUSSION: Our results suggest that open hemorrhoidectomy with LigaSure™ performed in selected patients under local anesthesia in the outpatient clinic is a well-tolerated, safe, and effective procedure.

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.

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.

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.

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.

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.

Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.

The COVID-19 Outbreak May Be Associated to a Reduced Level of Care for Breast Cancer. A Comparative Study with the Pre-COVID Era in an Italian Breast Unit.

The recent COVID-19 pandemic has caused profound changes to healthcare systems as well as had deleterious repercussions on the care of cancer patients. In this comparative study, we sought to evaluate the effects of the COVID-19 pandemic on the surgical management of breast cancer in a breast unit in an Italian region with a low incidence of COVID-19 infection. Eighty-three patients were included, of whom 41 received surgery during the height of the pandemic (Group A, operated on between March and April 2020), and 42 during the same period of the year in 2019 (Group B). Clinicopathological characteristics and surgical outcomes were compared between the two groups. There were no significant differences in the baseline characteristics of the two groups with regard to age (p = 0.62), tumour size (p = 0.25), grade (p = 0.27), histology (p = 0.43), positive lymph node status (p = 0.35), and ER positive status (0.35). Waiting time for surgery was slightly longer in Group A (49.11 vs. 46.39 days, p = 0.38). Patients receiving immediate breast reconstruction were significantly less in Group A (p < 0.001). The use of sentinel node biopsy was similar in the two groups (p = 0.84). Hospital stay was longer in patients of Group B (p = 0.008). The use of regional nerve blocks was lower in Group A (p < 0.001). Patients operated on during the height of the pandemic were less likely to receive immediate reconstruction and regional nerve blocks during surgery. These features configure a situation of reduced level of care for patients with breast cancer. Efforts should be taken by the healthcare systems to maintain standard of care, even in case of a new peak in the coronavirus outbreak.

Management of complex liver cystic hydatidosis: challenging benign diseases for the hepatic surgeon: A case series report from an endemic area.

Hydatid cysts of the liver are benign lesions which require a wide range of surgical strategies for their treatment. We hypothesized that cysts larger than 15 cm, or compressing main vascular structures, or located in both hemilivers should be considered, as well as complicated cysts, in the category of complex hydatid cysts.In a retrospective study including 55 patients, we evaluated the characteristics of complex hydatid cysts, and compared surgical outcomes between patients operated on for complex cysts (Complex Group) and those operated on for non-complex cysts (non-Complex Group).In the Complex Group, 19% of patients had cysto-biliary communication with recurrent cholangitis, 9.5% had cysts eroding the diaphragm or chest wall, or communicating with the bronchial tree, 31% had cysts with contact with main vascular structures, 11.9% had multiple bilobar cysts, 14.3% had giant cysts with organ displacement, and 14.3% had a combination of the above-mentioned types. Type of surgical treatment was different between the two groups (P < .001). Additional procedures were statistically more frequent in the Complex Group (P = .02). Postoperative morbidity was higher in the Complex Group, although not in a significant manner (P = .07). Median hospital stay was longer in the Complex Group (12 vs 7 days, P < .001). No 30-day mortality occurred. Four patients (7.3%), all belonging to the Complex Group, required reoperation for postoperative complications.Surgery for complex hydatid cysts of the liver is potentially burdened by serious complications. This kind of benign liver disease requires skill-demanding procedures and should be treated in centers with expertise in both hepato-biliary surgery and hydatid disease management.

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.

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.