A Scaffold-Assisted 3D Cancer Cell Model for Surface-Enhanced Raman Scattering-Based Real-Time Sensing and Imaging.

Despite recent advances in the development of scaffold-based three-dimensional (3D) cell models, challenges persist in imaging and monitoring cell behavior within these complex structures due to their heterogeneous cell distribution and geometries. Incorporating sensors into 3D scaffolds provides a potential solution for real-time, in situ sensing and imaging of biological processes such as cell growth and disease development. We introduce a 3D printed hydrogel-based scaffold capable of supporting both surface-enhanced Raman scattering (SERS) biosensing and imaging of 3D breast cancer cell models. The scaffold incorporates plasmonic nanoparticles and SERS tags, for sensing and imaging, respectively. We demonstrate the scaffold's adaptability and modularity in supporting breast cancer spheroids, thereby enabling spatial and temporal monitoring of tumor evolution.

Combination of Live Cell Surface-Enhanced Raman Scattering Imaging with Chemometrics to Study Intracellular Nanoparticle Dynamics.

Surface-enhanced Raman scattering (SERS)-encoded nanoparticles are used for bioimaging, on account of their well-defined Raman spectra and biocompatibility, which allow long incubation times with high signal stability and no cytotoxicity. However, reliable analysis of SERS bioimaging requires quantification of the amount of encoded nanoparticles that have been taken up by cells and the effect of subsequent dilution due to cellular division (mitosis). Although methods such as elemental analysis and flow cytometry can be used to quantify nanoparticle uptake, these are both end-point measurements in which a cell population is screened rather than looking at individual cells. In contrast, SERS imaging can be applied at multiple timepoints to the same individual cells without damaging the biological sample. We present the application of both supervised and unsupervised multivariate analyses, to quantify the intracellular amount of SERS tags in individual MCF7 living cells, toward the characterization of cellular uptake in vitro. The obtained results from both methodologies were validated by standard elemental analysis techniques.

SERS and Fluorescence-Active Multimodal Tessellated Scaffolds for Three-Dimensional Bioimaging.

With the ever-increasing use of 3D cell models toward studying bio-nano interactions and offering alternatives to traditional 2D in vitro and in vivo experiments, methods to image biological tissue in real time and with high spatial resolution have become a must. A suitable technique therefore is surface-enhanced Raman scattering (SERS)-based microscopy, which additionally features reduced photocytotoxicity and improved light penetration. However, optimization of imaging and postprocessing parameters is still required. Herein we present a method to monitor cell proliferation over time in 3D, using multifunctional 3D-printed scaffolds composed of biologically inert poly(lactic-co-glycolic acid) (PLGA) as the base material, in which fluorescent labels and SERS-active gold nanoparticles (AuNPs) can be embedded. The combination of imaging techniques allows optimization of SERS imaging parameters for cell monitoring. The scaffolds provide anchoring points for cell adhesion, so that cell growth can be observed in a suspended 3D matrix, with multiple reference points for confocal fluorescence and SERS imaging. By prelabeling cells with SERS-encoded AuNPs and fluorophores, cell proliferation and migration can be simultaneously monitored through confocal Raman and fluorescence microscopy. These scaffolds provide a simple method to follow cell dynamics in 4D, with minimal disturbance to the tissue model.

Surface-Enhanced Raman Scattering Tags for Three-Dimensional Bioimaging and Biomarker Detection.

We have recently witnessed a major improvement in the quality of nanoparticles encoded with Raman-active molecules (SERS tags). Such progress relied mainly on a major improvement of fabrication methods for building-blocks, resulting in widespread application of this powerful tool in various fields, with the potential to replace commonly used techniques, such as those based on fluorescence. We present hereby a brief Perspective on surface enhanced Raman scattering (SERS) tags, regarding their composition, morphology, and structure, and describe our own selection from the current state-of-the-art. We then focus on the main bioimaging applications of SERS tags, showing a gradual evolution from two-dimensional studies to three-dimensional analysis. Recent improvements in sensitivity and multiplexing ability have enabled great advancements toward in vivo applications, e.g., highlighting tumor boundaries to guide surgery. In addition, the high level of biomolecule sensitivity reached by SERS tags promises an expansion toward biomarker detection in cases for which traditional methods offer limited reliability, as a consequence of the frequently low analyte concentrations.

Fast-track surgery in real life: how patient factors influence outcomes and compliance with an enhanced recovery clinical pathway after colorectal surgery.

The aim of this prospective cohort study was to identify the patient factors that predict postoperative deviation from each item of a fast-track colorectal surgery protocol (FT) and these factors' influences on postoperative outcomes. A total of 606 patients with colorectal pathology from 2005 to 2011 were analyzed to assess the relationships between patient factors, the outcome variables, and the items of the FT program. The median length of stay was 5 days, and readmission rate was 2.3%. The morbidity rate was 26.7%. Independent predictors of prolonged length of stay were older than 75 years of age, ASA grade 3 and 4, and the presence of an ileostomy. Independent predictors of morbidity were age above 75 years old and ASA grade, whereas age was confirmed as an independent predictor of mortality. Male sex, age above 75 years old, and ASA 3 and 4 were identified as independent predictors of negative compliance to most of the postoperative FT items.

Intracorporeal versus extracorporeal anastomosis after laparoscopic right hemicolectomy for cancer: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review was to compare intracorporeal (IA) versus extracorporeal anastomosis (EA) after laparoscopic right hemicolectomy for cancer. METHODS: The meta-analysis was conducted following all aspects of the Cochrane Handbook for systematic reviews and Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Studies published from 2009 to 2012 that compare IA and EA after laparoscopic right hemicolectomy were identified. The included non-randomized studies were assessed for their methodological quality using the revised and modified grading system of the Scottish Intercollegiate Guidelines Network. Intraoperative, early postoperative, and postoperative recovery outcomes were compared using weighted mean differences and odds ratios. RESULTS: Five non-randomized controlled trials published between 2009 and 2011, comprising 425 patients, were included in this analysis. IA was associated with significant faster bowel movement, faster first flatus, shorter time to solid diet, decreased use of analgesics, and shorter duration of the hospital stay. No differences were observed for nasogastric tube reintroduction rate, operative time, incision length, number of nodes harvested, intraoperative complications, mortality, non-surgical site complications, surgical site complications (anastomotic leakage, anastomotic bleeding, wound infection, ileus), reintervention, and readmission rate. CONCLUSIONS: Even when the limitations are taken into account due to the observational nature of the included studies, the results suggest that the IA after laparoscopic right hemicolectomy for cancer results in better postoperative recovery outcomes, such as shorter hospital stay, faster bowel movement recovery, faster first flatus, faster time to solid diet, and lesser analgesic usage.

Fast-track colorectal surgery: protocol adherence influences postoperative outcomes.

PURPOSE: This single-center prospective cohort study, conducted outside of a clinical trial, tried to identify the importance of each fast-track surgery procedure and protocol adherence level on clinical outcomes after colorectal surgery. METHODS: From a prospectively maintained database, 606 patients who underwent elective laparoscopic or open colorectal resection within a well established fast-track surgery (FT) protocol, between 2005 and 2011, were identified. Univariate and multivariate analysis were performed to assess the relationship between each FT procedure with an adherence rate <100 % and the outcome variables (length of stay-LOS, 30-day morbidity and readmission rate). Patients were divided into four adherence level groups to FT procedures-100 %, 85-95 %,70-80 %, and <65 %. Each adherence group was compared with the other groups to evaluate differences in clinical outcome variables. RESULTS: Group comparisons revealed that higher levels of FT protocol adherence corresponded to significantly improved LOS and morbidity rates. Readmission rates were only significantly different between the full fast-track pathway and the less implemented groups. Multivariate analyses revealed that the fast removal of bladder catheter positively influenced length of stay (p < 0.0001) and 30-day morbidity (p < 0.0001). Laparoscopy surgery, no drain positioning and enforced mobilization improved LOS (p = 0.027, p < 0.0001, p = 0.002, respectively). Early solid feeding improved LOS (p < 0.0001), morbidity (p < 0.0001) and readmission rate (p = 0.011). CONCLUSION: Postoperative outcomes after colorectal surgery are directly proportional to FT protocol adherence. The early removal of the bladder catheter and early postoperative solid feeding independently influenced the length of hospital stay and 30-day morbidity rates.

Laparoscopic surgery improves postoperative outcomes in high-risk patients with colorectal cancer.

BACKGROUND: Patients with significant comorbidities often are denied laparoscopic colorectal resections, because they are thought to be too "high-risk." This study was designed to examine the feasibility and safety of laparoscopic colorectal resections in high-risk colorectal cancer patients and to compare them with a similar cohort of patients undergoing open resections in the same time period. METHODS: This was a single-center, prospective, cohort study conducted at a high-volume, nonuniversity, tertiary care hospital. From a database of 616 patients submitted to elective colorectal surgery for cancer within a fast-track protocol (January 2005 to November 2011), 188 patients who met at least one minor (age >80 years and body mass index (BMI) >30 m/kg(2)) and one major (cardiac, pulmonary, renal or liver disease, diabetes mellitus) criterion were classified as high-risk. Differences in baseline characteristics, intraoperative outcomes, and short-term (30-day) postoperative outcomes, as well as the pathology findings and the readmission and reoperation rates, were compared between the open and laparoscopic cohorts in both high- and low-risk groups and between high- and low-risk groups. RESULTS: During the study period, 68 high-risk patients underwent laparoscopic resections and 120 had open surgeries. A shorter length of postoperative stay (6 vs. 9 days, p < 0.0001) and fewer postoperative nonsurgical complications (4 % vs. 19 %, p = 0.003) were observed among the laparoscopic group. Postoperative major (p = 0.774) and minor complications (p = 0.3) and reoperations (p = 0.196) were similar between the two groups, and a significantly lower rate of mortality (1.5 vs. 7.5 %, p = 0.038) was observed in the laparoscopic group than in the open group. CONCLUSIONS: Laparoscopic colorectal resection can be safely performed on "high-risk" surgical patients with better results than a similar group of high-risk patients undergoing open colon resections.

General surgeons' views on Oncologic Multidisciplinary Group meetings as part of colorectal cancer care.

This study aimed to assess the current effectiveness of Oncologic Multidisciplinary Groups (OMGs) meetings across central Tuscany through surgeons' reports and their individual perceived benefits on colorectal cancer management. One hundred and sixty-seven general surgeons received a questionnaire with 21 questions covering organizational characteristics of OMGs and the individual perceived benefits of OMGs. The responses were analyzed by hospital setting (teaching vs. community hospital). The reply rate was 62.8 %, and 82 respondent surgeons (49.1 %) were involved in the treatment of colorectal cancer patients. At community hospitals, there was a more frequent participation of medical oncologists, radiation oncologists and pathologists; a less selection of discussed cases was performed; and almost all decisions were inserted into official patient charts (p < 0.05). Community hospital surgeons perceived more of a benefit than academic surgeons: OMGs ensure that all treatment options are considered and improve timeliness of care, patient outcomes, patient satisfaction and communication with patients (p < 0.05). The surveyed surgeons reported that OMGs offer a modest degree of protection from malpractice but improve communications between colleagues and are an opportunity for personal professional development. Professionals regularly participating in well-conducted and well-organized OMGs for colorectal cancer felt that the multidisciplinary strategy may be advantageous to both patients and caregivers.

Laparoscopy within a fast-track program enhances the short-term results after elective surgery for resectable colorectal cancer.

BACKGROUND: Whether laparoscopic colorectal resection improved recovery within an enhanced recovery program was investigated. METHODS: This study was designed as a query of a prospectively maintained colorectal database to identify 350 patients who underwent elective colorectal resection with primary anastomosis for colorectal cancer between January 1, 2005 and December 31, 2009. Patients were categorized into two groups (laparoscopic and open resection), and demographic, treatment, and outcome variables were independently reviewed for accuracy. A detailed fast-track protocol was prepared and distributed to all patients, department doctors, and nurses to standardize the treatment. RESULTS: A total of 209 patients underwent laparoscopic-assisted colorectal resection, and 141 had open surgery. There was no difference between the two groups in terms of age, sex, BMI, ASA, comorbidity, previous abdominal surgery, preoperative chemoradiotherapy, cancer site, and AJCC 2002 staging. Twenty-three patients in the laparoscopic group required conversion to an open procedure due to hemorrhage, tumor extension, or technical difficulties. Laparoscopic patients had earlier tolerance of diet, bowel movement, flatus and stool canalization, mobilization, suction drain removal, and interruption of analgesic drug administration. Length of postoperative stay was shorter (4 vs. 7 days, p = 0.0004) and fewer postoperative nonsurgical complications (3 vs. 13% p = 0.009) were registered for the laparoscopic group. CONCLUSIONS: This study suggests that within an enhanced recovery program, laparoscopic resection may provide the best short-term clinical outcomes for patients with resectable colorectal cancer.

A single-institution review of the absorbable clips used in laparoscopic colorectal and gallbladder surgery: feasibility, safety, and effectiveness.

This retrospective study was conducted to examine the safety and effectiveness of polymeric absorbable clips in laparoscopic gallbladder and colorectal surgery. The prospectively maintained database review included all patients undergoing elective laparoscopic cholecystectomy and colorectal resection at the institution between November 2004 and December 2009. In each patient, absorbable clips were used as the only system of vascular and cystic duct ligation. Of the 911 patients who satisfied the inclusion criteria, 664 underwent laparoscopic cholecystectomy and 247 underwent laparoscopic colonic resection. No intra-operative or post-operative bleeding related to absorbable clip use occurred in either procedure. No bile duct injuries or cystic duct leakages were observed. There were no peri-operative deaths with either procedure. In this experience, absorbable clips demonstrated easy handling and high reliability. They provided safe hemostasis and permitted complete and adequate oncologic resection.

Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer: a case-control study.

In a non-specialized setting, laparoscopic distal gastrectomy (LDG) for locally advanced diseases remains controversial, particularly given to the technical demands of the learning curve required to perform an adequate resection with D2 lymph node dissection. Inclusion criteria for this statistically generated matching controlled study were all patients who underwent subtotal laparoscopic gastrectomies from January 2006 until September 2009 for locally advanced gastric adenocarcinoma (stage II-IIIb), compared with matched patients who underwent the same procedure in an open fashion during the same period. Sixty case-matched patients were evaluated (30 laparoscopic vs. 30 open). Operative time was significantly longer (p < 0.05) for LDG. Benefits for LDG (p < 0.05) were observed among surgical short-term outcome (postoperative hospital stay, ambulation, first bowel movement, first flatus, first stool, first eating and use of analgesic drugs) and postoperative non-surgical site complications (cardiopulmonary, urinary, etc.). The 42 months' overall survival was similar (p = 0.646). Laparoscopic gastrectomy is a safe technique in a non-academic hospital setting for locally advanced gastric cancer; it seems to be adequate in terms of margin status and adequate lymph node retrieval and is associated with additional benefits as a decreased length of hospital stay, a decreased narcotic use and fewer complications.

Dexamethasone prophylaxis before thyroidectomy to reduce postoperative nausea, pain, and vocal dysfunction: a randomized clinical controlled trial.

BACKGROUND: The objective of this 2-arm, double-blind, randomized, controlled study was to assess the effects of a preoperative single dose steroid on postoperative nausea and vomiting (PONV), pain, and vocal function after thyroidectomy for benign disease. METHODS: We randomized 102 patients into 2 groups from January to December 2009: (1) treatment with 8 mg/2 mL of dexamethasone and (2) treatment with 2 mL NaCl 0.9%, both administered intravenously before anesthesia. RESULTS: The severity of nausea and the need for antiemetic drugs were reduced in patients receiving dexamethasone (p = .0001). Dexamethasone patients reported significantly less pain (p = .008); the need for analgesic drugs was lower in the dexamethasone group (p = .048). No differences were noted with regard to subjective voice analysis (p = .693). CONCLUSION: Dexamethasone (8 mg IV) is a safe and effective method to reduce PONV and pain after thyroid resection and should be used routinely.

Extracorporeal versus intracorporeal anastomosis after laparoscopic right colectomy for cancer: a case-control study.

BACKGROUND: The purpose of this study was to compare the short-term outcome (3 months) of laparoscopic right colectomy, between intra- and extracorporeal anastomosis techniques. METHODS: This study was designed as a case-controlled study from a prospective colorectal cancer database. Forty consecutive patients who underwent laparoscopic right hemicolectomy with intracorporeal anastomosis (totally laparoscopic colectomy, TLC) for adenocarcinoma, with the exception of T4 lesions and metastasis, were compared with 40 patients who underwent laparoscopic right hemicolectomy with extracorporeal anastomosis (laparoscopic-assisted colectomy, LAC). Controls were matched for stage, age, and gender via a statistically generated selection of all laparoscopic right hemicolectomies performed between October 2006 and August 2009. RESULTS: In terms of operating time (median 150 min), histopathological results, surgical site complications (5% for LAC and 2.5% for TLC), nonsurgical site complications (2.5% for LAC and 5% for TLC), hospitalization (median 5 days), there were no differences between the groups (p > 0.05). Incision length was significantly shorter for TLC (p < 0.05), but no differences were observed for postoperative use of analgesics. There were six postoperative cases of vomiting with reinsertion of nasogastric tube in the LAC group and only one case in the TLC group (p < 0.05). CONCLUSIONS: TLC seems feasible and safe, it does not significantly affect the length of surgery, and it guarantees maintenance of radical oncological standards. Furthermore, it significantly improves cosmesis and patient comfort postoperatively, reducing the rates of emesis, which leads to higher rates of early regular diet tolerance.

[Benefits and limits of minimally invasive techniques in thyroid surgery]. / Vantaggi e limiti delle tecniche mini-invasive nella chirurgia della tiroide.

The present study was designed to investigate the potential benefits and limits of two minimally invasive thyroidectomy procedures, namely minimally invasive video-assisted thyroidectomy (MIVAT) and open minimal-incision thyroidectomy (MIT). From May 2000 to June 2006, a prospective, non-randomised study was performed on 957 consecutive patients undergoing thyroid surgery. Fifty-six (5.8%) underwent MIVAT, 214 (22.4%) MIT and 687 (71.8%) conventional thyroidectomy (CT). Patients were selected for MIVAT when total thyroid volume was < or = 30 mL and for MIT when total thyroid volume was > 30 but < or = 80 mL, as determined by ultrasonography. The length of the central neck skin incision was 1.5-2 cm for MIVAT, 2.5-3.5 cm for MIT and 6-10 cm for CT. The incidence of definitive hypoparathyroidism or recurrent laryngeal palsy after MIVAT or MIT was comparable to that occurring after CT. Patients undergoing MIVAT or MIT experienced significantly less postoperative pain than those undergoing CT. Less pain was also registered in the MIVAT patient cohort as compared to the MIT group. Patients undergoing MIVAT or MIT were more satisfied with the cosmetic result as compared to those undergoing CT, whereas no significant differences were found between the MIVAT and MIT groups. As compared to CT, MIVAT and MIT provided a significant improvement in terms of cosmetic results and postoperative pain. Nevertheless, the main limiting factor for minimally invasive thyroid surgery still remains the size of the thyroid.