Impact of Intermittent Intraoperative Neuromonitoring (IONM) on the Learning Curve for Total Thyroidectomy by Residents in General Surgery.

INTRODUCTION: Recurrent laryngeal nerve (RNL) identification constitutes the standard in thyroidectomy. Intraoperative nerve monitoring (IONM) has been introduced as a complementary tool for RLN functionality evaluation. The aim of this study is to establish how routine use of IONM can affect the learning curve (LC) in thyroidectomy. METHODS: Patients undergoing total thyroidectomy performed by surgery residents in their learning curve course in 2 academic hospitals, were divided into 2 groups: Group A, including 150 thyroidectomies performed without IONM by 3 different residents, and Group B, including 150 procedures with routine use of intermittent IONM, by other 3 different residents. LC was measured by comparing operative time (OT), its stabilization during the development of the LC, perioperative complication rate. RESULTS: As previously demonstrated, the LC was achieved after 30 procedures, in both groups, with no differences due to the use of IONM. Similarly, there were no significant differences among the 2 groups, and between subgroups independently matched, for both OT and complications, even when comparing RLN palsy. Direct nerve visualization and IONM assessment rates were comparable in all groups, and no bilateral RLN palsy (transient or permanent) were reported. No case of interrupted procedure to unilateral lobectomy, due to evidence of RLN injury, was reported. CONCLUSIONS: The study demonstrates that the use of IONM thyroid surgery, despite requiring a specific training with experienced surgeons, does not particularly affect the learning curve of residents approaching this kind of surgery, and for this reason its routine use should be encouraged even for trainees.

5-year Follow-up of Reimplanted Parathyroid Glands in Forearm Subcutaneous Tissue During Thyroidectomy. A Confirmation of Graft Vitality in a Large Series of Patients.

INTRODUCTION: The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. MATERIALS AND METHODS: We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6 months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. RESULTS: Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. CONCLUSIONS: Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period.

Application of enhanced recovery after surgery (ERAS) protocols in adrenal surgery: A retrospective, preliminary analysis.

BACKGROUND: The present study was conducted to evaluate the impact of enhanced recovery after surgery (ERAS) pathway in patients undergoing laparoscopic adrenalectomy (LA) for primary and secondary adrenal disease, in reducing the length of primary hospital stay and return to daily activities. MATERIALS AND METHODS: This retrospective study was carried out on 61 patients who underwent LA. A total of 32 patients formed the ERAS group. A total of 29 patients received conventional perioperative care and were assigned as the control group. Groups were compared in terms of patient's characteristics (sex, age, pre-operative diagnosis, side of tumour, tumour size and co-morbidities), post-operative compliance (anaesthesia time, operative time, post-operative stay, post-operative numeric rating scale (NRS) score, analgesic assumption and days to return to daily activities) and post-operative complications. RESULTS: No significant differences in anaesthesia time ( P = 0.4) and operative time ( P = 0.6) were reported. NRS score 24 h postoperatively was significantly lower in the ERAS group ( P < 0.05). The analgesic assumption in post-operative period in the ERAS group was lower ( P < 0.05). ERAS protocol led to a significantly shorter length of post-operative stay ( P < 0.05) and to return to daily activities ( P < 0.05). No differences in peri-operative complications were reported. DISCUSSION: ERAS protocols seem safe and feasible, potentially improving perioperative outcomes of patients undergoing LA, mainly improving pain control, hospital stay and return to daily activities. Further studies are needed to investigate overall compliance with ERAS protocols and their impact on clinical outcomes.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

BACKGROUND: Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). METHODS: All relevant information was collected about PC and APT patients treated between 2009 and 2021. RESULTS: Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. CONCLUSIONS: Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

Definition of learning curve for thyroidectomy: systematic review on the different approaches.

Background: Thyroidectomy is one of the most common surgical procedures carried out worldwide and it has evolved in recent years with alternative approaches. With the advent of minimally invasive techniques, the learning curve (LC) concept has become a fundamental "dogma". Methods: A literature search, according to the PRISMA guidelines, was performed via PubMed (MEDLINE), Scopus, Cochrane Library, EMBASE, and Web of Science. Only studies assessing the learning process to thyroidectomy (including hemi- and total thyroidectomy), reporting a minimum of 30 procedures and describing clearly the minimum number of performances required to achieve proficiency and the main evaluation items used to establish it, were included. Conventional, endoscopic and robotic approaches were separately analyzed. Only English-language studies were considered. Results: Forty-five relevant studies were selected for the analysis [respectively 16 concerning robotic thyroidectomy (RT), 22 endoscopic thyroidectomy (ET), 6 mini-invasive video assisted thyroidectomy (MIVAT), 1 conventional thyroidectomy (CT)]. The number of procedures required for a single surgeon to achieve competence and the parameters used to define surgical proficiency were fully investigated for each individual technique. Conclusions: Our research shows how the current literature lacks an objective definition of the LC concept. The heterogeneity of analysis methodologies and parameters evaluated, the various surgical techniques and training background of single surgeons, make it impossible to draw univocal results. Future studies should consider confounding factors and establish criteria that should be consensually recognized in the assessment of surgical performances and skills.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Laparoscopic transversus abdominis plane block is useful in pain relief after laparoscopic stapled repair of diastasis recti and ventral hernia.

Background: There is still no consensus on perioperative pain control techniques in patients undergoing laparoscopic surgery; protocols of conventional therapy can be improved by the use of perioperative anaesthesiologic techniques, such as epidural or loco-regional analgesic administration as transversus abdominis plane (TAP) block. The aim of this evaluation was to investigate the role of laparoscopic-assisted TAP block during repair of diastasis recti associated with primary midline hernias in term of post-operative pain relief. Methods: This was a retrospective evaluation of a prospectively maintained database including patients undergoing laparoscopic repair of diastasis recti associated with primary ventral hernia. Patients were divided into two groups: Group A patients (n = 34) received laparoscopic-assisted bilateral TAP-block of 7.5 mg/ml ropivacaine for each side and Group B patients (n = 29) received conventional post-operative therapy. All patients received 24 h infusion of 20 mg morphine; pain was checked at 6, 24 and 48 h after surgery by numeric rating scale (NRS) score. A rescue analgesia by was given if NRS score was >4 or on patient request. Results: No differences in operative time, complications and post-operative stay, no complications related to TAP-block technique were found. Post-operative pain scores (determined by NRS) were found to be significantly different between groups. Group A patients showed a significant reduction in NRS score at 6, 24 and 48 h (P < 0.005) and in the number of patients requiring further analgesic drugs administration (P < 0.005) compared to Group B patients. Conclusions: Laparoscopic-guided TAP-block can be considered safe and effective in the management of post-operative pain and in the reduction of analgesic need in patients undergoing laparoscopic repair of diastasis recti and ventral hernias. The non-randomised nature of the study and the lack of a consistent series of patients require further evaluations.

Insights on the Association between Thyroid Diseases and Colorectal Cancer.

Benign and malignant thyroid diseases (TDs) have been associated with the occurrence of extrathyroidal malignancies (EMs), including colorectal cancers (CRCs). Such associations have generated a major interest, as their characterization may provide useful clues regarding diseases' etiology and/or progression, with the possible identification of shared congenital and environmental elements. On the other hand, elucidation of the underlying molecular mechanism(s) could lead to an improved and tailored clinical management of these patients and stimulate an increased surveillance of TD patients at higher threat of developing EMs. Here, we will examine the epidemiological, clinical, and molecular findings connecting TD and CRC, with the aim to identify possible molecular mechanism(s) responsible for such diseases' relationship.

Therapeutic Strategies and Oncological Outcome of Peritoneal Metastases from Lung Cancer: A Systematic Review and Pooled Analysis.

The peritoneum is an unusual site of metastases from lung cancer, and optimal management at the moment remains unclear and mostly based on palliative strategies. Therefore, the aim of the study was to investigate demographic characteristics, management and overall survival of patients with peritoneal metastases from lung cancer (PCLC). A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until December 2022. PROSPERO, CRD42022349362. Inclusion criteria were original articles including patients with peritoneal carcinomatosis from lung cancer, specifying at least one outcome of interest. Exclusion criteria were being unable to retrieve patient data from articles, and the same patient series included in different studies. Among 1746 studies imported for screening, twenty-one were included (2783 patients). Mean overall survival was between 0.5 and 5 months after peritoneal carcinomatosis diagnosis and 9 and 21 months from lung cancer diagnosis. In total, 27% of patients underwent first-line or palliative chemotherapy and 7% of them surgery. Management differs significantly among published studies. The literature on PCLC is scarce. Its incidence is low but appears to be substantially rising and is likely to be an underestimation. Prognosis is very poor and therapeutic strategies have been limited and used in a minority of patients. Subcategories of PCLC patients may have an improved prognosis and may benefit from an aggressive oncological approach, including cytoreductive surgery. Further investigation would be needed in this regard.

Ultrasound-guided Transversus Abdominis Plane Block is Effective as Laparoscopic Trocar site infiltration in Postoperative Pain Management in Patients Undergoing Adrenal Surgery.

BACKGROUND: Pain management in patients undergoing laparoscopy is still a matter of debate as several techniques have been proposed to reduce postoperative analgesic consumption and improve recovery. Among these, transversus abdominis plane (TAP) block is considered as safe, effective, and easy to perform under ultrasound guidance; even so, recently laparoscopically guided trocar site anesthetic infiltration has been proposed as a "surgeon-dependent alternative to TAP block." The aim of this evaluation is to compare these analgesic techniques in the setting of laparoscopic adrenalectomy. METHODS: This is a retrospective evaluation of a prospectively maintained database. Patients were divided into two groups: Group A patients received laparoscopic-assisted trocar site infiltration of ropivacaine; Group B patients received bilateral ultrasound-guided TAP block with ropivacaine. All patients received 24 h infusion of 20 mg morphine postoperatively; pain was checked at 6, 24 and 48 h after surgery. A rescue analgesia was given if numerical rating scale (NRS) score was > 4 or on patient request. RESULTS: One hundred and three patients were enrolled in the evaluation (57 in group A and 46 in group B). There were no differences in operative time, complications and postoperative stay, and no complications related to trocar site infiltration. There were no differences in NRS at 6, 24, and 48 hours as well as in patients requiring further analgesic administration. CONCLUSIONS: Laparoscopic-guided trocar site ropivacaine infiltration has similar pain outcomes compared to ultrasound-guided TAP block in the management of postoperative pain in patients undergoing laparoscopic adrenalectomy. Since there is no difference among these techniques, the decision can be based on surgeon or anesthesiologist preference.

Multicenter retrospective cohort Italian study on elective laparoscopic cholecystectomy performed by the surgical residents.

PURPOSE: This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers. METHODS: Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score > 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open. RESULTS: A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group. CONCLUSIONS: Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons.

Laparoscopic versus Open Total Gastrectomy for Locally Advanced Gastric Cancer: Short and Long-Term Results.

BACKGROUND: Laparoscopic gastrectomy for early gastric cancer is widely accepted and routinely performed. However, it is still debated whether the laparoscopic approach is a valid alternative to open gastrectomy in advanced gastric cancer (AGC). The aim of this study is to compare short-and long-term outcomes of laparoscopic (LG) and open (OG) total gastrectomy with D2 lymphadenectomy in patients with AGC. METHODS: A retrospective comparative study was conducted on patients who underwent LG and OG for ACG between January 2015 and December 2021. Primary endpoints were the following: recurrence rate, 3-year disease-free survival, 3-year and 5-year overall survival. Univariate and multivariate analysis was conducted to compare variables influencing outcomes and survival. RESULTS: Ninety-two patients included: fifty-three OG and thirty-nine LG. No difference in morbidity and mortality. LG was associated with lower recurrence rates (OG 22.6% versus LG 12.8%, p = 0.048). No differences in 3-year and 5-year overall survival; 3-year disease-free survival was improved in the LG group on the univariate analysis but not after the multivariate one. LG was associated with longer operative time, lower blood loss and shorter hospital stay. Lymph node yield was higher in LG. CONCLUSION: LG for AGC seems to provide satisfactory clinical and oncological outcomes in medium volume centers, improved postoperative results and possibly lower recurrence rates.

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia.

Background: Primary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA). Methods: The quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA). Results: Real-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA. Conclusion: This study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA.

A Case Report of Multiple Gastrointestinal Stromal Tumors: Imaging Findings, Surgical Approach, and Review of the Literature.

Introduction: Multiple gastrointestinal stromal tumors (GISTs) are rare tumors. Differential diagnosis between metastatic and multiple GISTs represents a challenge for a proper workup, prediction prognosis, and therapeutic strategy. Case presentation: We present the case of 67-year-old man with computed tomography (CT) evidence of multiple exophytic lesions in the abdomen, reaching diameters ranging from 1 to 9 cm, without any signs of organs infiltration, and resulting positive at 18F-FDG-PET/CT. Laparoscopic biopsy revealed multiple GISTs, and surgical resection by using an open approach was performed to achieve radicality. Moreover, an extensive review of the current literature was performed. Results: Small GISTs (<5 cm) can be treated by the laparoscopic approach, while in the case of large GISTs (>5 cm), tumor location and size should be taken into account to reach the stage of radical surgery avoiding tumor rupture. For metastatic GISTs, Imatinib represents the first choice of treatment, and surgery should be considered only in a few selected cases when all lesions are resectable. Conclusion: Sporadic multiple GISTs are a rare event, imaging findings are not specific for GISTs, and biopsy requires a secure diagnosis and proper management. In the case of large lesions, with a high risk of vessels injury, laparotomy excision should be considered to achieve radicality and to avoid tumor rupture.

Effect of Antibiotic Prophylaxis on Surgical Site Infection in Thyroid and Parathyroid Surgery: A Systematic Review and Meta-Analysis.

Thyroid and parathyroid surgery are considered clean procedures, with an incidence of surgical site infection (SSI) after thyroidectomy ranging from 0.09% to 2.9%. International guidelines do not recommend routine antibiotic prophylaxis (AP), while AP seems to be employed commonly in clinical practice. The purpose of this systematic review is analyzing whether the postoperative SSI rate in thyroid and parathyroid surgery is altered by the practice of AP. We searched Pubmed, Scopus, the Cochrane Library, and Web of Science (WOS) for studies comparing AP to no preoperative antibiotics up to October 2021. Data on the SSI rate was evaluated and summarized as relative risks (RR) with 95% confidence intervals (95% CI). Risk of bias of studies were assessed with standard methods. Nine studies (4 RCTs and 5 nRCTs), including 8710 participants, were eligible for quantitative analysis. A meta-analysis showed that the SSI rate was not significantly different between AP and no preoperative antibiotics (SSI rate: 0.6% in AP vs. 2.4% in control group; RR 0.69, 0.43-1.10 95% CI, p = 0.13, I2 = 0%). A sensitivity analysis and subgroup analysis on RCTs were consistent with the main findings. Evidence of low quality supports that AP in thyroid and parathyroid surgery produce similar SSI rates as to the absence of perioperative antibiotics.

Role of New Anatomy, Biliopancreatic Reflux, and Helicobacter Pylori Status in Postgastrectomy Stump Cancer.

Distal gastrectomy for benign gastroduodenal peptic disease has become rare, but it still represents a widely adopted procedure for advanced and, in some countries, even for early distal gastric cancer. Survival rates following surgery for gastric malignancy are constantly improving, hence the residual mucosa of the gastric stump is exposed for a prolonged period to biliopancreatic reflux and, possibly, to Helicobacter pylori (HP) infection. Biliopancreatic reflux and HP infection are considered responsible for gastritis and metachronous carcinoma in the gastric stump after oncologic surgery. For gastrectomy patients, in addition to eradication treatment for cases that are already HP positive, endoscopic surveillance should also be recommended, for prompt surveillance and detection in the residual mucosa of any metaplastic-atrophic-dysplastic features following surgery.

Prodrug based on halloysite delivery systems to improve the antitumor ability of methotrexate in leukemia cell lines.

The prodrug approach, as well as the development of specific systems able to deliver a chemotherapeutic agent in the target site, decreasing the side effects often associated with its administration, are still a challenging. In this context, both methotrexate drug molecules (MTX) and biotin ligand moieties, whose receptors are overexpressed on the surface of several cancer cells, were loaded on halloysite nanotubes (HNTs) to develop nanomaterial based on multifunctional and "smart" delivery systems. To highlight the crucial role played by biotin, carrier systems based on HNTs and MTX were also synthetized. In detail, several approaches were envisaged: i) a supramolecular interaction between the clay and the drug; ii) a covalent grafting of the drug onto the HNTs external surface and, iii) a combination of both approaches. The nanomaterials obtained were characterized by thermogravimetric analysis, FT-IR, and UV-vis spectroscopies, DLS and ζ-potential measurements and the morphologies were imaged by HAADF/STEM investigations. Kinetic release experiments at different pH conditions were also performed. Finally, as a proof-of-concept application of our pro-drug delivery systems based on HNTs in cancer therapy, the cytotoxic effects were evaluated on acute myeloid leukemia cell lines, HL60 and its multidrug resistance variant, HL60R. The obtained results showed that both the MTX prodrug system and the biotinylated ones played a crucial role in the biological activity and, they are promising agents for the cancer treatments.

Synchronous liver and peritoneal metastases from colorectal cancer: Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with liver resection a feasible option?

Background: Traditionally, synchronous liver resection (LR), cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have been contraindicated. Nowadays, clinical practice has promoted this aggressive treatment in selected cases. This study aimed to review surgical and survival results of an extensive surgical approach including CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) and LR. Methods: PubMed, EMBASE, and Web of Science databases were matched to find the available literature on this topic. The search period was limited to 10 years (January 2010-January 2021). A threshold of case series of 10 patients or more was applied. Results: In the search period, out of 114 studies found about liver and peritoneal metastases from colorectal cancer, we found 18 papers matching the inclusion criteria. Higher morbidity and mortality were reported for patients who underwent such an extensive surgical approach when compared with patients who underwent only cytoreductive surgery and HIPEC. Also, survival rates seem worse in the former than in the latter. Conclusion: The role of combined surgical strategy in patients with synchronous liver and peritoneal metastases from colorectal cancer remains controversial. Survival rates and morbidity and mortality seem not in favor of this option. A more accurate selection of patients and more restrictive surgical indications could perhaps help improve results in this subgroup of patients with limited curative options.

Laparoscopic-Guided Ropivacaine Trocar-Site Infiltration Can Improve Post-Operative Pain Control after Laparoscopic Adrenalectomy.

BACKGROUND: There is no consensus on pain control in patients undergoing laparoscopy; nowadays, conventional therapy may be improved by transversus abdominis plane block. The aim of this evaluation is to investigate the role of laparoscopic-assisted trocar-site ropivacaine infiltration during adrenalectomy in pain control. METHODS: This is a retrospective evaluation of a prospectively maintained database including patients undergoing adrenalectomy. Patients were divided into 2 groups: Group A patients received laparoscopic-assisted trocar-site infiltration of 7.5 mg/mL ropivacaine and Group B patients did not receive any infiltration. All patients received a 24-hour infusion of 20 mg morphine; pain was checked at 6, 24, and 48 hours after surgery by Visual Analogue Scale (VAS) score. A rescue analgesia by was given if VAS score was > 4 or on patient request. RESULTS: No differences in operative time, complications, and post-operative stay and no complications related to trocar-site infiltration were found. 6-hour and 48-hour VAS scores were not found to be significantly different between groups, even if a slight decrease in VAS score in Group A was reported. Group A showed significant reduction in VAS score at 24 hours (2.44 +/- .41 vs 3.01 +/- .78, P < .005) and in the number of patients requiring further analgesic drugs administration (40.6% vs 57.8%, P < .005). CONCLUSIONS: Laparoscopic-guided trocar-site ropivacaine infiltration can be considered safe and effective in the management of post-operative pain and in the reduction of analgesic need in patients undergoing laparoscopic adrenalectomy. The retrospective nature of the study and the lack of a consistent series of patients require further evaluations.

Complete mesocolic excision and central vascular ligation in colorectal cancer in the era of minimally invasive surgery.

Since the 19th century, appropriate lymphadenectomy has been considered a cornerstone of oncologic surgery and one of the most important prognostic factors. This approach can be applied to any surgery for gastrointestinal cancer. During surgery for colon and rectal cancer, an adequate portion of the mesentery is removed together with the segment of bowel affected by the disease. The adequate number of lymph nodes to be removed is standardized and reported by several guidelines. It is mandatory to determine the appropriate extent of lymphadenectomy and to balance its oncological benefits with the increased morbidity associated with its execution in cancer patients. Our review focuses on the concept of "complete mesenteric excision (CME) with central vascular ligation (CVL)," a radical lymphadenectomy for colorectal cancer that has gained increasing interest in recent years. The aim of this study was to evaluate the evolution of this approach over the years, its potential oncologic benefits and potential risks, and the improvements offered by laparoscopic techniques. Theoretical advantages of CME are improved local-relapse rates due to complete removal of the intact mesocolic fascia and improved distance recurrence rates due to ligation of vessels at their origin (CVL) which guarantees removal of a larger number of lymph nodes. The development and worldwide diffusion of laparoscopic techniques minimized postoperative trauma in oncologic surgery, providing the same oncologic results as open surgery. This has been widely applied to colorectal cancer surgery; however, CME entails a technical complexity that can limit its wide minimally-invasive application. This review analyzes results of these procedures in terms of oncological outcomes, technical feasibility and complexity, especially within the context of minimally invasive surgery.