How we do it: totally laparoscopic complete mesocolon excision for splenic flexure cancer.

BACKGROUND: Splenic flexure (SF) cancer is not a common condition and its treatment is still under discussion. Although laparoscopic surgery is well accepted for the treatment of colon cancer at any stage, complete mesocolon excision (CME) with selective vascular ligation using the laparoscopic approach for SF cancer remains technically demanding and represents a real challenge for surgeons. METHODS: We present a single-institution experience of laparoscopic CME for SF cancer. Intra-operative, pathologic, and post-operative data of patients who underwent laparoscopic SF resection were reviewed to assess the technical feasibility and oncologic safety. Technical features, histopathology, morbidity, and mortality were evaluated. RESULTS: From February 2015 to October 2017, a minimally invasive approach was proposed to 17 patients (M/F 14/3) affected by splenic flexure cancer. In all patients, the procedure was completed by laparoscopy. The anastomosis was completed intra-corporeally in 89% of cases. The distal margin was 3.1 ± 2.6 cm and the proximal margin was 6.5 ± 3.3 cm from the tumor site. The number of mean harvested nodes was 13.9 ± 7. The mean operative time was 215.5 ± 65 min, and blood loss was 80 ± 27. In one case, a laparoscopic partial gastrectomy was associated due to tumor invasion. The mean post-operative stay was 6.7 ± 3.3 days. Readmission was necessary for two patients. No major morbidity was recorded. CONCLUSIONS: Despite the wide spread and increasing confidence in laparoscopic colectomy, SF resection remains one of the most challenging procedures in colorectal surgery with a complex learning curve. SF resection with CME and CVL is feasible and safe for the treatment of early-stage and locally advanced SF cancer.

A surgical department for intensified care.

PURPOSE: The growing pressure to rationalize costs in the healthcare system demands the development of new healthcare models aimed at allowing patients to receive the best treatment, without ignoring the rising costs. METHODS: In the Healthcare Unit 2 located in the Abruzzo region in Italy, a new model of intensified care surgical department was designed in January 2013. The department was based on the selection of the degree of patient disease. Patients requiring a medium-low degree surgery were treated in the peripheral unit, in the Ortona hospital, while more complex surgical procedures, most cancer cases (including stomach, liver, pancreas, colon-rectum or multi-organ resections), were performed in the central unit in the Chieti hospital. RESULTS: The value of production at the peripheral unit, in Ortona, increased by 299.4% along with an increase in discharges of 112.6%, with an average DRG weight from 1.02 to 1.45. At the central unit, in Chieti, the average DRG weight produced was 3.328. In relation to quality assessment, pancreatic surgery morbidity was 27.0% and mortality was 1.7 % due to resection and 2.2% for other causes. Likewise, for colon-rectal surgery, a global morbidity of 35.0% and anastomotic leakage of 3.9% was seen. CONCLUSIONS: The 24-month preliminary results show that new models of intensified care surgical departments can be created. In addition, results clearly show that such model significantly improves both services and surgical results. This original model allows optimal use of resources favouring both service quality and patient satisfaction.

It is possible to avoid routine splenic flexure mobilization during left hemicolectomy and anterior rectal resection? A single center experience compared to the surgical reality.

BACKGROUND: Routine splenic flexure mobilization (SFM) during left hemicolectomy and high anterior rectal resection guarantees a well perfused and tension-free anastomosis, respecting current oncological criteria. According to the recent literature, only 70% of laparoscopic colorectal surgeons considered routine SFM mandatory. Because of its difficulty, SFM increases morbidity including surrounding organs injuries. The goal of the study is to report our experience in avoiding routine SFM during colorectal resection compared to the current surgical state of art. METHODS: Data were collected retrospectively on elective left hemicolectomy without routine SFM performed in our unit between January 2015 to April 2020. Patients were recruited according to diagnosis, histopathology, operative time, ASA score, post-operative morbidity and mortality. RESULTS: Seventy-five oncological patients, underwent to surgery without SFM. The other 13 patients underwent to SFM due to technical issues. The mean operative time was 160.2±44.7 mins, significantly shorter than in patients whose SFM occurred (210.3 min). The morbidity rate was 1%, reintervention occurred in one patient. Eighteen-month median follow-up morbidity was 11% while mortality was 3%. Recurrence rate was of about 5%. CONCLUSIONS: As results from study data analysis, left colectomy can be conducted safely in both laparoscopic and laparotomic approach without SFM in selected cases. As reported in a recent meta-analysis, benefits of avoiding SFM concern reduced operative time without compromising postoperative outcome and respecting oncological criteria, as emerged by our results. Colorectal resection without SFM when is feasible, improves surgical approach reducing technical difficulties and avoiding splenic injuries.

HER-3 surface expression increases in advanced colorectal cancer representing a potential therapeutic target.

HER-3 (also known as ErbB-3) is a human epidermal growth factor receptor tyrosine kinases family member, and its expression in CRC (colorectal cancer) tissues was previously associated with poor prognosis. In this study, HER-3 expression was analyzed by immunohistochemistry in two cohorts of early and advanced metastatic CRC patients. The first cohort included 180 patients diagnosed with CRC in absence of lymph nodes or distant metastases (Stage I and Stage II), while the second was obtained from 53 advanced metastatic CRC patients who developed synchronous (SM) and metachronous (MM) liver metastases. In the first early-stage CRC cohort, 86 out of 180 (47.8%) tumors showed membranous expression of HER-3, with a mean percentage of positive tumor cells of 25.7%; conversely, in advanced metastatic CRC primary tumors, HER-3 was detected in all specimens, with a mean percentage of positive tumor cells of 76.1%. Kaplan-Meier curves showed that in the advanced metastatic CRC group, patients with HER-3high tumors had a significantly lower Cancer-Specific Survival (CSS) rate compared to patients with HER-3low tumors (p = 0.021). Importantly, this worse CSS rate was observed only in the MM subgroup of patients with HER-3high tumors (p = 0.002). Multivariate analysis confirmed that high HER-3 expression represents a significant and strong risk factor for death in patients developing MM liver metastases (Hazard Ratio = 64.9; 95% Confidence Interval, 4.7-886.6; p = 0.002). In addition, using a specific anti-HER-3 antibody-drug conjugate, named EV20/MMAF, we showed that HER-3 + CRC cells can be efficiently targeted in vitro and in vivo. Overall, this study confirms that surface HER-3 is highly expressed in CRC and reveals that HER-3 expression increases in metastatic CRC patients compared to early stage. Importantly, the results suggest that HER-3 has a prognostic and therapeutic value in patients developing MM liver metastases.

High Blood Concentration of Leukocyte-Derived Extracellular Vesicles Is Predictive of Favorable Clinical Outcomes in Patients with Pancreatic Cancer: Results from a Multicenter Prospective Study.

Pancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide. Identification of novel tumor biomarkers is highly advocated in PC to optimize personalized treatment algorithms. Blood-circulating extracellular vesicles hold promise for liquid biopsy application in cancer. We used an optimized flow cytometry protocol to study leukocyte-derived EVs (CD45+) and PD-L1+ EVs in blood from 56 pancreatic cancer patients and 48 healthy controls (HCs). Our results show that PC patients presented higher blood levels of total EVs (p = 0.0003), leukocyte-derived EVs (LEVs) (p = 0.001) and PD-L1+ EVs (p = 0.01), as compared with HCs. Interestingly, a blood concentration of LEVs at baseline was independently associated with improved overall survival in patients with borderline resectable or primary unresectable PC (HR = 0.17; 95% CI 0.04-0.79; p = 0.02). Additionally, increased blood-based LEVs were independently correlated with prolonged progression-free survival (HR = 0.10; 95% CI 0.01-0.82; p = 0.03) and significantly associated with higher disease control rate (p = 0.02) in patients with advanced PC receiving standard chemotherapy. Notably, a strong correlation between a decrease in blood LEVs concentration during chemotherapy and disease control was observed (p = 0.005). These intriguing findings point to the potential of LEVs as novel blood-based EV biomarkers for improved personalized medicine in patients affected by PC.

The Complex Network between Inflammation and Colorectal Cancer: A Systematic Review of the Literature.

BACKGROUND: colorectal cancer (CRC) has a multifactorial etiology which comprises microbiota, genetic predisposition, diet, environmental factors, and last but not least, a substantial contribution by inflammation. The aim of this study is to conduct a systematic review of the literature regarding the strong link between inflammation and colorectal cancer. METHODS: A systematic review of the literature on PubMed (Medline), Scopus, Cochrane and EMBase databases was performed, following the PRISMA 2020 guidelines. Each paper was reviewed by two groups of researchers in a single-blind format by using a pre-planned Microsoft© Excel® grid. RESULTS: Using automated research filters, 14,566 studies were included, but 1% was found significant by the reviewers. Seventy pathways of inflammation were described in the sequence of inflammation-carcinogenesis, and anti-tumorigenic molecules were also found. CONCLUSION: several studies suggest a strong role of inflammation in the tumorigenesis of colorectal cancer through different pathways: this may have a diagnostic and clinical role and also therapeutic purpose in preventing carcinogenesis by treating inflammation. In vitro tests support this theory, even if many other clinical trials are necessary. The present paper was registered in the OpenScience Framework registry (Identifier: DOI 10.17605/OSF.IO/2KG7T).

Transduodenal surgical ampullectomy: a procedure that requires a multidisciplinary approach.

Trans-duodenal surgical ampullectomy (TSA) was first described in 1899. Nowadays its role in ampullary tumor surgery is still a matter of debate and requires a multidisciplinary approach. The aim of this study is to evaluate the results of TSA as a curative treatment for benign and selected malignant tumors arising from the ampulla in a single-institution experience. Sixteen patients with periampullary tumors that underwent TSA in our surgical units between January 2012 and January 2017 were included in the study. Patient demographic characteristics, pre or postoperative endoscopic interventions, operative procedures, postoperative morbidity and mortality, hospitalization, follow-up time, and quality of life questionnaire were analyzed. Mean operative time was 238.5 min (range 180-390), mean tumor size was 2.3 cm (range 1.5-3.9). The microscopic surgical outcome was R0 for 14 patients. The most frequent findings in terms of histological type were high-grade dysplasia/pTis (43.7%), low-grade dysplasia in 37.5% patients, invasive adenocarcinoma in 2 cases (12.5%), chronic inflammation in 1 case (6.3%). The readmission rate was 18.8% (3/16) and in 2 cases (12.5%) relaparotomy was required. The cumulative median duration of follow-up was 50 months (range 1-96). 90-days mortality was 6.2%. Mean hospital stay was 12 days (range 8-60). Our results confirm that TSA offers good results in terms of morbidity and mortality; still, it remains a challenging procedure that requires particular surgical experience and operative skills. A pre-operative planning in a multidisciplinary board should be carried out prior to the procedure.

Outcome after single-site robotic cholecystectomy: An initial single center's experience.

BACKGROUND: Although laparoscopic cholecystectomy (LC) is the gold standard for symptomatic gallbladder disease, a single-incision approach may be a new challenge in order to achieve minimization of surgical trauma. Single-site robotic cholecystectomy (SSRC) is able to offset the ergonomic limitation of laparoscopic single-site cholecystectomy and improves cosmesis. METHODS: We present a single-institution initial experience of SSRC for cholecystolithiasis. Intra-operative and post-operative data of patients were reviewed to assess the technical feasibility and cosmetic outcome. RESULTS: We evaluated a series of 27 consecutive patients retrospectively analyzed and prospectively collected who underwent SSRC. One patient was excluded from the final analysis because they converted to open procedure. The female/male ratio was 17/9, with mean age of 48 ± 12 years. The body mass index mean value was 26.0 ± 4.2. The mean operative time was 99.6 ± 21.5 minutes. No intra- or post-operative complications and readmissions were recorded. At 12 months follow up, every patient received the Body Image Questionnaire (BIQ) and a Photo Series Questionnaire. We recorded three patients (11.5%) with post-operative incisional hernia. Scores of the BIQ subscale for body image perception were 6 ± 1.2, while the scores of scar cosmesis were 21.1 ± 3.0. A statistically significant improvement in scar self-rating from T0 to T1 (P < .01) was found. CONCLUSION: In our initial experience SSRC may be preferred to treat patients with higher needs in terms of cosmesis and body image perception. Lower costs for rent, maintenance and consumables may allow the spread of robotic surgery also for singe site cholecystectomy.

Laparoscopic Versus Open Hartmann Reversal: A Case-Control Study.

BACKGROUND: Laparoscopic reversal of Hartmann's procedure (LHR) offers reduced morbidity compared with open Hartmann's reversal (OHR). The aim of this study is to compare the outcome of laparoscopic versus open Hartmann reversal. MATERIALS AND METHODS: Thirty-four patients who underwent Hartmann reversal between January 2017 and July 2019 were evaluated. Patients underwent either LHR (n = 17) or OHR (n = 17). Variables such as numbers of patients, patient's age, sex, body mass index (BMI), comorbidities, ASA (American Society of Anesthesiology) score, indication for previous open sigmoid resection, mean operation time, rate of conversion to open surgery, length of hospital stay, mortality, and morbidity were retrospectively evaluated. RESULTS: The two groups of patients were homogeneous for gender, age, body mass index, cause of primary surgery, time to reversal, and comorbidities. In 97% of the cases, HP was done by open surgery. Our data revealed no difference in mean operation time (LHR: 180.5 ± 35.1 vs. OHR: 225.2 ± 48.4) and morbidity rate, although, in OHR group, there were more severe complications. Less intraoperative blood loss (LHR: 100 ± 40 mL vs. OHR: 450 ± 125 mL; p value <0.001), shorter time to flatus (LHR: 2.4 days vs. OHR: 3.6 days; p value <0.021), and shorter hospitalization (LHR: 4.4 vs. OHR: 11.2 days; p value <0.001) were observed in the LHR group. Mortality rate was null in both groups. Discussion. LHR is feasible and safe even for patients who received a primary open Hartmann's procedure. We suggest careful patient's selection allowing LHR procedures to highly skilled laparoscopy surgeons.

End-to-side duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy A comparison trial of small versus larger jejunal incision. A single center experience.

AIM: The rates of post-operative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) are between 5% and 30%. Nowadays, pancreaticojejunostomy (PJ) represents the most common type of reconstruction after PD, but the ideal technique is still debated. Our randomized trial was conceived with the intent to evaluate if two variants of PJ could influence the post-operative outcome in term of early complications. MATERIAL AND METHODS: Forty-eight consecutive patients treated with PD were randomized into 2 groups (Group 1 or Large Jejunal Incision or LJI group and Group 2 or Small Jejunal Incision or SJI group). Outcome measures were the operative time, postoperative complications, length of postoperative hospital stay, amylase content in drains. RESULTS: wenty-two patients were enrolled in the LJI and 26 in the SJI group. Median operative times did not differ between the 2 groups. The groups were homogeneous in respect to the median age of patients, the clinical presentation of jaundice and the presence of percutaneous biliary drainage (PBD). POPF developed in 3/22 (13.6%) and 1/26 (4%) patients among the LJI and SJI group respectively (3 grade B and 1 grade C respectively) (p=0.341). PPH occurred in 8/22 (36%) and 2/26 (8%) patients among the LJI and SJI group, respectively (p=0.018). The Amylase content in the drainage fluid measured at the 5th postoperative day showed a higher value in patients who underwent LJI anastomosis compared to those with SJI anastomosis [LJI group: 26.5 (6-254) U/l vs SJI group: 7 (0-38) U/l; p=0.051]. Delayed Gastric Emptying (DGE) was not different. The multivariate logistic regression analysis demonstrated both LJI anastomosis and DGE as independent predictors for pancreatic fistula (DGE: OR=20.04, CI 95%=1.92-208.83, P=0.012; LJI anastomosis: OR=24.58, CI 95%=1.71-354.32, P=0.019) and PPH (DGE: 30.5, CI 95%=3.02-308.16, P=0.004; LJI anastomosis: OR=12.71, CI 95%=1.23-131.55, P=0.033). CONCLUSIONS: Based on the present results, we suggest to adopt what a "pancreas duct-oriented" approach: if pancreas duct is large a SJI-PJ is recommended; if the duct is < than 3 mm, a LJI must be preferred. Our conclusion is that the association of some surgeons to perform always the techniques with them are more confident is a concept of the past: recent data suggest that the pancreatic surgeon must have the different techniques in his "armamentarium" and varying the technique depending on local characteristic of the pancreas to allow a tailored approach to the patient. KEY WORDS: Pancreaticojejunostomy, Pancreatic fistula, Surgical Sutcome.

Extracorporeal versus intracorporeal anastomosis after laparoscopic right hemicolectomy: cost-effectiveness analysis.

AIM: The cost effectiveness of the laparoscopic right hemicolectomy is still debated, and the current literature does not allow to be drawn certain conclusion. Our study compared direct clinical costs and outcomes for laparoscopic right hemicolectomy with the two most used type of anastomosis, such as ExtraCorporeal Anastomosis (ECA) and IntraCorporeal Anastomosis (ICA). MATERIAL AND METHODS: In this retrospective study, all patients who underwent laparoscopic right hemicolectomy with intracorporeal and extracorporeal anastomosis between January 2016 and April 2018 were evaluated. Patients were divided into two groups according to the type of anastomosis: ECA or ICA. RESULTS: Thirty ECA and twenty-nine ICA patients were included in the study. Operative time was significantly longer in ICA group than ECA group (p < 0.001). No significant differences between the groups were seen in terms of timeto- first flatus, postoperative complications and re-admission rate. ICA group showed a shorter hospitalization (5 vs 6; p < 0.022). In the ICA group, considering only the surgical tools were more expensive than in ECA (1435.6 € vs 72 €). Nevertheless, the total cost of the two procedures in similar (14451.36 € in ECA group vs 14631.04 € in ICA group). CONCLUSION: ECA and ICA are comparable in terms of postoperative outcomes. ICA requires much more expensive charges, compared to a minor hospitalization. The ECA seems to be less expensive in terms of surgical supplies but the longer recovery determines an increase in the total cost resulting in a non-inferiority of one compared to the other technique. KEY WORDS: Cost-analysis, ExtraCorporeal Anastomosis, IntraCorporeal Anastomosis, Laparoscopy, Right Hemicolectomy.

Borderline resectable pancreatic cancer and the role of neoadjuvant chemoradiotherapy.

Borderline resectable pancreatic cancer is now recognized as a distinct clinical entity. In these cases, neoadjuvant treatment could maximize the potential for an R0 resection and avoid R1/R2 resections. In fact, by analyzing, the current literature is evident that approximately one-third of initially borderline resectable pancreatic tumors may undergo successful resection following neoadjuvant therapy. However, the enormous difficulties in achieving a consensus and the variability in therapeutic algorithms have delayed progress in establishing strong evidence-based practices for diagnosis and treatment. In addition, the absence of a unique definition of borderline resectable pancreatic cancer remains a great obstacle for planning a therapeutic strategy and surgical decision-making. If on the one hand, we can finally say that the presence of only few prospective trials generates no strong data to support a specific neoadjuvant therapy regimen in borderline resectable pancreatic cancer, on the other hand, there are many studies on patients with borderline resectable pancreatic cancer who receive neoadjuvant therapy that can enjoy an R0 resection with similar outcomes to up-front resectable disease.

Neuromuscolar and vascular hamartoma of the duodenum. A clinical case and review of the literature.

BACKGROUND AND AIMS: The NMVH of the intestine is a rare lesion, typical located in the small bowel. After the first 2 cases, reported in 1982, other 12 cases have been described, ten localized in the jejunual or ileal tract, only 1 in the cecum. SUBJECTS AND METHODS: A case of NMVH of the duodenum, simulating a Crohns disease, is described. The lesion extended about 12 cm. and it caused intestinal stenosis. The microscopic analysis on the operative specimen highlighted the presence of a neuronal hyperplasia at mucous membranae and submucosal levels, associated to muscolaris mucosae hypertrophy and disorganisation. Expanded and ectasic veins, proliferation of nervous fibres and ganglion cells in the submucosal were also observed. RESULTS: NMVH is a non-epithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. In the controversy about the nature of the NMVH, we consider it a separate entity, where the final diagnosis depend on the clinicopathologic setting, as well as on the location and number of the lesions. CONCLUSIONS: The Authors analyse the main characteristics of this rare pathology with regard to clinical, diagnostic and therapeutic aspects.