Enhanced perioperative care in emergency general surgery: the WSES position paper.

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients' outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

Outpatient Non-operative Management of Uncomplicated Acute Appendicitis: A Non-inferiority Study.

INTRODUCTION: Non-operative management (NOM) of uncomplicated acute appendicitis is a well-established alternative to upfront surgery. The administration of intravenous broad-spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non-inferiority study was to evaluate both safety and non-inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis. METHODS: The study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon's preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30-day appendectomy rate, with a non-inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30-day unplanned emergency department (ED) visits, and length of stay. RESULTS: 30-day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non-inferior to inNOM with a risk difference of-3.80% 97.5% CI (- 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty-six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1-4) days. In the outNOM group, the mean cumulative in-hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001). CONCLUSIONS: Outpatient NOM was non-inferior to inpatient NOM with regard to the 30-day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings.

Biliary Sepsis Due to Recurrent Acute Calculus Cholecystitis (ACC) in a High Surgical-Risk Elderly Patient: An Unexpected Complication.

Acute calculus cholecystitis (ACC) is increasing in frequency within an ageing population, in which biliary tract infection, including cholecystitis and cholangitis, is the second most common cause of sepsis, with higher morbidity and mortality rates. Patient's critical conditions, such as septic shock or anaesthesiology contraindication, may be reasons to avoid laparoscopic cholecystectomy-the first-line treatment of ACC-preferring gallbladder drainage. It can aid in patient's stabilization with also the benefit of identifying the causative organism to establish a targeted antibiotic therapy, especially in patients at high risk for antimicrobial resistance such as healthcare-associated infection. Nevertheless, a recent randomized clinical trial showed that laparoscopic cholecystectomy can reduce the rate of major complications compared with percutaneous catheter drainage in critically ill patients too. On the other hand, among the possibilities to control biliary sepsis in non-operative management of ACC, according to recent meta-analysis, endoscopic gallbladder drainage showed better clinical success rate, and it is gaining popularity because of the potential advantage of allowing gallstones clearance to reduce recurrences of ACC. However, complications that may arise, although rare, can worsen an already weak clinical condition, as happened to the high surgical-risk elderly patient taken into account in our case report.

Urgent and emergency surgery for secondary peritonitis during the COVID-19 outbreak: an unseen burden of a healthcare crisis.

The COVID-19 pandemic has raised concerns about the negative impact of the fear of contagion on people's willingness to seek medical care and the subsequent effects on patients' prognosis. To date, not much is known about the outcomes of acute surgical diseases in this scenario. The aim of this multicenter observational study is to explore the effects of COVID-19 outbreak on the outcomes of patients who underwent surgery for peritonitis. Patients undergoing surgery for secondary peritonitis during the first COVID-19 surge in Italy (March 23-May 4, 2020-COVID period group) were compared with patients who underwent surgery during the same time interval of year 2019 (no-COVID period group). The primary endpoint was the development of postoperative complications. Logistic regression analysis was conducted to identify predictors of complications. Of the 332 patients studied, 149 were in the COVID period group and 183 were in the no-COVID period group. Patients in the COVID period group had an increased frequency of late presentations to the emergency departments (43% vs. 31.1%; P = 0.026) and a higher rate of postoperative complications (35.6% vs. 18%; P < 0.001). The same results were found in the subset analysis of patients with severe peritonitis at surgical exploration. The ASA score, severity of peritonitis, qSOFA score, diagnosis other than appendicitis, and COVID period resulted independent predictors of complications. During the COVID-19 pandemic patients with peritonitis had a higher rate of complicated postoperative courses, weighing on hospital costs and assistance efforts already pressured by the ongoing sanitary crisis.

Intraoperative endoscopy with immediate suture reinforcement of the defect in colorectal anastomosis: a pilot study.

Colorectal anastomosis is the one at higher risk of complication in alimentary tract surgery. Several techniques have been used to intraoperatively check a colorectal anastomosis, without reaching a clear consensus. The aim of the present study is to evaluate the addition of intraoperative flexible endoscopy to indocyanine green fluorescence in detecting colorectal anastomotic defects in a consecutive series of patients. This was a pilot study conducted over a 15-month period. Patients were scheduled for an elective laparoscopic left colectomy or anterior resection with a planned stapled colorectal anastomosis. Pre-, intra- and postoperative data were collected. Intraoperative endoscopy was routinely performed and the anastomotic defects were classified. A suture reinforcement of the defect encountered was immediately performed either laparoscopically or transanally. The primary endpoint of the study was the rate of postoperative complications. Fitfty-two patients were enrolled. At intraoperative endoscopy, 12 anastomotic defects were detected and corrected with immediate suture reinforcement. Defects were classified as two leaks, two mucosal crash, one simultaneous leak and crash, one mucosal edema and six active bleedings. None of these patients developed any postoperative complication. Moreover, there was no postoperative bleeding complication in the entire cohort. The three patients developing a postoperative leak requiring anastomosis takedown were at high risk due to general status and cancer characteristics. Even though more data and a comparative group are needed, the results of this pilot study are very promising regarding the role of intraoperative endoscopy and suture reinforcement of a colorectal anastomotic defect.

Signet Ring Cell Carcinoma of the Ampulla of Vater With Focal Neuroendocrine Differentiation of the Amphicrine Type: Report of a Case With Long-Term Survival.

Carcinoma of the ampulla of Vater is an uncommon neoplasm and represents 0.5% of all gastrointestinal malignancies, being less common than carcinoma of the pancreas and bile ducts. The most common ampullary tumor is the adenocarcinoma with tubular growth pattern. Signet ring cell carcinoma is extremely rare. In this article, we report a case of signet ring cell carcinoma of the ampulla of Vater showing focal neuroendocrine amphicrine differentiation and intestinal phenotype, which occurred in a 49-year-old male who is still alive 7 years after surgery, without evidence of recurrence. This long-term survival might be attributed not only to the early stage of the disease but also to the neuroendocrine differentiation and the absence of genetic alterations.

Characterization of malignant gastrointestinal stromal tumors-a single center experience.

BACKGROUND: The recurrence rate, related to the unpredictable behavior of gastrointestinal stromal tumors (GISTs), continues to be a major topic of investigation, since no actual risk evaluation scales have proven to be exceedingly effective in predicting prognosis. We therefore focus in this study on investigating the predictive variables of disease recurrence. METHODS: Between September 2004 and January 2011, 34 patients, 18 males and 16 females with a median age of 62 (range, 27-87) years, underwent operations for primary, localized and advanced GISTs. Immunohistochemical profile, KIT and the platelet-derived growth factor receptor-alpha (PDGFR-α) gene mutations, tumor size, tumor site, mitotic index, synchronous tumors, adjuvant therapy, symptoms and gender were considered and analyzed as predictive variables. The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for tumor dimension to predict recurrence. RESULTS: The median follow-up (FU) was 20 months (range, 6-86 months). A first-line adjuvant therapy was performed in nine patients. Disease relapse occurred in five cases. The tumor size and the mitotic index were the strongest predictive factors (P<0.001). The optimal maximum value for the tumor size was 7 cm [area under the curve (AUC) =0.955]. CONCLUSIONS: In light of the most recent evidence, a tumor size of 7 cm should be considered the threshold value for malignancy, and smaller GISTs with low mitotic counts as tumors with a low-grade risk.

WSES classification and guidelines for liver trauma.

The severity of liver injuries has been universally classified according to the American Association for the Surgery of Trauma (AAST) grading scale. In determining the optimal treatment strategy, however, the haemodynamic status and associated injuries should be considered. Thus the management of liver trauma is ultimately based on the anatomy of the injury and the physiology of the patient. This paper presents the World Society of Emergency Surgery (WSES) classification of liver trauma and the management Guidelines.

Estimation of the prevalence of asymptomatic pancreatic cysts in the population of San Marino.

BACKGROUND: There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking. METHODS: All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1 year at the State Hospital were reviewed for asymptomatic pancreatic cysts. RESULTS: 1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p < .001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p = .038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p = .002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people. CONCLUSIONS: The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%.

Surgery for isolated liver metastases from pancreatic cancer.

The resection of liver metastases from pancreatic ductal adenocarcinoma has been discouraged because it is commonly thought that it does not improve survival. However, the role of potential prognostic factors is unclear, and universally accepted strategies have not been proposed. Between 2003 and 2014, 15 patients with isolated synchronous or metachronous metastases from pancreatic cancer underwent liver resection in our department. The role of potential prognostic factors was analyzed to predict survival. One right hepatectomy, 1 bisegmentectomy and 13 wedge resections were performed. Eleven patients underwent simultaneous pancreatic and liver resection for synchronous disease. The median overall survival (OS) was 9.1 months (95% CI 8.6-9.7). The only potential prognostic factor that significatively affected survival was the timing of metastases (metachronous vs. synchronous). Median OS in patients with metachronous disease was 11.4 months (95% CI 0-25.1) vs. 8.3 months (95% CI 6.9-9.7), p = 0.038. Surgery for liver metastases from pancreatic cancer is not suggested for most patients. If resection is considered, timing of metastatic disease could be a prognostic factor for survival after surgery.

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers.

Next generation sequencing improves the accuracy of KRAS mutation analysis in endoscopic ultrasound fine needle aspiration pancreatic lesions.

The use of endoscopic ultrasonography has allowed for improved detection and pathologic analysis of fine needle aspirate material for pancreatic lesion diagnosis. The molecular analysis of KRAS has further improved the clinical sensitivity of preoperative analysis. For this reason, the use of highly analytical sensitive and specific molecular tests in the analysis of material from fine needle aspirate specimens has become of great importance. In the present study, 60 specimens from endoscopic ultrasonography fine needle aspirate were analyzed for KRAS exon 2 and exon 3 mutations, using three different techniques: Sanger sequencing, allele specific locked nucleic acid PCR and Next Generation sequencing (454 GS-Junior, Roche). Moreover, KRAS was also tested in wild-type samples, starting from DNA obtained from cytological smears after pathological evaluation. Sanger sequencing showed a clinical sensitivity for the detection of the KRAS mutation of 42.1%, allele specific locked nucleic acid of 52.8% and Next Generation of 73.7%. In two wild-type cases the re-sequencing starting from selected material allowed to detect a KRAS mutation, increasing the clinical sensitivity of next generation sequencing to 78.95%. The present study demonstrated that the performance of molecular analysis could be improved by using highly analytical sensitive techniques. The Next Generation Sequencing allowed to increase the clinical sensitivity of the test without decreasing the specificity of the analysis. Moreover we observed that it could be useful to repeat the analysis starting from selectable material, such as cytological smears to avoid false negative results.

A case of lung metastasis in myxoinflammatory fibroblastic sarcoma: analytical review of one hundred and thirty eight cases.

PURPOSE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue tumour first identified at the end of the 1990s. This study presents our experience and literature reviews focusing on risk of recurrence. METHODS: Rizzoli Orthopaedic Institute database and literature were searched for patients with MIFS observed from 1997 to 2012. Data were analysed in a new database. RESULTS: Five patients underwent surgery at our institute, and 133 cases were retrieved from the literature. Not all clinicopathological data were available: 76/138 were men (55%), median age was 45 [interquartile range (IQR) 34-56] years, median tumour size was three (IQR two to five) centimetres. Common sites of occurrence were hand (24%), fingers (23%) and foot (20%). Pain was present at diagnosis in 14/82 patients (17%), with a median duration of seven (IQR three to 12) months. Surgery was performed for a suspected benign tumour in 88 patients (74%). Resection was incomplete in 45/71 cases (63%); re-excision was performed in 32/45 (71%). At a median follow-up of 26 months, 26/118 patients (22%) developed recurrent disease; median time to recurrence was 15 months (IQR seven to 26). Actuarial relapse-free survival (RFS) at one, three and five years was 93%, 72% and 67%, respectively. At univariate analysis, only symptom duration of six months or less was significantly associated with a worse RFS (p = 0.046). Metastatic disease to lymph nodes and/or lungs was observed in four patients (3%). CONCLUSIONS: Clinicopathological findings confirm the low-grade nature of MIFS. However, local recurrence occurs, and patients may be affected by aggressive forms with a potential for distant metastases. Follow-up is strongly advised.

Preoperative diagnosis of a solid pseudopapillary tumour of the pancreas by Endoscopic Ultrasound Fine Needle Biopsy: A retrospective case series.

BACKGROUND: A solid pseudopapillary tumour of the pancreas (SPTP) is a rare neoplasm. AIM: We herein present five cases of SPTP diagnosed using endoscopic ultrasound (EUS) guided fine-needle biopsy (FNB) using a needle with side fenestration (ProCore-needle). METHODS: From January 2011 to June 2012 in five patients with SPTP tissue acquisition was carried out with a 19-gauge (4 patients) or a 22-gauge (one patient) needle. RESULTS: The mean age of the patients was 30.8 years, the mean lesion size was 49mm and the most common location was the tail of the pancreas (3 cases). When the samples were evaluated macroscopically, small core fragments were observed in all cases. A preoperative diagnosis of SPTP was made in all patients on the basis of the histocytological and characteristic immunophenotypic patterns and was confirmed at final surgical histology. CONCLUSIONS: In our experience, EUS-FNB is an effective and secure method for a preoperative diagnosis of SPTP.

Impact of procedure volumes and focused practice on short-term outcomes of elective and urgent colon cancer resection in Italy.

BACKGROUND: The relationship between hospital volumes and short-term patients' outcomes of colon cancer (CC) surgery is not well established in the literature. Moreover, evidence about short-term outcomes of urgent compared with elective CC procedures is scanty. The aims of this study are 1) to determine whether caseloads and other hospital characteristics are associated with short-term outcomes of CC surgery; 2) to compare the outcomes of urgent and elective CC surgery. METHODS: A total of 14,200 patients undergoing CC surgery between 2005 and 2010 in the General Surgery Units (GSUs) of the hospitals of Emilia-Romagna region, Northern Italy, were identified from the hospital discharge records database. The outcomes of interest were 30-day in-hospital mortality, re-intervention and 30-day re-admission. Using multilevel analysis, we analyzed the relationship of GSU volumes and focused practice, defined as the percentage of CC operations over total operations, with the three outcomes. RESULTS: High procedure volumes were associated with a lower risk of 30-day in-hospital mortality, after adjusting for patients' characteristics [aOR (95% CI) = 0.51 (0.33-0.81)]. Stratified analyses for elective and urgent surgery showed that high volumes were associated with a lower 30-day mortality for elective patients [aOR (95% CI) = 0.35 (0.17-0.71)], but not for urgent patients [aOR (95% CI) = 0.72 (0.42-1.24)]. Focused practice was an independent predictor of re-intervention [aOR (95% CI) = 0.67 (0.47-0.97)] and re-admission [aRR (95% CI) = 0.88 (0.78-0.98)]. CONCLUSIONS: The present study adds evidence in support of the notion that patients with CC undergoing surgery at high-volume and focused surgical units experience better short-term outcomes.

Multiple KRAS mutations in pancreatic adenocarcinoma: molecular features of neoplastic clones indicate the selection of divergent populations of tumor cells.

KRAS is one of the most common genes mutated in pancreatic adenocarcinoma. Multiple KRAS mutations may be detected within the same pancreatic adenocarcinoma, but it is usually unclear whether the different mutations represent biologically irrelevant molecular events or whether they indicate the coexistence of distinct sizable neoplastic clones within a given tumor. We identified a case of pancreatic adenocarcinoma with 5 different mutations in the KRAS gene and have been able to characterize the allelic distribution of the KRAS mutations and the size of the neoplastic clones using allele-specific locked nucleic acid polymerase chain reaction and next-generation sequencing (454 GS-Junior). The results indicate that the tumor is composed of 5 distinct cell populations: one is KRAS G12V mutated (~38% of neoplastic cells), the second is KRAS G12V in one allele and KRAS G12D in the other (~32%), the third is KRAS G12V in one allele and KRAS G12R in the other (~24%), and the fourth is KRAS G12V in one allele and KRAS G12C in the other (~6%). The fifth clone, representing a minority of neoplastic cells, has a KRAS Q61H mutation in addition to one of the above alterations. Microsatellite analysis identified mutation of the NR21 marker out of the 13 tested, indicating that the tumor has a defect in maintaining DNA integrity different from loss of conventional DNA mismatch repair. These results are consistent with the successive selection of divergent populations of tumor cells and underscore the relevance of nucleotide instability in pancreatic adenocarcinoma.

Very high CEA level in a large pancreatic cyst: is it a surgical indication by itself?

BACKGROUND: Pancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. METHODS: A man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). RESULTS: The patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. CONCLUSIONS: Is it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value? Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.