MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

The Concept of Oncoplastic Breast Surgery Applied in Surgery for a Giant Fibroadenoma

The treatment of a 40-year-old woman with a giant fibroadenoma in her left breast is presented. The fibroadenoma measured 14 × 5 × 3 cm and weighed 170 g. We demonstrate that the surgical strategy and the reconstructive techniques in oncoplastic breast cancer surgery successfully can be applied to the treatment of these rare benign tumours improving the cosmetic and functional outcome.

Emergency surgery in COVID-19 outbreak:Has anything changed?Single center experience

BACKGROUND The current coronavirus disease 19(COVID-19)pandemic is changing the organization of health care and has had a direct impact on the management of surgical patients.At the General Surgery Department of Sant’Anna University Hospital in Ferrara,Italy,surgical activities were progressively reduced during the peak of the COVID-19 outbreak in Italy.During this period,only one operating room was available for elective cancer surgeries and another for emergency surgeries.Moreover,the number of beds for surgical patients had to be reduced to provide beds and personnel for the new COVID-19 wards.AIM To compare 2 different period(from March 9 to April 92019 and from March 9 to April 92020),searching differences in terms of number and type of interventions in emergency surgery of a main University Hospital in Ferrara,a city in Emilia Romagna region,North of Italy.METHODS This retrospective study was carried out at the General Surgery Department of Sant’Anna University Hospital in Ferrara,Italy.We examined the number of emergency surgeries performed and patient outcomes during the peak of the COVID-19 outbreak in Italy and subsequent total lockdown.We then drew a comparison with the number of surgeries performed and their outcomes during the same period in 2019.The study examined all adult patients who underwent emergency surgery from March 9 to April 9,2019(n=46),and those who underwent surgery during the first month of the lockdown,from March 9 to April 9,2020(n=27).Analyses were adjusted for age,gender,American Society of Anesthesiologists classification scores and types of surgery.RESULTS A total of 27 patients underwent emergency surgery at Sant’Anna University Hospital in Ferrara during the first month of the lockdown.This represents a 41.3%reduction in the number of patients who were hospitalized and underwent emergency surgery compared to the same period in 2019.The complication rate during the pandemic period was substantially higher than it was during the analogous period in 2019:15 out of 27 cases from March 9 to April 9,2020(55)vs 17 out of 46 cases from March 9 to April 9,2019(36.9).Of the 27 patients who underwent emergency surgery during the pandemic,10 were screened for COVID-19 using both thorax high resolution computerized tomography and a naso-pharyngeal swab,while 9 only underwent thorax high resolution computerized tomography.Only 1 patient tested positive for SARS-CoV-2 and died following surgery.CONCLUSION There was a significant reduction in emergency surgeries at our center during the COVID-19 pandemic,and it is plausible that there were analogous reductions at other centers across Italy.

Delta shock index predicts injury severity,interventions,and outcomes in trauma patients:A 10-year retrospective observational study

BACKGROUND Most trauma occurs among young male subjects in Qatar.We examined the predictive values of the delta shock index(DSI),defined as the change in the shock index(SI)value from the scene to the initial reading in the emergency unit(i.e.,subtracting the calculated SI at admission from SI at the scene),at a Level 1 trauma center.AIM To explore whether high DSI is associated with severe injuries,more interventions,and worse outcomes[i.e.,blood transfusion,exploratory laparotomy,ventilator-associated pneumonia,hospital length of stay(HLOS),and in-hospital mortality]in trauma patients.METHODS A retrospective analysis was conducted after data were extracted from the National Trauma Registry between 2011 and 2021.Patients were grouped based on DSI as low(≤0.1)or high(>0.1).Data were analyzed and compared usingχ^(2) and Student’s t-tests.Correlations between DSI and injury severity score(ISS),revised trauma score(RTS),abbreviated injury scale(AIS),Glasgow coma scale(GCS),trauma score-ISS(TRISS),HLOS,and number of transfused blood units(NTBU),were assessed using correlation coefficient analysis.The diagnostic testing accuracy for predicting mortality was determined using the validity measures of the DSI.Logistic regression analysis was performed to identify predictors of mortality.RESULTS This analysis included 13212 patients with a mean age of 33±14 years,and 24%had a high DSI.Males accounted for 91%of the study population.The trauma activation level was higher in patients with a high DSI(38%vs 15%,P=0.001).DSI correlated with RTS(r=-0.30),TRISS(r=-0.30),NTBU(r=0.20),GCS(r=-0.24),ISS(r=0.22),and HLOS(r=0.14)(P=0.001 for all).High DSI was associated with significantly higher rates of intubation,laparotomy,ventilator-associated pneumonia,massive transfusion activation,and mortality than low DSI.For mortality prediction,a high DSI had better specificity,negative predictive value,and negative likelihood ratio(77%,99%,and 0.49%,respectively).After adjusting for age,emergency medical services time,GCS score,and ISS,multivariable regression analysis showed that DSI was an independent predictor of mortality(odds ratio=1.9;95%confidence interval:1.35-2.76).CONCLUSION In addition to sex-biased observations,almost one-quarter of the study cohort had a higher DSI and were mostly young.High DSI correlated significantly with the other injury severity scores,which require more time and imaging to be ready to use.Therefore,DSI is a practical,simple bedside tool for triaging and prognosis in young patients with trauma.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms:A Chinese multicenter study of 12-year experience

BACKGROUND There is currently a shortage of accurate,efficient,and precise predictive instruments for rectal neuroendocrine neoplasms(NENs).AIM To develop a predictive model for individuals with rectal NENs(R-NENs)using data from a large cohort.METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China.Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival,and two nomograms were constructed.RESULTS A total of 1408 patients with R-NENs were included.Tumor grade,T stage,tumor size,age,and a prognostic nutritional index were important risk factors for prognosis.The GATIS score was calculated based on these five indicators.For overall survival prediction,the respective C-indexes in the training set were 0.915(95%confidence interval:0.866-0.964)for overall survival prediction and 0.908(95%confidence interval:0.872-0.944)for progression-free survival prediction.According to decision curve analysis,net benefit of the GATIS score was higher than that of a single factor.The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods.CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs,with efficacy superior to that of the World Health Organization grade and TNM stage.

国际胃袖状切除专家共识:基于>12000手术病例的最佳操作指南

腹腔镜胃袖状切除术（1aparoscopic sleeve gastrectomy，LSG）系相对较新的减重手术方式。因其操作相对简单、治疗肥胖合并疾病及减重效果明显，逐步得以广泛接受。目前美国代谢与减重手术协会将其推荐为肥胖症治疗的单独标准术式。2011年3月25～26日，

Risk factors for ventilator-associated pneumonia in trauma patients:A descriptive analysis

BACKGROUND:We sought to evaluate the risk factors for developing ventilator-associated pneumonia(VAP)and whether the location of intubation posed a risk in trauma patients.METHODS:Data were retrospectively reviewed for adult trauma patients requiring intubation for>48 hours,admitted between 2010 and 2013.Patients’demographics,clinical presentations and outcomes were compared according to intubation location(prehospital intubation[PHI]vs.trauma room[TRI])and presence vs.absence of VAP.Multivariate regression analysis was performed to identify predictors of VAP.RESULTS:Of 471 intubated patients,332 patients met the inclusion criteria(124 had PHI and208 had TRI)with a mean age of 30.7±14.8 years.PHI group had lower GCS(P=0.001),respiratory rate(P=0.001),and higher frequency of head(P=0.02)and chest injuries(P=0.04).The rate of VAP in PHI group was comparable to the TRI group(P=0.60).Patients who developed VAP were 6 years older,had significantly lower GCS and higher ISS,head AIS,and higher rates of polytrauma.The overall mortality was 7.5%,and was not associated with intubation location or pneumonia rates.In the early-VAP group,gram-positive pathogens were more common,while gram-negative microorganisms were more frequently encountered in the late VAP group.Logistic regression analysis and modeling showed that the impact of the location of intubation in predicting the risk of VAP appeared only when chest injury was included in the models.CONCLUSION:In trauma,the risk of developing VAP is multifactorial.However,the location of intubation and presence of chest injury could play an important role.

Adhesive small bowel obstruction: How long can patients tolerate conservative treatment?

AIM: To evaluate how long patients with small bowel obstruction caused by postoperative adhesions can tolerate conservative treatment.METHODS: The records of patients with small bowel obstruction due to postoperative adhesions were retrospectively reviewed. Data collected included the number of admissions, type of management for each admission,duration of conservative treatment, number of repeat laparotomies, and operative findings.RESULTS: One hundred fifty-five patients with this condition from January 1999 to December 2001, for a total of 293 admissions were enrolled in this study. Medical treatment alone was given in 220 admissions, and repeat laparotomy was performed in 73 admissions. The period of observation in patients managed medically ranged from 2 to 12 days (average: 6.9 days), while for those who underwent surgery,the range was 1 to 14 days (average 5.4 days). At surgery,adhesions were the only finding in 46 cases, while there were intestinal complications in 27, or 9.2 % of all 293admissions. Fever and leukocytosis greater than 15 000/mm3were prediction of intestinal complications.CONCLUSION: With closely monitoring, most patients with small bowel obstruction due to postoperative adhesions could tolerate supportive treatment and recover well averagely within 1 week, although some patients require more than 10 days of observation.

Evolution in the treatment of metastatic colorectal carcinoma of the liver

Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.

E2F transcription factors and digestive system malignancies: How much do we know?

E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumorpromoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

Pancreatic metastases:An increasing clinical entity

Pancreatic metastases,although uncommon,have been observed with increasing frequency recently,especially by high-volume pancreatic surgery centers.They are often asymptomatic and detected incidentally or during follow-up investigations even several years after the re-moval of the primary tumor.Renal cell cancer represents the most common primary tumor by far,followed by colorectal cancer,melanoma,sarcoma and lung cancer.Pancreatic metastasectomy is indicated for an isolated and resectable metastasis in a patient fit to tolerate pancreatectomy.Both standard and atypical pancreatic resection can be performed:a resection strategy providing adequate resection margins and maximal tissue preservation of the pancreas should be pursued.The effectiveness of resection for pancreatic metastases is mainly dependent on the tumor biology of the primary cancer;renal cell cancer is associated with the best outcome with a 5-year survival rate greater than 70%.

Antiviral therapy for hepatitis C: Has anything changed for pregnant/lactating women?

Hepatitis C virus(HCV) affects about 3% of the world'spopulation, with the highest prevalence in individuals under 40. The prevalence in pregnant women varies with geographical distribution(highest in developing countries). Prevalence also increases in sub-populations of women at high risk for blood-transmitted infections. HCV infection in pregnancy represents a non-negligible problem. However, most of the past antiviral regimens cannot be routinely offered to pregnant or breastfeeding women because of their side effects. We briefly reviewed the issue of treatment of HCV infection in pregnant/breastfeeding women focusing on the effects of the new direct-acting antivirals on fertility, pregnancy and lactation in animal studies and on the potential risk for humans based on the pharmacokinetic properties of each drug. Currently, all new therapy regimens are contraindicated in this setting because of lack of sufficient safety information and adequate measures of contraception are still routinely recommended for female patients of childbearing potential.

Predisposing factors, clinical assessment, management and outcomes of agitation in the trauma intensive care unit

BACKGROUND: Agitation occurs frequently among critically ill patients admitted to the intensive care unit(ICU). We aimed to evaluate the frequency, predisposing factors and outcomes of agitation in trauma ICU. METHODS: A retrospective analysis was conducted to include patients who were admitted to the trauma ICU between April 2014 and March 2015. Data included patient's demographics, initial vitals, associated injuries, Ramsey Sedation Scale, Glasgow Coma Scale, head injury lesions, use of sedatives and analgesics, head interventions, ventilator days, and ICU length of stay. Patients were divided into two groups based on the agitation status.RESULTS: A total of 102 intubated patients were enrolled; of which 46(45%) experienced agitation. Patients in the agitation group were 7 years younger, had significantly lower GCS and sustained higher frequency of head injuries(P<0.05). Patients who developed agitation were more likely to be prescribed propofol alone or in combination with midazolam and to have frequent ICP catheter insertion, longer ventilatory days and higher incidence of pneumonia(P<0.05). On multivariate analysis, use of propofol alone(OR=4.97; 95% CI=1.35–18.27), subarachnoid hemorrhage(OR=5.11; 95% CI=1.38–18.91) and ICP catheter insertion for severe head injury(OR=4.23; 95% CI=1.16–15.35) were independent predictors for agitation(P<0.01).CONCLUSION: Agitation is a frequent problem in trauma ICU and is mainly related to the type of sedation and poor outcomes in terms of prolonged mechanical ventilation and development of nosocomial pneumonia. Therefore, understanding the main predictors of agitation facilitates early risk-stratification and development of better therapeutic strategies in trauma patients.

Vertical hepatitis C virus transmission:Main questions and answers

Hepatitis C virus(HCV) affects about 3% of the world's population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low(1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behav-iors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV in-fection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related im-mune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune res-toration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunode-ficiency virus coinfection, prolonged rupture of mem-branes, fetal exposure to maternal infected blood con-sequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmis-sion. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antivi-ral therapy to HCV-infected pregnant women because it is based on ribavirin(pregnancy category X) because of its embryocidal and teratogenic effects in animal spe-cies. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.

Management of stage Ⅳ rectal cancer: Palliative options

Approximately 30% of patients with rectal cancer present with metastatic disease. Many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease patients.SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable source.Several mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune responses.Historically,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic choice.However,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been seen.Recently,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of cases.Consequently,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor outcomes.Theaim of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic strategies.An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.

Magnetic resonance imaging based rectal cancer classification: Landmarks and technical standardization

Rectal cancer classification is important to determine the preoperative chemoradiation therapy and to select appropriate surgical technique. We reviewed the Western and Japanese rectal cancer classification and we propose our new classification based of Magnetic resonance imaging(MRI). We determine the relation of the tumor to fixed parameters in MRI, which areperitoneal reflection and levator ani muscle. Then, we classify the rectal cancer into four levels based on tumor distal margin and invasion to MRI parameters. We applied all three classifications to 60 retrospectively collected patients of different rectal cancer distance and we compared our classifications to the others. Based on each level we standardize our surgical approach. For stages Ⅰ-Ⅲ, We found that level Ⅰ where tumor distal margin is located above the peritoneal reflection and all of them were received low anterior resection(LAR) without chemoradiation. Level Ⅱ where tumor distal margin is located from the peritoneal reflection and above the levator ani insertion on the rectum. 90% of them were received LAR ± chemoradiation. Level Ⅲ where tumor distal margin is located at the level of levator ani insertion or invading any part of the levator ani. 60% of them had ULAR + coloanal anastomosis ± chemoradiation. Level Ⅳ where the tumor distal margin is located below the levator ani insertion; 77% were received APR ± chemoradiation. The overall kappa for all levels between surgeons and radiologist was 0.93(95%CI: 0.87-0.99), which is indicating almost perfect agreement. We concluded that the management of rectal tumors differed among each tumor level and our new MRI based classification might facilitate the prediction of surgical and chemoradiation management with better communication among a multidisciplinary team comparing to other classifications.

Human endogenous retroviruses and cancer:Causality and therapeutic possibilities

A substantial part of the human genome is derived from transposable elements;remnants of ancient retroviral infections.Conservative estimates set the percentage of human endogenous retroviruses(HERVs) in the genome at 8%.For the most part,the interplay between mutations,epigenetic mechanisms and posttranscriptional regulations silence HERVs in somatic cells.We first highlight mechanisms by which activation of members of several HERV families may be associated with tumor development before discussing the arising chances for both diagnosis and therapy.It has been shown that at least in some cases,tumor cells expressing HERV open reading frames(ORFs) thus gain tumor-promoting functions.However,since these proteins are not expressed in healthy tissues,they become prime target structures.Of potential pharmacological interest are the prevention of HERV transposition,the inhibition of HERV-encoded protein expression and the interference with these proteins' activities.Evidence from recent studies unequivocally proves that HERV ORFs represent a very interesting source of novel tumor-specific antigens with even the potential to surpass entity boundaries.The development of new tumor(immune-) therapies is a very active field and true tumor-specific targets are of outstanding interest since they minimize the risk of autoimmunity and could reduce side effects.Finally,we postulate on main future research streams in order to stimulate discussion on this hot topic.

The impact of emergency department length of stay on the outcomes of trauma patients requiring hospitalization: a retrospective observational study

BACKGROUND: We aimed to explore the impact of the emergency department length of stay(EDLOS) on the outcome of trauma patients.METHODS: A retrospective study was conducted on all trauma patients requiring hospitalization between 2015 and 2019. Patients were categorized into 4 groups based on the EDLOS(<4 h, 4–12 h,12–24 h, and >24 h). Data were analyzed using Chi-square test(categorical variables), Student’s t-test(continuous variables), correlation coefficient, analysis of variance and multivariate logistic regression analysis for identifying predictors of short EDLOS and hospital mortality.RESULTS: The study involved 7,026 patients with a mean age of 32.1±15.6 years. Onefifth of patients had a short EDLOS(<4 h) and had higher level trauma team T1 activation(TTA-1), higher Injury Severity Score(ISS), higher shock index(SI), and more head injuries than the other groups(P=0.001). Patients with an EDLOS >24 h were older(P=0.001) and had more comorbidities(P=0.001) and fewer deaths(P=0.001). Multivariate regression analysis showed that the predictors of short EDLOS were female gender, GCS, SI, hemoglobin level, ISS, and blood transfusion. The predictors of mortality were TTA-1(odds ratio [OR]=4.081, 95%CI: 2.364–7.045), head injury(OR=3.920, 95%CI: 2.413–6.368), blood transfusion(OR=2.773, 95%CI: 1.668–4.609), SI(OR=2.132, 95%CI: 1.364–3.332), ISS(OR=1.077, 95%CI: 1.057–1.096), and age(OR=1.040, 95%CI: 1.026–1.054). CONCLUSIONS: Patients with shorter EDLOS had different baseline characteristics and hospital outcomes compared with patients with longer EDLOS. Patients with prolonged EDLOS had better outcomes;however, the burden of prolonged boarding in the ED needs further elaboration.

Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.