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Background Peptic ulcer disease is common with a lifetime prevalence in the general population of 5–10% and an incidence of 0.1–0.3% per year. Despite a sharp reduction in incidence and rates of hospital admission and mortality over the past 30 years, complications are still encountered in 10–20% of these patients. Peptic ulcer disease remains a significant healthcare problem, which can consume considerable financial resources. Management may involve various subspecialties including surgeons, gastroenterologists, and radiologists. Successful management of patients with complicated peptic ulcer (CPU) involves prompt recognition, resuscitation when required, appropriate antibiotic therapy, and timely surgical/radiological treatment. Methods The present guidelines have been developed according to the GRADE methodology. To create these guidelines, a panel of experts was designed and charged by the board of the WSES to perform a systematic review of the available literature and to provide evidence-based statements with immediate practical application. All the statements were presented and discussed during the 5th WSES Congress, and for each statement, a consensus among the WSES panel of experts was reached. Conclusions The population considered in these guidelines is adult patients with suspected complicated peptic ulcer disease. These guidelines present evidence-based international consensus statements on the management of complicated peptic ulcer from a collaboration of a panel of experts and are intended to improve the knowledge and the awareness of physicians around the world on this specific topic. We divided our work into the two main topics, bleeding and perforated peptic ulcer, and structured it into six main topics that cover the entire management process of patients with complicated peptic ulcer, from diagnosis at ED arrival to post-discharge antimicrobial therapy, to provide an up-to-date, easy-to-use tool that can help physicians and surgeons during the decision-making process.

Background To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis. Methods We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. With the aim to analyze actual application in the daily clinical practice, papers including trials with fluorophores other than ICG, in vitro and animals series were excluded. Data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules were extracted and analyzed. Results Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients and 353 peritoneal nodules. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were harvested and singularly evaluated. Sensitivity varied from 72.4 to 100%, specificity from 54.2 to 100%. Two series reported that planned intervention changed in 25 and 29% of patients, respectively. Conclusion Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed to fix its actual diagnostic value on these and other abdominal malignancies with frequent spread to peritoneum.

Background Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80–85%. Multiple gland disease or hyperplasia accounts for 10–15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2–1.3% and 1% or less of primary hyperparathyroidism, respectively. Methods We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma. Results Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion ( p  <  0.001), bands of fibrosis ( p  <  0.001), pronounced trabecular growth ( p  <  0.001), mitotic rates of > 1/10 high-power fields (HPFs) ( p  <  0.001), nuclear pleomorphism ( p  = 0.036), thick capsule ( p  <  0.001), Ki-67+ > 4% ( p  <  0.001), galectin-3 + ( p  = 0.002), and protein gene product (PGP) 9.5 + ( p  = 0.038). Conclusions Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

BackgroundDetecting small nodules that are grossly unidentifiable remains a major challenge in liver resection for cancer. Novel developments in navigation surgery, especially indocyanine green (ICG)-based fluorescence imaging, are making a clear breakthrough in addressing this issue. ICG is almost routinely administered during the preoperative stage in hepatobiliary surgery. However, its full potential has yet to be realized, partly because there are no precise guidelines regarding the optimal dose or timing of ICG injections before liver surgery. The main goal of this study was to design an algorithm for the management of ICG injections to achieve optimal liver staining results.MethodsTwenty-seven consecutive, unselected patients undergoing liver resection for cancer were enrolled and underwent preoperative liver function assessment by the LiMON test. Extra ICG i.v. injections at different doses and timings were performed. In vivo intraoperative analysis of the stain detected by near-infrared fluorescence imaging of the liver and ex vivo analysis of each resected nodule was performed and compared to the pathological analysis.Results(i) The success rate of ICG injections in terms of liver staining was 92.6%; (ii) in the absence of or with 7 or more days from a previous ICG injection, the best dose to inject before the operation was 0.2 mg/kg, and the best timing was between 24 and 48 h before the scheduled surgery; and (iii) the ICG fluorescence patterns observed in the tumors were total fluorescence staining (41% of the cases), partial fluorescence staining (15%), rim fluorescence staining surrounding the tumor (30%), and no staining (15%).ConclusionsThis study is a building block for the characterization of liver nodules and the search for additional surface lesions undetected by preoperative radiological work-up—a crucial task for the successful treatment of liver cancer at an early stage using a safe, minimally invasive, and inexpensive technique.

Background Resection margin (RM) involvement is associated with negative prognosis after gastrectomy. Intraoperative frozen section (IFS) analysis allows radical resection to be achieved in a single operation but is time-consuming and resource-consuming. The aim of this study was to assess risk factors associated with RM involvement to identify patients who would benefit from IFS analysis. Methods We retrospectively analyzed patients who underwent gastrectomy with curative intent for gastric or esophagogastric junction (EGJ) cancer from 2000 to 2014 in six Italian hospitals. RM status was assessed by IFS analysis and/or definitive histopathology examination. A set of 21 potential risk factors were compared in a multivariate analysis between patients with positive RMs on IFS analysis or definitive histopathology examination and a control cohort of similar patients with negative RMs, with the samples stratified into three subgroups (T1, T2–T4 Lauren intestinal pattern, T2–T4 Lauren diffuse/mixed pattern). Results One hundred forty-five patients had positive RMs. Survival was significantly worse in positive RM patients than in negative RM patients (89.5 months vs 28.9 months). Multivariate analysis showed that in T1 cancers a margin distance of less than 2 cm is a risk factor for RM involvement (odds ratio 15.7), in T2–T4 intestinal pattern cancers, serosa invasion (odds ratio 6.0), EGJ location (odds ratio 4.1), and a margin distance of less than 3 cm (odds ratio 4.0) are independent risk factors, and in T2–T4 diffuse/mixed pattern cancers, lymphatic infiltration (odds ratio 4.2), tumor diameter greater than 4 cm (odds ratio 3.5), EGJ location (odds ratio 2.8), and serosa invasion (odds ratio 2.2) are independent risk factors. Conclusions Survival after gastrectomy is negatively affected by positive RMs. IFS analysis should be routinely used in patients with a high risk of positive RMs, especially in diffuse pattern cancers.

Polychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case–control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62–5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development.

Background Nowadays, very few patients with non-variceal upper gastrointestinal bleeding fail endoscopic hemostasis (refractory NVUGIB). This subset of patients poses a clinical dilemma: should they be operated on or referred to transcatheter arterial embolization (TAE)? Objectives To carry out a systematic review of the literature and to perform a meta-analysis of studies that directly compare TAE and surgery in patients with refractory NVUGIB. Materials and methods We searched PubMed, Ovid MEDLINE, and Embase. A combination of the MeSH terms “gastrointestinal bleeding”; “gastrointestinal hemorrhage”; “embolization”; “embolization, therapeutic”; and “surgery” were used ((“gastrointestinal bleeding” or “gastrointestinal hemorrhage”) and (“embolization” or “embolization, therapeutic”) and “surgery”)). The search was performed in June 2018. Studies were retrieved and relevant studies were identified after reading the study title and abstract. Bibliographies of the selected studies were also examined. Statistical analysis was performed using RevMan software. Outcomes considered were all-cause mortality, rebleeding rate, complication rate, and the need for further intervention. Results Eight hundred fifty-six abstracts were found. Only 13 studies were included for a total of 1077 patients (TAE group 427, surgery group 650). All selected papers were non-randomized studies: ten were single-center and two were double-center retrospective comparative studies, while only one was a multicenter prospective cohort study. No comparative randomized clinical trial is reported in the literature. Mortality . Pooled data (1077 patients) showed a tendency toward improved mortality rates after TAE, but this trend was not statistically significant (OD = 0.77; 95% CI 0.50, 1.18; P  = 0.05; I 2  = 43% [random effects]). Significant heterogeneity was found among the studies. Rebleeding rate . Pooled data (865 patients, 211 events) showed that the incidence of rebleeding was significantly higher for patients undergoing TAE (OD = 2.44; 95% CI 1.77, 3.36; P  = 0.41; I 2  = 4% [fixed effects]). Complication rate . Pooling of the data (487 patients, 206 events) showed a sharp reduction of complications after TAE when compared with surgery (OD = 0.45; 95% CI 0.30, 0.47; P  = 0.24; I 2  = 26% [fixed effects]). Need for further intervention . Pooled data (698 patients, 165 events) revealed a significant reduction of further intervention in the surgery group (OD = 2.13; 95% CI 1.21, 3.77; P  = 0.02; I 2  = 56% [random effects]). A great degree of heterogeneity was found among the studies. Conclusions The present study shows that TAE is a safe and effective procedure; when compared to surgery, TAE exhibits a higher rebleeding rate, but this tendency does not affect the clinical outcome as shown by the comparison of mortality rates (slight drift toward lower mortality for patients undergoing TAE). The present study suggests that TAE could be a viable option for the first-line therapy of refractory NVUGIB and sets the foundation for the design of future randomized clinical trials. Limitations The retrospective nature of the majority of included studies leads to selection bias. Furthermore, the decision of whether to proceed with surgery or refer to TAE was made on a case-by-case basis by each attending surgeon. Thus, external validity is low. Another limitation involves the variability in etiology of the refractory bleeding. TAE techniques and surgical procedure also differ consistently between different studies. Frame time for mortality detection differs between the studies. These limitations do not impair the power of the present study that represents the largest and most recent meta-analysis currently available.

Background Few studies have focused on risk factors which may predict an intrahepatic local recurrence (LR) on the surgical edge rather than a distant recurrence (DR) in other liver segments after surgery for hepatocarcinoma (HCC). The purpose of this study was to assess the risk factors for both patterns of recurrence. Methods An international, multicentre, retrospective study was conducted by collecting data on all consecutive patients with a first diagnosis of HCC who were treated between 2010 and 2017. The presence of macrovascular invasion was an exclusion criteria. Results About 376 patients were enrolled, and, among them, 62 presented LR, while 90 had DR. Baseline characteristics were comparable between the two groups, but the DR group had a much higher rate of HCV infection (48.9% vs 29%, p 0.014) and a higher median nodule size (3.40 cm IQR 2.2–5.5 versus 3.0 cm IQR 2.0–5.0 in the LR group, p 0.025). A positive surgical margin (R1, HR 4.721; 95% CI 1.83–12.17; p 0.001) was the only independent risk factor for LR, while MVI (HR 1.837; 95% CI 1.03–3.77; p 0.039) and satellitosis (HR 2.440, 95% CI 1.43–3.77, p 0.001) were the only predictive factors for DR. Conclusion MVI and satellitosis are predictive factors of intrahepatic distant recurrence, configuring a probable hallmark of advanced systemic disease, regardless of the treatment. LR has to be considered the expression of surgical failure.

Human hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver and the third cause of cancer-related deaths. The multikinase inhibitor sorafenib is a systemic drug for unresectable HCC. The identification of molecular biomarkers for the early diagnosis of HCC and responsiveness to treatment are needed. In this work, we performed an exploratory study to investigate the longitudinal levels of cell-free long ncRNA GAS5 and microRNAs miR-126-3p and -23b-3p in a cohort of 7 patients during the period of treatment with sorafenib. We used qPCR to measure the amounts of GAS5 and miR-126-3p and droplet digital PCR (ddPCR) to measure the levels of miR-23b-3p. Patients treated with sorafenib displayed variable levels of GAS5, miR-126-3p and miR-23b-3p at different time-points of follow-up. miR-23b-3p was further measured by ddPCR in 37 healthy individuals and 25 untreated HCC patients. The amount of miR-23b-3p in the plasma of untreated HCC patients was significantly downregulated if compared to healthy individuals. The ROC curve analysis underlined its diagnostic relevance. In conclusion, our results highlight a potential clinical significance of circulating miR-23b-3p and an exploratory observation on the longitudinal plasmatic levels of GAS5, miR-126-3p and miR-23b-3p during sorafenib treatment.

Background About 10% of cervico-mediastinal goiter need to associate cervicotomy with a total or partial sternotomy to allow a safe removal of the goiter. Aim of this study is to identify preoperative predictors of sternotomy for mediastinal goiter. Methods Between January 2008 and December 2015, 586 patients were submitted to total thyroidectomy at Surgical Clinic of Brescia, Italy. Among these, patients with cervico-mediastinal goiter have been divided in two groups based on the necessity of an associated sternotomy in the operating field: Group 1 ( n  = 40 patients) did not need sternotomy and Group 2 (n = 4 patients) underwent cervicotomy associated with sternotomy. Clinical and pathological characteristics of patients were retrospectivelly recorded. Results Among study group, 44 patients had cervico-mediastinal goiter. Thoracic CT was performed in all patients: an extension above aortic arch was found in 41 patients (93.18%) while an extention below aortic arch was found in 3 patients (6.82%). The extension of the goiter below the aortic arch resulted as a predictive value in the choice of surgical treatment ( p  = 0.0001). The thyroiditis process was found to be a significant predictive of the extention to a sternotomic approach ( p  = 0.029). The years of goiter’s presence were on average 8.40 years in Group 1 and 14.75 years in Group 2. These parameters proved to be predictive when choosing a cervicotomy with sternotomy. Conclusions: Our study, despite limitations posed by small sample and its retrospective analisys, highlights the role of goiter’s extention (below the aortic arch), disease length (for more than 14.75 years) and flogistic process (positivity of Tg Ab and anti-TPO-Ab) in the choice of combined (cervicotomic and sternotomic) approach to goiter’s removal.