Management of duodenal stump fistula after gastrectomy for gastric cancer: systematic review

AIM: To identify the most effective treatment of duodenal stump fistula (DSF) after gastrectomy for gastric cancer. METHODS: A systematic review of the literature was performed. PubMed, EMBASE, Cochrane Library, CILEA Archive, BMJ Clinical Evidence and UpToDate databases were analyzed. Three hundred eighty-eight manuscripts were retrieved and analyzed and thirteen studies published between 1988 and 2014 were finally selected according to the inclusion criteria, for a total of 145 cases of DSF, which represented our group of study. Only patients with DSF after gastrectomy for malignancy were selected. Data about patients' characteristics, type of treatment, short and long-term outcomes were extracted and analyzed. RESULTS: In the 13 studies different types of treatment were proposed: conservative approach, surgical approach, percutaneous approach and endoscopic approach (3 cases). The overall mortality rate was 11.7% for the entire cohort. The more frequent complications were sepsis, abscesses, peritonitis, bleeding, pneumonia and multi-organ failure. Conservative approach was performed in 6 studies for a total of 79 patients, in patients with stable general condition, often associated with percutaneous approach. A complete resolution of the leakage was achieved in 92.3% of these patients, with a healing time ranging from 17 to 71 d. Surgical approach included duodenostomy, duodeno-jejunostomy, pancreatoduodenectomy and the use of rectus muscle flap. In-hospital stay of patients who underwent relaparotomy ranged from 1 to 1035 d. The percutaneous approach included drainage of abscesses or duodenostomy (32 cases) and percutaneous biliary diversion (13 cases). The median healing time in this group was 43 d. CONCLUSION: Conservative approach is the treatment of choice, eventually associated with percutaneus drainage. Surgical approach should be reserved for severe cases or when conservative approaches fail

Extra-Anatomic Jump Graft from the Right Colic Vein: A Novel Technique to Manage Portal Vein Thrombosis in Liver Transplantation

In the context of cirrhosis, portal vein thrombosis (PVT) is present in 2.1% to 26% of patients. PVT is no longer considered an absolute contraindication for liver transplantation, and nowadays, surgical strategies depend on the extent of PVT. Complete PVT is associated with higher morbidity rates and poor prognosis, while comparable long-term outcomes can be achieved as long as physiological portal inflow is restored

The Evolving Role of Local Treatments for HCC in the Third Millennium

Hepatocellular carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. The aim of this review was to clarify the role of local treatments for HCC, analyzing the indications and defining future perspectives

SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer

Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation andmigration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.Peer reviewe

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers

TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma

: This study assesses the expression of all TNF-related apoptosis-inducing ligand (TRAIL) receptors in pancreatic ductal adenocarcinoma (PDAC) tumor tissue. We aimed to include TRAIL receptor expression as an inclusion parameter in a future clinical study using a TRAIL-based therapy approach for PDAC patients. Considering the emerging influence of PDAC desmoplastic stroma on the efficacy of anti-PDAC therapies, this analysis was extended to tumor stromal cells. Additionally, we performed PDAC stroma characterization. Our retrospective cohort study (N=50) included patients with histologically confirmed PDAC who underwent surgery. The expression of TRAIL receptors (DR4, DR5, DcR1, DcR2, and OPG) in tumor and stromal cells was evaluated by immunohistochemistry (IHC). The amount of tumor stroma was assessed by anti-vimentin IHC and Mallory's trichrome staining. The prognostic impact was determined by the univariate Cox proportional hazards regression model. An extensive expression of functional receptors DR4 and DR5 and a variable expression of decoy receptors were detected in PDAC tumor and stromal cells. Functional receptors were detected also in metastatic tumor and stromal cells. A poor prognosis was associated with low or absent expression of decoy receptors in tumor cells of primary PDAC. After assessing that almost 80% of tumor mass was composed of stroma, we correlated a cellular-dense stroma in primary PDAC with reduced relapse-free survival. We demonstrated that TRAIL functional receptors are widely expressed in PDAC, representing a promising target for TRAIL-based therapies. Further, we demonstrated that a low expression of DcR1 and the absence of OPG in tumor cells, as well as a cellular-dense tumor stroma, could negatively impact the prognosis of PDAC patients

Recommended vaccinations for asplenic and hyposplenic adult patients

Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals

Liver resection vs radiofrequency ablation in single hepatocellular carcinoma of posterosuperior segments in elderly patients

Background: Liver resection and radiofrequency ablation are considered curative options for hepatocellular carcinoma. The choice between these techniques is still controversial especially in cases of hepatocellular carcinoma affecting posterosuperior segments in elderly patients. Aim: To compare post-operative outcomes between liver resection and radiofrequency ablation in elderly with single hepatocellular carcinoma located in posterosuperior segments. Methods: A retrospective multicentric study was performed enrolling 77 patients age ≥ 70-years-old with single hepatocellular carcinoma (≤ 30 mm), located in posterosuperior segments (4a, 7, 8). Patients were divided into liver resection and radiofrequency ablation groups and preoperative, peri-operative and long-term outcomes were retrospectively analyzed and compared using a 1:1 propensity score matching. Results: After propensity score matching, twenty-six patients were included in each group. Operative time and overall postoperative complications were higher in the resection group compared to the ablation group (165 min vs 20 min, P < 0.01; 54% vs 19% P = 0.02 respectively). A median hospital stay was significantly longer in the resection group than in the ablation group (7.5 d vs 3 d, P < 0.01). Ninety-day mortality was comparable between the two groups. There were no significant differences between resection and ablation group in terms of overall survival and disease free survival at 1, 3, and 5 years. Conclusion: Radiofrequency ablation in posterosuperior segments in elderly is safe and feasible and ensures a short hospital stay, better quality of life and does not modify the overall and disease-free survival