Proposing a Scientific and Technological Approach to the Summaries of Clinical Issues of Inpatient Elderly with Delirium: A Viewpoint.

Background/rationale: Despite mounting evidence about delirium, this complex geriatric syndrome is still not well managed in clinical contexts. The aging population creates a very demanding area for innovation and technology in healthcare. For instance, an outline of an aging-friendly healthcare environment and clear guidance for technology-supported improvements for people at delirium risk are lacking. Objective: We aimed to foster debate about the importance of technical support in optimizing healthcare professional practice and improving the outcomes for inpatients' at delirium risk. We focused on critical clinical points in the field of delirium worthy of being addressed by a multidisciplinary approach. Methods: Starting from a consensus workshop sponsored by the Management Perfectioning Course based at the Marco Biagi Foundation (Modena, Italy) about clinical issues related to delirium management still not addressed in our healthcare organizations, we developed a requirements' analysis among the representatives of different disciplines and tried to formulate how technology could support the summaries of the clinical issues. We analyzed the national and international panorama by a PubMed consultation of articles with the following keywords in advanced research: "delirium", "delirium management", "technology in healthcare", and "elderly population". Results: Despite international recommendations, delirium remains underdiagnosed, underdetected, underreported, and mismanaged in the acute hospital, increasing healthcare costs, healthcare professionals' job distress, and poor clinical outcomes. Discussion: Although all healthcare professionals recognize delirium as a severe and potentially preventable source of morbidity and mortality for hospitalized older people, it receives insufficient attention in resource allocation and multidisciplinary research. We synthesized how tech-based tools could offer potential solutions to the critical clinical points in delirium management.

Short-term and long term morbidity in robotic pancreatic surgery: a systematic review.

BACKGROUND: Pancreatic cancer is one of the most aggressive and lethal tumours in Western society. Pancreatic surgery can be considered a challenge for open and laparoscopic surgeons, even if the accuracy of gland dissection, due to the close relationship between pancreas, the portal vein, and mesenteric vessels, besides the reconstructive phase (in pancreaticoduodenectomy), lead to significant difficulties for laparoscopic technique. Minimally invasive pancreatic surgery changed utterly with the development of robotic surgery. However, this review aims to make more clarity on the influence of robotic surgery on long-term morbidity. METHODS: A systematic literature search was performed in PubMed, Cochrane Library, and Scopus to identify and analyze studies published from November 2011 to September 2020 concerning robotic pancreatic surgery. The following terms were used to perform the search: "long term morbidity robotic pancreatic surgery". RESULTS: Eighteen articles included in the study were published between November 2011 and September 2020. The review included 2041 patients who underwent robotic pancreatic surgery, mainly for a malignant tumour. The two most common robotic surgical procedures adopted were the robotic distal pancreatectomy (RDP) and the robotic pancreaticoduodenectomy (RPD). In two studies, patients were divided into groups; on the one hand, those who underwent a robotic pancreaticoduodenectomy (RPD), on the other hand, those who underwent robotic distal pancreatectomy (RDP). The remaining items included surgical approach such as robotic middle pancreatectomy (RMP), robotic distal pancreatectomy and splenectomy, robotic-assisted laparoscopic pancreatic dissection (RALPD), robotic enucleation of pancreatic neuroendocrine tumours. CONCLUSIONS: Comparison between robotic surgery and open surgery lead to evidence of different advantages of the robotic approach. A multidisciplinary team and a surgical centre at high volume are essential for better postoperative morbidity and mortality.

The using of sealants in pancreatic surgery: A Systematic Review.

BACKGROUND: POPF derives from the pancreatic stump, which follows pancreatic resection and the pancreatoenteric anastomosis following pancreaticoduodenectomy. Since 1978 sealants have been used in pancreatic surgery to prevent pancreatic fistula after resection of the pancreatic head and tail or for the management of trauma and the treatment of low-output pancreatic fistula. Different types of fibrin sealants have been evaluated for their potential to reduce the occurrence of POPF. METHODS: A systematic search of the electronic literature was performed using PubMed, Cochrane Library, and Scopus databases to obtain access to all publications, especially clinical trials, randomised controlled trials, and systematic reviews concerning fibrin sealants pancreatic surgery. Searching for "fibrin sealants pancreas," we found a total of 73 results on Pubmed, 61 on Scopus, and 14 on Cochrane Library (148 total results). RESULTS: Eighteen studies were found on literature, following the criteria already described, concerning the use of fibrin sealants in pancreatic surgery. All articles described were published in the period between 1989 and 2019.Most of these were single centre studies. A total of 1032 patients were enrolled in this review. In the studies, sealants were used to reinforce pancreatic anastomoses and for the occlusion of the main pancreatic duct. CONCLUSION: CR-POPF is a fearful complication of pancreatic surgery; among the possible solutions to reduce the risk of onset, sealants were used on the pancreatic stump; today the sealants should be considered such as an option to reduce the CR-POPF, but the routine use in clinical practice has to be validated.

Neurological complications after liver transplantation as a consequence of immunosuppression: univariate and multivariate analysis of risk factors.

Neurological complications (NCs) can frequently and significantly affect morbidity and mortality of liver transplant (LT) recipients. We analysed incidence, risk factors, outcome and impact of the immunosuppressive therapy on NC development after LT. We analysed 478 LT in 440 patients, and 93 (19.5%) were followed by NCs. The average LOS was longer in patients experiencing NCs. The 1-, 3- and 5-year graft survival and patient survival were similar in patients with or without a NC. Multivariate analysis showed the following as independent risk factors for NC: a MELD score ≥20 (OR = 1.934, CI = 1.186-3.153) and an immunosuppressive regimen based on calcineurin inhibitors (CNIs) (OR = 1.669, CI = 1.009-2.760). Among patients receiving an everolimus-based immunosuppression, the 7.1% developed NCs, vs. the 16.9% in those receiving a CNI (P = 0.039). There was a 1-, 3- and 5-year NC-free survival of 81.7%, 81.1% and 77.7% in patients receiving a CNI-based regimen and 95.1%, 93.6% and 92.7% in those not receiving a CNI-based regimen (P < 0.001). In patients undergoing a LT and presenting with nonmodifiable risk factors for developing NCs, an immunosuppressive regimen based on CNIs is likely to result in a higher rate of NCs compared to mTOR inhibitors.

Wernicke's encephalopathy in a malnourished surgical patient: a difficult diagnosis.

BACKGROUND: Wernicke's encephalopathy is an acute neurological disorder resulting from thiamine deficiency mainly related to alcohol abuse. Severe thiamine deficiency is an emerging problem in non-alcoholic patients and it may develop in postoperative surgical patients with risk factors. CASE PRESENTATION: We reported a case of a 46 years old woman who underwent, one year before, to cephalic duodenopancreatectomy complicated with prolonged recurrent vomiting. She underwent to a second surgical operation for intestinal sub-occlusion and postoperatively she developed septic shock and hemorrhagic Wernicke's disease. After ICU admission, because of neurological deterioration, she underwent CT scan and MRI that highlighted a strong suspicion for Wernicke's disease. We treated her with an initially wrong low dose of thiamine, then after MRI we increased the dosage with a neurological status improvement. Despite therapeutic efforts used to control septic shock and thrombocytopenia, she died on the 21st day after surgery because of massive cerebral bleeding and unresponsive cerebral edema. CONCLUSION: Early detection of subclinical thiamine deficiency is a difficult task, as symptoms may be nonspecific. Wernicke's disease remains a clinical diagnosis because there are no specific diagnostic abnormalities revealed in cerebrospinal fluid, electroencephalogram or evoked potentials. About this, the best aid for a correct diagnosis is the clinical suspicion and clinicians should consider the disorder in any patients with unbalanced nutrition, increased metabolism or impaired food absorption. A hallmark of our case was the brain hemorrhage in the typical areas of the Wernicke's disease, maybe triggered by the thrombocytopenia secondary to sepsis. It might be a good clinical practice administer thiamine to all patients presenting with coma or stupor and risk factors related with thiamine deficiency. Any therapeutic delay may result in permanent neurological damage or death.

Results of salvage liver transplantation.

BACKGROUND & AIMS: Salvage liver transplantation (SLT) is an attractive sequential strategy which combines liver resection (LR) for hepatocellular carcinoma (HCC), followed by liver transplant (LT) in the event of HCC recurrence or progressive liver deterioration. To compare the long-term results of SLT with primary liver transplant (PLT). METHODS: Between 2000 and 2011, 125 patients (72 transplantable) underwent LR and 226 underwent LT in our unit. The outcome of SLT was analysed in a two-step fashion: firstly, SLT (n = 28) was compared with PLT (n = 198), secondly an intention-to-treat analysis was performed on all transplantable HCC patients who underwent LR (LRT group = 72) compared to PLT (n = 198). RESULTS: The five-year overall survival (OS) was 65.4% vs. 49.2% (P = 0.63), and disease-free survival (DFS) was 89.7% vs. 80.6% (P = 0.31) for PLT and SLT respectively. Predictive factors for DFS after LT included HCC total diameter [hazard ratio (HR) 1.29 P = 0.003], alpha-foetoprotein (HR 1.002 P < 0.001) and number of HCC nodules (HR 1.317 P = 0.035), whereas viral hepatitis C positivity (HR 1.911 P = 0.03) and outside Up-to-seven criteria (HR 2.652 P < 0.001) were negative independent prediction factors of OS. Intention-to-treat analysis showed that OS at 5 years was improved in PLT vs. LRT (LRT n = 72 including SLT plus LR group) and was 69.4% vs. 42.2% (P < 0.004), with an additional increase in DFS (89.2% vs. 54.5% respectively P < 0.001). CONCLUSION: Salvage liver transplantation is a safe treatment strategy, as it does not impair long-term survival. At intention-to-treat analysis, PLT showed improved survival compared with LRT.

Absence of viable HCC in the native liver is an independent protective factor of tumor recurrence after liver transplantation.

BACKGROUND: Prognostic factors for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) are still a matter of debate. The absence of viable tumor in the native liver, due to effectiveness of pre-LT locoregional treatment or liver resection, is an intriguing prognostic factor that had never been evaluated. METHODS: Between November 2000 and December 2011, 210 LTs were performed in patients with evidence of HCC and cirrhosis. RESULTS: Fifty-three (25.2%) patients did not show any evidence of active residual HCC in the native liver (Group NVH), whereas 157 (74.8%) patients showed viable HCC (Group VH). All patients in Group NVH were treated before LT with a multimodal approach combining transarterial chemoembolization, liver resection, radiofrequency ablation, percutaneous ethanol injection, or sorafenib, whereas, in Group VH, 110 of the 157 (70.1%) patients received bridging therapy (P<0.001). HCC recurrence occurred in none of the patients in Group NVH (0%) and in 25 (15.9%) patients in Group VH (P=0.003). Liver resection was the most effective treatment in obtaining absence of HCC on liver explantation. The results of multivariate analysis showed that existence of pathologic HCC findings outside of the University of California-San Francisco criteria (P=0.001; odds ratio, 4; confidence interval, 1.7-9.2) and the presence of viable HCC (P=0.003; odds ratio, 5.9; confidence interval, 1.5-17.6) were independently associated with HCC recurrence. CONCLUSIONS: The histologic absence of viable HCC in the native liver after LT and morphologic criteria, due to the high effectiveness of pre-LT bridging treatments, is a highly positive prognostic factor against HCC recurrence after LT.

Multicenter italian experience in liver transplantation for hepatocellular carcinoma in HIV-infected patients.

BACKGROUND: The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS: We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS: HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION: LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation.

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.

Pancreatic metastases from renal cell carcinoma: the state of the art.

Pancreatic metastases are rare, with a reported incidence varying from 1.6% to 11% in autopsy studies of patients with advanced malignancy. In clinical series, the frequency of pancreatic metastases ranges from 2% to 5% of all pancreatic malignant tumors. However, the pancreas is an elective site for metastases from carcinoma of the kidney and this peculiarity has been reported by several studies. The epidemiology, clinical presentation, and treatment of pancreatic metastases from renal cell carcinoma are known from single-institution case reports and literature reviews. There is currently very limited experience with the surgical resection of isolated pancreatic metastasis, and the role of surgery in the management of these patients has not been clearly defined. In fact, for many years pancreatic resections were associated with high rates of morbidity and mortality, and metastatic disease to the pancreas was considered to be a terminal-stage condition. More recently, a significant reduction in the operative risk following major pancreatic surgery has been demonstrated, thus extending the indication for these operations to patients with metastatic disease.

Liver resection for colorectal metastases in older adults: a paired matched analysis.

OBJECTIVES: To assess the safety and long-term results of hepatic resection of colorectal liver metastases (CLM) in older adults. DESIGN: Case-control. SETTING: Single liver and multivisceral transplant center. PARTICIPANTS: Individuals with CLM: 32 aged 70 and older (older group) and 32 younger than 70 (younger group) matched in a 1:1 ratio according to sex, primary tumor site, liver metastases at diagnosis, number of metastases, maximum tumor size, infiltration of cut margin, type of hepatic resection, and hepatic resection timing. MEASUREMENTS: Postoperative complications and survival rates. RESULTS: There was no significant difference in preoperative clinical findings between the two study groups. The incidence of cumulative postoperative complications was similar in the older (28.1%) and younger (34.4%) groups (P = .10). One-, 3-, and 5-year disease-free survival rates were 57.6%, 32.9%, and 16.4%, respectively, in the younger group and 67.9%, 29.2%, and 19.5%, respectively, in the older group (P = .72). One-, 3-, and 5-year participant survival rates were 84.1%, 51.9%, and 33.3%, respectively, in the older group and 93.6%, 63%, and 28%, respectively, in the younger group (P = .50). CONCLUSIONS: Resection of colorectal liver metastases in older adults can be performed with low mortality and morbidity and offers a long-time survival advantage to many of these individuals. Based on the results of this case-control study, older adults should be considered for surgical treatment whenever possible.

Long-term follow-up and outcome of liver transplantation from anti-hepatitis C virus-positive donors: a European multicentric case-control study.

BACKGROUND: The growing prevalence of hepatitis C virus (HCV) infection in the general population has resulted in an increased frequency of potential organ donors that carry the virus. Given the significant disparity between organ supply and demand for transplantation, it becomes essential to consider whether livers from anti-HCV-positive donors may be considered suitable for transplantation. METHODS: Based on a multicenter European database, 694 patients with HCV-related cirrhosis underwent liver transplantation and 11% of them received the graft from anti-HCV-positive donors. Of this group, we selected 63 patients (study group) and, after a 1:1 case-control approach, compared them with 63 patients that received an anti-HCV-negative donor graft (control group). Only grafts with preperfusion liver biopsy results with a fibrosis score of not more than 1 were used for transplantation. RESULTS: Patients who received anti-HCV-positive grafts had a cumulative survival rate of 83.6% and 61.7% at 1 and 5 years, respectively, vs. 95.1% and 68.2% for the control group. In comparing overall patient and graft survival, there was no statistically significant difference between the two groups (P=0.22 and 0.11). Recurrence of hepatitis C tended to be more rapid in the group of patients who received anti-HCV-positive grafts, although it did not reach statistical significance (P=0.07). CONCLUSIONS: We do not recommend the indiscriminate use of anti-HCV-positive donors, especially if HCV-RNA positive, as the use of this kind of graft could be linked to an advanced stage of fibrosis, the main risk factor we observed for earlier hepatitis C recurrence.

Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma.

Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.

Does HIV-related cholangiopathy exist in the setting of liver transplantation?

Biliary tract complications after liver transplantation represent a source of morbidity and mortality. Performing an analysis to evaluate whether HIV infection and its related comorbidities, such as HIV-related cholangiopathy, could be an unknown risk factor for biliary stricture, we found that HIV-positivity could lead to greater susceptibility to biliary damage. The pathogenesis of the damage seems to involve the pretransplant immunological status and the number and type of posttransplant infections, although further studies are needed.