Cholangiocarcinoma (CCC) is the most aggressive malignant tumor of the biliary tract. Perihilar CCC (pCCC) is the most common CCC and is burdened by a complicated diagnostic iter and its anatomical ...location makes surgical approach burden by poor results. Besides its clinical presentation, a multimodal diagnostic approach should be carried on by a tertiary specialized center to avoid miss-diagnosis. Preoperative staging must consider the extent of liver resection to avoid post-surgical hepatic failure. During staging iter, magnetic resonance can obtain satisfactory cholangiographic images, while invasive techniques should be used if bile duct samples are needed. Consistently, to improve diagnostic potential, bile duct drainage is not necessary in jaundice, while it is indicated in refractory cholangitis or when liver hypertrophy is needed. Once resecability criteria are identified, the extent of liver resection is secondary to the longitudinal spread of CCC. While in the past type IV pCCC was not considered resectable, some authors reported good results after their treatment. Conversely, in selected unresectable cases, liver transplantation could be a valuable option. Adjuvant chemotherapy is the standard of care for resected patients, while neoadjuvant approach has growing evidences. If curative resection is not achieved, radiotherapy can be added to chemotherapy. This multistep curative iter must be carried on in specialized centers. Hence, the aim of this review is to highlight the main steps and pitfalls of the diagnostic and therapeutic approach to pCCC with a peculiar attention to type IV pCCC.
Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the ...death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients' cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
Mucosal healing has been proposed as an important sign of the efficacy of medical treatment of inflammatory bowel disease; however, direct evidence in ulcerative colitis (UC) is scarce. We evaluated ...the usefulness of colonoscopy and bowel ultrasound (US) as indexes of response to short-term therapy and as predictors of subsequent outcome in UC.
A total of 83 patients with moderate-to-severe UC were recruited; endoscopic and US severity was graded 0-3 at entry according to validated scores. Of the recruited patients, 74, who were clinically responsive to steroids, were followed up with repeated colonoscopy and bowel US at 3, 9, and 15 months from recruitment. Concordance between clinical, endoscopic, and US scores at various visits was determined by kappa statistics. Multiple unconditional logistic regression models were used to assess the predictivity of clinical, endoscopic, and US scores measured at 3 and 9 months on the development of endoscopic UC relapse within 15 months.
A variable concordance was found over time between endoscopic and clinical score (weighted kappa between 0.38 and 0.95), with high and consistent concordance between endoscopic and US scores (weighted kappa between 0.76 and 0.90). On logistic regression analysis, moderate-to-severe endoscopic and US scores at 3 months were associated with a high risk of endoscopic activity at 15 months (odds ratio (OR): 5.2; 95% confidence interval (CI): 1.6-17.6 and OR: 9.1; 95% CI: 2.5-33.5, respectively).
Bowel US may be used as a surrogate of colonoscopy in assessing the short-term response of severe forms of UC to therapy. Both US score and endoscopic score after 3 months of steroid therapy predict outcome of disease at 15 months.
Indocyanine
green (ICG) is a fluorescent dye with a strong emission
in the near-infrared spectral range that allows deep signal penetration
and minimal interference of tissue autofluorescence. It has ...been employed
in clinics for different applications, among which the more interesting
is certainly near-infrared fluorescence image-guided surgery. This
technique has found wide application in surgical oncology for lymph
node mapping or for laparoscopic surgery. Despite ICG being useful
for tracking loco-regional lymph nodes, it does not provide any information
about cancer involvement of such lymph nodes or lymphatic vessels,
lacking any tumor-targeting specificity. However, the clinical need
in surgical oncology is not only a specific tracking of metastatic
nodes but also the intraoperative detection of micrometastatic deposits.
Here, we have exploited a nanotechnological solution to improve ICG
usefulness by its encapsulation in H-ferritin (HFn) nanocages. They
are natural protein-based nanoparticles that exhibit some very interesting
features as delivery systems in oncological applications because they
display specific tumor homing. We show that HFn loaded with ICG exhibits
specific uptake into different cancer cell lines and is able to deliver
ICG to the tumor more efficiently than the free dye in an
in vivo
model of TNBC. Our results pave the way for the
application of ICG-loaded HFn in fluorescence image-guided surgery
of cancer.
Introduction
Despite the effectiveness of new therapies and awareness campaigns, the number of seropositive patients is increasing every year. Recently, other causes of death, not directly related to ...HIV, have emerged, such as chronic liver disease. The risk of hepatocellular carcinoma (HCC) is seven times greater in HIV patients than in noninfected patients, and it is especially attributable to HCV infection. The aim of our study was to evaluate clinical outcomes of HCC in HIV-HCV co-infected patients after liver resection (LR).
Materials and methods
The current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with HCC treated by LR from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection.
Results
We identified 16 patients with HCV infection and precisely five with HIV-HCV co-infection and eleven with HCV infection alone. All HIV patients were male against 72.7% in the non-HIV group (
p
= 0.509). All patients had optimal HIV virologic control and a normal CD4 T-cell count. The mean diagnosis-to-treatment interval was statistically different between the two groups (HIV versus non-HIV: 1.2 ± 0.55 months versus 2.39 ± 1.09 months,
p
= 0.039).
No other significant differences were found between HIV-HCV co-infected patients and HCV-infected patients. Long-term outcomes in terms of OS and RFS were similar between the two groups.
Conclusions
With a multidisciplinary approach and intensive support, LR can be a safe and efficacious procedure in HIV-HCV patients. For these reasons, we should not exclude potential patients merely on the basis of their HIV seropositivity.
Abstract Background Achieving clear margins with adequate resection volumes is one of the principal goals of breast-conserving surgery. The aim of our study was to compare preoperative localization ...using 2 different clips, radiopaque or sonographically visible, to reach this goal. Methods We reviewed 209 consecutive nonpalpable breast cancers that were treated with lumpectomy: 59 with radiopaque and 150 with sonographically visible clip positioned during biopsy procedure. In the former case, preoperative localization was performed with mammography and in the latter by ultrasonography. Results Clear margins were achieved in 80.4% of patients: 57.6% in the first and 89.3% in the second group ( P < .0001; odds ratio, 7.6; 95% confidence interval, 3.4 to 17.2). By using sonographically visible clips, the re-excision rate has decreased from 42.4% to 10.7%, ( P < .0001), and resections resulted smaller with average calculated resection ratio of 3.54 vs 5.08 ( P = .03). Conclusions Preoperative localization using a sonographically visible clip allows a more tailored breast-conserving surgery and reduces the re-excision rate.
Duodenal diverted sleeve gastrectomy with ileal interposition (DDSG-II) is a bariatric-metabolic operation designed to treat type 2 diabetes mellitus (T2DM). It is restrictive (SG) but also acts on ...the small bowel with functional effects. The objective of the present study was to investigate whether or not it is also a malabsorptive operation.
Twelve obese patients (9 female and 3 male) affected by T2DM had DDSG-II. Follow-up was every 3 months, and the results after 1 year are reported here. Clinical conditions, related to diabetes and malnutrition, changes in weight, body mass index, fasting glucose plasma levels, HbA1c (glycated hemoglobin %), basal insulin, vitamin B12, folic acid, vitamin D, total proteins, albumin, and hemoglobin were recorded. Basal plasma levels of FGF19 (pg/mL) and of 7α-hydroxy-4-cholesten-3-one (C4) (μg/dL) were also determined for the diagnosis of biliary salt malabsorption. The results were expressed as mean±SEM, and the differences between times compared by the Mann Whitney U test; P<.05 was considered significant.
After 1 year, all patients had a significant weight loss (-33.2±3 kg) with T2DM remission according to the American Diabetes Association criteria (11), criteria. No significant changes in total proteins, albumin, hemoglobin, and vitamins (B6, B12, and D) were detected. C4 did not change after the operation (2±.5 µg/dL versus 1.6±.5 µg/dL), whereas FGF19 significantly increased (from 85±11.2 pg/mL to 166.4±28.2 pg/mL, P<.04). Only 2 patients had mild symptoms of malabsorption.
DDSG-II is effective for treatment of T2DM obese patients, increases the enterokine FGF19, and does not cause biliary salt malabsorption.
The Milan Charter on Urban Obesity highlights the challenges of urban environments as a battleground for human health, as cities are often organized to subvert public health goals, and promote rather ...than prevent the development of obesity and consequent non-communicable diseases. The Charter articulates ten principles which detail actions and strategies through which general practitioners, diverse medical specialists, related healthcare professionals, administrators and healthcare practice managers, policy actors – within health systems and at a national level – along with experts across disciplines, and citizens, can work in cooperation to meet this challenge and improve public health. The Charter urges the adoption of decisions that deliver the following: (i) policies which enable our cities to become healthier and less obesogenic, more supportive of well-being and less health-disruptive in general, and (ii) policies that fully support primary prevention strategies, that address social stigma, and that ensure fair access to treatment for people living with obesity. The Milan Charter on Urban Obesity aims to raise awareness of our shared responsibility for the health of all citizens, and focuses on addressing the health of people living with obesity – not only as a challenge in its own right, but a gateway to other major non-communicable diseases, including cardiovascular diseases, type 2 diabetes, and some cancers.
Sciatic hernia is a very rare pelvic floor hernia, but apparently its incidence has been growing in the past few years. The symptomatology is usually aspecific or absent, but in some cases ...complications such as intestinal obstruction, intractable pain, or urinary sepsis can occur. The usual treatment is the surgical correction of the defect, mainly with an open approach.
We describe a case of sciatic hernia causing intermittent abdominal pain and subocclusive symptoms. The hernia has been treated with a laparoscopic technique using a polypropylene extraperitoneal mesh fixed with biological glue. The postoperative course of our patient was uneventful and at 3 months follow-up, no relapse or symptoms occurred.
The laparoscopic treatment of this rare type of hernia appears to be a feasible and safe surgical option with all the advantages of the mini-invasive technique.
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