Treatment options for PNET liver metastases. a systematic review

Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs

Distinctive patterns of placental lesions in preeclampsia versus fetal growth restriction and their association with fetoplacental Doppler

OBJECTIVES: The aim of this study was to describe placental histopathological findings in a large cohort of pregnancies complicated by preeclampsia and/or fetal growth restriction, and to investigate its association with fetoplacental Doppler. METHODS: This was a prospective observational study including pregnancies complicated by: 1) normotensive FGR defined as birthweight 95th centile for uterine and umbilical artery, or <5th centile for middle cerebral artery and CPR. Placental lesions were categorized to vascular (maternal/fetal side), inflammatory and other lesions according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Univariate and multiple regression analysis were performed for the comparison between the study groups. Logistic regression was used to determine abnormal Doppler association with placental lesions. RESULTS: Maternal side vascular lesions are significantly higher in PE compared to controls and normotensive FGR (PE&FGR: 73%, PE: 46%, FGR: 38% vs. controls: 31%; p=0.01) including 2 types of lesions: developmental (PE&FGR: 13%, PE: 5%, FGR: 3% vs. controls: 2%, p<0.001) and malperfusion (PE&FGR: 70%, PE: 39%, FGR: 32% vs. controls: 25%, p=0.001). In contrast, fetal side developmental lesions are significantly higher in normotensive FGR compared to controls and PE (PE&FGR: 0%, PE: 3%, FGR: 8% vs. controls 2%, p=0.001). All cases displayed lower prevalence of infectious lesions, with a high prevalence of immune lesions in PE&FGR (PE&FGR: 17.5%, PE: 7.8%, FGR: 9.8% vs. controls 9.4%, p=0.001). All fetoplacental Doppler parameters are associated with maternal side vascular lesions -mainly malperfusion- [uterine arteries mean PI (Odds ratio(OR)=2.45, 95% confidence interval (CI): 1.51 - 3.97), umbilical artery PI (OR=2.05, 95% CI: 1.02 - 4.47), middle cerebral artery PI (OR=2.75, 95% CI: 1.4 - 5.42), CPR (OR=1.75, 95% CI: 1.04 - 2.95)]. This association was evident mainly in the FGR groups -with and without PE-, being nonsignificant in controls or PE without FGR. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. CONCLUSIONS: PE and FGR exhibit different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs. fetal). Fetoplacental Doppler shows an association with placental malperfusion lesions in the maternal side, reinforcing its use as a surrogate of placental insufficiency

Postoperative Pancreatic Fistula. Is Minimally Invasive Surgery Better than Open? A Systematic Review and Meta-analysis

Background/Aim: Minimally invasive pancreatico-duodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF) after minimally invasive versus open procedures. Materials and Methods: Following the PRISMA statement, literature research was conducted focusing on papers comparing the incidence of POPF after open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD). Results: Twenty-one papers were included in this meta -analysis, for a total of 4,448 patients. A total of 2,456 patients (55.2%) underwent OPD, while 1,992 (44.8%) underwent MIPD. Age, ASA score III patients, incidence of pancreatic ductal adenocarcinoma and duct diameter were significantly lower in the MIPD group. No statistically significant differences were found between the OPD and MIPD regarding the incidence of major complications (15.6% vs. 17.0%, respectively, p=0.55), mortality (3.7% vs. 2.4%, p=0.81), and POPF rate (14.3% vs. 12.9%, p=0.25). Conclusion: MIPD and OPD had comparable rates of postoperative complications, postoperative mortality, and POPF

SARS-CoV-2 RNA and antibody detection in breast milk from a prospective multicentre study in Spain

This study has been supported by a research grant from Fundacion La Marato-TV3 (MilkCORONA, ref 202106).Objectives To develop and validate a specific protocol for SARS-CoV- 2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV- 2 infection on the presence, concentration and persistence of specific SARS-CoV- 2 antibodies. Design and patients This is a prospective, multicentre longitudinal study (April–December 2020) in 60 mothers with SARS-CoV- 2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. Setting Seven health centres from different provinces in Spain. Main outcome measures Presence of SARS-CoV- 2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV- 2-specific immunoglobulins (Igs)—IgA, IgG and IgM—in breast milk samples from patients with COVID-19. Results All breast milk samples showed negative results for presence of SARS-CoV- 2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV- 2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%–87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). Conclusions Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV- 2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence.Fundacion La Marato-TV3 20210

SARS-CoV-2 RNA and antibody detection in human milk from a prospective multicenter study in Spain

Objectives To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies. Design and patients This is a prospective, multicentre longitudinal study (April-December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. Setting Seven health centres from different provinces in Spain. Main outcome measures Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)¿IgA, IgG and IgM¿in breast milk samples from patients with COVID-19. Results All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%-87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). Conclusions Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol

Neoadjuvant therapy for pancreatic cancer

Multimodal treatment including surgery and chemotherapy is considered the gold standard treatment of pancreatic cancer by most guidelines. Neoadjuvant therapy (NAT) has been seen as a possible treatment option for resectable, borderline resectable and locally advanced PaC. The aim of this paper is to offer a state-of-the-art review on neoadjuvant treatments in the setting of pancreatic ductal adenocarcinoma. A systematic literature search was performed using PubMed, Cochrane, Web of Science and Embase databases, in order to identify relevant studies published up to and including July 2021 that reported and analyzed the role of neoadjuvant therapy in the setting of pancreatic carcinoma. Most authors are concordant on the strong role of neoadjuvant therapy in the setting of borderline resectable pancreatic cancers. Recent randomized trials demonstrated improvement of R0 rate and survival after NAT in this setting. Patients with locally advanced cancers may become resectable after NAT, with better results than those obtained with palliative therapies. Even in the setting of resectable cancers, NAT is being evaluated by ongoing randomized trials. Chemotherapy regimens in the setting of NAT and response to NAT are discussed. NAT has an important role in the multimodal treatment of patients with borderline resectable pancreatic cancer. It has a role in patients with locally advanced tumors as it can allow surgical resection in a relevant proportion of patients. For resectable pancreatic cancers, the role of NAT is under evaluation by several randomized trials

ACANTHOSIS NIGRICANS: THE TELLTALE SIGN OF A GASTRIC CANCER RECURRENCE

Background: Acanthosis nigricans (AN) is a skin condition characterized by focal or diffuse hyperkeratotic, symmetrically distributed hyperpig- mented lesions of skin or mucous membranes. It has been associated with a wide spectrum of diseases such as type 2 diabetes mellitus, obesity, drugs and malignancies (Malignant Acanthosis Nigricans, MAN). MAN mostly occurs in elderly patients, without gender differences and its most com- mon cause is gastric cancer (55-61%), followed by pancreatic, gynecolog- ical and pulmonary malignancies. Coexisting neoplasm should always be suspected in elders with new onset AN. Here we present the case of a woman with severe MAN associated with gastric adenocarcinoma. Skin lesions disappeared after treatment. In our case, development of MAN represented the first sign of tumour recurrence. Materials and Methods: We report a case of malignant acanthosis nig- ricans associated with both onset and recurrence of gastric carcinoma. A 63 years old woman presented with hyperkeratotic, papillomatous plaques on neck, armpits and chest. Endoscopy revealed an extensive ulcerated gastric neoplasm. Surgical resection and adjuvant chemotherapy were followed by complete regression of the skin lesions. Unfortunately after 8 months cancer recurrence occurred and it was preceded by development of malignant acanthosis nigricans. Results: MAN is a rare paraneoplastic condition often associated with malignancies: the most common is gastric carcinoma (55-61% of all MAN cases). Prevalence of MAN is estimated to be 2/12000 cancer patients. Its pathogenesis remains unclear: TGF-alpha secretion and EGF-R hyper- expression may play a role in the development of skin lesions. Usually MAN is more severe and spreads faster than AN associated with benign pathologies. MAN regression is observed in 90-95% of patients who un- dergo treatment of the primary tumour: the skin lesions usually are resistant to conventional treatments such as corticoids or vitamin D. Although in literature there are several cases of MAN in patients with primary gastric neoplasm, to our knowledge only one paper reports the development of MAN in gastric cancer recurrence (Tab. 1). Conclusions: In conclusion, acanthosis nigricans has a wide range of underlying causes but it always has to be investigated as it may lead to the diagnosis either of a malignancy either of its recurrence. It could be therefore considered pathognomonic for tumour recurrence in elder pa- tients with positive history for abdominal neoplasms

LIVER TRANSPLANT FOLLOWING BARIATRIC SURGERY: A MINI REVIEW

Background: As obesity prevalence has been increasing dramatically in the last decades, bariatric surgery is on the rise as an effective and feasible option to treat metabolic diseases related to overweight. One rare, but potentially fatal, complication of bariatric surgery is hepatic failure requiring rescue liver transplantation. Materials and Methods: Following the criteria of the PRISMA statement, a literature search was conducted focusing on papers concerning patients who underwent liver transplantation for hepatic failure following bariatric surgery. Due to the rarity of the described condition, both retrospective studies and case reports were included in this mini-review. Results: Literature review was performed on PubMed, Embase and Med- line, using (“liver transplantation” OR “liver graft”) AND (“bariatric sur- gery” OR “obesity surgery” OR “metabolic surgery”) as search terms. This led to the identification of 145 papers. We restricted the search to humans and english language articles resulting in 101 eligible articles to review. Title and abstract revision led to the identification of 14 papers for full text analysis. Cross-reference check provided 4 more articles to review. After final full text review, 6 papers, of which 2 were case reports and 4 case series, were included in this study. The timeframe between bariatric sur- gery and liver transplant varied between bariatric surgery techniques, ranging from 7 months to 25 years: jejunoileal bypass had a longer latency of hepatic failure, while biliopancreatic diversion, long limb gastric bypass and biliointestinal bypass showed a more rapid decay of liver function. Out of 24 patients listed for liver transplant, 3 died on waiting list and 1 was still on transplant list at the time of publication. Conclusions: Liver failure following bariatric surgery is an extremely serious condition, that can occur in both sub-acute and chronic setting. Although rare, its real incidence is not known and probably underreported in literature. Due to the worldwide spread of bariatric surgery, our goal is to highlight the importance of early recognition of liver failure in those patients

Is Complete Pathologic Response in Pancreatic Cancer Overestimated? A Systematic Review of Prospective Studies

Background: In literature, percentages of pathologic complete response (pCR) in patients presenting with resectable (RES), borderline resectable (BLR) or locally advanced (LA) pancreatic cancer (PaC) after neoadjuvant treatment (NADT) are variable, ranging 0–33%. Those data come mostly from retrospective reviews of single centres. The objective of this systematic review is to assess the incidence of pCR. Methods: Following the criteria of the PRISMA statement, a literature search was conducted looking for prospective papers focusing on neoadjuvant treatment in PaC. Retrospective papers, other than ductal carcinoma histologies and trials including metastatic patients, were excluded from the present review. Data extraction was carried out by 3 independent investigators. Meta-analysis was performed with ProMeta3 Software (Internovi, 2015). PROSPERO registry: CRD42018095641. Results: The literature search of Embase, Cochrane and Medline with the terms “neoadjuvant OR preoperative”, “pancreatic OR pancreas” and “cancer OR adenocarcinoma OR tumor” led to the identification of 3128 papers. We restricted the search to humans, last 10&nbsp;years and English language articles resulting in 1158 eligible articles to review. Extended paper revision led to the inclusion of 27 papers. Complete pathologic response ranged 0–11.11%, at the meta-analysis 4% (95% CI 3–5%), in prospective studies 0–9.09% and in prospective databases 1.63–11.11%. Conclusions: Pathologic complete response in pancreatic cancer is actually infrequent: high-quality studies provide a more reliable picture of neoadjuvant effects, high rates of pCR are reported in selected retrospective studies but it is overestimated