To the Editor: Pathophysiology of Splenic Arteriovenous Fistula.

A splenic arteriovenous fistula causes a "prehepatic" hypertension in the portal venous system with the double mechanism of an increased blood amount and mainly its high pressure inflow. It aggravates for a secondary fibrosis of the portal vein branches and "capillarization" of the hepatic sinusoids, adding a further "intra-hepatic" component. The subsequent development of portosystemic collaterals induces the risk of gastrointestinal hemorrhages All this suggests to perform a close monitoring of every case of splanchnic aneurysm or pseudo-aneurysm, through the current cross-section imaging tools, for their possible evolution in an arteriovenous fistula, and to consider an early therapy, also endovascular, before any secondary damage of the liver parenchyma. In this case the treatment of the portal vein hypertension can be "ethiological" and resolutive.

Type 3 hypersensitivity in COVID-19 vasculitis.

Coronavirus Disease 2019 (COVID-19) is an ongoing public health emergency and new knowledge about its immunopathogenic mechanisms is deemed necessary in the attempt to reduce the death burden, globally. For the first time in worldwide literature, we provide scientific evidence that in COVID-19 vasculitis a life-threatening escalation from type 2 T-helper immune response (humoral immunity) to type 3 hypersensitivity (immune complex disease) takes place. The subsequent deposition of immune complexes inside the vascular walls is supposed to induce a severe inflammatory state and a cytokine release syndrome, whose interleukin-6 is the key myokine, from the smooth muscle cells of blood vessels.

Appendix Tumor Microenvironment.

The pathological features of the appendix tumors fundamentally recall those of the more frequent colorectal neoplasms, although with a higher relative incidence of carcinoids, due to the abundant presence of enteroendocrine cells in the appendix wall. Moreover, different types of lymphomas, Hodgkin and non-Hodgkin, arising from the extra-nodal mucosal-associated lymphatic tissue, can be encountered. The appendix tumor microenvironment (TME) consists of a cellular component and of a noncellular component: the former includes the immunocompetent cells, while the latter represents the support stroma. Particularly in carcinoids, the immune cell reaction can be explicated by tumor-infiltrating lymphocytes, which, in some circumstances, may arrange around and inside the tumor in a brisk fashion influencing favorably the prognosis. This active reaction has to be distinguished from any preexisting inflammatory condition of the appendix and from superimposed tumor complications, such as infection or ischemia. In practice, we consider the appendix TME a complex framework with immunological, mechanic, and metabolic functions, all supported by a marked neo-lymphoangiogenesis.

Correction to: Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature.

Following publication of the original article [1], the authors have notified us that due to administrative reasons they would like to modify the first affiliation from.

Management of duodenal stump fistula after gastrectomy for malignant disease: a systematic review of the literature.

BACKGROUND: Duodenal stump fistula (DSF) remains one of the most serious complications following subtotal or total gastrectomy, as it endangers patient's life. DSF is related to high mortality (16-20%) and morbidity (75%) rates. DSF-related morbidity always leads to longer hospitalization times due to medical and surgical complications such as wound infections, intra-abdominal abscesses, intra-abdominal bleeding, acute pancreatitis, acute cholecystitis, severe malnutrition, fluids and electrolytes disorders, diffuse peritonitis, and pneumonia. Our systematic review aimed at improving our understanding of such surgical complication, focusing on nonsurgical and surgical DSF management in patients undergoing gastric resection for gastric cancer. METHODS: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. PubMed/MEDLINE, EMBASE, Scopus, Cochrane Library and Web of Science databases were used to search all related literature. RESULTS: The 20 included articles covered an approximately 40 years-study period (1979-2017), with a total 294 patient population. DSF diagnosis occurred between the fifth and tenth postoperative day. Main DSF-related complications were sepsis, abdominal abscess, wound infection, pneumonia, and intra-abdominal bleeding. DSF treatment was divided into four categories: conservative (101 cases), endoscopic (4 cases), percutaneous (82 cases), and surgical (157 cases). Length of hospitalization was 21-39 days, ranging from 1 to 1035 days. Healing time was 19-63 days, ranging from 1 to 1035 days. DSF-related mortality rate recorded 18.7%. CONCLUSIONS: DSF is a rare but potentially lethal complication after gastrectomy for gastric cancer. Early DSF diagnosis is crucial in reducing DSF-related morbidity and mortality. Conservative and/or endoscopic/percutaneous treatments is/are the first choice. However, if the patient clinical condition worsens, surgery becomes mandatory and duodenostomy appears to be the most effective surgical procedure.

Primary pancreatic perivascular epithelioid cell tumor (PEComa): A surgical enigma. A systematic review of the literature.

BACKGROUND: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor, with distinctive morphology and expression of myo-melanocytic markers. Current scientific literature reported just 24 cases of pancreatic PEComas. With our systematic review, we aimed at improving our understanding of the disease, focusing on the knowledge gained on epidemiology, etiology, clinical presentation, diagnosis, treatment and prognosis. METHODS: Based on the PRISMA guidelines, a systematic research was carried out on PubMed/MEDLINE, Web of Science, Scopus, EMBASE, and EBSCO using the search terms: ("perivascular epithelioid cell tumor" OR ″PEComa") and ("pancreas "OR″ pancreatic"). RESULTS: The 4th-6th decades of life and female sex (86.9%) turned out as the most affected. Pancreatic head was the most involved site (50%), with a single lesion in almost all cases. The diagnosis was only obtained after histopathological examination (70.8%). The clinical presentation was non-specific, abdominal pain being the main symptom (60.9%). At immunohistochemistry, PEComa showed benign epithelioid predominance and a strong positivity for HMB-45, Melan-A, and α-SMA. Surgical resection was performed in almost all cases, while for one patient the multidisciplinary group chose just endoscopic and imaging follow-up, based on the benign nature of the lesion. CONCLUSIONS: The biological characteristics of pancreatic PEComa remain an enigma. Its prognosis seems to depend on whether atypical ("worrisome") histological features are available or not. Surgery turned out as the most appropriate treatment, without reaching any agreement on surgery timing. Further studies on larger population are needed to better understand the biological features of pancreatic PEComa, in order to set up guidelines in the diagnosis, treatment and follow-up.

Pancreaticojejunostomy with or without reinforcement after pancreaticoduodenectomy: surgical technique of ligamentum teres hepatis wrap around pancreaticojejunostomy.

In a previous issue of the Journal, Zhong et al. reported a retrospective study that compared the perioperative outcomes of the mesh-reinforced pancreaticojejunostomy with conventional pancreaticojejunostomy. They concluded that mesh-reinforced pancreaticojejunostomy was a safe and effective technique, as it provided a safe anchor site for suture, thus reducing the risk of pancreatic leakage. Considering these encouraging results, we present a further simple technique using ligamentum teres hepatis wrap around pancreatojejunostomy for prevention of postoperative pancreatic fistula after pancreaticoduodenectomy.