A prognostic score for predicting survival in patients with pancreatic head adenocarcinoma and distal cholangiocarcinoma

Background/aim: Survival of patients with pancreatic cancer remains poor despite improvements in therapeutic strategies. This study aims to create a novel preoperative score to predict prognosis in patients with tumors of the pancreaticobiliary head. Patients and methods: Data on 190 patients who underwent to pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2018 were retrospectively analyzed. After exclusion criteria, 101 patients were considered eligible for retrospective study. Preoperative biological, clinical and radiological parameters were considered. Results: Pancreatic ductal adenocarcinoma [hazard ratio (HR)=1.995, 95% confidence intervaI (CI)=1.1-3.3; p=0.01], carbohydrate antigen 19.9 (CA 19.9) >230 U/ml (HR=2.414, 95% CI=2.4-1.5, p<0.0001) and Wirsung duct diameter >3 mm (HR=1.592, 95% CI=1.5-0.9; p=0.08) were the only parameters associated with poor prognosis. Through these parameters, a prognostic score (PHT score) was developed which predicted worst survival when exceeding 2 and better survival when ≤2. Conclusion: The PHT score may have a potential impact on predicting overall survival and consequently modulate the timing and type of treatment (up-front surgery vs. neoadjuvant therapy) patients are offered

Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis

Purpose:The differential diagnosis between primary adenocarcinoma of the pancreas head and distalcholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms ofsurvival between these tumors. Therefore, different treatments should be considered, but the preoperativehistological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differentialdiagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma.Methods:One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at SapienzaUniversity of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria werepancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteriawere diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, andbenign disease. One hundred one patients were considered eligible for the retrospective study. Preoperativebiological, clinical, and radiological parameters were considered.Results:CRP > 10 mg/dL (p= 0.001), modified Glasgow Prognostic Score 2 (p= 0.002), albumin < 35 g/L (p= 0.05),CA 19-9 > 230 U/mL (p= 0.001), and Wirsung diameter > 3 mm (p< 0.001) were significant at univariate logisticanalysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreaticadenocarcinoma were CRP > 10 mg/dL (p= 0.012), CA 19-9 > 230 U/mL (p= 0.043), and diameter of the Wirsung> 3 mm (p= 0.005). Through these parameters, a diagnostic score has been developed to predict a primarypancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1.Conclusion:This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreaticcancer histologic origin and to improve target therapeutic strategy

Metastatic renal cell carcinoma invading liver, duodenum and ivc, surgical treatment and literature review. A case report

Renal Cell Carcinoma has a biologic predisposition for direct vascular invasion: intravascular tumor thrombus is found in 5% to 20% of the cases inside the renal vein or the inferior vena cava. Despite new and effective conservative therapy such as targeted therapy and immunotherapy, cytoreductive nephrectomy and palliative nephrectomy continues to have an important role in T4 patient. The patient selection for cytoreductive nephrectomy should be done carefully. This report present an unique case of metastatic RCC with invasion of the duodenum, liver and retrohepatic IVC, the adopted surgical approach and a review of the literature. Complete surgical extirpation is possible in cases of RCC invading other organs such as pancreas, duodenum, liver, retroperitoneum and IVC. In this scenario, to narrow the possible intraoperative complication, a multidisciplinary approach and equipe is recommended

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

A Woman’s Place Is in Theatre, but Are Theatres Designed with Women in Mind? A Systematic Review of Ergonomics for Women in Surgery

Background: Literature regarding ergonomic protocols for surgery is lacking, and there is a paucity of information on how this impacts on gender differences with regards to the barriers faced by women in surgery. Methods: This article reviews current literature addressing women in surgery and ergonomics through a systematic search including the Web of Science, Scopus, and PubMed databases. Results: Searches retrieved 425 items, and after a thorough evaluation for inclusion, 15 studies were examined—predominantly surveys (n = 9) and originating from the USA (n = 9). Identified ergonomic challenges included the general shorter height and smaller glove size of women. Furthermore, women experienced more musculoskeletal pain than men, potentially because the size and design of theatre tools are designed for male and tall individuals, highlighting an unconscious gender bias still pervading the surgical field. Conclusions: As more women enter medicine and pursue surgical careers, it is essential to foster a culture of diversity and inclusion in theatre to develop more ergonomic environments

Abdominal Lymphadenopathy: Hypothesize Cat-Scratch Disease and Avoid Abdominal Excisional Biopsy

The finding of lymphadenopathy is usually the consequence of a benign infection, although a neoplastic origin must always be excluded. Through a careful anamnesis, physical examination, and serological tests several differential diagnoses are frequently possible. Nevertheless, sometimes an excisional biopsy of superficial lymph nodes is required, which is the best means to reach a definitive diagnosis. More concerns arise when lymphadenopathy is only abdominal/retroperitoneal: percutaneous biopsy is often inconclusive and the excisional node biopsy becomes a surgical procedure, certainly indicated in case of malignancy but avoidable in case of inflammatory diseases. We present the case of a 30-year-old man with a deep iliac lymphadenopathy who was evaluated at the Hematological Unit of Sapienza University of Rome. The enlargement of an iliac lymph node is quite unusual for an infectious disease. Although symptoms such as pain, fever, and chills suggested it was the case, cat-scratch disease was not hypothesized. Radiological investigations did not exclude a malignant disease and a laparoscopic excisional biopsy was scheduled, but the slight improvement of his spontaneous symptoms suggested a careful follow-up. Given the lack of disappearance of lymphadenopathy, the lack of diagnosis, and an ipsilateral superficial (inguinal) lymph node with similar ultrasonographic and radiological features, the patient underwent biopsy, which disclosed a diagnosis of cat-scratch disease, avoiding more invasive surgical procedures

Abdominal Lymphadenopathy: Hypothesize Cat-Scratch Disease and Avoid Abdominal Excisional Biopsy

The finding of lymphadenopathy is usually the consequence of a benign infection, although a neoplastic origin must always be excluded. Through a careful anamnesis, physical examination, and serological tests several differential diagnoses are frequently possible. Nevertheless, sometimes an excisional biopsy of superficial lymph nodes is required, which is the best means to reach a definitive diagnosis. More concerns arise when lymphadenopathy is only abdominal/retroperitoneal: percutaneous biopsy is often inconclusive and the excisional node biopsy becomes a surgical procedure, certainly indicated in case of malignancy but avoidable in case of inflammatory diseases. We present the case of a 30-year-old man with a deep iliac lymphadenopathy who was evaluated at the Hematological Unit of Sapienza University of Rome. The enlargement of an iliac lymph node is quite unusual for an infectious disease. Although symptoms such as pain, fever, and chills suggested it was the case, cat-scratch disease was not hypothesized. Radiological investigations did not exclude a malignant disease and a laparoscopic excisional biopsy was scheduled, but the slight improvement of his spontaneous symptoms suggested a careful follow-up. Given the lack of disappearance of lymphadenopathy, the lack of diagnosis, and an ipsilateral superficial (inguinal) lymph node with similar ultrasonographic and radiological features, the patient underwent biopsy, which disclosed a diagnosis of cat-scratch disease, avoiding more invasive surgical procedures

Lymphadenopathies before and during the Pandemic COVID-19: Increasing Incidence of Metastases from Solid Tumors

Since December 2019, the world has experienced a pandemic caused by SARS-CoV-2, a virus which spread throughout the world. Anti-COVID19 measures were applied to limit the spread of the infection, affecting normal clinical practice. In 2020, studies on the possible impact of the pandemic considering the screening programs for early diagnosis of cancer were conducted, resulting in a prediction of delayed diagnosis of cancer. We performed a retrospective monocentric study on patients who present with the onset of lymphadenomegalies evaluated at our Hematological Department from February 2019 to October 2021 and undergoing excisional lymph-node biopsy. Three periods were considered: pre-pandemic, first pandemic period and second pandemic period (Group A, B and C). We included 258 patients who underwent a surgical biopsy and received a histological diagnosis. Hematological evaluation of outpatients sent by the general practitioner and surgical biopsies did not decrease among the three groups, despite limitations placed during this pandemic as well as new diagnoses of hematological malignancies. However, the diagnosis of metastatic cancer significantly increased from 2019 (7.8%) to 2021 (22.1%) (p = 0.042). Our data supports the hypothesis that the pandemic affected the national screening programs of early cancer detection

Transforming growth factor-beta-induced protein as a novel secreted immune check-point in colorectal cancer

We set up a LC/Mass-spectometry (Orbitrap)-based platform to identify the secreted proteome (secretome) in conditioned medium (CM) from fresh tumor and non-tumor surgery samples. By this approach, we selected a multitude of secreted proteins that were upregulated in colorectal cancer (CRC) secretome as compared to the non-tumor, in order to identify those potentially acting as secreted immune check-points (sICs). Their discovery may represent a tremendous resource for tumor specific drug targets, potentially acting as sIC inhibitors in both cold and hot tumors, unlike current IC inhibitors (e.g., IpilumumAb and NivolumAb) causing a partial or no remission in the majority of cold tumors. The transforming growth factor-beta-induced (TGFBI) protein (previously called BIG-H3) was found significantly upregulated in CRC secretome (as compared with the non-tumor). TGFBI is an RGD-containing extracellular matrix protein that binds to type I, II and IV collagens, serves as a ligand recognition sequence for several integrins, and inhibits cell adhesion. Release of TGFBI from primary tumors has been associated with increased tumor proliferation/migration/metastasis, indirectly inhibits adhesion of mononuclear cells by occupancy of various integrins on endothelial cells, but its role as sIC has not been fully investigated. We first validated by Elisa that TGFBI was overexpressed in CM from CRC tissue samples (as compared with non-tumor CM), in serum from CRC patients (as compared with HD sera), and positively correlated with the tumor stage (according to the TNM classification). Interestingly, tissue-IHC and confocal microscopy revealed that TGFBI was overexpressed by tumor cells, T cells, monocytes and plasma cells in tumors in a significantly higher extent than in non-tumor, suggesting a massive involvement of the tumor microenvironment (TME) in secreting it. These data are also confirming at the level of the same cell populations isolated from tumor tissues. Importantly, the recombinant form of TGFBI, as well as the tumor CM containing high levels of native TGFBI, significantly inhibited various functions (IFN- and TNF- production, GZB and T-bet expression…) of anti-CD3/CD28-activated CD4 and CD8 T cells, which could be restored by the addition of the neutralizing anti-TGFBI mAb in vitro. Finally, we are validating that TGFBI can act as a sIC by using human 3D CRC organoids as a surrogate of animal models in vivo. Human 3D-organoids generated from various tumor tissues allow to determine the interaction between tumor and immune system, the response (activation, cytokine production, killing…) by autologous CD8 and CD4 T cells derived from cancer patients, the role of sICs in inhibiting anti-tumor T cell response, the role of related sIC inhibitors in unlashing the anti-tumor T cell response. Human-based models, such as human organoids, can offer effective ways “to accelerate transition to a research system that does not involve testing on animals”, as the European Parliament has recently declared (see go.nature.com/3hzprhj). Anti-tumor immune responses are often unable to clear stabilized tumors due to the presence of various T cell membrane immune checkpoints (mICs) delivering inhibitory signals into tumor-infiltrating lymphocytes (TILs) (i.e., T cell exhaustion). Monoclonal antibodies (mAbs) against mICs (acting as mIC inhibitors [mICIs]) restore anti-tumor responses by TILs leading to a dramatic reduction of several metastatic tumors. This occurs mainly with the so defined “hot tumors” – including melanoma, non-small cell lung cancer, bladder, kidney, head and neck cancer – which are characterized by significant DNA instability, due to the lack of mismatching repair mechanisms, very high mutational burden and thus generating a huge repertoire of mutated (passenger) neoantigens, and a high number of TILs. However, current mICIs (e.g., IpilumumAb and NivolumAb) cause a partial or no remission in the majority of the so-called “cold tumors” expressing a low rate of somatic mutations and, as a consequence, showing low frequencies of TILs. Cold tumors are most breast, ovarian, prostate, pancreatic cancers, glioblastomas, but also the majority of colorectal or hepatocellular carcinomas (CRC or HCC), which are microsatellite stable (MSS) tumors with effective DNA mismatching repair system. In addition to poor T cell infiltration, tumor microenvironment (TEM) in “cold tumors” is characterized by low major histocompatibility complex (MHC) class I and PD-L1 expression, high infiltration of immunosuppressive (IS) cell populations (e.g., tumor-associated macrophages [TAMs], regulatory T cells [Tregs], myeloid-derived suppressor cells [MDSCs], cancer-associated fibroblasts [CAFs]), and high density of secreted IS molecules (e.g., TGF-, IL-10, IL-6, Arginase, VEGF, GM-CSF, Wnts)(3-5). Therefore, a main objective of the scientific community is the development of novel strategies addressed to restore anti-tumor immunosuppression in order to meet the medical need to cure cold tumors (e.g., to convert them into hot tumors)

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis): The MANCTRA-1 international audit

Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines