Pancreatic resection is contraindicated in the case of advanced cancer (carcinomatosis, distant metastasis). Pre-operative imaging may fail to show advanced disease. The aim of the study was to ...identify pre-operative biomarkers of occult advanced disease (OAD) that could advice surgeons to abort the planned surgery. From January 2011 to September 2019, 100 consecutive patients underwent laparotomy for pancreatic cancer. All patients had blood test at admission and their pre-operative biomarker data were retrieved. Their medical history was collected, and the intraoperative findings were recorded. Non-parametric tests, multiple regression analysis, and ROC curve analyses were performed. OAD was found at laparotomy in 24 patients (24%). In pancreatic head cancer only, serum amylase showed a significant accuracy in predicting OAD (AUC 72.1%,
p
= 0.003). Platelet-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), and prognostic nutritional index (PNI) resulted to be accurate markers of OAD in M1 or T4 body/tail cancer (AUC = 100%,
p
< 0.001, AUC = 79%,
p
= 0.02, AUC 76%,
p
= 0.04, and AUC = 90%,
p
= 0.008, respectively). PNI resulted to be an independent predictor of OAD in a multivariable model (
r
= − 0.6,
p
= 0.04). In the pancreatic body/tail cancer, PNI could be further tested to use it as an alert for possible OAD.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumor microenvironment (TME). The aim of this study is to determine the potential significant TME immune markers ...of long-term survival.
We retrospectively included patients with a diagnosis of resectable PDAC having undergone upfront surgery. Immunohistochemical (IHC) staining using tissue microarray for PD-L1, CD3, CD4, CD8, FOXP3, CD20, iNOS and CD163 was performed in order to characterize the TME. The primary endpoint was long-term survival, defined as the Overall Survival > 24 months from surgery.
A total of 38 consecutive patients were included, and 14 (36%) of them were long-term survivors. Long-term survivors showed a higher density of CD8+ lymphocytes intra- and peri-acinar (
= 0.08), and a higher CD8/FOXP3 intra- and peri-tumoral ratio (
= 0.05). A low density of intra- and peri-tumoral FOXP3 infiltration is a good predictor of long-term survival (
= 0.04). A significant association of the low density of intra- and peri-tumoral tumor-associated macrophages (TAMs) iNOS+ with long-term survival was detected (
= 0.04).
Despite the retrospective nature and small sample size, our study showed that the high infiltration of CD8+ lymphocytes and low infiltration of FOXP3+ and TAMs iNOS+ are predictors of good prognosis. A preoperative assessment of these potential immune markers could be useful and determinant in the staging process and in PDAC management.
One of the most potent costimulatory molecules involved in the recognition and killing of tumor cells is CD80. However, its role and the molecular mechanisms regulating its expression in sporadic ...colorectal carcinogenesis remain elusive. Here, we provide evidence for CD80 overexpression in human colon epithelial cells derived from preneoplastic mucosa.
Expression of CD80 on colonic epithelial cells isolated from normal human colonic mucosa, preneoplastic and neoplastic specimens was assessed by flow cytometry. WT and CD80KO mice received azoxymethane to induce colon preneoplastic lesions and sacrificed to perform histology, flow cytometry analysis and immunohistochemistry of colonic mucosa. Some WT mice were treated with a monoclonal anti-CD80 antibody following AOM administration. Primary colon epithelial cells and CT26 cell line were used to quantify the expression of CD80 in response to pro-oxidant stimuli. Specific pharmacological inhibitors and siRNA silencing were used to inhibit MAPK pathways and STAT3.
CD80 expression was significantly increased in colon epithelial cells of human preneoplastic lesions. In the AOM model, CD80 impairment by administration of neutralizing antibodies or use of CD80 knockout mice enhanced dysplasia development. In vitro, CD80 upregulation was induced by oxidative stress in colon cancer cells and primary colon epithelial cells. In addition, reactive oxygen species could induce CD80 expression via the JNK and p38 MAPK pathways, that activated STAT3 transcription factor in colon cancer epithelial cells.
This study provide evidence for a major role of CD80 in orchestrating immune surveillance of colon preneoplastic lesions and might help to develop novel approaches that exploit anti-tumor immunity to prevent and control colon cancer.
Often, in perineal Crohn's disease (CD), a seton is placed to guarantee a constant drainage and prevent septic complication while biologic therapy is ongoing. This study aimed to assess the long-term ...quality of life after surgery for perineal CD in relation to seton placing.
Data of 65 consecutive patients with CD and non-CD operated on from 2014 to 2019 for perianal fistula or abscess were retrieved. Forty-three had CD and 14 of them had a seton placed during surgery and they kept it on while they had anti-TNF-alpha therapy. Patients were interviewed with the Cleveland Global Quality of Life (CGQL) and SF-12 quality of life questionnaires. Disease activity was defined as Harvey-Bradshaw Index (HBI) and Perianal Disease Activity Index (PDAI). Comparisons between groups were carried out with the nonparametric tests, and multiple regression models were used to assess predictors of quality of life.
The total CGQL score and SF-12 mental component score (MCS) were significantly higher (and thus better) in the seton group than in patients treated without seton. On the contrary, SF-12 physical component score (PCS) was not different between the two groups. HBI was significantly better in patients in the seton group. At multivariate analysis, seton placement and HBI were confirmed to be independent predictors of long-term SF-12 MCS whereas only HBI confirmed to be a predictor of total CGQL score.
Seton placing during anti-TNF-alpha therapy is independently associated with a better MCS. Unexpectedly, this device, instead of to cause psychological distress, seems to assure patients during their biologic therapy providing psychological benefit beyond the mere medical effect.
Background. Although mortality and morbidity of pancreatoduodenectomy (PD) have improved significantly over the past years, the impact of age for patients undergoing PD is still debated. This study ...is aimed at analyzing short- and long-term outcomes of PD in elderly patients. Methods. 124 consecutive patients who have undergone PD for pancreas neoplasms in our center between 2012 and 2017 were analyzed. Patients were divided into two groups: group I (<75 years) and group II (≥75 years). Demographic features and intraoperative and clinical-pathological data were collected. Primary endpoints were perioperative morbidity and mortality; complications were classified according to the Clavien-Dindo Score. Secondary endpoints included feasibility of adjuvant treatment and overall survival rates. Results. A total of 106 patients were included in this study. There were 73 (68.9%) patients in group I and 33 (31.1%) in group II. Perioperative deceases were 4 (3.6%), and postoperative pancreatic fistulas were 34 (32.1%). Significant difference between two groups was demonstrated for the ASA Score (p=0.004), Karnofsky Score (p=0.025), preoperative jaundice (p=0.004), and pulmonary complications (p=0.034). No significance was shown for diabetes, radicality of resection, stage of disease, operative time, length of stay, postoperative complications according to the Clavien-Dindo Score, postoperative mortality, pancreatic fistula, and reoperation rates. 69.9% of the patients in group I underwent adjuvant treatment vs. 39.4% of the older ones (p=0.012). Mean overall survival was 28.5 months in group I vs. 22 months in group II (p=0.909). Conclusion. PD can be performed safely in elderly patients. Advanced age should not be an absolute contraindication for PD, even if greater frailty should be considered. The outcome of elderly patients who have undergone PD is similar to that of younger patients, even though adjuvant treatment administration is significantly lower, demonstrating that surgery remains the main therapeutic option.
Background
In 10%–20% of cases it is impossible to make a differential diagnosis between ulcerative colitis and Crohn's colitis. A 50% failure rate of J pouch ilea-anal anastomosis is observed in ...Crohn's colitis. In 2009, we created the Padua Prognostic Score for Colitis (PPSC) to predict the long-term clinical and functional outcome and quality of life of patients undergoing restorative proctocolectomy with J pouch. The aim of the present study is to establish and validate the accuracy of a prognostic score for chronic inflammatory bowel diseases (IBD).
Patient population and methods
The PPSC was created in 2009 by integrating clinical and histological information of patients undergoing RPC. It included preoperative perianal abscess or fistula, rectal sparing, terminal ileum involvement, skip lesions and histological diagnosis of indeterminate colitis or Crohn's colitis on the operative specimen. The validity of this score was tested in predicting postoperative abscess or fistula, anal canal disease, pouchitis, pouch failure and new diagnosis of Crohn's disease. Correlation analysis, ROC curve analysis and survival analysis were used to validate the PPSC in a different cohort from the previous one.
Results
We retrospectively enrolled in this study 138 consecutive patients undergoing CPR for ulcerative colitis (
n
= 127) or indeterminate colitis (
n
= 11) in our institution since 2005 to 2020. In this period, we observed 11 patients with postoperative abscess or fistula, 3 with anal canal disease, 40 with pouchitis, 6 with pouch failure and 6 with new diagnosis of Crohn's disease. In the new validation cohort, the PPSC confirmed to have a good accuracy in predicting the onset of postoperative CD (AUC = 74.5%,
p
= 0.018). Kaplan Meier curves demonstrate how a PPSC over 1 can reliably predicts the long-term onset of, pouchitis (
p
= 0.002) and anal abscess or fistulae (
p
= 0.04).
Conclusions
In this validation study we confirmed the accuracy of the PPSC in predicting postoperative fistulas or abscesses and pouchitis. Therefore, we believe that in clinical practice patients with a PPSC score greater than 1 should be warned of this risk of possible Crohn’s disease diagnosis and pouch failure.
Background
Superior mesenteric artery syndrome (SMAS) is a rare cause of duodenal obstruction, resulting from the compression of the duodenum between superior mesenteric artery and aorta. This ...prospective registry aims to describe demographic, clinical, and outcome features of patients suffering from SMAS and to point out the indications for surgery.
Methods
Between 2008 and 2016, patients with chronic gastrointestinal symptoms and diagnosis of SMAS were included. Demographics, clinical presentation, diagnosis, and surgical outcome were recorded. Symptoms were investigated with a standardized questionnaire. The diagnosis was achieved through barium swallow, CT/MR angiography (aortomesenteric angle ≤ 22°, distance ≤ 8 mm), endoscopy. All patients underwent duodenojejunostomy ± distal duodenum resection. At follow-up, symptom score and barium swallow were re-evaluated.
Results
Thirty-nine patients (11 M/28 F, median age 38 years, median BMI 17.8 kg/m
2
) were included. Barium swallow showed a gastroduodenal dilation in 57% of patients, and a delayed gastroduodenal emptying in 38%. Median aortomesenteric angle was 11° and distance was 5 mm. All patients underwent duodenojejunostomy, and in 32 patients, a distal duodenum resection was also performed. At a median follow-up of 47 months, the overall symptom score significantly dropped (10 vs. 32,
p
< 0.0001) and BMI increased (19.5 vs. 17.8,
p
< 0.0001). Barium swallow at 2 months postoperatively showed an improvement in terms of gastroduodenal dilation and emptying in 38% of patients with preoperative pathological findings.
Conclusions
SMAS is a rare condition that should be suspected in cases of chronic, refractory upper digestive symptoms, particularly in females with low BMIs. Surgical treatment may improve symptoms and quality of life, although it is not curative in all cases.
ClinicalTrials.gov
Identifier: NCT03416647
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