Molecular genetic analysis of colorectal carcinoma with an aggressive extraintestinal immunohistochemical phenotype.

Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers' prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct "non-intestinal" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in TP53, APC, BRAF, KRAS, PIK3CA, FBXW7, and SMAD4, consistent with known CRC mutation patterns. NGS also identified druggable variants in BRAF, PIK3CA, and KRAS. CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.

Early-onset pancreatic cancer: A national cancer registry study from the Czech Republic and review of the literature.

BACKGROUND: The aim of this study was to compare trends in mortality and incidence, clinicopathological features and survival of patients diagnosed with pancreatic ductal adenocarcinoma under 50 years of age (early-onset pancreatic cancer [EOPC]) with patients diagnosed over 50 years of age (late-onset pancreatic cancer [LOPC]). METHODS: The national oncological registry of the Czech Republic was reviewed to identify all patients with histologically confirmed pancreatic ductal adenocarcinoma diagnosed between the years 1985 and 2015. Incidence, mortality, clinicopathological and survival data were analyzed and compared between patients with EOPC and LOPC. RESULTS: From a total of 18 888 patients included in the study, 1324 patients were under the age of 50 years (7.0%). The average annual percentage changes (AAPC) in incidence of all patients with EOPC was -1.0%. The APPC for male patients with EOPC was -2.0% and for female patients was +0.6%. The AAPC in incidence for LOPC was +1.3%. There were no differences in tumor stage, grade or location between EOPC and LOPC. Young patients were more frequently male (64.4% vs. 52.9%), more frequently underwent treatment and had better overall survival. The median survival interval for EOPC was 5.9 months and for LOPC was 4.5 months (p < .001). CONCLUSIONS: The clinicopathological features of pancreatic ductal adenocarcinoma were similar in patients under and over the age of 50 years. Patients with EOPC survived longer than patients with LOPC. Continued efforts should be made to diagnose early and treat young patients aggressively.

The posterior gastric artery: A meta-analysis and systematic review.

The aim of this study was to review the literature on the posterior gastric artery, estimate its prevalence and summarize its reported origins. The databases Pubmed, Scopus, Web of Science and Google Scholar were searched to find all studies describing the prevalence and origin of the posterior gastric artery. Pooled prevalences were estimated using a random effects model. Thirty-eight studies with a total of 3366 subjects were included in the analysis. The overall prevalence of the posterior gastric artery was 57.4% (95% CI = 49.1%-65.7%). The prevalence of the posterior gastric artery was significantly higher in surgical studies than in cadaveric and angiographic studies. There were no differences in prevalence between multi-detector computed tomography studies and cadaveric studies, nor were there differences when comparing geographical location or study size. Origin data were extracted from 34 studies, with a total of 1533 cases. The posterior gastric artery arose as a single vessel from the splenic artery in 1160 cases (pooled prevalence 86.5% [95% CI = 78.5%-94.7%]), from the superior polar splenic artery in 339 cases (pooled prevalence 11.8% [95% CI = 3.7%-19.9%]) and from other origins in 50 cases (pooled prevalence 0.27% [95% CI = 0.00-0.71%]). The posterior gastric artery is present in 57.4% of cases and most commonly arises from the splenic artery. It should be identified before gastric resections as it may be an important source of blood to the gastric stump. Multi-detector computed tomography has sufficient sensitivity to detect it before surgery.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Loss of SATB2 expression correlates with cytokeratin 7 and PD-L1 tumor cell positivity and aggressiveness in colorectal cancer.

Colorectal carcinoma (CRC) is a disease that causes significant morbidity and mortality worldwide. To improve treatment, new biomarkers are needed to allow better patient risk stratification in terms of prognosis. This study aimed to clarify the prognostic significance of colonic-specific transcription factor special AT-rich sequence-binding protein 2 (SATB2), cytoskeletal protein cytokeratin 7 (CK7), and immune checkpoint molecule programmed death-ligand 1 (PD-L1). We analyzed a cohort of 285 patients with surgically treated CRC for quantitative associations among the three markers and five traditional prognostic indicators (i.e., tumor stage, histological grade, variant morphology, laterality, and mismatch-repair/MMR status). The results showed that loss of SATB2 expression had significant negative prognostic implications relative to overall survival (OS) and cancer-specific survival (CSS), significantly shortened 5 years OS and CSS and 10 years CSS in patients with CRC expressing CK7, and borderline insignificantly shortened OS in patients with PD-L1 + CRC. PD-L1 showed a significant negative impact in cases with strong expression (membranous staining in 50-100% of tumor cells). Loss of SATB2 was associated with CK7 expression, advanced tumor stage, mucinous or signet ring cell morphology, high grade, right-sided localization but was borderline insignificant relative to PD-L1 expression. CK7 expression was associated with high grade and SATB2 loss. Additionally, a separate analysis of 248 neoadjuvant therapy-naïve cases was performed with mostly similar results. The loss of SATB2 and CK7 expression were significant negative predictors in the multivariate analysis adjusted for associated parameters and patient age. In summary, loss of SATB2 expression and gain of CK7 and strong PD-L1 expression characterize an aggressive phenotype of CRC.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

The dorsal pancreatic artery: A meta-analysis with clinical correlations.

BACKGROUND/OBJECTIVES: The dorsal pancreatic artery is the main artery of the body and tail of the pancreas. Its origin and branching is highly variable. The aim of this study was to perform a meta-analysis to generate pooled prevalence data on the presence and origin of the dorsal pancreatic artery. Clinically important aspects of the dorsal pancreatic artery were summarised during the literature review. METHODS: Major medical databases were searched. Data on the presence and point of origin of the dorsal pancreatic artery were extracted and quantitatively synthesised. The obtained data of anatomical based studies and computed tomography based studies were statistically analysed. RESULTS: In total, 30 studies, comprising 2322 anatomical and computed tomography based cases were included. The dorsal pancreatic artery was present in 95.8% of cases. It originated from the splenic artery in 37.6% of cases, common hepatic artery in 18.3% of cases, coeliac trunk in 11.9% of cases and the superior mesenteric artery in 23.9% of cases. Other rare origins were present in 2.77% of cases. Multiple dorsal pancreatic arteries were found in 1,7% of cases. There was no significant difference in the presence or origin of the dorsal pancreatic artery between anatomical and computed tomography based studies. CONCLUSION: The dorsal pancreatic artery is present in the vast majority of cases. Its origin and branching are highly variable. Multiplicity of the dorsal pancreatic artery is infrequent.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment.

IMPORTANCE: The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear. OBJECTIVE: To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment. DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded. EXPOSURES: The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise. RESULTS: We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73). CONCLUSIONS AND RELEVANCE: These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

Hepatopancreatoduodenectomy -a controversial treatment for bile duct and gallbladder cancer from a European perspective.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

Gastric duplication cyst communicating to accessory pancreatic lobe: A case report and review of the literature.

BACKGROUND: The combination of a gastric duplication cyst and duplicated part of the pancreas is an extremely rare developmental defect. The incidence in the population, or the clinical impact thereof, has not been uncovered. Symptoms are unspecific. Surgery is the treatment of choice. Timely diagnostics are of utmost importance, albeit they might be challenging at times. Being so rare, case reports are currently the only relevant source of information about the condition. Therefore each published finding is of a clinical impact. CASE SUMMARY: Our work describes the case of a 22 year-old patient, who developed idiopathic acute pancreatitis. A computed tomography scan discovered liquid collection between the antrum of the stomach and the head of the pancreas. Initially, the collection was thought to be a pancreatic pseudocyst. Endoscopic ultrasound-guided transgastric drainage showed to have only a temporary therapeutic effect. Magnetic resonance cholangiopancreatography showed an accessory pancreatic lobe with a separate duct system. The accessory pancreatic lobe exited the body of the pancreas and was in contact with the cystic collection. The patient was indicated for surgical resection. Within the surgery, an en bloc resection of the accessory pancreatic lobe was performed with the antrum of the stomach containing the gastric duplication cyst. No complications were observed in the surgery or thereafter. In the five months follow-up period, the patient was completely symptom free. Histopathological findings confirmed the gastric duplication cyst communicating to accessory pancreatic lobe. CONCLUSION: This developmental defect is extremely rare. It can cause recurrent acute pancreatitis. Diagnostics are challenging. Surgery is treatment of choice.