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Adenoma detection rate (ADR) is challenging to measure, given its dependency on pathology reporting. Polyp detection rate (PDR) (percentage of screening colonoscopies detecting a polyp) is a proposed alternative to overcome this issue. Overall PDR from all colonoscopies is a relatively novel concept, with no large-scale studies comparing overall PDR with screening-only PDR. The aim of the study was to compare PDR from screening, surveillance, and diagnostic indications with overall PDR and evaluate any correlation between individual endoscopist PDR by indication to determine if overall PDR can be a valuable surrogate for screening PDR. Our study analyzed a prospectively collected national endoscopy database maintained by the National Institute of Health from 2009 to 2014. Out of 354,505 colonoscopies performed between 2009–2014, 298,920 (n = 110,794 average-risk screening, n = 83,556 average-risk surveillance, n = 104,770 diagnostic) met inclusion criteria. The median screening PDR was 25.45 (IQR 13.15–39.60), comparable with the median overall PDR of 24.01 (IQR 11.46–35.86, p = 0.21). Median surveillance PDR was higher at 33.73 (IQR 16.92–47.01), and median diagnostic PDR was lower at 19.35 (IQR 9.66–29.17), compared with median overall PDR 24.01 (IQR 11.46–35.86; p < 0.01). The overall PDR showed excellent concordance with screening, surveillance, and diagnostic PDR (r > 0.85, p < 0.01, 2-tailed). The overall PDR is a reliable and pragmatic surrogate for screening PDR and can be measured in real time, irrespective of colonoscopy indication. [ABSTRACT FROM AUTHOR]

Background and Objectives: Conflicting guidelines exist for initiating average-risk colorectal cancer screening at the age of 45 years. The United States Preventive Services Task Force (USPSTF) changed its guidelines in 2021 to recommend initiating screening at 45 years due to an increasing incidence of young-onset colorectal cancer. However, the American College of Physicians (ACP) recently recommended not screening average-risk individuals between 45 and 49 years old. We aim to study the national trends in the incidence of sporadic malignant polyps (SMP) in patients from 20 to 49 years old. Materials and Methods: We analyzed the Surveillance, Epidemiology, and End Results database (2000–2017) on patients aged 20–49 years who underwent diagnostic colonoscopy with at least a single malignant sporadic colorectal polyp. Results: Of the 10,742 patients diagnosed with SMP, 42.9% were female. The mean age of incidence was 43.07 years (42.91–43.23, 95% CI). Approximately 50% of malignant polyps were diagnosed between 45 and 49 years of age, followed by 25–30% between 40 and 45. There was an upward trend in malignant polyps, with a decreased incidence of malignant villous adenomas and a rise in malignant adenomas and tubulovillous adenomas. Conclusions: Our findings suggest that almost half of the SMPs under 50 years occurred in individuals under age 45, younger than the current screening threshold recommended by the ACP. There has been an upward trend in malignant polyps in the last two decades. This reflects changes in tumor biology, and necessitates further research and support in the USPSTF guidelines to start screening at the age of 45 years. [ABSTRACT FROM AUTHOR]

Background: Effect of biofeedback on improving anorectal manometric parameters in incomplete spinal cord injury is unknown. A short‐term biofeedback program investigated any effect on anorectal manometric parameters without correlation to bowel symptoms. Methods: This prospective uncontrolled interventional study comprised three study subject groups, Group 1: sensory/motor‐complete American Spinal Injury Association Impairment Scale (AIS) A SCI (n = 13); Group 2 (biofeedback group): sensory incomplete AIS B SCI (n = 17) (n = 3), and motor‐incomplete AIS C SCI (n = 8), and AIS D SCI (n = 6); and Group 3: able‐bodied (AB) controls (n = 12). High‐resolution anorectal manometry (HR‐ARM) was applied to establish baseline characteristics in all subjects for anorectal pressure, volume, length of pressure zones, and duration of sphincter squeeze pressure. SCI participants with motor‐incomplete SCI were enrolled in pelvic floor/anal sphincter bowel biofeedback training (2 × 6‐week training periods comprised of two training sessions per week for 30–45 min per session). HR‐ARM was also performed after each of the 6‐week periods of biofeedback training. Results: Compared to motor‐complete or motor‐incomplete SCI participants, AB subjects had higher mean intra‐rectal pressure, maximal sphincteric pressure, residual anal pressure, recto‐anal pressure gradient, and duration of squeeze (p < 0.05 for each of the endpoints). No significant difference was evident at baseline between the motor‐complete and motor‐incomplete SCI groups. In motor‐incomplete SCI subjects, the pelvic floor/anal sphincter biofeedback protocol failed to improve HR‐ARM parameters. Conclusion: Biofeedback training program did not improve anal manometric parameters in subjects with motor‐incomplete or sensory‐incomplete SCI. Biofeedback did not change physiology, and its effects on symptoms are unknown. Inferences: Utility of biofeedback is limited in patients with incomplete spinal cord injury in terms of improving HR‐ARM parameters. [ABSTRACT FROM AUTHOR]

Objectives: The US Preventive Services Task Force lowered the recommended starting age for colorectal cancer (CRC) screening in average‐risk adults from 50 to 45 years. We aimed to estimate the global burden and trends of colorectal cancer in adults aged 20–49 years (early‐onset CRC). Methods: This is an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). The GBD 2019 estimation methods were used to describe the incidence, mortality, and disability‐adjusted life years (DALYs) of early CRC from 1990 to 2019. Data from 204 countries and geographic areas were available. Results: The global incidence rate of early‐onset CRC increased from 4.2/100 000 to 6.7/100 000 from 1990 to 2019. Mortality and DALYs of early‐onset CRC also increased. The CRC incidence rate increased faster in younger adults (1.6%) than in adults aged 50–74 years (0.6%) as measured by the annual percentage change. The increase in early‐onset CRC incidence was consistently observed in all five socio‐demographic index (SDI) regions and 190 out of 204 countries and territories. Middle and high‐middle SDI regions had faster annual increases in early‐onset CRC, which warrants further attention. Conclusions: The global incidence, mortality, and DALYs of early‐onset CRC increased from 1990 to 2019. The increase in early‐onset CRC incidence was prevalent worldwide. Several countries were found to have higher incidence rates than the United States or fast increase in early‐onset CRC, which warrants further attention. [ABSTRACT FROM AUTHOR]

Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily available, non-invasive marker to aid in monitoring and prognosticating hepatic disorders. Recently, red blood cell distribution width (RDW) has been found to be associated with various inflammatory conditions with implications for its use as a potential marker for assessing disease progression and prognosis in multiple conditions. Multiple factors effect red blood cell production whereby a dysfunction in any process can lead to anisocytosis. Furthermore, a chronic inflammatory state leads to increased oxidative stress and produces inflammatory cytokines causing dysregulation and increased intracellular uptake and use of both iron and vitamin B12, which leads to a reduction in erythropoiesis causing an increase in RDW. This literature review reviews in-depth pathophysiology that may lead to an increase in RDW and its potential correlation with chronic liver diseases, including hepatitis B, hepatitis C, hepatitis E, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and hepatocellular carcinoma. In our review, we examine the use of RDW as a prognostic and predictive marker for hepatic injury and chronic liver disease. [ABSTRACT FROM AUTHOR]

Over 17.7 million gastrointestinal (GI) endoscopic procedures are performed annually, contributing to 68% of all endoscopic procedures in the United States. Usually, endoscopic procedures are low risk, but adverse events may occur, including cardiopulmonary complications, bleeding, perforation, pancreatitis, cholangitis, and infection. Infections after the GI endoscopies most commonly result from the patient's endogenous gut flora. Although many studies have reported infection after GI endoscopic procedures, a true estimate of the incidence rate of post-endoscopy infection is lacking. In addition, the infection profile and causative organisms have evolved over time. In recent times, multi-drug-resistant microorganisms have emerged as a cause of outbreaks of endoscope-associated infections (EAI). In addition, lapses in endoscope reprocessing have been reported, with some but not all outbreaks in recent times. This systematic review summarizes the demographical, clinical, and management data of EAI events reported in the literature. A total of 117 articles were included in the systematic review, with the majority reported from North America and Western Europe. The composite infection rate was calculated to be 0.2% following GI endoscopic procedures, 0.8% following ERCP, 0.123% following non-ERCP upper GI endoscopic procedures, and 0.073% following lower GI endoscopic procedures. Pseudomonas aeruginosa was the most common culprit organism, followed by other Enterobacteriaceae groups of organisms and Gram-positive cocci. We have also elaborated different prevention methods such as antimicrobial prophylaxis, adequate sterilization methods for reprocessing endoscopes, periodic surveillance, and current evidence supporting their utilization. Finally, we discuss disposable endoscopes, which could be an alternative to reprocessing to minimize the chances of EAIs with their effects on the environmental and financial situation. [ABSTRACT FROM AUTHOR]

Background Direct-acting oral anticoagulants (DOACs) are increasingly used, with studies showing a lower risk of gastrointestinal bleeding (GIB), but overall data for GIB risk remains debatable. The objective was to assess non-fatal and fatal GIB risk in patients on DOACs compared with warfarin from randomized clinical trials (RCTs). Methods RCTs comparing warfarin and DOACs for various indications (atrial fibrillation, thromboembolism, insertion of mechanical heart valves) were included. The primary endpoint was any GIB event. Other clinical events, such as fatal GIB, and effects of age (=60 years or older), time in therapeutic range for warfarin, and choice of individual DOACs on GIB risk, were also assessed. Results 14 RCTs were included, comprising 87,407 participants (DOACs n=46,223, warfarin control n=41,184). The risk of GIB with DOACs was similar to that of warfarin (relative risk [RR] 1.04, 95% confidence interval [CI] 0.85-1.27). Compared with warfarin, rivaroxaban (RR 1.23, 95%CI 1.03-1.48) and dabigatran (RR 1.38, 95%CI 1.12-1.71) had a higher risk of any GIB, whereas fatal GIB risk was lower in the DOACs group (RR 0.36, 95%CI 0.15-0.82). The risk of DOAC-related fatal GIB was lower in patients aged =60 years and in those with poor coagulation control (RR 0.39, 95%CI 0.15-0.98). Conclusions DOACs compared with warfarin have a lower risk of fatal GIB, especially in those aged <60 years and those with poor coagulation control. However, the risk of GIB was comparable with warfarin and DOACs, except for rivaroxaban and dabigatran. [ABSTRACT FROM AUTHOR]

Abstract Background Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS), Disease Free Survival (DFS) and Overall Survival (OS). Methods Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m2) or four cycles of 3-weekly docetaxel (100 mg/m2). The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%), pathological complete response (20% vs. 27%), and breast-conserving surgery (BCS) rates (49% vs. 42%). Disease-free survival and overall survival were similar between treatment groups. Conclusions Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS) or survival outcomes in the neoadjuvant setting. Trial registration ISRCTN: ISRCTN09184069

Abstract Background Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis. Methods This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. Results MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours. Conclusions Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.

Abstract Background Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas. Methods Immunohistochemical staining was performed with mouse anti-M2-PK monoclonal antibody (clone DF-4) at an optimal dilution of 1:25 on tissue microarrays constructed from formalin-fixed paraffin-embedded pancreatic tissue of 126 consecutive patients undergoing pancreatic resections between June 2001 and June 2006. 104 underwent resection for cancer and 22 for chronic pancreatitis. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. A further 11 premalignant pancreaticobiliary and duodenal lesions were studied. M2-PK expression was quantified with the immunohistochemical score (IHS; Range 0-12). Results Benign non-ductal tissue in chronic pancreatitis and normal pancreas showed variable expression of M2-PK (IHS = 1 in 25%, IHS = 2-3 in 40%, IHS>3 in 40%). Benign pancreatic ductal epithelium, all primary pancreaticobiliary and duodenal premalignant lesions and cancers (and lymph node metastasis) showed complete lack of expression (IHS = 0). Conclusion Complete lack of M2-PK expression was observed in benign pancreatic ducts, premalignant lesions and cancer. M2-PK is present only in benign non-ductal epithelium in normal pancreas and peri-tumoural tissue.

Abstract Background Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses. Methods Autologous DCs were generated from 10 patients (HLA-0201) with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI) was pulsed with only one type of hTERT peptide (p540 or p865) and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865)-loaded DCT with or without class II cognate help (p766 and p672) in 6 patients. T regulatory cells were evaluated in 8 patients. Results (i) DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test) in inducing peptide-specific CD8+ T cell responses. (ii) Class II cognate help, significantly enhanced (p < 0.05, t-test) peptide-specific CD8+T cell responses, compared with class I pulsed DCs alone. (iii) Clinical responders had significantly lower (p < 0.05, Mann-Whitney U test) T regs, compared with non-responders. 4/16 patients experienced partial but transient clinical responses during vaccination. Vaccination was well tolerated with minimal toxicity. Conclusion Addition of IFN-α to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-α alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients with low levels of circulating T regs.

Abstract Background Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses. Results Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-α+IFN-α) or 3 CCM (GM-CSF+IL-4+TNF-α) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001). Conclusion Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-α. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-α. However, 4 CCM containing IFN-α generated-PBDCs, do not produce and secrete IL-12p70 in vitro.

A 29-year-old Dominican man with a history of intravenous heroin use and hepatitis C presented with a 5-day history of fever, dyspnoea, haemoptysis, pleuritic chest pain, abdominal pain, haematochezia and haematemesis. Initial physical examination was significant for scleral icterus, generalised abdominal tenderness to palpation, melaena and blood-tinged sputum. Blood cultures grew Fusobacterium species. CT scan of the chest revealed multiple bilateral cavitary features in lung fields. At the same time, a neck ultrasound performed demonstrated thrombophlebitis in the right internal jugular vein, confirming the diagnosis of ’Lemierre’s syndrome’. Treatment was with antibiotics and supportive care for 6 weeks. [ABSTRACT FROM AUTHOR]

Pheochromocytoma is a rare adrenal tumor that is classically associated with the triad of paroxysmal tachycardia, diaphoresis, and headaches. However, it can have myriad manifestations. We present a case of a 31-year-old male who presented with abdominal pain, hypertensive emergency, and renal failure. Abdominal imaging demonstrated a left adrenal mass. Plasma metanephrines (153 pg/ml, n < 57) and normetanephrines (1197 pg/ml, n < 148) were noted to be elevated, leading to the diagnosis of pheochromocytoma. Intravenous antihypertensives were utilized to control his blood pressure. Hemodialysis was initiated given the degree of renal dysfunction. The patient subsequently developed hemolytic anemia, requiring the transfusion of multiple units of packed red cells. He developed acute respiratory failure leading to intubation, but was thereafter liberated from the ventilator following clinical stabilization. Uncontrolled hypertension precipitated by pheochromocytoma can cause microangiopathic hemolytic anemia and renal insufficiency. This case is notable not only for the occurrence of this rare presentation, but also for the severity of manifestations in a young male with no known significant comorbidities. [ABSTRACT FROM AUTHOR]

Objectives: Study national hospitalization trends for colorectal cancer in patients younger than 50 years of age. Methods: Patients under age 50 years hospitalized for colorectal cancer were studied using the national inpatient sample databases (2010–2014), using validated ICD-CM-9 codes and hospitalizations represented per 100,000 total inpatient population. Results: Colorectal cancer hospitalizations demonstrated a significant uptrend in the 41–50 years age group, with Caucasians and females most affected, stratifying for age and excluding those with a family history of colorectal cancer (p trend < 0.001). Conclusions: Younger colorectal cancer patients aged 41–50 years (especially younger Caucasian females) are burdened with increasing hospitalization rates. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 45-year-old woman presented with diarrhea, abdominal discomfort and significant weight loss. It mentions diagnosis of colonic amebiasis presenting as an ameboma or an inflammatory mass which mimicked a colonic tumor; and also mentions treatment with Nitazoxanide.

Background: Weekly docetaxel has occasionally been used in the neoadjuvant to downstage breast cancer to reduce toxicity and possibly enhance quality of life. However, no studies have compared the standard three weekly regimen to the weekly regimen in terms of quality of life. The primary aim of our study was to compare the effects on QoL of weekly versus 3-weekly sequential neoadjuvant docetaxel. Secondary aims were to determine the clinical and pathological responses, incidence of Breast Conserving Surgery (BCS), Disease Free Survival (DFS) and Overall Survival (OS). Methods: Eighty-nine patients receiving four cycles of doxorubicin and cyclophosphamide were randomised to receive twelve cycles of weekly docetaxel (33 mg/m²) or four cycles of 3-weekly docetaxel (100 mg/m²). The Functional Assessment of Cancer Therapy-Breast and psychosocial questionnaires were completed. Results: At a median follow-up of 71.5 months, there was no difference in the Trial Outcome Index scores between treatment groups. During weekly docetaxel, patients experienced less constipation, nail problems, neuropathy, tiredness, distress, depressed mood, and unhappiness. There were no differences in overall clinical response (93% vs. 90%), pathological complete response (20% vs. 27%), and breast-conserving surgery (BCS) rates (49% vs. 42%). Disease-free survival and overall survival were similar between treatment groups. Conclusions: Weekly docetaxel is well-tolerated and has less distressing side-effects, without compromising therapeutic responses, Breast Conserving Surgery (BCS) or survival outcomes in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis. Methods: This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied. Results: MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours. Conclusions: Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets. [ABSTRACT FROM AUTHOR]

Background: Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)- pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses. Methods: Autologous DCs were generated from 10 patients (HLA-0201) with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI) was pulsed with only one type of hTERT peptide (p540 or p865) and both preparations were injected into separate lymph node draining regions every 2-3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865)-loaded DCT with or without class II cognate help (p766 and p672) in 6 patients. T regulatory cells were evaluated in 8 patients. [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses. Results: Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-α+IFN-α) or 3 CCM (GM-CSF+IL-4+TNF-α) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001). Conclusion: Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-α. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-α. However, 4 CCM containing IFN-α generated-PBDCs, do not produce and secrete IL-12p70 in vitro. [ABSTRACT FROM AUTHOR]

Summary: Background: The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications, but meta-analyses have not demonstrated a survival advantage. The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer. Methods: A total of 120 patients undergoing resection for cancers of the pancreas, oesophagus and stomach were randomized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet (Stresson—Group A) or an isonitrogenous, isocaloric feed (1250 Calories and 75gprotein/l—Nutrison High Protein—Group B) for 10–15 days. Feeding was commenced 4h postoperatively and continued for 20h/day. The target volume (ml/h) was 25 on day 0, 50 on day 1, and 75 thereafter. Outcome measures included complications, hospital stay and mortality. Results: A total of 108 patients (54 in each group) were analysed. Feed delivery, although less than targeted, was similar in both groups. There were 6 (11%) deaths in each group. Median (IQR) postoperative hospital stay was 14.5 (12–23) days in Group A and 17.5 (13–23) days in Group B (). A total of 24 (44%) patients in each group had infective complications (). A total of 21 (39%) patients in Group A and 28 (52%) in Group B had non-infective complications (). Jejunostomy-related complications occurred in 26 (48%) patients in Group A and 30 (56%) in Group B (). Conclusion: Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a standard feed. [Copyright &y& Elsevier]

Simple Summary: The results of this study show the effects of socio-economic determinants, such as higher income levels, high school education, private insurance, and married marital status, have favorable survival in patients with young-onset colorectal cancer (YoCRC). Moreover, most of the positive social factors are often interrelated. The inclusion of these factors could further prognosticate and help with healthcare resource allocation for successful interventions through public health measures. Colorectal cancer awareness, knowledge, and even utilization of medical services would differ with the education and health literacy. Introduction: We aimed to assess the impact of socio-economic determinants of health (SEDH) on survival disparities within and between the ethnic groups of young-onset (<50 years age) colorectal adenocarcinoma patients. Patients and Methods: Surveillance, epidemiology, and end results (SEER) registry was used to identify colorectal adenocarcinoma patients aged between 25–49 years from 2012 and 2016. Survival analysis was performed using the Kaplan–Meir method. Cox proportional hazards model was used to determine the hazard effect of SEDH. American community survey (ACS) data 2012–2016 were used to analyze the impact of high school education, immigration status, poverty, household income, employment, marital status, and insurance type. Results: A total of 17,145 young-onset colorectal adenocarcinoma patients were studied. Hispanic (H) = 2874, Non-Hispanic American Indian/Alaskan Native (NHAIAN) = 164, Non-Hispanic Asian Pacific Islander (NHAPI) = 1676, Non-Hispanic black (NHB) = 2305, Non-Hispanic white (NHW) = 10,126. Overall cancer-specific survival was, at 5 years, 69 m. NHB (65.58 m) and NHAIAN (65.67 m) experienced worse survival compared with NHW (70.11 m), NHAPI (68.7), and H (68.31). High school education conferred improved cancer-specific survival significantly with NHAPI, NHB, and NHW but not with H and NHAIAN. Poverty lowered and high school education improved cancer-specific survival (CSS) in NHB, NHW, and NHAPI. Unemployment was associated with lowered CSS in H and NAPI. Lower income below the median negatively impacted survival among H, NHAPI NHB, and NHW. Recent immigration within the last 12 months lowered CSS survival in NHW. Commercial health insurance compared with government insurance conferred improved CSS in all groups. Conclusions: Survival disparities were found among all races with young-onset colorectal adenocarcinoma. The pattern of SEDH influencing survival was unique to each race. Overall higher income levels, high school education, private insurance, and marital status appeared to be independent factors conferring favorable survival found on multivariate analysis. [ABSTRACT FROM AUTHOR]