The Percentage of Signet Ring Cells Is Inversely Related to Aggressive Behavior and Poor Prognosis in Mixed-Type Gastric Cancer.

Background and Objectives: Only recently the percentage of signet ring cells (SRCs) in gastric cancer (GC) has been proposed as an independent predictor of survival. High amounts of SRCs have been related to lower recurrence and mortality rates, better prognosis, and favorable clinicopathological features in a poorly cohesive histotype. It is not known what the effect of SRC percentage in mixed-type GC is. We investigate the role of SRCs as a prognostic marker in mixed-histotype GC. Methods: A retrospective analysis was performed through a prospectively maintained database of patients with diagnosed "mixed-type" gastric carcinoma, defined according to 2019 WHO classification. These patients underwent surgery between 1995 and 2016, and their tissue samples were stored in a tissue bank. All slides were analyzed, and patients were divided into three groups according to the percentage of SRCs: "Group 1" (displaying ≤10% of SRCs), "Group 2" (displaying <90% but >10% of SRCs), and "Group 3" (displaying ≥90% of SRCs). We compared clinical and pathological features as well as prognostic factors between the different groups. Results: Among 164 enrolled patients, 68.9% were male and 31.1% were female (p = 0.612). The mean (±SD) age at diagnosis was 71.4 ± 9.6 years. Ninety-eight (59.7%) patients were classified as "Group 1", 66 (40.3%) as "Group 2", and none as "Group 3". Five-year overall survival was remarkably higher in Group 2 (73.8%) in comparison to Group 1 (35.4%), p < 0.001. Mortality risk was three times higher in patients with ≤10% SRC pattern compared to those with >10% [HR 2.70 (95% CI 1.72-4.24)]. After adjusting according to potential confounding factors, SRC percentage was still an independent predictor of survival. Conclusions: The proportion of SRCs is inversely related to aggressive behavior and poor prognosis in mixed-type GCs, highlighting the role of SRC amount as an independent predictor of survival.

Effectiveness and Safety of Nonmedical Switch From Adalimumab Originator to SB5 Biosimilar in Patients With Inflammatory Bowel Diseases: Twelve-Month Follow-Up From the TABLET Registry.

BACKGROUND: Few data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA. METHODS: We prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months. RESULTS: In the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch. CONCLUSIONS: We found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing.

Signet ring cell percentage in poorly cohesive gastric cancer patients: A potential novel predictor of survival.

BACKGROUND AND OBJECTIVES: Signet ring cells (SRC) are widely acknowledged as a prognostically unfavorable histotype amongst poorly cohesive gastric cancer. In this study we evaluated the impact of SRC percentage on the clinical, pathological and prognostic features of these tumors according to the classification by the European Chapter of the IGCA. METHODS: We retrospectively reviewed records of patients with poorly cohesive gastric cancer that underwent surgery between 1995 and 2016, whose tissue specimens were available in a biological bank. All slides were put under revision, patients were reclassified into three groups according to the proportion of signet ring cells: "pure" SRC (containing ≥90% of SRCs), Poorly Cohesive-Not Otherwise Specified (PC-NOS) (containing ≤10% of SRCs), and PC-NOS/SRC (containing <90% but >10% of SRCs). The clinicopathological factors between different types were analyzed and prognostic differences were compared. RESULTS: Among 143 enrolled patients, 51% were male and 49% were female. The mean (±SD) age at diagnosis was 61 ± 13.9 years. Eighty-seven patients (60.8%) were reclassified as PC-NOS, 56 (39.2%) as PC-NOS/SRC and none as "pure" SRC. Five-years overall survival was significantly higher in PC-NOS/SRC group (63.3%) compared with PC-NOS group (12.7%). The increase in mortality risk was more than four-fold in patients with PC-NOS pattern compared to those with PC-NOS/SRC (HR 4.32 [95% CI 2.5-7.4]. After adjustment for potential confounding factors, SRC pattern was still an independent predictor of survival. CONCLUSIONS: The percentage of SRCs is inversely related to tumor aggressiveness, confirming the role of SRC pattern as an independent predictor of survival.

Effect of ambient temperature on daily hospital admissions for acute pancreatitis in Nanchang, China: A time-series analysis.

The aim of this study was to evaluate the short-term effect of temperature on the risk of acute pancreatitis (AP) in southern China. We performed a time-series study of 2822 patients admitted with a first episode of AP in Nanchang between May 2014 and June 2017. A generalized additive model combined with a distributed lag non-linear model was applied to assess the association of temperature and AP. In subgroup analysis, according to different etiologies of pancreatitis, significant associations were found between daily average temperature and non-biliary pancreatitis hospitalization at lags of 0-7 days, but not for biliary pancreatitis or total AP. Higher daily average temperature tended to increase the occurrence of non-biliary pancreatitis at lags of 0-7 days. These findings suggest that high temperature is associated with higher non-biliary pancreatitis risk in Nanchang, China. In the context of global warming, the morbidity of non-biliary pancreatitis may increase.

Testing for fecal gluten immunogenic peptides: a useful tool to evaluate compliance with gluten-free diet by celiacs.

BACKGROUND: Although experts agree that strict dietary compliance is fundamental for the health of celiac patients, there are no evidence-based recommendations on the best way to assess dietary compliance. Detection of gluten immunogenic peptides (GIPs) in feces was recently proposed as an effective method of assessing the dietary compliance of celiac patients. METHODS: Fifty-five consecutive celiac patients (27 adults and 28 children, age 6-72 years), who had been on a gluten-free diet for at least 2 years, were enrolled. All patients were evaluated clinically for symptoms, physical parameters and laboratory parameters. Dietary compliance was assessed with the Biagi questionnaire and serum anti-tissue transglutaminase (tTG) IgA antibodies were measured. GIPs were determined by immunoenzymatic assay on an automated Chorus analyzer (DIESSE Diagnostica Senese), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Eight patients tested positive for GIPs (GIPs+); 71.4% of GIP-positive patients were asymptomatic; tTG antibodies were detected in 3/8 GIP+ patients. The Biagi score was significantly associated with fecal positivity for GIPs (P=0.02). However, according to the Biagi score, 57.1% of GIP+ patients followed the diet strictly and 5.4% of GIP- subjects did not comply with the diet or made substantial mistakes. CONCLUSIONS: Assay of fecal GIPs identified more patients who did not comply with the diet than did the Biagi questionnaire, evaluation of symptoms or anti-tTG antibodies. Detection of fecal GIPs offers a direct, objective, quantitative assessment of even occasional exposure to gluten and is confirmed as a practical way to check dietary compliance.

Preoperative oral immunonutrition in gastrointestinal surgical patients: How the tumour microenvironment can be modified.

BACKGROUND & AIMS: This study is focused on the impact of enteral immunonutrition on the cell-mediated immune response in the microenvironment of gastric and colorectal cancers. METHODS: This is a prospective pilot study approved by the local Ethics Committee. The immunophenotypic structure of the immune cells before (on the biopsy) and after (on the surgical sample) the administration of the immunonutrition in 16 patients is compared with 8 patients receiving regular diet. The samples of non-tumour tissue from sleeve-gastrectomy are used as non-neoplastic control. Antibodies were tested: CD4, CD8, PD-1, FOX-P3, CD68, CD163, CD80, CD21, CD56, PD-L1. We applied already well-known scoring systems for the evaluation of the immunohistochemistry and compared our data in the different groups by statistical analysis. RESULTS: In treated patients, we detected a modulation of the immune response with higher number of cytotoxic and helper T-lymphocytes in the tumour microenvironment of the surgical specimens compared to the pre-operative biopsy, and a lower number of lymphocytes presenting an exhausted (i.e. double positive CD8 and PD-1 lymphocytes) and regulatory (i.e. double positive CD4 and FOX-P3 lymphocytes) phenotype. Moreover we observed the M1 polarization with a lower number of CD163 positive macrophages and the inhibition of the PD-1/PD-L1 pathway in treated patients. CONCLUSIONS: The immunonutrition impacts on the tumoral microenvironment of gastric and colorectal cancer activating the inflammatory pathway, in terms of humoral and cellular response.

Fecal gluten immunogenic peptides as indicators of dietary compliance in celiac patients.

BACKGROUND: It is important to have methods for evaluating dietary compliance in patients with celiac disease (CD). Determination of fecal gluten immunogenic peptides (GIPs) was recently proposed as a method of detecting gluten intake. The aim of this study was to evaluate whether determination of GIPs can be used as an indicator of compliance with a gluten-free diet (GFD). METHODS: Twenty-five persons with CD on a gluten-free diet for at least one year were enrolled in the study. Compliance with the diet was assessed by the Biagi questionnaire, evaluation of symptoms and assay of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG). GIPs were determined by iVYLISA GIP-S test (Biomedal S.L., Seville, Spain) on an automated Chorus analyzer (DIESSE Diagnostica Senese, Siena, Italy), after extraction of fecal samples by the method developed by DIESSE. RESULTS: Four patients tested positive for GIPs (GIP+), two of whom complied strictly with the gluten-free diet according to the Biagi questionnaire. None of the four GIP-positive patients manifested symptoms. IgA anti-tTG was significantly higher in GIP+ than in GIP- subjects. CONCLUSIONS: Assay of fecal GIPs identified more patients who were not complying with the diet than the Biagi questionnaire or evaluation of symptoms. The anti-tTG and GIP results agreed perfectly; however, since anti-tTG antibodies remain high for longer and are not a completely reliable marker of GFD intake, detection of fecal GIPs offers a direct, objective, quantitative assessment of exposure, even occasional, to gluten and could be used to check dietary compliance.

Early and late effects of the sequential transfixed stich technique for the treatment of the symptomatic rectocele without rectal mucosa prolapse.

BACKGROUND: Different surgical techniques have been proposed for rectocele repair. However, controversial aspects exist on the best approach to use. The study aims to report the early and late outcomes of the sequential transfixed stich technique (STST) for the treatment of rectocele in the absence of mucosal prolapse. METHODS: One hundred patients presenting a symptomatic rectocele were treated with STST from January 2010 through August 2015. Patients with mucosal prolapse were not considered eligible for STST. After a period of 24 months from surgery, all the patients were clinically evaluated with the intent to investigate the risk of recurrence of the preoperative symptoms. RESULTS: All the patients were women (median age=54.7 years; ranges=37-75). Median discharge time was 1.5 days. One-month severe complications were: hemorrhoid thrombosis (6.0%), self-solved bleeding (6.0%), urinary retention (4.0%), anal secretion (4.0%) and urinary incontinence (1.0%). No post-operative cases of fecal incontinence were observed. Two years after surgery, 76.0% of patients reported a global improvement of the preoperative symptoms, with 73 and 35% of cases showing a reduced difficulty in the evacuation and need for digitation. Only 8.0% of patients showed a recurrence of the initial symptoms. CONCLUSIONS: The STST is a feasible, safe, and cost-effective technique for the treatment of the rectocele without rectal mucosal prolapse. The method does not increase the risk of postoperative anal incontinence and presents a short hospital stay. STST presents long-term results in line with other transvaginal and transanal approaches.

Plasma claudin-3 is associated with tumor necrosis factor-alpha-induced intestinal endotoxemia in liver disease.

OBJECTIVE: To investigate intestinal endotoxemia (IETM), intestinal permeability (IP) and cytokine activity in patients with liver cirrhosis (LC). MATERIALS AND METHODS: Twenty-nine patients with chronic hepatitis B (CHB), 28 with compensated LC, 33 with decompensated LC, 24 with spontaneous bacterial peritonitis (SBP), 26 with acute-on-chronic liver failure (ACLF), and 24 with decompensated LC complicated by hepatocellular carcinoma (HCC) were recruited. Thirty-one healthy people were included as a control group. Plasma tumor necrosis factor (TNF)-α, interferon (IFN)-γ, D-lactate, endotoxin, and claudin-3 levels were assayed. Data were compared using Pearson correlation testing and analysis of variance, with P < 0.05 considered significant. RESULTS: TNF-α, claudin-3, and endotoxin levels were significantly increased (P < 0.05) in the plasma of all patients with liver disease compared with that of controls, particularly in patients with decompensated LC, SBP, ACLF, or HCC (P < 0.01). IFN-γ was significantly higher in HCC than in other liver diseases (P < 0.01). Plasma D-lactate was significantly decreased in all liver diseases, except SBP (P < 0.01). TNF-α, endotoxin, and claudin-3 levels were positively correlated (P < 0.01), but correlations of IFN-γ with endotoxin or claudin-3 were not significant. The plasma D-lactate level did not significantly correlate with either TNF-α, endotoxin, or claudin-3 levels. CONCLUSION: Plasma claudin-3, but not D-lactate, was found to be a marker of IP in patients with liver diseases. Elevated plasma TNF-α in such patients was likely to have injured the intestinal barrier, leading to IETM, especially in end-stage LC.

Anal self-massage in the treatment of acute anal fissure: a randomized prospective study.

BACKGROUND: An anal fissure (AF) is a tear in the epithelial lining of the anal canal. This is a very common condition, but the choice of treatment is unclear. The use of anal dilators is effective, economic, and safe. The aim of the study was to compare the efficacy of two conservative treatments, the use of anal dilators or a finger for anal dilatation, in reducing anal pressure and resolving anal fissures. METHODS: Fifty patients with a clinical diagnosis of AF were randomly assigned to one of the treatments, self-massage of the anal sphincter (group A, 25 patients) or passive dilatation using dilators (group B, 25 patients). All patients were evaluated at baseline, at the end of treatment, and after 12 weeks and 6 months. Pain was measured using a visual analog scale. RESULTS: After the treatment, 60% of patients treated with dilators and 80% of patients treated with anal self-massage using a finger showed disappearance of their anal fissures. A comparison between signs and symptoms reported by the patients in the two groups showed a statistically significant reduction in anal pain (group A, P=0.0001; group B, P=0.0001) and bleeding after defecation (group A, P=0.001, group B, P=0.001). At 6 months after treatment, a significantly greater reduction in anal pain was observed in Group A compared to Group B (P=0.02). CONCLUSION: The use of anal self-massage with a finger appears to induce a better resolution of acute anal fissure than do anal dilators, and in a shorter time.

Low energy manual anal stretch: an approach in the treatment of chronic anal fissure.

BACKGROUND: Anal fissure is a tear in the epitelial lining of the anal canal. This is a very common anorectal disorder, but the choice of treatment is unclear. Sphincterotomy is effective but it is affected by a high risk of fecal incontinence. Manual anal stretch is aN efficacious, economic and safe maneuver. The aim of this prospective study was to assess the safety and effectiveness of anal stretch in resolving chronic anal fissures. METHODS: Twenty-five patients with a clinical diagnosis of chronic anal fissure were submitted to anal stretch. All patients were submitted to anal stretch, after clinical evaluation. All patients were studied at basal time, and at 7 days, 3, 6 and 12 months after the treatment. RESULTS: At 3 months and 6 months after the anal stretch, 88% and 94% of patients showed a resolution of anal fissures and only 12% have relapsed at 12 months, without complications, such as faecal incontinence. CONCLUSIONS: The anal stretch appears to induce better resolution of chronic anal fissure with a very low risk of fecal incontinence.

The effect of parathyroidectomy on chronic constipation in patients affected by primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is usually associated with chronic constipation; however, its prevalence is not defined by standardized criteria. The aim of the study was to evaluate both the prevalence of chronic constipation, defined by the standardized Rome diagnostic criteria III (Rome III) in PHPT, and the effect of parathyroidectomy (PTx). Fifty postmenopausal PHPT patients and 50 sex- and age-matched controls were studied. Each patient underwent mineral metabolism biochemical evaluation and completed a questionnaire and a 2-week diary card about bowel habits. PHPT patients were reevaluated after 6 months. According to Rome III, 40 % of PHPT patients had chronic constipation compared with 12 % of controls (p = 0.0002). The only difference between constipated PHPT patients (group A, n = 20) and those without constipation (group B, n = 30) was higher mean PTH values (79.9 ± 18.7 ng/l vs. 65.4 ± 26.0 ng/l; p = 0.03), which predicted the presence of constipation (p = 0.004, OR 1.059, CI 1.011-1.059). Forty percent of PHPT patients had undergone PTx. In group A, constipation was resolved in 80 % of patients after PTx compared to none of the same group who had not undergone PTx (p = 0.0007). In group B, 17.6 % of patients who had not undergone PTx became, after 6 months, constipated. According to Rome III, a higher prevalence of chronic constipation in PHPT patients was observed compared with controls. PTH levels predicted constipation. A significant reduction of chronic constipation was reported following successful surgery.

Comparative outcome of stapled trans-anal rectal resection and macrogol in the treatment of defecation disorders.

AIM: To prospectively assess the efficacy and safety of stapled trans-anal rectal resection (STARR) compared to standard conservative treatment, and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR. METHODS: Thirty patients (Female, 28; age: 51 ± 9 years) with rectocele or rectal intussusception, a defecation disorder, and functional constipation were submitted for STARR. Thirty comparable patients (Female, 30; age 53 ± 13 years), who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol, were assessed. Patients were interviewed with a standardized questionnaire at study enrollment and 38 ± 18 mo after the STARR procedure or during macrogol treatment. A responder was defined as an absence of the Rome III diagnostic criteria for functional constipation. Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients, respectively. RESULTS: After STARR, 53% of patients were responders; during conservative treatment, 75% were responders. After STARR, 30% of the patients reported the use of laxatives, 17% had intermittent anal pain, 13% had anal leakage, 13% required digital facilitation, 6% experienced defecatory urgency, 6% experienced fecal incontinence, and 6% required re-intervention. During macrogol therapy, 23% of the patients complained of abdominal bloating and 13% of borborygmi, and 3% required digital facilitation. No preoperative symptom, defecographic, or manometric finding predicted the outcome of STARR. Post-operative defecography showed a statistically significant reduction (P < 0.05) of the rectal diameter and rectocele. The post-operative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified, and that rectal compliance was reduced (P = 0.01). CONCLUSION: STARR is not better and is less safe than macrogol in the treatment of defecation disorders. It could be considered as an alternative therapy in patients unresponsive to macrogol.