The Relationship between Tumor Budding and Tumor Deposits in Patients with Stage III Colorectal Carcinoma.

Background/Objectives: Recently, some new morphological features of colorectal cancer have been discovered as important prognostic factors; in this paper, we study the relationship between tumor budding (TB) and tumor deposits (TDs). Methods: The retrospective cohort study included 90 patients with pathohistologically confirmed stage III CRC who were treated with radical surgical resection. All hematoxylin and eosin (H and E)-stained slides from each patient were reviewed, and histological parameters were recorded. The samples were divided into two groups with similar sizes: a group without TDs (N = 51) and a control group with TDs (N = 39). The presence and TB grade were further analyzed in these groups and compared with other clinical and histological features. Results: The prevalence of TB in the investigated cohort was unexpectedly high (94.4%). Overall, there were 23 (25.6%) Bd1, 20 (22.2%) Bd2, and 47 (52.2%) Bd3 cases. The presence of TDs was significantly associated with a higher number of TB (p < 0.001, OR 16.3) and, consequently, with a higher TB grade (p = 0.004, OR 11.04). A higher TB grade (p = 0.001, HR 2.28; 95% CI 1.93-4.76) and a growing number of TDs (p = 0.014, HR 1.52; 95% CI 1.09-2.1) were statistically significantly associated with shorter survival. Conclusions: TDs appear more often in patients with higher TB grades in stage III CRC. A higher TB grade and a growing number of TDs were statistically significantly associated with shorter overall survival. These results could give additional emphasis to the importance of TB as an adverse prognostic factor since a strong relationship with TDs has been demonstrated.

Expression and Prognostic Significance of PD-L1 and NY-ESO1 in Gallbladder Carcinoma.

BACKGROUND/AIM: Gallbladder cancer is a rare malignancy with a very high mortality, usually due to diagnosis in an advanced stage of the disease. Therefore, the aim of this study was to evaluate the clinical significance of cancer/testis antigen 1A (CTAG1A, NY-ESO1) and CD274 molecule (PD-L1, the ligand for programmed cell death protein 1) and their impact on the overall survival of patients with gallbladder cancer. PATIENTS AND METHODS: Using immunohistochemical staining, we determined the expression of NY-ESO1 in tumor cells (positivity: cytoplasmic/nuclear staining of any intensity in ≥50%) and PD-L1 in tumor cells and intratumoral immune cells (positivity: cytoplasmic/membranous staining of any intensity in ≥1%). RESULTS: The median overall survival (OS) of 58 patients with gallbladder cancer in our cohort was 7 months, and depended on the clinical stage of the disease; the 5-year OS rate was 10%. NY-ESO1 was expressed in 69.1% of cases. Immune cells were PD-L1-positive in 36.4% of cases, while tumor cells expressed PD-L1 in only 10.9% of cases. In six cases (10.9%), neither of the studied proteins were expressed. NY-ESO1 expression was negatively correlated with PD-L1 expression in immune cells (p=0.021). NY-ESO1 showed no correlation with any clinicopathological parameters or OS. PD-L1 expression in immune cells was significantly higher in tumors with perineural invasion (rs=0.318; p=0.018) and higher clinical disease stage (rs=0.339; p=0.013) but showed no correlation with OS. CONCLUSION: Patients whose gallbladder cancer expresses NY-ESO1 or PD-L1 might be candidates for immunotherapy.

COMPARISON OF C-REACTIVE PROTEIN LEVELS IN SERUM AND PERITONEAL FLUID IN EARLY DIAGNOSIS OF ANASTOMOTIC LEAKAGE AFTER COLORECTAL SURGERY.

In colorectal surgery, anastomotic leakage is a serious complication, leading to higher postoperative morbidity and mortality. The aim of this study was to evaluate the accuracy of serum and intraperitoneal C-reactive protein (CRP) in early diagnostics of anastomotic leakage on the first four postoperative days after colorectal surgery. From January to October 2019, fifty-nine patients with colorectal carcinoma were operated on, with formation of primary anastomosis. Anastomotic leakage was diagnosed in eight patients. Comparing the levels of serum and intraperitoneal CRP, our study showed that serum CRP was a better predictor of anastomotic leakage. Serum CRP levels lower than 121 mg/L on postoperative day 4 were predictive of good healing of anastomosis.

Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine.

AIM: To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement. METHODS: Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 µg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 µg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum. RESULTS: Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues. CONCLUSION: BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation.

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights.

AIM: To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS: Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. RESULTS: Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 µg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. CONCLUSION: BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.