Favorable prognostic significance of membranous ß-catenin expression and negative prognostic significance of cytoplasmic ß-catenin expression in pancreatic cancer.

The aim of this study was to investigate the prognostic significance of membranous ß-catenin and cytoplasmic ß-catenin expression in pancreatic cancer patients (pts). One hundred pts with histologically verified exocrine pancreatic ductal adenocarcinoma were retrospectively studied. The membranous ß-catenin, cytoplasmic ß-catenin, and cell nucleus ß-catenin expression were immunohistochemically evaluated. The expression of membranous ß-catenin was <5% in none of the pts, 5-25% in one patient, 26-50% in 2 pts, 51-75% in 14 pts, and >75% in 81 pts. The expression of cytoplasmic ß-catenin was <5% in 34 pts, 5-25% in 42 pts, 26-50% in 18 pts, 51-75% in 3 pts, and >75% in one patient. The expression of ß-catenin in the cell nucleus was negative in all pts. At the time of the last follow-up, 21 pts were alive and 79 pts had died. Median OS was 1.3 (0.4-2.3) years in pts with membranous ß-catenin expression ≤75% and 1.7 (1.3-2.1) years in pts with membranous ß-catenin expression >75% (p=0.045). Median OS was (1.3-2.0) 1.6 years in pts with cytoplasmic ß-catenin expression ≤25% and 0.9 (0.5-1.2) years in pts with cytoplasmic ß-catenin expression >25% (p=0.040). In the univariate Cox proportional hazard models HR (95% CI) was 0.556 (0.311-0.995) in pts with membranous ß-catenin expression >75% (p=0.048) and 2.200 (1.216-3.980) in pts with cytoplasmic ß-catenin expression >25% (p=0.009). The present results indicate a favorable prognostic significance of membranous ß-catenin expression in pancreatic cancer.

Association of the combined parameters including the frequency of primary cilia, CD8+ tumor infiltrating lymphocytes and PD-1 expression with the outcome in intestinal cancer.

PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer. METHODS: The frequency of PC, programmed cell death protein-1 receptor (PD-1) expression and the frequency of stromal and intraepithelial CD8+TILs were evaluated in samples of colorectal adenocarcinoma (32 patiens) and small bowel cancer (8 patients). RESULTS: The median frequency of PC was 0.25%. The expression of PD1 was <5% in 34 patients, 5-25% in 5 patients and 26-50% in 1 patient. The frequency of stromal CD8+ TILs was negative in 3 patients, <25% in 26, 26-50% in 10 and >50% in 1 patient, respectively. Intraepithelial CD8+ TILs were not detectable in 14, <25% in 24 and 26-50% in 2 patients, respectively. Statistically, the frequency of PC and PD-1 positivity were significantly associated (p=0.004). An association between the PC frequency and intraepithelial CD8+ TILs was of borderline statistical significance (p=0.059). An index combining the frequency of PC and stromal CD8+ TILs, but not the combination of frequency of PC and intraepithelial CD8+ TILs, was of borderline prognostic significance (p=0.067). CONCLUSIONS: The present study provides the first data on the potential association and combined prognostic significance of frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer.

Prognostic significance of the frequency of primary cilia in cells of small bowel and colorectal adenocarcinoma.

PURPOSE: The primary cilium is a solitary, sensory, immotile microtubule-based structure that arises from the centrosome and is projected from the surface of most human cell types. It has been hypothesized that primary cilia could serve as a tumor suppressor organelle. The objective of this pilot study was to investigate the presence and frequency of primary cilia in cells of small bowel and colorectal adenocarcinoma and to evaluate the prognostic significance of their frequency. METHODS: The presence of primary cilia in cells in samples of small bowel (8 patients) and colorectal adenocarcinoma (32 patients) was evaluated. The primary cilia of cells were immunofluorescently labeled using primary monoclonal anti-acetylated agr;-tubulin antibody and cell nuclei were labeled using DAPI. RESULTS: Primary cilia were identified in all examined specimens. The median frequency of primary cilia was 0.49% in cells of small bowel cancer and 0.22% in cells in colorectal cancer. Overall survival according to frequency of primary cilia in all intestinal adenocarcinomas was significantly longer in patients with higher frequency (≥ 0.187) than in patients with lower frequency of primary cilia (< 0.187) in univariate analysis (p=0.007) and also in the Cox proportional hazard model (p=0.032). Overall survival according to frequency of primary cilia in colorectal adenocarcinoma was significantly longer in patients with higher frequency (≥ 0.187) than in patients with lower frequency of primary cilia (< 0.187) (p=0.028). CONCLUSIONS: The present pilot study provides the first evidence of the prognostic significance of the frequency of primary cilia in small bowel and colorectal adenocarcinoma. Because of significantly higher median frequency of primary cilia in the rare small bowel adenocarcinoma than in the frequent colorectal adenocarcinoma (p<0.001), the results of this study support a potential role for primary cilia as a biomarker in these types of cancer.

Neoadjuvant chemoradiotherapy of rectal carcinoma : Baseline hematologic parameters influencing outcomes.

BACKGROUND: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). RESULTS: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01-1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). CONCLUSION: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma.

Gastric and Colorectal Metastases of Lobular Breast Carcinoma: A Case Report.

BACKGROUND: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. CASE REPORT: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. CONCLUSIONS: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

Dermatofibroma-like granular cell tumour: a potential diagnostic pitfall.

Dermatofibroma-like granular cell tumour (GCT) is a rare entity, with only two cases having been described so far. We report another case in a 62-year-old woman, discuss histopathological features, and review other tumours in which granular changes have been observed. Our tumour was composed predominantly of oval-to-spindle granular cells with prominent nucleoli, arranged in short fascicles and storiform pattern, infiltrating around collagen bundles. Immunohistochemical analysis with antibodies against CD31, CD56, CD68, CD117, S-100 protein, inhibin, calretinin, EMA, p53 and MIB-1 was performed, showing expression of CD56, CD68, S-100 protein, inhibin and calretinin. The diagnosis of atypical dermatofibroma-like GCT was made.

Suture-free anastomosis of the colon. Experimental comparison of two cyanoacrylate adhesives.

BACKGROUND: We explored the potential of two cyanoacrylate tissue adhesives for constructing colonic anastomoses. METHOD: The study involved 12 female domestic pigs. The animals were divided into two equal groups. In both groups, the sigmoid colon was transected. An intestinal anastomosis was constructed with a modified circular stapler (all staples were withdrawn) and cyanoacrylate tissue adhesives. Glubran 2 was used in group A and Dermabond was applied in group B. Fourteen days after the first operation, a follow-up surgery was performed in both groups. The glued section of the colon was resected, processed with the standard paraffin technique and stained with haematoxylin-eosin. The finished specimens were examined under light microscopy. Assessments were made for the presence of fibroblasts, neutrophils, giant polynuclear cells, neovascularisation and collagen deposits. Adhesions, anastomotic dehiscence, peri-anastomotic inflammation and intestinal healing were assessed peri-operatively. RESULTS: All anastomoses in group A healed with no signs of pathology. In group B, fibrotic adhesions and stenoses tended to occur in areas surrounding the anastomoses. Histological examinations confirmed increased fibrosis. CONCLUSION: The tissue adhesive Glubran 2 appears to be (under experimental conditions) a promising synthetic adhesive for colonic anastomosis construction; conversely, the tissue adhesive Dermabond was unsuitable for suture-free anastomosis construction.

Laparoscopic diagnostics of acute bowel ischemia using ultraviolet light and fluorescein dye: an experimental study.

PURPOSE: The aim of the study was to show the diagnostic potential of laparoscopy using fluorescein dye and ultraviolet light in acute bowel ischemia. MATERIALS AND METHODS: The study involved 12 domestic pigs. Under general anesthesia, the peripheral branch of the superior mesenteric artery was embolized using polyvinyl-alcohol microparticles. Two hours after the embolization, optical filters were placed into the laparoscopic set to produce ultraviolet light. Fluorescein dye was given intravenously, and the bowel was inspected. Clips were placed on the border of the ischemia that was visualized with fluorescein. Resection of the ischemic part of the bowel and anastomosis of the viable parts were carried out using laparoscopic linear cutting staplers. After 24 hours, a laparoscopic second-look procedure was carried out to verify the viability of the anastomosis. RESULTS: The method was in all cases able to recognize intestinal ischemia and reliably differentiate ischemic bowel segments from viable bowel. Microscopic analysis of the ischemic specimens showed beginning ischemic changes of the bowel tissues. CONCLUSIONS: The method should be considered a valuable diagnostic procedure both for diagnostics of early stage of acute bowel ischemia and for second-look procedures.

Diverting ileostomy set removable without laparotomy--feasibility study.

We constructed an ileostomy set that creates a diverting ileostomy not requiring surgery for closure. The set has two primary components: a double-balloon drainage catheter and a plastic holder. The plastic holder has a rotary component that is used to tighten a percutaneosly placed lasso-loop stitch and purse the enterotomy after the drainage catheter is removed. We tested the ileostomy set in 10 experimental pigs. The drainage catheter was introduced transcecally into the terminal ileum behind Bauhin's valve, and the balloon was inflated. Three to seven days later the drainage catheter was removed, and the cecotomy was closed by percutaneous tightening of the lasso-loop stitch. One week later each animal underwent relaparotomy, and we examined the abdominal cavity for peritonitis. An ileocecal resection was performed, and specimens were collected and evaluated microscopically to ensure that the catheter had not damaged the intestinal wall. The only change noted in the terminal ileum was submucosa lymphatic tissue hyperplasia. No intestinal leaks occurred, and percutaneous enterotomy closure was successful.

Radio-guided sentinel node detection during the surgical treatment of rectal cancer.

OBJECTIVE: The detection of sentinel nodes is performed in various types of malignant disease. The aim of this study was to evaluate the results of the radiodetection of sentinel nodes, based on the use of Tc-colloid, during the surgical treatment of rectal cancer. METHODS: In 2003-2004, 42 patients (24 males and 18 females; average ages of 62.4 and 67 years, respectively) were examined during rectal carcinoma surgical procedures. Miles abdominoperineal rectal resection was performed in nine cases; 33 patients underwent low anterior rectum resection by total mesorectal excision. On the day of the operation, a transanal submucosal infiltration of colloid labelled with radioactive 99mTc was performed; infiltration was performed strictly peritumorally. After the operation, radiodetection of the surgical specimens (using a hand-held gamma probe) was performed. The areas of higher radioactivity were marked. The specimens were then examined by a histopathologist. The nodes found closest to the marked areas were considered to be 'sentinel nodes'. The results of scintigraphy and postoperative radiodetection were checked by histological examination. All the discovered lymph nodes were examined by haematoxylin and eosin staining; when this was negative, immunohistochemical examination with cytokeratin was used for the sentinel nodes. RESULTS: In 36 of the 42 patients, the data obtained by scintigraphy and radiodetection were in agreement with histopathological proof of a sentinel node. The sensitivity of the method in this group of patients was 86% (95% confidence limits: 70.75-94.05). CONCLUSIONS: The scintigraphic method of detection of sentinel nodes in total mesorectal excision is not therapeutic, but diagnostic, and demonstrates a high level of reliability. It can be used to indicate the nodes that should be examined to detect the presence of possible micrometastases immunohistochemically. However, this method cannot be used for all detected nodes as it is very demanding. In the evaluated group of patients, there were no intraoperative or postoperative complications caused by this diagnostic method.