The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Unusual cause of upper gastrointestinal bleeding. Report of the case of hemorrhagic duodenal lipoma with review of the literature.

Duodenal lipomas are uncommon and rare causes of gastrointestinal bleeding. Here, we present the case of a 45-yearold male patient who was admitted to University Clinical Centre because of melaena. After initial diagnostics, including echosonography, esophagogastroduodenoscopy revealed bleeding from protruding blood vessel at the polypoid submucosal change in the posterior duodenal bulb. Upon two urgent unsuccessful endoscopic hemostasis, a duodenotomy was performed. Definitive diagnosis was based on histological findings, describing duodenal lipoma with Bruner's gland hyperplasia. Upper GI bleeding is a serious challenge that requires adequate diagnostics necessary for the right choice of therapeutic approach. Unsuccessful endoscopic hemostasis could be followed by serious complications in bleeding duodenal lipoma when surgery should be always considered as the treatment of choice in patients with this kind of bleeding tumor. KEY WORDS: Bruner Glands Hyperplasia, Duodenal Lipoma, Upper Gastrointestinal Bleeding.

Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma-A Single-Center Study.

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018-2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.

Nitric oxide synthesis modulation - a possible diagnostic and therapeutic target in colorectal cancer.

PURPOSE: Considering the contradictory literature data about the role of nitric oxide (NO) in colon carcinogenesis, the purpose of this study was to examine the changes of L-arginine metabolites in colon cancer and surrounding tissue as possible molecular markers of tumor behavior after surgery and the possibility of NO synthesis modulation in new individualized therapeutic strategies. METHODS: The study encompassed 50 patients who underwent surgery for colorectal cancer (CRC). The three tissue specimens were taken by surgery (tumor, adjacent and healthy tissue) and the concentrations of NO2+NO3, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in the tissue specimens. RESULTS: The results proved higher NO2+NO3 concentrations in adjacent tissue compared to the tumor, implicating high angiogenic potential of the tumor-surrounding tissue, which could have clinical importance in the assessment of the probability of tumor local recurrence and metastasis. Increased ADMA concentrations in tumor tissue associated with low NO levels, could lead to new therapeutic strategies directed to the use of inhibitors of NO synthesis as ideal candidates for molecular therapy of CRC. ADMA concentration in adjacent tissue was an independent predictor of distant metastasis. CONCLUSIONS: The obtained results suggest that determination of the examined biomarkers in CRC and adjacent tissue samples could give useful information about tumor proliferative and angiogenic potential, which in turn could enable individualization of therapy and the choice of proper adjuvant therapy in patients with CRC.

Case of rectal angioleiomyoma in a female patient.

Angioleiomyoma represents a benign stromal tumor, which usually occurs in the subcutaneous tissue of the extremities, although its occurrence in the gastrointestinal tract is very rare. A case of rectal angioleiomyoma in a 40 year-old female patient is described here. Six months earlier, the patient suffered from periodical prolapse of an oval tumor from the anus, along with difficulties in bowel movement. A transanal extirpation of the tumor was performed. This is the first reported case in the English literature of a patient presenting with prolapsed angioleiomyoma of the rectum. During the immediate postoperative period, as well as 6 mo later, the patient had an unremarkable postoperative recovery.

Ileocolic intussusception as a presenting sign of primary lymphoma of the colon.

INTRODUCTION: Intussusception is a rare phenomenon in adults. It is caused mainly by malignant neoplasm. Primary lymphoma of the colon is a rare malignancy of the large intestine. The association of intussusception in adult and primary colorectal lymphoma is a diagnostic challenge, since they occur with a variety of atypical symptoms. CASE OUTLINE: We report a case of ileocolic intussusception in a 26-year-old man induced by primary lymphoma of the cecum. He was admitted to our hospital for incomplete intestinal obstruction. After thorough diagnostic work-up (plain abdominal radiography, abdominal ultrasonography, multi-slice computerized tomography, colonoscopy with biopsy), the patient underwent surgery. Intraoperative findings confirmed lymphoma as the cause of intussusception. The right hemicolectomy was carried out with end-to-side ileo-transverse anastomosis. CONCLUSION: Primary colorectal lymphomas should be considered in differential diagnosis of intussusceptions in adults. The treatment of choice is a radical resection where all oncological standards must be fulfilled.

Primary colorectal lymphoma: An overview.

Lymphomas represent common hematological malignancies with increasing incidence in recent years. The major site of extranodal non-Hodgkin lymphoma is the gastrointestinal tract. Involvement of the large intestine is rare in comparison to the stomach or small bowel. The disease appears later in life, predominantly in the male population. Complaints are nonspecific, requiring a high index of suspicion in order to establish the diagnosis. The treatment varies from chemotherapy alone to multimodal therapies combining surgery, chemotherapy and radiotherapy. The small number of patients with various histological subtypes and different stage at presentation results in unclear protocol for the treatment of primary colorectal lymphoma. The purpose of this paper is to review current data on primary lymphoma of the colon and rectum while analyzing reported case series and published material on the subject.

Nonfunctional retroperitoneal paraganglioma presenting as acute upper gastrointestinal hemorrhage.

Paragangliomas are very rare tumors arising from extraadrenal chromaffin cells. Clinical presentation of benign retroperitoneal nonfunctional paraganglioma is unspecific. Symptoms may occur when tumor attains a remarkable size or when complications arise. This article reports a case of nonfunctional retroperitoneal paraganglioma as a cause of acute upper gastrointestinal hemorrhage which represents the unusual urgent clinical manifestation of these tumors. The presented case emphasizes the necessity to include extraadrenal paraganglioma in the differential diagnosis in all patients with retroperitoneal mass found even in the presence of at first appearance non-related emergency condition like acute upper gastrointestinal bleeding.

[Preoperative identification of bleeding site caused by angiodysplasia of the small bowel by means of selective arteriography and application of methylene blue].

BACKGROUND: Small bowel hemorrhages are rare and account for 2-10% of all gastrointestinal bleedings. In case that surgery is necessary, identification of the bleeding site is the most important problem. CASE REPORT: We presented here the case of a 65-year old man, admitted for urgent care of massive lower gastrointestinal bleeding. After reanimation and normalization of vital parameters, selective arteriography was done. A contrast extravasation site was identified at the level of jejunal branches of a. mesenterica superior and labeled by means of methylene blue application. Immediately after we performed conservative resection of the labeled jejunal loop in 10 cm length and terminoterminal anastomosis. The preparation was sent for histopathologic examination--small bowel angiodysplasia was identified. The patient was monitored in three month intervals in the next two years and new bleeding events were not observed. CONCLUSION: Bleeding caused by small bowel angiodysplasia is a significant diagnostic problem in cases in whom urgent surgery is required. Combined preoperative selective arteriography and methylene blue application make possible precise identification of the bleeding site as well as conservative small bowel surgery, avoiding thus the risk and danger of malabsorption syndrome.

[Safety of simultaneous colon and liver resection for colorectal liver metastases].

BACKGROUND/AIM: Surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer (CRC) remains controversial. The aim of this study was to assess safety of simultaneous colon and liver rese cions and the direct effects of this type of treatment upon morbidity and mortality of the patients with synchronus hepatic metastases of CRC. METHODS: Intraoperative and postoperative data of 31 patients with simultaneous liver and colorectal resection were compared with the data of 51 patients who had undergone colon and hepatic resection in the staging setting. Analized were demographic data, number of metastases, type of the liver resection, operation time, intraoperative blood loss, percentage of postoperative complications, morbidity and mortality and lenght of hospitalisation. RESULTS: In the group of the patients operated simultaneously 5 hepatectomies, 3 sectionectomies, 2 trisegmentectomies, 3 bisegmentectomy, 6 segmentectomies, and 12 metastasectomies were combined with colon resection. In this group operation time (280 vs. 330 minutes) and in traoperative blood loss (450 vs. 820 ml) were lower than those in the two staged operation group. Postoperative complication rate was lower in the simultaneous group (19.35%o) than in the two-staged operation group (19.60%), without statistical significance. There was no hospital mortality in both groups. The patients having simultaneous resection required fewer days in the hospital (median 10.2 days) than the patients undergone operation in the two stage (18.34 days). CONCLUSION: By avoiding a second laparotomy, overall operation time, blood loss, hospital stay and complication rate are reduced with no change in hospital mortality, so simultaneous colon and hepatic resection performed by the competent surgeons are safe and efficient for the treatment of synchronous colorectal liver metastases.