Tumor Budding as a Prognostic Marker in Primary Colon Cancer - A Single Center Experience.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.

Patient-reported health-related quality of life after colorectal surgery.

<b>Introduction:</b> Colorectal cancer is one of the most common cancers worldwide. In most of these patients, quality of life is deteriorated. </br></br> <b>Aim:</b> The aim of our study was to analyze how the disease affects health-related quality of life (HRQoL) and to examine the role of demographic, disease-related, and other factors in the overall quality of life. The second aim was to identify areas where HRQoL could be improved. </br></br> <b> Material and methods:</b> A cross-sectional questionnaire survey was conducted. The study included a modified version of EQ-5D, as well as clinical and socioeconomic characteristics of the country. Patients over the age of 18, who had colorectar surgery, and were followed up at our clinic, were included in the survey. </br></br> <b>Results:</b> In patients after colorectal surgery, bowel control is a major concern that has an impact on their quality of life. The majority of patients expressed gratitude for the care they received and thanked the health-care providers for it. With the EQ-5D modified questionnaire, the concept of "perfect" health was reviewed and analyzed. A response "no difficulty" in any of the five domains was classified as perfect health. Only one-third of the patients said their health was "ideal" (no problems in any of the EQ-5D five domains). </br></br> <b>Discussion:</b> According to the results of this study, patients with CRC have considerably poorer HRQoL than the general population, as indicated by the EQ-5D utility scores. This discovery is in line with some previous research. </br></br> <b>Conclusion:</b> Colorectal surgery survivors' total HRQoL has been found to be lower than in the general population.

High expression of CD133 - stem cell marker for prediction of clinically agressive type of colorectal cancer.

<b> Background:</b> Colorectal cancer (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The objective of the study was to evaluate the CD133 expression and to correlate it with clinicopathological features in patients with CRC. <br><b>Material and Methods:</b> Our study included ninety patients with CRC who underwent curative surgical resection from 2012 to 2017 at the University Clinic for Digestive Surgery, Skopje, North Macedonia. Tumor samples were first analyzed with standard histopathological methods and then the CD133 expression was investigated immunohistochemically. The level of expression of CD133 was classified semiquantitatively. Low positivity was defined as positive immunoreactivity in <50% of tumor glands, and high positivity was defined as positive immunoreactivity in ≥50% of tumor glands. Furthermore, clinicopathological features of patients were retrospectively reviewed. <br><b>Results:</b> High expression of CD133 was found in 47.8% of patients' CRC samples. In 69.6% of patients with metastatic lesions in visceral organs we found high expression of CD133. We found statistically significant differences in the expression of CD133 between patients with and without visceral metastatic lesions (P = 0.0153), between patients with a different T category (P = 0.0119), N status (P = 0.0066) and grade (G) (P = 0.0115). Our results showed that the stage of disease has the greatest impact on expression of CD133 (P < 0.00001). <br><b>Conclusion:</b> High expression of CD133 is a useful marker for prediction of the clinically aggressive type of CRC and can be routinely implemented in standard pathohistological diagnostics.

Hypernatremia-induced Neurologic Complications After Hepatic Hydatid Cyst Surgery: Pretreat to Prevent.

INTRODUCTION: Surgery is effective treatment for echinococcosis; however, there is a risk of hypertonic saline resorption and acute hypernatremia. AIM: We report two cases of severe hypernatremia following hydatid cyst removal. CASE REPORTS: A 17-year-old girl underwent surgical removal of hepatic hydatid cyst. Following the surgery, she developed seizures evolving to status epilepticus, and was sedated and mechanically ventilated. Blood chemistry showed hypernatremia. Fluid resuscitation with 5% dextrose infusions was started in combination with furosemide. Electrolytes were monitored frequently until plasma sodium levels normalized, 30 hours later. The patient was seizure free 48 hours later. The second patient is a 70-year-old man with hepatic hydatid cyst. After the surgery he became somnolent and confused due to severe hypernatremia. Intravenous administration of five percentage dextrose was initiated and high doses of furosemide. Sodium level normalized within 38 hours. The patient's mental status improved. CONCLUSION: A hospital protocol was established aiming to prevent hypernatremia and neurological complications.

New technique of compression anastomosis in colorectal surgery - first results in 25 patients in Macedonia.

AIM: Clinical evaluation of the safety and effectiveness of compression anastomosis with ColonRing™ for large-bowel end-to-end anastomosis for rectal cancer and explanation of the procedure and the device itself since this device is used for the first time in our clinic. MATERIAL AND METHODS: In November, 2012, a team of surgeons from our clinic attended the Clinical practice workshop in Belgrade, Serbia which was organized by the World Congress of Compression Anastomosis (WCCA) and held by its President Prof. Dr. Steven Wexner from Cleveland Clinic in USA. On this workshop, all aspects of technical point of view were obtained and surgeons were certified for the technique. A total of 25 patients have been scheduled for elective colorectal surgery with subsequent compression anastomosis using ColonRing. All patients were operated for high and mid rectal cancers excluding the low rectal cancers, since those patients are usually diverted with decompressive ileostomy. Patients, who are diverted, are at higher risk of retaining the ring, after its dislodgement, in the ampulla of the rectum since they do not have natural excretion of stool via the anus. All patients were followed for anastomotic leak, anastomotic bleeding, stricture formation, device (ColonRing) handling in general and time of expulsion of the ring via anus. RESULTS: We used this technique for the first time in 2013 and since then a total of 25 patients underwent anterior resection of the rectum with subsequent colorectal compression anastomosis using ColonRing. Of all patients, 9 were female while 16 were male with median age of 64 years. All patients were operated for rectal cancers. The mean length of hospital stay was 7.4 days (range 5 to 9 days). None of the patients developed anastomotic bleeding or dehiscence. To date none of the patients developed anastomotic stricture, although some patients were followed for almost two years. The average day of expulsion from the body could not be calculated since despite, and although all patients were given instruction on how to check for ring expulsion, 21 of them did not report this event. Only 2 patients brought the ring to us. In two cases after 2 week of the initial operation, the ring was find and palpated on digital rectal examination, free in the ampulla of the rectum and was easily removed via the anus during the examination. Misfiring was reported in 1 patient (first patient) and reanastomosis was employed using another ColonRing, No perioperative mortality was observed in this patient population. CONCLUSION: End-to end colorectal anastomosis with the ColonRing is feasible and safe procedure with fast learning curve. To date, this type of anastomosis is possible in left sided colon lesions where anastomosis is contemplated below the promontory. We find the device easy to use with high level of confidence. Further prospective studies including comparison between the ColonRing device and the conventional staplers evaluating long-term anastomotic complications (i.e., leak or stricture) are needed to evaluate the benefits and limitations of this device.

Laparoscopic Adrenalectomy: First Single-Center Experience in the Balkans.

INTRODUCTION: Laparoscopic adrenalectomy has become the preferred approach for removal of the adrenal gland for the management of benign or malignant functioning or nonfunctioning adrenal masses. We aimed to present our initial experience with this procedure. In addition, we compare the clinical outcomes of laparoscopic (LA) vs. the open adrenalectomies (OA) performed at our institutions. Also we report a case of successful laparoscopic treatment of splenic artery aneurism involving laparoscopic splenectomy. PATIENTS AND METHODS: A retrospective analysis of the data of all patients who underwent adrenalectomy at three institutions, over the last 12-year period, since the laparoscopic adrenal surgery was introduced in our country. All patients were assessed regarding the demographic data, hormonal status, operative time, estimated blood loss, complications, size of the tumor, number of patients requiring blood transfusion, hospital stay and conversion to open surgery for LA. RESULTS: Thirty five consecutive patients, aged from 33 to 67 (average age 54 years) underwent unilateral LA adrenalectomy during the study period including 14 right and 21 left sided. The laparoscopic procedure was successfully completed in all except 4 cases, which were converted to open surgery to control bleeding from the avulsed adrenal veins. LA proved superior to OA, resulting in less estimated blood loss, shorter operating time, shorter time to resumption of oral intake, shorter postoperative hospital stay and less analgesic requirements. During the follow-up of 3 to 36 months no tumor recurrence and/or metastasis developed. CONCLUSIONS: Our results concur with other retrospective reviews comparing laparoscopic and open adrenalectomy, demonstrating unequivocal advantages in terms of reduced length of hospital stay, blood loss, return of bowel function, functional recovery and post-operative morbidity.

Splenectomy for haematological disorders.

Splenectomy is therapeutic for a large host of conditions. It is a consequence of expanding the list of disorders and liberalizing the indications for splenectomy in many diseases. Red blood cells disorders: autoimmune hemolytic anemia, hereditary spherocytosis, hemoglobinopathies and thalassemia are prone to splenectomy after failure of medical therapy. A variety of thrombocytopenic disorders are improved by splenectomy, and the most common indication for splenectomy is ITP (idiopathic thrombocytopenic purpura). Splenectomy is successful in reversing hypersplenism in a spectrum of disease called myeloproliferative disorders. Relief of symptoms from splenomegaly is also achieved, but it does not affect the inexorable course of the disorder. The role of splenectomy in white blood cells disorders (leukemias and lymphomas) is only palliative and facilitates chemotherapy. Splenectomy in patients with hemathologic disorders imparts a risk of fulminant and life threatening infection "overwhelming postsplenectomy sepsis" that can be obviated by appropriate treatment. Although splenectomy for hemathologic disorders is only therapeutic and not curative, the relief of symptoms and for some disorders facilitation of chemotherapy leads to better quality of life and longer survival.

Multivisceral resection for advanced duodenal adenocarcinoma: a case report and review of literature.

The aim of this paper is to address adenocarcinoma of the duodenum by reporting a case, reviewing the literature and discussing current knowledge, diagnostic modalities and treatment options. We present a case of a 42-year-old patient with duodenal adenocarcinoma at the second portion invading surrounding organs. The patient had a previous history of colon malignancy and was diagnosed with a new tumour formation on regular CT (computed tomography) follow-up. Pylorus-preserving pancreaticoduodenectomy (PPPD) was preformed for this T4 N2 M1 tumor. Duodenal adenocarcinoma is a rare tumor, most frequently involving the second duodenal portion. It has no specific symptoms and it is difficult to diagnose it due to its rarity and clinical presentation. Diagnosis, exact localization, and involvement of lymph nodes and surrounding organs have an impact on surgical strategy and prognosis.

Laparoscopic versus open splenectomy: a single center eleven-year experience.

The 11-year experience with open (OS) and laparoscopic (LS) splenectomy at a single center is reported. A total of 201 splenectomies were performed and clinical and demographic data were retrospectively analyzed. Patients were classified according to the type of operation as LS or OS. The mean age of patients was 45.1 +/- 17.1, and 141 patients were male. Out of 43 LS, 40 were done for hematologic causes, and they had a significantly shorter hospital stay compared to OS for hematologic causes (6.87 +/- 2.2 vs. 9.84 +/- 2.9 days; p = 0.000003) and significantly less requirement for blood transfusion (26.2 +/- 93.4 vs. 132.4 +/- 252.3 mL; p = 0.0152). In the OS group, comparison of patients with trauma and those with hematologic causes showed that significantly more males underwent surgery for trauma causes (35 of 43 vs. 16 of 21), hospital stay was longer (18.9 +/- 27.4 vs. 9.8 +/- 2.9 days) and blood requirement higher (708.1 +/- 603.7 mL vs. 132.4 +/- 252.3 mL; p = 0.0004, p = 0.047 and p = 0.000001, respectively). Laparoscopic splenectomy is a safe procedure for spleen removal.

A true epidermotropic apocrine neoplasm in the form of perianal Paget's disease: a case report.

INTRODUCTION: Extramammary Paget's disease is an uncommon intraepithelial neoplasm that arises in areas rich in apocrine glands. Treatment includes wide surgical excision and nonsurgical modalities. We present the case of a patient with perianal Paget's disease with no recurrent disease after wide surgical resection. CASE PRESENTATION: Our patient was a 46-year-old man of Macedonian ethnicity who presented with a pruritic perianal lesion measuring up to 6cm without pain or bleeding. Two biopsies and a perianal wide surgical excision were performed. The tissue specimens were formalin-fixed and the paraffin-embedded samples analyzed according to standard histochemical and immunohistochemical procedures.Surgical perianal skin excision revealed diffuse eczematoid, whitish plaques. Pathohistology showed Paget cells infiltrating his epidermis and adnexal epithelium, with ulceration. Immunohistochemical analysis revealed positive Paget cell expression for cytokeratin 7, epithelial membrane antigen, carcinoembryonic antigen, androgen receptor and human epidermal growth factor receptor 2, and negative expression for cytokeratin 20 and melan-A. CONCLUSION: Paget's disease is a rare disorder that should be considered in the differential diagnosis of perianal lesions. Reporting cases of extramammary Paget's disease is crucial for diagnostic guidelines and different therapeutic options.

Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer.

Uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) is the key hepatic detoxification enzyme involved in the biotransformation of many carcinogens implicated in the development of colon, breast, and prostate cancers in humans. A polymorphism in the UGT1A1 promoter containing a TA-repeat element [(TA)5-8TAA] is involved in the modulation of UGT1A1 transcriptional activity. The wild-type activity is associated with the (TA)6TAA allele (UGT1A1*1), whereas UGT1A1 expression decreases with the increase of the TA-repeat number. We hypothesize that the low-activity allele UGT1A1*28 with seven TA repeats is associated with a higher risk for colorectal cancer. Our study involved 168 patients with histopathologically confirmed sporadic colorectal cancer and a control group of 96 individuals with no personal history of colorectal cancer. We detected a higher frequency of UGT1A1*28 than the wild-type UGT1A1*1 allele in colorectal cancer patients as compared with that of controls (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.07-2.26, P = 0.021). The frequency of genotypes containing the UGT1A1*28 allele in the homozygous or heterozygous state was significantly higher than the frequency of the wild-type UGT1A1*1/*1 genotype in colorectal cancer patients as compared with controls (OR = 2.0, 95% CI = 1.19-3.34, P = 0.007). Our results indicate that the UGT1A1*28 allele is a risk factor for colorectal cancer in the Macedonian male population, whereas no significant risk was detected among women.

L-2-oxothiazolidine-4-carboxylate influence on age- and heat exposure-dependent redox changes in rat's blood plasma.

In the present study, we investigated both the age- and heat exposure-related redox changes of blood plasma by analyzing GSH, thiol status and carbonyl groups. Our results clearly indicated that the plasma redox balance shifted toward oxidation during both aging and acute heat exposure. To further confirm this age- and heat exposure-related redox shift, we quantified the changes in thiol content. The total thiol level was found to be significantly decreased in the aged group. A similar pattern can be explained by low levels of serum GSH in old rats compared to young rats. The significance of the present study are the data showing increased oxidative stress in plasma during aging, attributed to a decrease in major antioxidant components in serum. OTC treatment, in relation to C=O regarded as a marker of oxidative damage was probably much more effective in increasing of GSH synthesis than in prevention of protein oxidation.

Presenting colorectal carcinoma cases in our department.

BACKGROUND: Colorectal carcinoma is second commonest cancer causing death in Kosova. METHODOLOGY: In our study we present diagnostic methods, treatment, localization and laboratory findings in 155 patients, during 4 year period in patients with colorectal carcinomas treated in our clinic. RESULTS: Ninety four 94 (61.4%) of patients were male gender and 59 (38.6%) were female. Eritrosedimentation was elevated in 103 (67.3%) of patients, number of white blood cells was increased in 21 (7.2%) of patients and high level of glycemia is present in 11 (7.2%) of patients. The most involved age is from 41-50 years. The most common site of involvement was the rectum in 79 (51.6%), localization in sigma was in 37 (23.5%), the transverse colon in 21 (13.7%) of cases and the ascendant colon in 18 (11.1%) patients. Adenocarcinoma (98%) was the most common histiotype. CONCLUSION: We concluded, that all patients, especially with positive familial history must begin screening in age 40, during which colorectal carcinoma can be diagnosed in an early stage.

Isolated malignant peripheral nerve sheath tumor of kidney capsule.

The occurrence of an isolated malignant peripheral nerve sheath tumor (MPNST) of the kidney capsule is extremely rare and its presence may only be expressed by an insidious onset of non-specific and misleading symptoms with a predominance of lower back pain. A computer tomography (CT) scan (as the imaging procedure of choice) will demonstrate the tumor location and its relation to the surrounding structures. Tumor excision in toto is considered the treatment of choice, but it can be hazardous, especially if the tumor is adhering to the surrounding structures. Severe bleeding complications due to the damage of venous structures have to be considered, and establishing hemostasis may pose considerable difficulties. Therefore surgery should be attempted with full precautions and the patient must receive preoperative counseling. If malignancy can safely be excluded, a laparoscopic excision should be considered as an alternative treatment as recurrence is unlikely. Definition of the originating nerve might not always be possible, and a minor degree of neurological impairment has therefore to be anticipated. A case of an isolated MPNST of the kidney capsule without neurofibromatosis is presented. The tumor was located in the fatty and fibrous capsule. It was surgically removed. The patient was further managed with radiotherapy and chemotherapy. An MPNST in such a location is very unusual.