Faculty of Medicine

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CLINICAL-PATHOLOGICAL EVALUATION AND FOLLOW-UP OUTCOMES IN PRIMARY BLADDER TUMOR PATIENTS TREATED AT UROLOGY CLINIC
(Македонско лекарско друштво = Macedonian medical association, 2024)
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Trifunoski, Aleksandar
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Janchulev, Josif
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Aim. To evaluate the clinical-pathological characteristics, recurrence rate, and progression of primary bladder tumors in patients treated at a tertiary urology center, with a focus on histologic grade, tumor size, and number assessed via cystoscopy. Methods. This retrospective, observational study included 117 patients with histologically confirmed urothelial carcinoma who underwent initial transurethral resection of bladder tumor (TURBT) at the University Clinic for Urology in Skopje from January 2019 to December 2024. Patients were categorized by gender, tumor invasiveness (pTa, pT1, pT2), histologic grade (PUNLMP, low-grade, high-grade), tumor count, and size. Follow-up was performed using cystoscopy, urine cytology, and ultrasound at 3, 6, 9, and 12 months. Recurrence was defined as tumor relapse at any of these intervals. Exclusion criteria were: non-urothelial histology, missing data, prior bladder cancer treatment, or carcinoma in situ (CIS), which was excluded due to its distinct biological behavior. Results. The mean age of patients was 66.5±9.6 years (range 41-88), with a male-to-female ratio of 3.5:1. Pathological staging showed 43 patients (33.9%) had pTa, 37(29.1%) had pT1, and 37(29.1%) had pT2 tumors. Histologic grading revealed 2 patients (1.6%) with PUNLMP, 37 (29.1%) with low-grade carcinoma, and 78 (64.6%) with high-grade tumors. Non-muscle invasive bladder cancer (NMIBC) was present in 80 patients (63.0%), and muscle-invasive bladder cancer (MIBC) in 37 (29.1%). Recurrence occurred in 14 of 117 followed patients (12.0%). There was no recurrence in PUNLMP cases: 16.2% of low-grade tumors, and 10.2% of high-grade tumors. The relatively lower recurrence in high-grade cases is attributed to the high proportion of pT2 tumors managed by cystectomy. Tumor multiplicity and size were significant predictors: recurrence was 4.8% in solitary tumors and 50.0% in patients with 3-5 tumors. Tumors >3 cm had a recurrence rate of 24.0%, compared to 5.7% in those <3 cm. Conclusion. Tumor grade, size, and multiplicity were strongly associated with recurrence following TURBT. These findings emphasize the importance of personalized follow-up based on pathological and cystoscopic features.
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Rectal Metastasis from Early-Stage Endometrial Carcinoma Not Associated with Endometriosis: A Case Report and Literature Review
(Kurume University School of Medicine, 2025-11-13)
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Jovcheva, Ana
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Endometrial cancer (EC) is the third most common malignancy in woman with excellent prognosis when diagnosed in early-stage. Recurrences are extremely rare in Stage I EC especially in rectum when not associated with endometriosis. We present a case of rectal metastasis from endometrial carcinoma after 8 years of primary diagnosis. A review of the literature showed only 6 published cases.
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INCARCERATED INCISIONAL HERNIA: AN UNUSUAL PRESENTATION OF LIPOSARCOMA MYXOIDES METASTATICUM
(Македонско лекарско друштво = Macedonian medical association, 2025-09)
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Frosina Jovanovska
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Bisera Popovska
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Svetlana Jovevska
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Abdominal wall hernia is a common condition seen in the clinical practice of surgery. Soft tissue sarcomas are rare neoplasms, representing less than 1% of tumors in adults. However, recurrent liposarcoma reason for incarcerated incisional are rare and there are limited studies on this subject. We report a case of a 43-year-old female who presented with generalized abdominal pain and vomiting. She was treated for an incarcerated incisional hernia and underwent an exploratory laparotomy, which showed a multiseptated incisional hernia sac, with small bowel loops and the presence of recurrent liposarcoma in the mesentery. Desincarceration with maximal adhesiolysis and total extirpation of the recurrent liposarcoma and abdominal wall hernioplasty were performed. Contrast-enhanced CT is the first-line investigation, complete surgical excision remains the gold standard treatment for primary and even recurrent tumors. Prognosis depends on the histological type and grade. Histopathological examination revealed a liposarcoma myxoides metastaticum. The patient had surgeries for liposarcoma three and one years ago, and appropriate oncological treatment. The operative and postoperative course were uneventful. Postoperatively, she continued with oncological treatment. Follow-up after 6 months remains clean and is ongoing. Conclusion: Liposarcomas are aggressive malignant tumors with frequent recurrences.
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RECURRENT CLOSTRIDIOIDES DIFFICILE COLITIS – CASE REPORT
(Peytchinski Publishing Ltd., 2024-10-06)
Georgievska, Dajana
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Vidinic, Ivan
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Shopova, Zhaklina
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Rangelov, Goran
Recurrent Clostridium difficile infection (rCDI) is usually defined as the reappearance of enteral symptoms 2-8 weeks after resolution of the initial episode with an appropriate therapy. Recurrence occurs in approximately 25% of patients within the first 30 days of the treatment. A 62-year-old female was initially hospitalized at our hospital within the intensive care unit (ICU) due to acute encephalitis and bilateral bronchopneumonia. Her comorbidities were diabetes mellitus and hypertension. She was treated with a combination of parenteral beta-lactam antibiotics for 35 days, acyclovir, probiotics, gastric suppression, and other supportive therapies. On the 18th hospital day, she developed diarrhea with liquid mucous green stools, prompting stool cultures and a C.difficile toxins test, which were negative and her condition stabilized spontaneously. A week later, she experienced a recurrence of enteral symptoms when stool cultures showed C.difficile positivity, but negative toxin tests. A colonoscopy was performed, revealing pseudomembranous pancolitis. Treatment continued with intravenous metronidazole and oral vancomycin for two weeks, alongside probiotics. This led to gradual improvement and normalization of stool consistency. Control cultures were C.difficile negative, and she was discharged after 49 days. Three weeks later, she complained of persistent watery stools and malaise, thus she was readmitted. New stool cultures confirmed C.difficile positivity with negative toxin tests. A repeat colonoscopy showed significant regression of pseudomembranous colitis and biopsy results indicated chronic nonspecific colitis. She was treated with probiotics, intravenous metronidazole for a week, and oral vancomycin. On first follow-up visit after three weeks, she returned asymptomatic with normal stools, and was advised to continue oral vancomycin, rifaximin, and probiotics. A second follow-up visit two weeks later confirmed normal stool characteristics. Prolonged use of antibiotics, extended hospital stays, advanced age, severe preexisting illness are significant risk factors for recurrent CDI. Prolonged oral vancomycin therapy has shown high efficacy in treatment of this serious condition.
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Malignant transformation and tumour recurrence in sacrococcygeal teratoma: a global, retrospective cohort study
(Wolters Kluwer, 2024-11)
van Heurn, Lieke J
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Derikx, Joep
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Hall, Nigel
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Aldrink, Jennifer H.
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Bailez, Maria M.
Introduction: Sacrococcygeal teratoma (SCT) is a rare congenital tumour. The risk of malignancy and recurrence is not well defined. Previous studies are small and report differing conclusions about the timing of surgery and the duration of follow-up. The authors studied the risk of malignant transformation and SCT recurrence after surgery to address these gaps. Methods: This was a global retrospective cohort study. Data of consecutive SCT patients was obtained from 145 institutes in 62 countries. Malignant transformation, defined as malignancy at initial resection, malignant recurrence or death due to malignancy, and its risk factors were analysed. Results: Of the 3612 included patients, 3407 entered analysis. The risk of malignant transformation of the initial tumour was 3.3, 5.1, 10.1, and 32.9% at age 3 months, 6 months, 1 year, and 2 years, respectively. After 6 years, the censored risk of malignancy (64%) did not further increase. Recurrent SCT was diagnosed in 349 (10.2%) children with 126 (36.1%) malignant recurrences. Risk factors for recurrence were Altman type II [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.2–2.2], Altman type III (OR: 1.6, 95% CI: 1.2–2.3), initial immature histology (OR: 1.9, 95% CI: 1.4–2.6), and initial malignant histology (OR: 4.0, 95% CI: 2.9–5.4). Conclusion: The risk of malignancy at initial resection in SCT increases with age reaching a plateau at 6 years of age. Recurrence after resection occurred in 10% of patients and 36% of these were malignant at that time. Altman type II or type III, and immature or malignant histology were associated with recurrence.
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INVASIVE SKINCARCINOMA OF THE SKULLTREATED WITH A ROTATIONALFLAP-A CASE REPORT
(Macedonian Association of Anatomists and Morphologists, 2023-12-26)
Tomevska, Ana
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Mikjunovikj, Mikjun
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Bitrakov, Zoran
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Trajanoska, Biljana
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Ivanoski, Slavcho
The escalating incidence of skin malignancies, particularly in sun-exposed areas such as the head and neck, requiresinnovative approaches for challenging cases. Squamous cell carcinoma, though common, rarelyinfiltrates the skull, presenting unique challenges in treatment and reconstruction.In this case report, we describethe management of a 77-year-old patient with recurrent invasive squamous cell carcinomaof the left temporal region extending into the skull. The patient underwent three surgeries within our institution due to squamous cell carcinomarecurrence, leading to a complex skin defect unsuitable for conventional closure methods.Ourapproach involved the use of a local rotational flap, usingthe robust vascularity of the scalp, allowing versatile orientation relative to the defect. The operating techniqueconsisted of a craniectomy, removal of infiltrated tissue, and affected dura, followed by plastic reconstruction of the skin with a rotational flap, preserving healthy periosteum and temporal fascia.As the population with cutaneous neoplasms ages, the demand for expeditious and less morbid reconstructive options grows. This case underlinesthe effectiveness of the local rotational flap for reconstructing medium-sized complex scalp defects post-cancer resection. Our experience suggests that the rotational scalp flap is a reliable and safe choice, offering a favorable balance between surgical outcomes and patient well-being.
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Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry
(Thieme Medical Publishers, 2017)
Alatri A
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Mazzolai L
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Font C
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Tafur A
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Valle R
Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41 %) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI 5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI 18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI: 0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.
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Predictive value of estrogen receptors evaluated by immunocytochemical analysis in breast cancer patients
(Gustav Fischer, 1997-09)
Yashar, Genghis
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Ivkovski, Ljube
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Zografski, George
BACKGROUND: The determination of estrogen receptor (ER)status is valuable in selecting the appropriate therapy and predicting prognosis for patients with invasive breast carcinoma. OBJECTIVE: The aim of our study was to assess the predictive value of ER status evaluated preoperatively by immunocytochemical analysis and compared with recurrence rate, clinical and histopathological features in 52 patients with breast carcinoma. MATERIALS AND METHODS: Fifty-two aspirates obtained by fine-needle-aspiration biopsy (FNAB) were prepared as cytospin samples for ER-immunocytochemical analysis (ER-1CA). Cytospin slides were stained using a standard procedure with horseradish peroxidase-antiperoxidase (PAP) method, utilising monoclonal antibody to ER (H222SP, ER-ICA kit, Abbott Laboratories, USA). The assessment of staining was scored in a semiquantitative fashion incorporating the intensity and the distribution of stained cells and the values were designated as IS-CYTOSCORE. All the patients underwent radical mastectomy with axillar lymphadenectomy during the period from September 1990 to March 1992 and were staged according to the postoperative pTNM classification of UICC (1987) guidelines. During the follow-up period (range, 2-75 months, mean 32) recurrences were observed in 25 (48%) patients.ER status was correlated to recurrence rate, age of the patients, type of the breast carcinoma, tumor size, grade of histologic differentiation, desmoplastic reaction, elastosis, necrosis and calcifications. The comparison was made by cross-classification and statistical significance determined by χ2 and Fisher's exact test. RESULTS: ER status was positively detected in 28 (53.8%) patients. There is significant association between ER status and age of the patients (p = 0.02), the type of the breast carcinoma (p = 0.018), and the recurrence rate (p = 0.012). Eighteen out of 26 (70%) patients 50 years or older, were positively related to ER status. In 22 (42.3%) lobular carcinomas, ER status was positive in 16 (73%) patients, compared with 30 (57.7%) ductal carcinomas, with ER status positive for 12 (40%) patients, only. Recurrences were observed in 16 (64%) patients with ER- breast carcinomas and 9 (36%) patients with ER+ breast carcinomas. Less important histopathological features as elastosis and calcifications, demonstrated statistically significant positive relation with ER status (p = 0.004 and p = 0.005, respectively). No significant association was found between the ER status and other histopathological characteristics. CONCLUSION: Our results suggest that recurrences, age of the patients and the lobular type of breast carcinoma are positively correlated with ER status. These data are consistent with the results of other similar studies. On the other hand, the stage of the disease as well as the grade of histologic differentiation and lymph node involvement, demonstrated no significant association with ER status as expected. A small number of cases studied and the heterogeneous stages included, could explain some of the differences between our data and the results from other studies. Semiquantitative ER-1CA, as fast and simple method, is especially useful in determination of ER status in recurrent, metastatic and small-sized breast carcinomas. The great advantage of ER-ICA is in a possibility of ER status preoperative determination, and repeating the procedure, if necessary. Despite the good performances, some inherent difficulties must be noted: subjectivity in scoring and detection by antigenicity of ER. Therefore, ER status quantitative assessment by using Cell-Analysing-System (CAS) and concomitant quantitative measurements of progesterone receptor status, should be of additional benefit.
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Human papilloma virus DNA presence in early stage cervical carcinomas: Correlation with other prognostic factors and recurrence rate
(Gustav Fischer, 1997-09)
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Ivkovski, Ljube
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Yashar, Genghis
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Stavrik, George
BACKGROUND: Although the role of human papillomavirus (HPV) in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. OBJECTIVE: The objective of our study was to assess the prognostic significance of the presence of HPV DNA by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 92 patients with cervical carcinoma..In this report the preliminary results of a larger programme aimed to search for the prognostic factors in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy, followed by postoperative adjuvant pelvic radiotherapy, are presented MATERIALS AND METHODS: Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51 (Enzo Diagnostics, New York). Clinical data and histopathologic features of these patients were analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 48 (52.2%) patients, while local extension to vagina and parametrial tissues was found in 10 (10.9%) and 34 (36.9%) patients, respectively. Pelvic lymph node involvement was found in 25 (27.2%) patients. During the follow-up period (range, 2-87, mean, 35 months), recurrences were observed in 13 patients. Variables were compared by cross-classification and statistical significance was determined by χ2 and Fisher`s exact test. RESULTS: HPV DNA was detected in 41 (44.6%) cervical carcinoma specimens. The prevalence rate of different HPV types was 37% (34) for HPV 16/18, 6.5% (6) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate was significantly higher in patients with HPV DNA negative cervical carcinomas (P=0.02). Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 4.9% (2 cases), compared to 21.6% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, number of positive lymph nodes, histologic subtype, maximum depth of cervical stromal invasion, maximal tumor diameter, longitudinal endocervical involvement, proportionate longitudinal endocervical involvement, tumor-cervix area quotient, maximal and minimal sagittal tumor area, parametrial involvement, vaginal involvement, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, surgical margins involvement, age) were also correlated with the presence of HPV DNA. No statistically significant association was found between the presence of HPV DNA and 17 other clinical and histopathologic variables. On the other hand recurrence rates were significantly related to tumor extent (P=0.0001), presence of regional lymph nodal metastases (P=0.0002), maximal tumor diameter (P=0.14), proportionate longitudinal endocervical involvement (P=0.007), maximal sagittal tumor area (P=0.038), parametrial involvement (P=0.0001), vaginal involvement (P=0.03), and lymph-vascular space invasion (P=0.0023). CONCLUSIONS: The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be related to recurrence rate and unrelated to various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.
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Prognostic significance of the human papillomavirus DNA presence in early stage cervical carcinoma
(1996-05)
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Stavrik, George
Although the role of human papillomavirus in cervical carcinogenesis is reasonably well established, the attempts to determine the prognostic value of presence or absence of detectable human papillomavirus DNA and HPV type in cervical carcinoma have yielded conflicting results. The objective of our study was to assess the prognostic significance of the presence of HPV DNA in a fairly homogenous population of patients with early stage cervical carcinomas who underwent abdominal hysterectomy with pelvic lymphadenectomy as primary therapy. In this report the preliminary results of this larger study are presented by exploring the relationship of HPV presence to the recurrence rate and clinical and histopathologic features of 44 patients with cervical carcinoma. Routinely processed formalin-fixed paraffin-embedded cervical carcinoma surgical specimens were examined for the presence of HPV DNA by in situ hybridization technique using mixed biotinylated probes to identify HPV types 6/11, 16/18 and 31/33/51. Clinical and histopathologic data of these patients was analyzed retrospectively to determine their relation to presence or absence of HPV DNA. All the patients were staged according to the postoperative TNM classification of UICC (1987) guidelines. In our case series the tumor was limited to cervix in 24 (54.6%) patients, while local extension to vagina and parametrial tissues was found in 6 (13.6%) and 14 (31.8%) patients, respectively. Pelvic lymph node involvement was found in 15 (34%) patients. During the follow up period (range, 2-72, mean, 39 months), recurrences were observed in 6 patients. HPV DNA was detected in 20 (45%) cervical carcinoma specimens. The prevalence rate of different HPV types was 34% (18) for HPV 16/18, 9% (4) for HPV 31/33/5, while HPV type 6/11 was detected only in one case of verrucous carcinoma. Recurrence rate in relation to the presence of HPV DNA exhibited a trend but was not statistically significant. Among the HPV DNA positive patients with cervical carcinoma the recurrence rate was 5% (1 case), compared to 21% (5 cases) for the HPV DNA negative group. Various clinical and histopathologic features of the patients with cervical carcinomas (tumor extent, grade, presence of regional lymph nodal metastases, histologic subtype, maximum depth of cervical stromal invasion, longitudinal tumor diameter, tumor-cervix area quotient, parametrial involvement, vaginal invasion, lymph-vascular space invasion, peri- and intra-tumoral lymphocytic infiltration, age) were also correlated with the presence of HPV. None of these factors was found to have statistically significant relationship to the presence of HPV DNA. The preliminary results of our study are consistent the observations reported by several other authors. The presence of HPV DNA appeared to be unrelated to recurrence rate and various histopathologic characteristics of well-known prognostic significance. However, having in mind the limited number of cases studied, as well as a lower sensitivity of in situ hybridization technique, an analysis of larger series, as well as introducing a more sensitive technique like PCR assay, will be necessary to determine whether the presence of HPV DNA and HPV type should be considered when developing treatment strategies and assessing prognosis in patients with early stage cervical carcinomas.

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