Search Results (105)

Colorectal cancer (CRC) exhibits profound molecular heterogeneity between left-sided and right-sided tumors with distinct therapeutic responses that current static genomic analyses incompletely explain. We developed Dynamic Functional Influence Computation (DynaFIC), a computational framework modeling time-resolved signal propagation through biological networks to quantify functional influence beyond static expression levels. Using the GSE39582 dataset comprising 583 primary CRC samples, we performed confounder-adjusted differential expression analysis controlling for microsatellite instability status, BRAF mutations, Tumor Node Metastasis (TNM) stage, age, and sex, identifying 105 laterality-associated genes that underwent DynaFIC temporal network analysis. Right-sided tumors exhibited dramatically higher network connectivity density despite fewer nodes, creating distributed vulnerability patterns with HOXC6 as the dominant regulator, achieving 200-fold influence through network amplification. Left-sided tumors showed compartmentalized, hierarchical organization with PRAC1 as the primary regulator and predictable expression-influence scaling. Temporal clustering revealed distinct propagation kinetics: right-sided tumors demonstrated rapid signal saturation requiring early intervention, while left-sided tumors exhibited sustained propagation permitting sequential approaches. Stability Volatility Index analysis showed right-sided tumors maintain significantly higher systemic vulnerability. These findings establish anatomical location as a fundamental network organizational principle, suggesting that incorporating temporal dynamics into cancer analysis reveals therapeutically relevant differences for precision medicine applications in colorectal cancer. Full article

Background: Tumor sidedness in colon cancer has been linked to biological and clinical differences, but its impact on survival and prognostic factors remains unclear. This study aimed to find the predictors of overall survival (OS) in patients with right-sided colon cancer (RCC) and left-sided colon cancer (LCC) undergoing surgical treatment. Methods: A retrospective single-center study was conducted on 247 patients with colon cancer, including 117 with RCC and 130 with LCC. Clinical, surgical, and pathological variables were analyzed. Cox regression and ROC curve analyses were used to identify independent predictors of OS in the overall cohort and tumor-side subgroups. Results: RCC patients were older (69 vs. 68 years, p = 0.03), had lower hemoglobin levels (11.7 vs. 12.95 g/dL, p < 0.01), and more often presented with anemia (34.18% vs. 11.48%, p < 0.001). LCC patients more frequently underwent emergency surgery (13.74% vs. 5.69%, p = 0.03). Mucinous adenocarcinomas were more frequent in RCC (12.82% vs. 5.38%, p = 0.03), whereas distant metastases (15.38% vs. 6.84%, p = 0.03) and liver metastases (14.61% vs. 6.84%, p = 0.04) were more common in LCC. The one-year overall survival was similar between LCC and RCC before (88.09% vs. 91.52%, p = 0.15) and after propensity score matching (89.32% vs. 91.87%, p = 0.60) In multivariate Cox regression, independent predictors of lower OS included advanced AJCC stage (HR = 34.54, p < 0.001) in RCC, while, in LCC, AJCC stage (HR = 31.14, p = 0.001 and stoma (HR = 5.86, p = 0.01) were significant. Tumor location itself was not associated with OS (p = 0.18). Conclusions: Prognostic factors in colon cancer vary with tumor location. Side-specific risk stratification may improve outcome prediction and guide personalized management. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Background and Objectives: This study aimed to assess the frequency and distribution of facial bone injuries in terms of age, sex, residence, location, and etiology in the north-eastern region of Romania. Materials and Methods: This retrospective study was conducted within the Oral and Maxillofacial Clinics of “Sf. Spiridon” Hospital, Iași. The study group included 701 subjects (mean age 41.02 ± 18.45; sex: 603 males and 98 females) who were diagnosed with an orbital wall disorder. The epidemiological data on orbital wall fractures—including sociodemographic features, etiology, and location—were statistically analyzed. Results: The prevalence of orbital pathology was 1.47% congenital cases, 1.75% tumors, and 96.7% orbital fractures. The distribution of sex, age group, residence, and orbital localization varied significantly among the three diagnostic categories: tumors, congenital conditions, and fractures. Regarding sex, fractures were significantly more frequent in males (87.0%) compared to congenital cases (70.0%) and tumors (41.7%), while tumors showed a female predominance (58.3%) (p < 0.001). Congenital conditions predominantly affected patients under 20 years old (90.0%), whereas fractures were more evenly distributed across age groups, with higher frequencies between 31 and 50 years. In contrast, tumors involving the orbital walls were more frequent in older patients, with 33.3% in the 61–70 age group and 25.0% over 70 years. Regarding orbital localization, fractures were more likely to be bilateral (37.3%) or on the right side (44.3%), whereas congenital orbital defects and orbital tumors were predominantly unilateral and left-sided (70.0% and 66.7%, respectively). Bilateral involvement was rare in congenital cases (10.0%) and absent in tumors. Conclusions: The data support the finding that men are significantly more prone to trauma and orbital fractures, especially as a result of interpersonal violence and accidents, highlighting the need for preventive measures tailored to sex and socio-professional context. Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article

Background/Objectives: Stereotactic body radiotherapy is frequently used in patients with adrenal metastases. Motion of adherent radiosensitive organs at risk (OARs) and tumors influence OAR toxicity and tumor control. Online-adaptive Magnetic Resonance-guided radiotherapy (MRgRT) can address and mitigate interfractional changes. However, the impact of intrafractional variations in adrenal MRgRT is unknown. Methods: A total of 23 patients with 24 adrenal metastases were treated with MRgRT. After daily plan adaptation and before beam application, an additional (preRT) 3d MRI was acquired. PreRT target volumes and OARs were retrospectively recontoured in 200 fractions. The delivered, online-adapted treatment plans, as well as non-adapted baseline plans, were calculated on these re-contoured structures to quantify the dosimetric impact of intrafractional variations on target volume coverage and OAR doses with and without online adaptation. Normal tissue complication probabilities (NTCPs) were calculated. Results: The median time between the two MRIs was 56.4 min. GTV and PTV coverage (dose to 95% of the PTV, D95%, and volume covered by 100% of the prescription dose, V100%) were significantly inferior in the preRT plans. GTV D_mean was significantly impaired in left-sided metastases, but not in right-sided metastases. Compared to non-adapted preRT plans, adapted preRT plans were still significantly superior for all GTV and PTV metrics. Intrafractional violations of OAR constraints were frequent. D0.5cc and the volume exposed to the near-maximum dose constraint were significantly higher in the preRT plans. The volume exposed to the D0.5cc constraints in single fractions escalated up to 1.5 cc for the esophagus, 3.2 cc for the stomach, 5.3 cc for the duodenum and 7.3 cc for the bowel. This led to significantly elevated NTCPs for the stomach, bowel and duodenum. Neither PTV D95%, nor gastrointestinal OAR maximum doses were significantly impaired by longer fraction duration. Conclusions: Intrafractional motion in adrenal MRgRT caused significant impairment of target volume coverage (D95% and V100%), potentially undermining local control. Frequent violation of gastrointestinal OAR constraints led to elevated NTCP. Compared to non-adaptive treatment, online adaptation still highly improved GTV and PTV coverage. Full article

Background: Colorectal surgery remains a cornerstone in the management of colorectal cancer, yet postoperative complications continue to impact surgical outcomes. This study investigates key risk factors influencing morbidity, focusing on patient comorbidities, tumor characteristics, surgical techniques, and anastomotic methods. Methods: A retrospective analysis was conducted on 195 patients who underwent colorectal cancer surgery between January 2021 and December 2024 at the Clinical Hospital of Nephrology “Carol Davila”. Variables analyzed included patient demographics, comorbidities, tumor staging, surgical approach, and postoperative complications. Statistical methods included chi-square tests and multivariate logistic regression (significance threshold: p < 0.05). Results: The overall complication rate was 21%, with anastomotic leakage observed in 8.2% of cases. Significant risk factors for morbidity included cardiovascular disease (p = 0.001), chronic respiratory failure (p = 0.003), and chronic renal failure (p = 0.002). Laparoscopic surgery had a lower complication rate (7.1%) than open surgery (28%) (p = 0.003). Mechanical anastomosis showed lower complication rates than manual suturing (p = 0.009). Left-sided resections were associated with higher morbidity than right-sided procedures (p = 0.013). Conclusions: Optimizing colorectal surgery outcomes requires personalized perioperative strategies. Laparoscopic approaches and mechanical anastomosis significantly reduce complications. Further multicenter studies are needed to confirm these findings and enhance surgical guidelines. Full article

Background: The reconstruction of extensive full-thickness lower eyelid defects constitutes a challenge for plastic surgeons. Various techniques have been described to cater to patients’ specific defect needs, with the aim of achieving the best results. Materials and Methods: We performed a retrospective observational study assessing our experience with a combination of a single-stage procedure consisting of a hard palate graft and a Fricke flap for patients with complex lower lid resections undergoing immediate total reconstruction at our institution. Clinical data, histological type and results, size of tumor, recurrences, and post-operative complications were collected to evaluate outcomes. A Visual Analogue 10-point scale was administered to all patients to assess esthetic and functional outcomes. Results: Seven lower lid reconstructions were performed, with all patients receiving immediate reconstruction. The age of the patients ranged from 55 to 82. Five skin cancers were located on the right side and three on the left side. In all cases, histological diagnosis was non-melanoma skin cancers. The mean size of the tumor was 1.7 × 1.7. In all patients, negative surgical margins were obtained. All patients underwent 24-month follow up. No immediate complication from surgery was recorded within the first 30 days. During follow-up, lower lid ectropion was observed in one patient due to the development of a retracting scar. No local cancer recurrence or nodal metastasis were detected until 2 years follow-up. In only one case, adjuvant therapy was required. The aesthetic results were deemed satisfactory by all patients. Conclusions: According to our experience, the combination of a Fricke flap and hard palate graft is an excellent option for total lower eyelid reconstruction, with low morbidity and favorable outcomes, even in elderly and frail patients where satisfactory results were achieved in a single-stage procedure and short operative times. Full article

Background/objectives: Common carotid artery occlusion can cause oxidant and inflammatory damage to the optic nerve. In this study, the effect of sunitinib was investigated, the antioxidant and anti-inflammatory properties of which have been previously reported and shown to be protective in I/R injury and in preventing bilateral optic nerve ischemia–reperfusion (I/R) injuries after unilateral common carotid artery ligation in rats. Methods: In this study, 18 Albino Wistar male rats were divided into SG (sham-operated), CCU (clamping and unclamping), and SCCU (sunitinib + clamping and unclamping) groups. One hour before the surgical procedures, sunitinib (25 mg/kg, oral) was given to SCCU rats. Anesthesia was induced with ketamine (60 mg/kg, ip) and sevoflurane. The right common carotid arteries of all rats were accessed under anesthesia. While the skin opened in SG rats was closed with sutures, the right common carotid arteries of CCU and SCCU rats were clipped, and an ischemia period was created for 10 min. Then, reperfusion (6 h) was achieved by unclipping. After euthanasia with ketamine (120 mg/kg, intraperitoneally), the right and left optic nerves of the rats were removed and examined biochemically and histopathologically. Results: Malondialdehyde, tumor necrosis factor α, interleukin-1β, and interleukin-6 were increased, and total glutathione levels had decreased in both ipsilateral and contralateral optic nerves (p < 0.05). These changes were more prominent on the ipsilateral side. Similarly, histopathological damage was observed to be more on the ipsilateral side (p < 0.05). Biochemical and histopathological changes were significantly suppressed in rats receiving sunitinib treatment (p < 0.05). Conclusions: Sunitinib may protect optic nerve tissue against I/R injury by reducing oxidative stress and inflammation. Full article

Background: Colorectal cancer (CRC) remains a global health challenge. Metabolic disorders, including dyslipidemia, have been linked to CRC progression, yet the relationship between lipid profiles, tumor location, and survival outcomes remains controversial. This study investigates the association between blood lipid parameters, tumor localization, and survival in CRC patients. Methods: A retrospective analysis was conducted on 126 CRC patients diagnosed between 2017 and 2024 at Kartal Dr. Lütfi Kırdar City Hospital. Patients with comorbidities affecting lipid metabolism or who were on lipid-lowering drugs were excluded. Clinical, pathological, and lipid data, including total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and carcinoembryonic antigen (CEA), were analyzed. Tumor location was categorized as right-sided or left-sided. Overall survival (OS) was evaluated with a statistical analysis using Kaplan–Meier and Cox regression models. Results: Higher HDL-C levels and a lower TC/HDL-C ratio were significantly associated with improved OS (p: 0.004 and p: 0.016, respectively). This relationship remained significant in early- and advanced-stage disease (p: 0.04 for HDL-C and p: 0.03 for TC/HDL-C). In patients with tumors located in the right colon, LDL-C levels of 150 mg/dL and below were found to be statistically positively correlated with overall survival, while in patients with tumors located in the left colon, HDL-C levels of 45 mg/dL and above and TC/HDL-C levels of 4.16 and above were found to be statistically positively correlated with overall survival. A multivariate analysis confirmed that age, stage, HDL-C, and TC/HDL-C were independent predictors of OS. Conclusions: Our study highlights the potential role of lipid profiles, particularly HDL-C and the TC/HDL-C ratio, as prognostic factors in CRC. Further research, including molecular and genetic analyses, is needed to better understand the mechanisms underlying the relationship between lipid metabolism and CRC progression. Full article

A single testicular microlithiasis is a common finding during sonography, while macrocalcification is a rare and incidental finding. The literature on macrocalcification is limited. Typically, testicular calcifications, whether microscopic or macroscopic, are benign but they can have a clinical significance. This multicenter study aimed to investigate the symptoms and prevalence of testicular cancer in patients with macrocalcification. Methods: Testicular ultrasound examination reports from four hospitals’ PACS database, covering the period 2014–2023, were screened for diagnoses of macrocalcification. Inclusion criteria required that the radiology report described macrocalcification supported by ultrasound images. Results: Macrocalcifications were identified in 42 male patients, with a mean age of 45 years. Sixteen macrocalcifications were in the right testicle, twenty in the left, and six were bilateral. Microlithiasis were found in 22 patients (52.4%), with 11 (26.2%) bilateral, 3 (7.1%) left-sided, and 8 (19.1%) right-sided. Testicular tumors were found in six patients. Conclusion: Testicular macrocalcification exhibited large visual variation and diverse clinical history. However, we found a low number of patients with testicular macrocalcification and testicular tumors, indicating that macrocalcifications have a benign nature, and that macrocalcification alone should not be a primary concern for malignancy, but this needs to be confirmed in further studies. Full article

Background: Unilateral basal ganglia calcinosis (BGC) is a rare radiological finding that can be diagnosed on computed tomography (CT) and magnetic resonance imaging (MRI) but often presents challenges for clinicians and radiologists in determining its underlying cause. So far, only a few potential causes that could explain unilateral BGC have been described in the literature. Case Report: A 54-year-old Caucasian male was admitted to a tertiary university hospital due to the sudden onset of speech impairment and right-sided weakness. The patient had no significant medical history prior to this event. Non-enhanced computed tomography (NECT) of the brain revealed no evidence of acute ischemia; CT angiography (CTA) showed acute left middle cerebral artery (MCA) M2 segment occlusion. CT perfusion (CTP) maps revealed an extensive penumbra-like lesion, which is potentially reversible upon achieving successful recanalization. However, a primary neoplastic tumor with calcifications in the basal ganglia was initially interpreted as the potential cause; therefore, acute stroke treatment with intravenous thrombolysis was contraindicated. A follow-up CT examination at 24 h revealed an ischemic lesion localized to the left insula, predominantly involving the left parietal lobe and the superior gyrus of the left temporal lobe. Subsequent gadolinium-enhanced brain MRI revealed small blood vessels draining into the subependymal periventricular veins on the left basal ganglia. Digital subtraction angiography was conducted, confirming the diagnosis of venous angioma. Conclusions: Unilateral BGC caused by venous angioma is a rare entity with unclear pathophysiological mechanisms and heterogeneous clinical presentation. It may mimic conditions such as intracerebral hemorrhage or hemorrhagic brain tumors, complicating acute stroke management, as demonstrated in this case. Surrounding tissue calcification may provide a valuable radiological clue in diagnosing venous angiomas DVAs and vascular malformations. Full article

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases. Full article

Background/Objective: Studies have shown an association between colorectal cancer (CRC) sidedness and gene mutations that may affect CRC clinical behavior. This study examined the association between specific KRAS, NRAS, and BRAF hot-spot mutations and primary CRC sidedness. Methods: We performed a retrospective cohort analysis of 722 patients diagnosed with primary CRC and tested for KRAS, NRAS, and BRAF hot-spot mutations at the University of Texas Medical Branch (UTMB) from January 2016 through July 2023. Multivariable logistic regressions analyses were conducted. Results:KRAS, NRAS, and BRAF hot-spot mutations rates were 37.8%, 4.6%, and 6.1%, respectively. Right-sided primary CRC had the highest prevalence of mutated tumors (64%). KRAS and BRAF hot-spot mutations were significantly different according to tumor sidedness. KRAS p.Gly12Asp, p.Gly12Val, and p.Gly13Asp showed a significantly increased likelihood of right-sided primary CRC compared to KRAS wildtype, 128%, 134%, and 221% higher, respectively. Conversely, KRAS p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer (53% lower) and left-sided tumors (56% lower), respectively. BRAF p.Val600Glu mutation, as opposed to BRAF wildtype, was associated with a 278% higher likelihood of right-sided CRC. No significant associations were observed between NRAS mutations and primary CRC sidedness. Conclusions: In primary CRC, specific mutations in KRAS (p.Gly12Asp, p.Gly12Val, and p.Gly13Asp) and BRAF p.Val600Glu were associated with increased likelihood of right-sided tumors. KRAS p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer and left-sided tumors, respectively. These findings suggest that tumorigenesis and mutational processes differ based on tumor sidedness. Further studies are needed to substantiate these findings. Full article

Chordomas are a low-to-intermediate-grade slow-growing subtype of sarcoma, but show propensity to grow and invade locally with recurrence and metastasis in 10–40% of cases. We describe the first case of spontaneous regression of a solid tumor (histologically and immunohistochemically proven chordoma) after COVID-19. A female patient with clival chordoma underwent occipitocervical fixation prior to tumor resection. In the early post-operative stage following the arthrodesis procedure, she was diagnosed with COVID-19. Six months after COVID-19, she finally came back for endoscopic endonasal resection of the tumor and pre-operative MRI surprisingly showed 98.9% regression of the tumor volume. Tumor resection was performed, and both histopathological and immunohistochemistry confirmed diagnosis of chordoma with positive brachyury levels. She showed improvement of right hemiparesis and left-sided tongue palsy. The tumor was comprised of tumor-infiltrating inflammatory cells. CD3 and CD68 were positive, suggesting the presence of T-lymphocytes and macrophages. CD20 and CD56 were negative, suggesting the absence of B-lymphocytes and NK-cells. The authors believe that the onset of COVID-19 exacerbated the patient’s immune response and improved anti-tumor immunity. It was concluded that T-cells, which are involved in the COVID-19 immune response and were found infiltrating the tumor, acted as a critical pathway to this event. Further studies are encouraged in order to gain a better understanding of the SARS-CoV-2–chordoma interaction. Full article