The effects of the COVID-19 pandemic on the diagnosis and prognosis of melanoma 2 years after the pandemic in two Romanian counties.

Background: The COVID-19 pandemic disrupted the healthcare system and negatively affected the diagnosis and management of melanoma worldwide. The purpose of this study is to investigate the long-term effects of the COVID-19 pandemic on the diagnosis and prognosis of melanoma. Materials and methods: This retrospective cohort study included histopathologically confirmed melanoma cases from March 2019 to February 2023 in Cluj and Bihor counties. Data from the post-COVID-19 period (March 2021 to February 2023) were compared to the pre-COVID-19 period (March 2019 to February 2020) and the COVID-19 period (March 2020 to February 2021). Patient characteristics, monthly diagnostics, histological subtypes, and key histological features were analyzed using statistical tests. Results: The number of melanoma cases diagnosed annually decreased by 31.37 and 23.75% in the first and second post-pandemic years, respectively, compared to pre-pandemic numbers. Diagnostic rates also decreased by 14.9 and 5.4% in the first and second post-pandemic years, respectively, compared to the pandemic period. Prognostic factors worsened in the post-pandemic period, with higher Breslow index and mitotic rate, and increased ulceration and thick melanomas compared to the pre-pandemic period. Conclusion: The COVID-19 pandemic had a long-lasting impact on the diagnosis of melanoma in Romania, resulting in advanced stages and unfavorable prognostic factors. Larger global studies are needed to comprehensively understand the pandemic's long-term effects on the diagnosis of melanoma.

Custom-Made 3D-Printed Prosthesis after Resection of a Voluminous Giant Cell Tumour Recurrence in Pelvis.

Giant-cell tumours are benign aggressive bone lesions that can affect any part of the skeleton. In early stages, curettage is preferred, but in case of local recurrence or voluminous lesions in the periacetabular region, wide resection and reconstruction are recommended. The purpose of this article is to increase clinicians' awareness of the importance of the follow-up of these patients and to describe a case of a voluminous recurrence of a giant-cell tumour in the pelvis. We present a 25-year-old female who underwent internal hemipelvectomy assisted by 3D cutting-guides and reconstruction with a custom-made 3D-printed pelvic prosthesis, hip arthroplasty and ilio-sacral arthrodesis. No postoperative complications occurred and, at long-term follow-up, the patient had a stable and painless hip joint, good bone-implant osteointegration, with an excellent functional outcome. In spite of all available reconstructive techniques, in well-selected patients with voluminous pelvic resections, custom-made 3D-printed implants allow patients to have a good mechanical outcome.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis in Romania-Data from Two University Centers.

The COVID-19 pandemic affected the healthcare system in our country and led non-COVID patients to postpone medical visits that were not urgent. The purpose of this study was to investigate the impact of the first year of the COVID-19 pandemic on the trends in melanoma diagnosis and to compare the pathological characteristics of melanoma patients before and during the pandemic. The number of primary cutaneous melanomas diagnosed each month between 1 March 2019 and 29 February 2020 (pre-COVID-19) and between 1 March 2020 and 28 February 2021 (COVID-19) in the North-Western Region of Romania (Cluj and Bihor counties) was determined. The pathological characteristics of melanomas diagnosed in the two intervals were compared. The number of melanoma diagnoses substantially decreased during the pandemic, with 66 (-19.3%) fewer cutaneous melanomas being diagnosed in the first year of the pandemic when compared with the previous year. The tumor thickness and mitotic rate were significantly higher in cases found during the COVID-19 pandemic. Our study suggests that COVID-19 has delayed diagnosis in patients with melanoma, leading to the detection of thicker melanomas that may increase morbidity and mortality. Further studies are needed to determine the consequences of this delay on outcomes.

Cervical intranodal schwannoma - a rare diagnosis.

Intranodal schwannoma is a rare benign tumor, which originates from the peripheral nerve sheath (Schwann cells), fewer cases being reported with lymphatic involvement. We present the case of a middle-aged female patient, with one-year growing mass in the lateral-cervical area, in intimate relation with the vascular package of the neck. Preoperative cervical computed tomography examination showed the tumor features. There was no intraoperative complication, with the piece being completely removed. The morphological examination revealed the structure of a lymph node, and after Hematoxylin-Eosin staining, there were eosinophilic cytoplasm, euchromatic nuclei, with round, elongated or slightly wavy form and reduced pleomorphism, rare degenerative nuclear atypia, and no mitotic activity nor necrosis. The expression of S100 protein on immunohistochemistry, along with negative results for smooth muscle actin and desmin sustained the diagnosis of intranodal schwannoma of the neck. With a low index of cellular proliferation (Ki67), this case is in line with the reported features of schwannoma having extremely rare malignant transformation.

Quantitative contrast-enhanced endoscopic ultrasound in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors: can we predict survival using perfusion parameters? A pilot study.

AIM: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. MATERIAL AND METHODS: Thirty patients with PDAC or pNET who underwent CEH-EUS and EUS-guided fine needle aspiration (EUS-FNA) were included. Quantitative analysis of tumor vascularity was performed using time-intensity curve (TIC) analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software (VueBox). Cox proportional hazards models were used to determine associations with survival outcome. RESULTS: Median overall survival (OS) for PDAC patients was 9.61 months (95% CI: 0.1-38.7) while the median OS for pNET patients was 15.81 months (95% CI: 5.8-24.75. In a multivariate model for OS, a lower peak enhancement (HR=1.76, p=0.02) and a lower wash-in area under the curve (HR=1.06, p=0.001) were associated with worse survival outcome for patients with PDAC. CONCLUSIONS: CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support.

Technical Performance, Overall Accuracy and Complications of EUS-Guided Interventional Procedures: A Dynamic Landscape.

Endoscopic ultrasound (EUS) gained wide acceptance as the diagnostic and minimally invasive therapeutic approach for intra-luminal and extraluminal gastrointestinal, as well as various non-gastrointestinal lesions. Since its introduction, EUS has undergone substantial technological advances. This multi-centric study is a retrospective analysis of a prospectively maintained database of patients who underwent EUS for the evaluation of lesions located within the gastrointestinal tract and the proximal organs. It aimed to extensively assess in dynamic the dual-center EUS experience over the course of the past 20 years. Hence, we performed a population study and an overall assessment of the EUS procedures. The performance of EUS-FNA/FNB in diagnosing pancreatic neoplasms was evaluated. We also investigated the contribution of associating contrast-enhanced ultrasound imaging (CE-EUS) with EUS-FNA/FNB for differentiating solid pancreatic lesions or cystic pancreatic lesions. A total of 2935 patients undergoing EUS between 2002-2021 were included, out of which 1880 were diagnostic EUS and 1052 EUS-FNA/FNB (80% FNA and 20% FNB). Therapeutic procedures performed included endoscopic transmural drainage of pancreatic fluid collections, celiac plexus block and neurolysis, while diagnostic EUS-like CE-EUS (20%) and real-time elastography (12%) were also conducted. Most complications occurred during the first 7 days after EUS-FNA/FNB or pseudocyst drainage. EUS and the additional tools have high technical success rates and low rates of complications. The EUS methods are safe, cost effective and indispensable for the diagnostic or therapeutic management in gastroenterological everyday practice.

Buschke-Löwenstein tumors: A series of 7 case reports.

Giant condyloma acuminatum (GCA), or Buschke-Löwenstein tumor (BLT), represents an infrequent sexually transmitted disease (STD), caused by human papillomavirus (HPV), especially genotype 6 or 11. There are numerous risk factors for HPV, such as multiple sexual partners, homosexuality, prostitution, chronic genital infections, as well as the lack of proper hygiene. HPV infection is a field infection, where large areas of cells at a tissue surface are affected by the HPV virus; therefore, once the GCA is excised, treatment of the whole affected genital area needs to be undertaken. The treatment is classified into topical therapy (podophyllin, 5-FU, radiotherapy, topical photodynamic therapy), excisional therapy (CO2 laser, cryotherapy, electrotherapy, surgery) and immunotherapy (imiquimod). However, the 'gold standard' therapy is represented by wide surgical excision without grafting, since it is considered that healing per secundam is an improved approach, because there is no risk of recurrences on fibrotic tissue. A total of 7 cases of the BLT with comorbidities and particularities are presented and it is recommended that it be taken into consideration that the incidence of the disease is increasing, emphasizing the importance of an early diagnosis, as well as an adequate treatment.

Evaluation of MMR Status and PD-L1 Expression Using Specimens Obtained by EUS-FNB in Patients with Pancreatic Ductal Adenocarcinoma (PDAC).

Deficient DNA mismatch repair status (dMMR)/high microsatellite instability have been shown to be predictive biomarkers for immune checkpoint inhibitor drugs which block the programmed death protein-1/programmed death ligand-1 (PD-1/PD-L1) interaction between tumor cells and activated T cells. The aim of this study was to determine the prevalence of MMR status and quantification of PD-L1 expression in pancreatic endoscopic ultrasound-guided fine-needle biopsy (EUS FNB) specimens. Immunochemistry (IHC) was performed on consecutive archived treatment-naïve formalin-fixed paraffin-embedded EUS-FNB samples. The specimens were considered to have PD-L1 expression if PD-L1 was expressed in ≥1% of tumor cells and a high level of expression if ≥50%. Tumors with absent nuclear staining of DNA mismatch repair proteins (MLH1, MSH2, MSH6, or PMS2) were classified as dMMR. A total of 28 treatment-naïve patients who underwent EUS-FNB and had a final diagnosis of pancreatic ductal adenocarcinoma (PDAC) were included in the study. All the EUS-FNB samples were adequate for the evaluation of MMR and PD-L1 expression. None of the patients with PDAC included in the study had a dMMR tumor. PD-L1 expression was identified in 39% of the cohort (n = 11). Expression thresholds of ≥1%, ≥10%, and ≥50% in tumor cells were identified in 11 (39%), 4 (14%), and 1 (4%) patients, respectively. The evaluation of MMR status and PD-L1 can be successfully performed on EUS-FNB pancreatic specimens. Furthermore, MMR expression failed to show utility in recognizing immunotherapy vulnerability in pancreatic cancer; the only recommendation for testing remains for patients with heritable cancers. Meanwhile high PD-L1 expression was correlated with poor prognosis. This association may identify a subgroup of patients where immune checkpoints inhibitors could provide therapeutic benefits, spotlighting the role of EUS-FNB in the field of immune-oncology.

UEG and EAES rapid guideline: Systematic review, meta-analysis, GRADE assessment and evidence-informed European recommendations on TaTME for rectal cancer.

BACKGROUND: Evidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting. OBJECTIVE: We aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology. METHODS: We developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus. RESULTS: This rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp: https://app.magicapp.org/#/guideline/4494 . CONCLUSIONS: This rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.

UEG and EAES rapid guideline: Systematic review, meta­analysis, GRADE assessment and evidence­informed European recommendations on TaTME for rectal cancer

Evidence and practice recommendations on the use of transanal total mesorectal excision (TaTME) for rectal cancer are conflicting. We aimed to summarize best evidence and develop a rapid guideline using transparent, trustworthy, and standardized methodology. We developed a rapid guideline in accordance with GRADE, G-I-N, and AGREE II standards. The steering group consisted of general surgeons, members of the EAES Research Committee/Guidelines Subcommittee with expertise and experience in guideline development, advanced medical statistics and evidence synthesis, biostatisticians, and a guideline methodologist. The guideline panel consisted of four general surgeons practicing colorectal surgery, a radiologist with expertise in rectal cancer, a radiation oncologist, a pathologist, and a patient representative. We conducted a systematic review and the results of evidence synthesis by means of meta-analyses were summarized in evidence tables. Recommendations were authored and published through an online authoring and publication platform (MAGICapp), with the guideline panel making use of an evidence-to-decision framework and a Delphi process to arrive at consensus. This rapid guideline provides a weak recommendation for the use of TaTME over laparoscopic or robotic TME for low rectal cancer when expertise is available. Furthermore, it details evidence gaps to be addressed by future research and discusses policy considerations. The guideline, with recommendations, evidence summaries, and decision aids in user-friendly formats can also be accessed in MAGICapp. This rapid guideline provides evidence-informed trustworthy recommendations on the use of TaTME for rectal cancer.

Predictive factors for the recurrence of surgically excised basal cell carcinomas: A retrospective clinical and immunopathological pilot study.

Basal cell carcinoma (BCC) is the most frequent form of skin cancer and is not a tumor with a lethal outcome if diagnosed and treated adequately. The gold standard for treatment is surgical excision with histologically safe margins. Even so, tumors excised with free margins may recur after a period of time. The identification of predictive factors for the recurrence of BCCs besides the localization, size and aggressive histology may be useful for the clinician. The aim of the present study was to identify clinical and pathological factors associated with recurrence in tumors with histologically free margins and assess via immunohistochemical staining, the expression of glioma-associated oncogene homolog 1 (GLI1), yes-associated protein (YAP), connective tissue growth factor (CTGF) and E-cadherin as they are involved in the development of BCCs, in the hope of identifying markers that are predictive for recurrence. In total, 8 recurrent BCCs and 38 non-recurrent tumors were analyzed. A Breslow index >2 (Se 100.0%, Sp 67.5%, P=0.008), Clark level >3 (Se 100.0%, Sp 47.5%, P<0.001), and excision margins both lateral (Se 87.5%, Sp 60.0%, P=0.04) and deep (Se 75.0%, Sp 82.5%, P<0.001) free from tumoral cells ≤1 mm proved to be predictive for recurrence in the present study. Recurrence may appear even after more than 3 years since the initial excision (Se 87.50%, Sp 70.0%, P<0.001). The expression levels of GLI1, YAP and E-cadherin were not different in the recurrent vs. non-recurrent BCCs. However, the low expression of CTGF may indicate a tumor with a higher aggressiveness. In conclusion, close follow-up of patients with excised BCCs at least annually is recommended and re-excision should be taken into consideration for locally advanced tumors especially if they are located in high-risk areas or those with histologically free margins <1 mm.

Acute Kidney Injury in a Patient With Cryoglobulinemia Secondary to Hepatic Mucosa-Associated Lymphoid Tissue Lymphoma: Case Report and Literature Review.

We report a patient with IgM-predominant type I cryoglobulinemia (CG), who presented to our nephrology department with acute kidney injury. He was previously diagnosed with sensorimotor neuropathy, which was in remission with maintenance dose of corticosteroids. Upon admission, there were ulcerated, necrotic cutaneous lesions localized to the inner aspect of the thighs bilaterally. Further workup revealed a mucosa-associated lymphoid tissue lymphoma, causing type I CG. Screening tests for hepatitis viruses were negative at this time. Under treatment with diuretics and high-potency glucocorticoids, the patient had an acceptable recovery of renal function and was referred to oncology for treatment. Unfortunately, three months later the patient succumbed to fulminant hepatitis, presumably secondary to reactivation of an occult hepatitis B/D co-infection. We further conducted a literature review to better describe patient characteristics and renal involvement in type I CG.

Krukenberg Tumor in Association with Ureteral Stenosis Due to Peritoneal Carcinomatosis from Pulmonary Adenocarcinoma: A Case Report.

Krukenberg tumors from pulmonary adenocarcinoma represent an extremely rare situation; only a few cases have been reported. The aim of this paper is to report an unusual such case in which almost complete dysphagia and ureteral stenosis occurred. The 62-year-old patient was initially investigated for dysphagia and weight loss. Computed tomography showed the presence of a thoracic mass compressing the esophagus in association with a few suspect pulmonary and peritoneal nodules, one of them invading the right ureter. A biopsy was performed laparoscopically on the peritoneal nodules. The right adnexa presented an atypical aspect; right adnexectomy was also found. The histopathological and immunohistochemical studies confirmed that the primitive origin was pulmonary adenocarcinoma. Although both peritoneal carcinomatosis and ovarian metastases from pulmonary adenocarcinoma represent a very uncommon situation, this pathology should not be excluded, especially in cases presenting suspect pulmonary lesions.

Complete regression of primary melanoma associated with nevi involution under BRAF inhibitors: A case report and review of the literature.

Melanoma is one of the most immunogenic tumors among human neoplasms, with numerous clinical observations of partial or completely regressed tumors. It is an aggressive tumor, with the greatest reported number of somatic mutations, BRAF mutation being the most common one. BRAF mutation is also present in a higher percentage in benign nevi. Complete regression of primary tumor and involution of nevi are, however, rare phenomenon in melanoma that can appear in relation with UV exposure, surgical trauma, target therapy in melanoma, pregnancy or host immune response to an evolving melanoma tumor. We present the case of a 58-year-old man with a completely regressed metastatic melanoma who developed a second melanoma with concomitant involution of papillomatous nevi under BRAF inhibitors treatment. In reviewed literature we have found 53 cases of completely regressed primary melanomas, neither of them reporting nevi involution. Complete regression of primary tumor can occur as an immune response to tumor progression. Nevi can involute under BRAF inhibitor therapy, but development of new malignant lesions under BRAF inhibitors is linked to BRAF wild-type. Documentation of primary tumor and dynamic changes in nevi highlight the need of a good clinical skin examination and increase the utility of baseline and sequential dermoscopy in melanoma.

Biomarkers for the early detection of relapses in metastatic colorectal cancers.

PURPOSE: To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), ß2-microglobulin (ß2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. METHODS: 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). RESULTS: Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, ß2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). CONCLUSIONS: The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.

A phase II single institution single arm prospective study with paclitaxel, ifosfamide and cisplatin (TIP) as first-line chemotherapy in high-risk germ cell tumor patients with more than ten years follow-up and retrospective correlation with ERCC1, Topoisomerase 1, 2A, p53 and HER-2 expression.

PURPOSE: One half of high-risk germ cell tumor (HRGCT) patients relapse after standard chemotherapy. This phase II study evaluated prospectively the toxicity and efficacy in first-line of the paclitaxel-ifosfamide-cisplatin combination (TIP) in HRGCT patients and tried to identify biomarkers that may allow patient-tailored treatments. METHODS: Between October 1997- September 2000, 28 chemo-naive HRGCT patients were enrolled. Patients received 4 cycles of TIP (paclitaxel 175 mg/m(2) day 1/; ifosfamide 1.2 g/m(2)/day, days 1-5; Mesna 1.2 g/m(2)/day, days 1-5; and cisplatin 20 mg/m(2)/day, days 1-5 every 3 weeks). A non-randomized comparison was made between HRGCT patients treated in the same period with first-line TIP and bleomycin-etoposide-cisplatin (BEP) (28 patients vs 20). In 17 HRGCT patients treated between 1998-2006, ERCC1, Topoisomerase 1 and 2A, p53 and HER-2 expression was retrospectively analysed by immunohistochemistry (IHC) (7 patients with TIP, 10 with BEP), and correlations were made with response to chemotherapy and survival. RESULTS: With a median follow-up of 72 months [range 48+...89+], 5-year disease free survival (DFS) was 55%, with 95% CI 36-72, and the overall survival (OS) was 63%, with 95% CI 44-78. In June 2015, with a median follow-up of 196.47 months (range 177.30-209.27) (>15 years), 12 [%?] patients were alive and disease-free, and 16 [%?] had died (12 specific causes). There was no significant correlation between the expression of ERCC1, Topoisomerase 1 and 2A, HER-2 and p53 and response to treatment. CONCLUSION: Long-term follow-up showed no difference in OS between TIP vs BEP as first-line therapy. Both regimens had mild toxicity.