Mutational Profiles of Cutaneous Squamous Cell Carcinomas with Different Patterns of Clinical Aggression from Head and Neck Regions.

Cutaneous squamous cell carcinoma is a prevalent malignancy with a rising incidence and a notably high mutational load. Exploring the genetic nuances of cSCC and investigating molecular approaches stands as a potential avenue for improving outcomes in high-risk patients. This retrospective case-control study involved two cohorts, one of 14 patients (the "discovery cohort") and the other of 12 patients (the "validation cohort"), with cSCC located in the head/neck anatomical region and diagnosed at the pT2 stage. Overall, cases developed early local relapses of the disease, whereas controls never relapsed during the entire follow-up period. A next-generation sequencing (NGS) approach conducted on histological samples revealed that TP53 and CDKN2A were the most frequently mutated genes in our series. No specific mutations were identified as potential prognostic or therapeutic targets. Controls exhibited a tendency toward a higher mutational rate compared to cases. It is possible that an increased number of mutations could prompt the cSCC to expose more antigens, becoming more immunogenic and facilitating recognition by the immune system. This could enhance and sustain the immunological response, potentially preventing future recurrences.

Multidisciplinary Management of Cutaneous Squamous Cell Carcinoma of the Scalp: An Algorithm for Reconstruction and Treatment.

Background: Scalp-associated cutaneous squamous cell carcinoma (cSCC) presents formidable treatment challenges, especially when it leads to full-thickness defects involving bone. Aggressive or recurring cases often demand a multidisciplinary approach. Leveraging our surgical experience and a literature review, we introduce a therapeutic algorithm to guide the selection of reconstruction methods, particularly for locally advanced lesions, furthermore showing the synergy between surgery and other therapies for comprehensive, multidisciplinary disease management. Methods: Our algorithm stems from a retrospective analysis of 202 patients undergoing scalp cSCC resection and reconstruction over a 7-year period, encompassing 243 malignancies. After rigorous risk assessment and documentation of surgical procedures, reconstruction methods were therefore related to malignancy extent, depth, and individual clinical status. Results: The documented reconstructions included 76 primary closures, 115 skin grafts, 7 dermal substitute reconstructions, 33 local flaps, 1 locoregional flap, and 1 microsurgical free flap. Patients unsuitable for surgery received radiotherapy or immunotherapy after histological confirmation. Precise analysis of tumor characteristics in terms of infiltration extent and depth guided the selection of appropriate reconstruction and treatment strategies Combining these insights with an extensive literature review enabled us to formulate our algorithm for managing scalp cSCCs. Conclusions: Effectively addressing scalp cSCC, especially in locally advanced or recurrent cases, demands a systematic approach integrating surgery, radiotherapy, and immunotherapy. Our multidisciplinary team's decision-making algorithm improved patient outcomes by offering a broader spectrum of therapeutic options that can synergistically achieve optimal results.

Squamous cell carcinoma of the scalp: a combination of different therapeutic strategies.

A case study of a 71-year-old man with a giant cutaneous squamous cell carcinoma of the scalp and calvaria is presented, where a combination of surgical excision, reconstruction with a latissimus dorsi muscular free flap, immunotherapy, and radiotherapy were used to control the disease for two years without recurrence.

[Management of small cell lung cancer patient in the regions of Lazio, Umbria and Sardinia.] / Gestione del paziente con microcitoma nelle regioni Lazio, Umbria e Sardegna.

Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no significant therapeutic advances over platinum and etoposide chemotherapy in the last 20 years until the introduction of immunotherapy. In 2020 atezolizumab, an immune checkpoint inhibitor against PD-L1 was approved in Italy in combination with carboplatin and etoposide for the first-line treatment of patients with extensive stage disease (ES-SCLC), becoming the new standard treatment. On May 20, 2021, a virtual meeting, directed by profs. Federico Cappuzzo and Emilio Bria, was held in which 14 clinicians from different oncology centers in Lazio, Umbria and Sardinia discussed the issues of ES-SCLC patients treatment, after the advent of immunotherapy. The aim of the meeting was to share their clinical experience and to provide a series of practical indications that can support clinicians in the management of ES-SCLC patients in first-line with chemo-immunotherapy.

Impact of tissue type and content of neoplastic cells of samples on the quality of epidermal growth factor receptor mutation analysis among patients with lung adenocarcinoma.

Assessment of the epidermal growth factor receptor (EGFR) mutational status has become crucial in recent years in the molecular classification of patients with lung cancer. The impact of the type and quantity of malignant cells of the neoplastic specimen on the quality of mutation analysis remains to be elucidated, and only empirical and sporadic data are available. The aim of the present study was to investigate the impact of tissue type and content of neoplastic cells in the specimen on the quality of EGFR mutation analysis among patients with lung adenocarcinoma. A total of 515 patients with histologically-confirmed disease were included in the present study. Formalin-fixed paraffin embedded tissue samples were used for the mutation analysis and the content of the neoplastic cells was evaluated using light microscopy. Genomic DNA was isolated using a standard protocol. The coding sequences and splice junctions of exons 18, 19 and 21 in the EGFR gene were then screened for mutations by direct automated sequencing. The mean age of the patients examined was 64.9 years and 357 (69.3%) were male. A total of 429 tissue samples (83.3%) were obtained by biopsy and the remaining samples were obtained by surgery. A total of 456 samples (88.5%) were observed from primary lung adenocarcinomas, while 59 (11.5%) were from metastatic lesions. EGFR mutations occurred in 59 cases (11.5%); exon 18 mutations were detected in one case (1.7%), whereas exon 19 and 21 mutations were detected in 30 (51%) and 28 (47.3%) cases, respectively. EGFR mutations were more frequent in females and patients that had never smoked. The distribution of the mutations among primary and metastatic tissues exhibited no significant differences in the proportions of EGFR mutations detected. However, a statistically significant difference in the number of mutations detected was found between samples with at least 50% of neoplastic cells (450 cases-57 mutations; 12.7%) and those with <50% of neoplastic cells (65 cases-2 mutations; 3.1%).

Retentive strength and sealing ability of new self-adhesive resin cements in fiber post luting.

OBJECTIVE: To assess by means of "thin-slice" push-out test, light and scanning electron microscopy, the interfacial strength and sealing ability of new self-adhesive resin cements when used to lute fiber posts into endodontically treated teeth. METHODS: RelyX Unicem 2 Automix (3M ESPE, RUA), Maxcem Elite (Kerr, ME) and seT (SDI, S) were utilized in combination with RelyX Fiber Posts (3M ESPE). In each group 5 posted roots were used for push-out testing and 5 were processed for observations of interfacial morphology and nanoleakage under light microscope and scanning electron microscope. Five to six slices were obtained from each posted root. The statistical significance of the influence on post push-out strength of luting agent, dowel space level, and between-factor interaction was assessed using Two-Way Analysis of Variance (ANOVA) and Tukey test as needed. Differences in nanoleakage scores were also statistically evaluated (Kruskal-Wallis ANOVA) (p<0.05). RESULTS: Luting agent was a significant factor for post push-out strength. The interfacial strength achieved by RUA (9.3±2.6MPa) was significantly higher than that of ME (6.7±2.7MPa) and that of S (5.4±3.1MPa), which were comparable to each other. Dowel space level and between factor interaction were not statistically significant. Statistically comparable interfacial nanoleakage was observed in all the groups. SIGNIFICANCE: The three new self-adhesive resin cements exhibited similar sealing properties, although the post retentive ability was superior with RUA.

Fulminant liver failure in a patient affected by polycystic liver disease and liver metastases from breast carcinoma.

BACKGROUND: Polycystic liver disease (PLD) is a rare, congenital, benign condition characterized by the presence of multiple bile-duct-derived epithelial cysts in the liver parenchyma. The disease is usually asymptomatic, but cyst growth can result in complications such as ascites, esophageal varices, jaundice and hepatic failure. The exact mechanism leading to cyst growth is unclear, but estrogenic stimulation and paracrine action of vascular endothelial growth factor (VEGF) are thought to play a role in the growth of cyst epithelium. CASE REPORT: We report a case of acute liver failure in a young woman with PLD and liver metastases from breast carcinoma. RESULTS: No data are available in the literature about metastatic liver involvement in PLD patients affected by breast cancer. The prognosis of patients with liver metastases is generally poor but fulminant liver failure is a very rare occurrence. Estrogen stimulation seems to be a risk factor for breast cancer and severe PLD. In the reported case, the presence of either the cysts or the metastatic lesions may have resulted in more extensive liver damage. CONCLUSIONS: The adoption of drugs selected in relation to their hepatic toxicity together with careful monitoring of liver function is warranted in the management of breast cancer patients affected by PLD, in order to reduce the risk of liver failure.

A case report of Sheehan's syndrome with acute onset, hyponatremia and severe anemia.

Sheehan's syndrome is a well-known cause of panhypopituitarism secondary to pituitary apoplexy, that generally occurs after an intra- or postpartum bleeding episode characterized by severe hypertension or hemorrhagic shock. The diagnosis can be difficult and is often formulated after some years from the syndrome occurrence. We report the case of a woman with an early diagnosis of early-onset Sheehan's syndrome associated with severe hyponatremia following dystocic childbirth complicated by postpartum hemorrhage.

Routine second trimester ultrasound screening for prenatal detection of fetal malformations in Sassari University Hospital, Italy: 23 years of experience in 42,256 pregnancies.

OBJECTIVE: To establish, for a determined period of time, the effectiveness of a program of ultrasound screening in detecting fetal malformations in prenatal time. To assess the sensitivity, the specificity, the positive and the negative predictive value of the ultrasound screening. To examine the trend of such indexes of diagnostic accuracy in a long time period. STUDY DESIGN: The patients admitted to the study had effected at least one ultrasound examination within the second trimester of pregnancy (< or =23 gestational weeks). The examined pregnant women were 42,256 and the period of reference ranged from January 1981 to December 2004. All patients delivered in Gynecologic and Obstetric Clinic of Sassari University, Sassari, Italy. RESULTS: In the considered period were reported 1050/42,256 (2.48%) cases of fetal malformations, of which 974 single and 76 multiple malformations. The cases of malformations diagnosed in prenatal period were 578/1050 (55.05%), of which 65/578 (11.24%) multiple anomalies. The overall sensitivity was 55.05% (95% confidence interval: 52-58%), with a variability from the 32.95% (cardiovascular system) to 81.05% (central nervous system) in relationship to the typology of the examined apparatus. The overall specificity was 99.88% (95% confidence interval: 98-99.9%), the predictive positive value 91.89% (95% confidence interval: 89-93%) and the negative predictive value 98.87% (95% confidence interval: 95-99%). CONCLUSION: The sensitivity of the ultrasound screening undoubtedly appeared to be satisfactory. We believe that, for the examination of some apparatuses, as for the cardiovascular apparatus, with the extension of the standard examination (four-chamber view) to further plans of scanning, sensitivity could subsequently be improved.

Intrapancreatic rupture of a splenic artery aneurysm during pregnancy - a rare case report with fetal and maternal survival.

Rupture of a splenic artery aneurysm (SAA) during pregnancy is a rare and severe condition. A 35-year-old woman at 34 weeks' gestation came to our observation for acute abdominal pain. After being diagnosed with intra-pancreatic SAA rupture, she was delivered of a live fetus by cesarean section. This is a rare case with both fetal and maternal survival.

Effect of pre-cure temperature on the bonding potential of self-etch and self-adhesive resin cements.

OBJECTIVES: To assess whether the pre-cure temperature of resin cements significantly influenced the bonding potential to dentin. METHODS: Forty extracted molars were randomly divided into 8 groups (n=5): Groups (1-4) RelyX Unicem (RU, 3 M ESPE) and Groups (5-8) Panavia F 2.0 (PF, Kuraray Co.), at pre-cure temperatures of 4, 24, 37, and 60 degrees C, respectively. Cements were used in dual-cure mode for luting composite overlays (Paradigm MZ100, 3 M ESPE) to dentin. Microtensile bond strength testing and scanning electron microscope (SEM) observations of cement-dentin interfaces were performed. RESULTS: Group 4 had to be eliminated as RU at 60 degrees C underwent such an accelerated curing that was already set at the time of dispensing. The bond strengths (MPa) measured at refrigerator, room, and intraoral temperature were, respectively: RU 5.4+/-1.7, 11.4+/-6.1, 10.6+/-4.2; PF 7.4+/-3.7, 13.9+/-6.2, 12+/-5.2. The statistical analysis revealed that both luting agents developed a significantly weaker adhesion when used at refrigerator temperature (p<0.05). No statistically significant differences in bond strength were recorded when either cement was used at 24 or 37 degrees C (p>0.05). Pre-heating of PF to 60 degrees C resulted in a significant increase in bond strength (20.7+/-9.4 MPa; p<0.05). SEM observations disclosed an enhanced potential of PF to form a hybrid layer as the temperature increased over 4 degrees C. RU exhibited a less porous and more homogeneous layer at intraoral than at refrigerated temperature. SIGNIFICANCE: It is advisable to let refrigerator-stored resin cements warm up to at least room temperature prior to clinical use. Pre-heating to 60 degrees C enhances the bonding potential of PF.

Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse.

Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients present with metastatic EC and most patients with localized EC will have local recurrence or develop metastases, despite potentially curative local therapy. The most common sites of distant recurrence are represented by lung, liver and bone while brain and breast metastases are rare. Usually patients with advanced disease are not treated aggressively and their median survival is six months. We report a woman patient who developed breast and brain metastases after curative surgery. We treated her with a highly aggressive chemotherapeutic and surgical combination resulting in a complete remission of the disease even after 11-year follow-up. We think that in super selected patients with more than one metastasis, when functional status is good and metastases are technically resectable, a surgical excision may be considered as a salvage option and chemotherapy should be delivered to allow a systemic control.

Small cell lung cancer in a young patient with osteopetrosis.

BACKGROUND: Osteopetrosis or Albers-Schönberg's disease is a heterogeneous group of rare hereditary troubles of the bone characterized by bone sclerosis due to an alteration of the bone reabsorption mediated by osteoclasts. The defect in the osteoclastic activity is responsible for complete or partial medullary cavities occlusion, with consequent reduced hemopoiesis, and for the excessive fragility of the affected bone segments. CASE REPORT: We reported the case of a young man of 31 years affected by osteopetrosis in which a small cell lung cancer developed. RESULTS: Small cell lung cancer is a particularly rare neoplasm in the young, and even though it is highly sensitive to chemotherapeutic treatment its prognosis remains poor. The greatest clinical problem connected with chemotherapeutic treatment of patients affected by osteopetrosis is the variability of the reduction of their bone marrow reserve, which could expose them to an excessive hematological toxicity caused by the therapy. CONCLUSIONS: The adoption of suitable prophylactic measures, such as the use of growth factors and drugs selected in relation to their toxicity or given in reduced doses, should be appropriately considered in these subjects.

Effect of amalgam fillings on the mercury concentration in human amniotic fluid.

BACKGROUND: Methyl mercury (MeHg) and metallic Hg are well known as neurotoxic agents. Dental amalgam contributes significantly to elemental Hg vapour exposure in the general population. There is little information about Hg concentration in human amniotic fluid (AF) of pregnant women and its potential toxic effect on the fetuses. OBJECTIVE: Primary to assess the relationship between the presence of detectable mercury (Hg) concentration in human AF, number and surface areas of amalgam fillings of pregnant women; secondary to analyse their obstetric history and perinatal complications. METHODS: Seventy-two pregnant women took part in this prospective study. One dentist recorded the dental status, presence, number and surface areas of amalgam fillings. Total Hg concentration in AF was determined in digested samples using automatic cold vapour atomic absorption equipment. The detection limit of Hg in AF, determined from blank readings, was 0.08 ng/ml. To estimate the dependence of the explanatory variables (such as number and surface areas of amalgam fillings, fish consumption, presence of liver or neurological diseases and smoking habits) on mercury concentration several linear regression models were built up. Stepwise logistic regression procedures were running on total sample and on patients with at least one amalgam filling (Positive Filling group = PF). Principal component analysis (PCA) provided two factors, which explained for more the 60% of the variance among the variables. RESULTS: The overall mean Hg concentration in AF among all patients was 0.37+/-0.49 ng/ml. Nineteen (26.4%) women had a Hg concentration <0.08 ng/ml (Hg negative group). In 53 (73.6%) patients, with a concentration > or = 0.08 ng/ml (Hg positive group), the mean value of Hg was 0.49+/-0.52 ng/ml. The average number of amalgam fillings was 2.26 +/- 3.19 in the Hg negative group and 5.32+/-3.03 in the Hg positive group (ANOVA one-way p=0.04). A dependence of mercury concentration on number of amalgam fillings (p=0.03), surface area of the amalgam fillings (p=0.04) and fish consumption (p=0.04) was observed but not at a significant level. In stepwise logistic procedure the number of amalgam fillings gave a contribution to the model (p=0.04), although null value was included in the confidence intervals. We observed no statistically significant differences (chi2 test) among the patients with a Hg concentration <0.08 ng/ml (n=19) and those with a concentration > or = 0.08 (n=53) with regard to obstetric history and perinatal complications. CONCLUSIONS: Number and surface areas of amalgam fillings influenced positively Hg concentration in AF but not at a significant level. Moreover Hg levels detected in AF were low and no adverse outcomes were observed through pregnancies and in the newborns.