Investigation of Clinically Significant Molecular Aberrations in Patients with Prostate Cancer: Implications for Personalized Treatment, Prognosis and Genetic Testing.

The data on tumor molecular profiling of European patients with prostate cancer is limited. Our aim was to evaluate the prevalence and prognostic and predictive values of gene alterations in unselected patients with prostate cancer. The presence of gene alterations was assessed in patients with histologically confirmed prostate cancer using the ForeSENTIA® Prostate panel (Medicover Genetics), targeting 36 clinically relevant genes and microsatellite instability testing. The primary endpoint was the prevalence of gene alterations in homologous recombination repair (HRR) genes. Overall, 196 patients with prostate cancer were evaluated (median age 72.2 years, metastatic disease in 141 (71.9%) patients). Gene alterations were identified in 120 (61%) patients, while alteration in HRR genes were identified in 34 (17.3%) patients. The most commonly mutated HRR genes were ATM (17, 8.7%), BRCA2 (9, 4.6%) and BRCA1 (4, 2%). The presence of HRR gene alterations was not associated with advanced stage (p = 0.21), age at diagnosis (p = 0.28), Gleason score (p = 0.17) or overall survival (HR 0.72; 95% CI: 0.41-1.26; p = 0.251). We identified clinically relevant somatic gene alterations in European patients with prostate cancer. These molecular alterations have prognostic significance and therapeutic implications and/or may trigger genetic testing in selected patients. In the era of precision medicine, prospective research on the predictive role of these alterations for innovative treatments or their combinations is warranted.

Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group.

BACKGROUND: Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. METHODS: We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). RESULTS: Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40-5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25-0.92, p = 0.026). Both parameters maintained their independent prognostic significance. CONCLUSIONS: ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. CLINICAL TRIAL IDENTIFIER: NCT04805099.

Challenges in sarcoidosis and sarcoid-like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case.

Sarcoidosis and sarcoid-like reactions (SLRs) may develop in association with various malignancies, as well as in association to certain oncologic drugs, including immune checkpoint inhibitors (ICIs). We aimed to perform a narrative review with regard to the development of ICIs-associated sarcoidosis or SLRs, and to discuss the corresponding diagnostic and therapeutic challenges raised in this scenario. Apropos of a melanoma patient developing SLRs while treated with ipilimumab and nivolumab, we searched for clinically evident, ICIs-associated sarcoidosis or SLRs in the English literature. We recorded the oncologic characteristics, including type of malignancy and type of ICI, the phenotypic characteristics of sarcoidosis/SLRs, as well as the impact on immunotherapy. Including our patient, we identified 80 ICIs-associated sarcoidosis or SLRs cases. Both sexes were equally affected (40 F/40 M) and the most common malignancy was melanoma (65/80, 81.3%). Concerning the oncologic treatment, there was a predilection for pembrolizumab (23/80, 28.7%), followed by the ipilimumab/nivolumab combination (21/80, 26.3%), ipilimumab (18/80, 22.5%), nivolumab (16/80, 20.0%). Although in the majority of the cases (52/80, 65.0%) there was no need for systemic prednisolone for the management of sarcoidosis, a significant proportion of patients finally discontinued ICIs treatment (44/80, 55.0%). Phenotypically, sarcoidosis and SLRs highly imitate oncologic progression posing diagnostic difficulties. A therapeutic dilemma is also raised when there is a need for systemic prednisolone, since the latter may jeopardize the therapeutic efficacy of immunotherapy. Sarcoidosis and SLRs, though rare, can present in oncologic patients treated with ICIs. Clinicians should be aware of this possibility and the related diagnostic and therapeutic challenges they have to face in this scenario.

A Collective Intelligence Platform to Support Older Cancer Survivors: Towards the Definition of LifeChamps System and Big Data Reference Architecture.

Within the most recent years, most of the cancer patients are older age, which implies the necessity to a better understanding of aging and cancer connection. This work presents the LifeChamps solution built on top of cutting-edge Big Data architecture and HPC infrastructure concepts. An innovative architecture was envisioned supported by the Big Data Value Reference Model and answering the system requirements from high to low level and from logical to physical perspective, following the "4+1 architectural model".

Synchronous colorectal adenocarcinoma and gastrointestinal stromal tumor in Meckel's diverticulum; an unusual association.

BACKGROUND: Coexistence of gastrointestinal stromal tumor with synchronous or metachronous colorectal cancer represents a phenomenon with increasing number of relative reports in the last 5 years. Synchronous occurence of GISTs with other gastrointestinal tumors of different histogenesis presents a special interest. We herein report a case of GIST in Meckel's diverticulum synchronous with colorectal adenocarcinoma. CASE PRESENTATION: A 69 year old man, presented with abdominal distension and anal bleeding on defecation. Colonoscopy revealed colorectal cancer and a low anterior resection was performed, during which a tumor in Meckel's diverticulum was discovered. Histologic examination revealed GIST in Meckel's diverticulum and a rectosigmoid adenocarcinoma. CONCLUSION: Whenever GIST is encountered, the surgeon should be alert to recognize a possible coexistent tumor with different histological origin. Correct diagnosis of synchronous tumors of different origin is the cornerstone of treatment.

Proposal for classification of the circumaortic renal collar's morphology.

In the present study, we propose a classification of the different forms of the circumaortic renal collar based on the findings of 319 patients and on a literature review. The patients underwent a CT angiography scan of the abdomen for various diagnostic reasons. The different forms in which the circumaortic renal collar may appear were categorized. The renal collar was observed in eight of the 319 (2.5%) patients. The classification we propose is the following: Type I, one left renal vein splitting into two branches, a preaortic and a retroaortic, draining into the inferior vena cava; Type II, two different left renal veins, the one preaortic and the other retroaortic, draining into the inferior vena cava; and Type III, either anastomoses between the preaortic and retroaortic vein, being multiple or not, or multiple preaortic or retroaortic renal veins without anastomoses. Although the circumaortic renal collar is usually asymptomatic, the knowledge of this variation is useful, mainly before abdominal aortic aneurysm surgery and renal transplantation. Failure to recognize the collar's retroaortic component may lead to hemorrhage and death during retroperitoneal surgery. We believe that our classification contributes to recognize the circumaortic renal collar's morphology both preoperatively and intraoperatively.

Treating EGFR-Mutated Oncogene-Addicted Advanced Non-Small-Cell Lung Cancer in the Era of Economic Crisis in Greece: Challenges and Opportunities.

PURPOSE: Because of the profound financial crisis that commenced in Greece in 2010, severe cuts in health care spending and other restriction measures led to significant delays in the reimbursement of novel antineoplastic agents. In 2011, the Hellenic Society of Medical Oncology initiated a program of early access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of patients with advanced, EGFR-mutant non-small-cell lung cancer (NSCLC). We evaluated treatment patterns and clinical outcomes in patients with EGFR-mutant or wild-type disease treated at a large center in Greece throughout the period of financial crisis. PATIENTS AND METHODS: From 2011 through 2015, 252 patients with newly diagnosed advanced NSCLC were treated at the Department of Medical Oncology of the Papageorgiou Hospital, a tertiary cancer center in northern Greece. We retrospectively reviewed patient medical records to obtain clinicopathologic characteristics, EGFR mutation status, and follow-up data. The primary end point was time to treatment failure. RESULTS: Of the 198 evaluable patients, 25 (12%) had EGFR mutations. All patients with EGFR mutations except one received treatment with an EGFR tyrosine kinase inhibitor. Median times to treatment failure for patients with EGFR-mutant and wild-type disease were 15.8 and 7.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.35 to 0.95; P = .031). There was no difference in overall survival between the two groups ( P = .293). No deviation from treatment guidelines or discontinuation of treatment regimens occurred because of logistic reasons or drug shortages. CONCLUSION: Despite restrictions in the reimbursement policy and accompanying controls in the use of high-cost medicines, the national program enabled treatment of patients with EGFR-mutant NSCLC according to established guidelines. Therefore, the clinical outcomes of such patients treated in Greece during the economic crisis were in accordance with international standards.

Three-headed reversed palmaris longus muscle and its clinical significance.

The palmaris longus muscle originates from the medial epicondyle of the humerus. After a short distance, almost in the middle of the forearm, the muscle belly is toggled into a broad tendon which is inserted into the flexor retinaculum and the palmar aponeurosis. After dissection of the left forearm of a 73-year-old female cadaver we found a reversed palmaris longus muscle. This means that the palmaris longus muscle was tendinous in its upper part and muscular in its lower part. Additionally, the muscle belly was triple, thus our finding was characterized as "three-headed reversed palmaris longus muscle". Rarely is the palmaris longus muscle double, whereas the three-headed reversed palmaris longus muscle is mentioned only once in the literature as a surgical finding, in a patient who suffered from edema and pain in the wrist [Yildiz, M., Sener, M., Aynaci, O., 2000. Three-headed reversed palmaris longus muscle: a case report and review of the literature. Surg. Radiol. Anat. 22, 217-219]. The overuse of the reversed palmaris longus muscle can lead to the muscle's local hypertrophy. According to the literature a reversed palmaris longus muscle may cause a compartment syndrome with pain and edema in the wrist's area, the carpal tunnel syndrome and Guyon's syndrome. The described variation is also useful to the hand surgeon, as the palmaris longus muscle is an anatomical landmark for operations at this area.

Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers.

BACKGROUND: Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with operable TNBC treated with adjuvant anthracycline-based chemotherapy. MATERIALS AND METHODS: We evaluated the prognostic impact of EGFR gene status by fluorescent in situ hybridization (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53 protein expression by immunohistochemistry (IHC), in 352 centrally-assessed tumors from an equal number of TNBC patients. RESULTS: Approximately 53.5% of the tumors expressed EGFR, 59.3% p53 and 35.9% both EGFR and p53 proteins; 4.1% showed EGFR gene amplification and 4.4% carried EGFR mutations. The latter were located outside the druggable kinase domain region and presented at low frequencies. Amplification and mutations overlapped only in one case of glycogen-rich carcinoma. EGFR and CEN7 copies were higher in tumors from older patients (p=0.002 and p=0.003, respectively). Patients with amplified tumors (n=11) had excellent prognosis (0 relapses and deaths). Upon multivariate analysis, high EGFR copies conferred significantly favorable disease-free survival (HR=0.57, 95% CI 0.36-0.90, Wald's p=0.017) and high CEN7 copies favorable overall survival (HR=0.49, 95% CI=0.29-0.83, Wald's p=0.008). Patients with EGFR-/p53+ and EGFR+/p53- tumors had significantly higher risk for relapse than those with EGFR-/p53- and EGFR+/p53+ tumors (HR=1.73, 95% CI=1.12-2.67, Wald's p=0.013). CONCLUSION: EGFR gene amplification and mutations are rare in TNBC, the latter of no apparent clinical relevance. Surrogate markers of EGFR-related chromosomal aberrations and combined EGFR/p53 IHC phenotypes appear to be associated with favorable prognosis in patients with operable TNBC receiving conventional adjuvant chemotherapy.

Total laparoscopic distal pancreatectomy for a benign appearing tumor: a case report.

INTRODUCTION: Therapeutic laparoscopy of the pancreas is still described as experimental surgery by many surgeons. Many issues remain to be clarified in determining the future of this new method. CASE PRESENTATION: The objective of the present study was to present a case of a patient who underwent totally laparoscopic distal pancreatectomy for a benign appearing tumor in the tail of the pancreas and to critically discuss the treatment of the pancreatic remnant and the need to perform splenectomy with or without ligation of the splenic vessels. CONCLUSION: Laparoscopic distal pancreatectomy is usually performed en-bloc along with resection of the spleen, for technical reasons, making the operation short and easy. However, it should only be performed in centers with expertise in both pancreatic surgery and advanced laparoscopy. Furthermore, the use of linear stapler to cut the pancreas (4.5-mm staples) seems to prevent fistula formation and ischemia of the pancreatic stump.

Barber's hair sinus in a female hairdresser: uncommon manifestation of an occupational disease: a case report.

BACKGROUND: Barber's disease is an acquired occupational disease produced by short customers' hairs that penetrate the interdigital spaces of the hands. The lesion has been reported to occur mostly on the hands of male hairdressers. The purpose of this article is to report a rare case of a female hairdresser who developed a pilonidal sinus in the interdigital web of her non-dominant hand and review the relevant literature. CASE PRESENTATION: A 29 year-old Greek female hairdresser underwent surgical excision of the pilonidal sinus and curettage. She was not hospitalised, while prompt resolution of the condition and prevention of recurrence was achieved. CONCLUSION: Pilonidal sinus of the interdigital spaces of the hand is a rare and preventable acquired occupational disease. The personal hygiene with thorough removal of any hairs that have penetrated the epidermis during the working day could prevent the formation of the disease. Surgical excision, curettage and primary healing seem to be a safe method of treatment.

Adrenalectomy for solitary adrenal metastasis from colorectal cancer: A case report.

BACKGROUND: Patients with adrenal metastasis from various primary tumours are regarded as cases of diffuse systemic spread and considered unsuitable for surgical resection. We herein report an operable case of heterochronic adrenal metastasis from colorectal carcinoma in a 63-year-old woman. CASE PRESENTATION: Sixteen months after low anterior resection for the primary tumour, left lower pneumonectomy was performed for a solitary lung metastasis. Four months later a right adrenal metastasis was detected by magnetic resonance imaging (MRI), as sole evidence of metastatic disease. A right adrenalectomy was performed. The histopathological examination revealed adenocarcinoma compatible with the colorectal carcinoma resected 19 months earlier. The patient received adjuvant chemotherapy after each operation and is alive and free of disease 21 months after the adrenalectomy. CONCLUSION: The possibility of adrenal metastasis should be considered in the follow-up of patients after primary surgery for colorectal cancer, even though other sites are the main metastatic sites. Although the prognosis of adrenal metastasis from colorectal cancer is poor, we suggest that patients with solitary adrenal metastasis may benefit from complete removal of it.