Prognostic value of genotyping in hepatocellular carcinoma: A systematic review.

Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death. Advances in sequencing technology are opening genomics to widespread application for diagnosis and research. The poor prognosis of advanced HCC warrants a personalized approach. The objective was to assess the value of genotyping for risk stratification and prognostication of HCC. We performed a systematic review of manuscripts published on MEDLINE from 1 January 2009 to 1 January 2022, addressing the value of genotyping for HCC risk stratification and prognostication. Publication information for each has been collected using a standardized data extraction form. Twenty-five articles were analysed. This study showed that various genomics approaches (i.e., NGS, SNP, CASP or polymorphisms in circadian genes' association) provided predictive and prognostic information, such as disease control rate, median progression-free survival, and shorter median overall survival. Genotyping, which advances in understanding the molecular origin, could be a solution to predict prognosis or treatment response in patients with HCC.

miRNA implication in the pathogenesis and the outcome of Tunisian endemic pemphigus foliaceus.

Pemphigus foliaceus (PF) is a bullous autoimmune skin disease diagnosed through sera and skin analyses. PF severity is associated with maintained anti-Dsg1 sera levels and its prognosis is unpredictable. MicroRNA (miRNA), dynamic regulators of immune function, have been identified as potential biomarkers for some autoimmune diseases. This study aimed to assess the miRNA expression of miR-17-5p, miR-21-5p, miR-146a-5p, miR-155-5p and miR-338-3p using quantitative real-time PCR in peripheral blood mononuclear cells (PBMC) and lesional skin samples from untreated and treated PF patients (both remittent and chronic) over 3 months. Overall, miRNA expression was significantly higher in PBMC than in biopsy samples. Blood miR-21 expression was increased in untreated patients compared to controls and had a diagnostic value with an AUC of 0.78. After 6 weeks, it decreased significantly, similar to anti-Dsg1 antibodies and the PDAI score. In addition, a positive correlation was observed between cutaneous miR-21 expression and the disease activity score. Conversely, cutaneous expressions of miR-17, miR-146a and miR-155 were significantly higher in treated chronic patients compared to remittent ones. The cutaneous level of miR-155 positively correlated with pemphigus activity, making it a potential predictive marker for patients' clinical stratification with an AUC of 0.86.These findings suggest that blood miR-21 and cutaneous miR-155 can be used as supplemental markers for PF diagnosis and activity, respectively in addition to classical parameters.

[An unusual brain lesion]. / Un lésion cérébrale déroutante.

A 31-year-old man, with no past medical history, presented with headaches, sudden loss of vision, right exophtalmia, bilateral papilledema, and fever. Brain imaging noted a right basi-temporal lesion. Excision of the lesion was performed. The histological examination noted a glial tissue with acute inflammatory changes and multinucleated giant cells. Within this infiltrate there were septate and branched hyphae consistent with aspergillosis. These filaments were stained with PAS. The patient died post-operatively.

Direct comparison between Grade Group assessed on systematic and MRI/ultrasound fusion targeted biopsies correlated to the radical prostatectomy specimens in patients with prostate cancer.

OBJECTIVES: To compare the correlation of Gleason score (GS) and ISUP grade determined by prostate biopsies (PBx) and radical prostatectomy (RP) specimens according to the biopsy technique: ultrasound randomised (RBx) vs. MRI/ultrasound fusion targeted (TBx). MATERIALS AND METHODS: Between March 2013 and June 2018, we retrospectively included patients who underwent RP for prostate cancer (PCa) histopathologically proven by RBx and/or TBx. All patients had a prebiopsy MRI by a single radiologist (using PI-RADS score), then transrectal RBx (12cores, blinded to MRI lesions) and TBx (2-4 cores/target) with elastic MRI/ultrasound fusion (UroStation™, Koelis, Grenoble, France). Histological findings were compared: PBx vs. RP. RESULTS: One hundred and four patients underwent RP after RBx and/or TBx. ISUP concordance rate was better with the association RBx+TBx 49% (51/104) vs. 43.3% with TBx (P=0.07) and 43.3% with RBx (P=0.13). With RBx, 50% of the patients were downgraded (52/104) against 42.3% (44/104) with TBx (P=0.088). The association RBx+TBx significantly decreased the rate of downgrading of the ISUP score compared to the ISUP score of RP 35.6% (37/104) vs. RBx (50%, P=0.0001) and vs. TBx (42.3%, P=0.016). CONCLUSION: In half of cases, the ISUP score was underestimated in RBx compared to RP specimens. Adding TBx to RBx significantly reduced downgrading. The combination of both biopsy techniques appeared to be the best protocol to get closer to ISUP score and GS of the RP specimens. LEVEL OF EVIDENCE: C.

Small proline-rich protein 1A promotes lung adenocarcinoma progression and indicates unfavorable clinical outcomes.

Small proline-rich protein 1A (SPRR1A) plays a critical role in regulating squamous cell differentiation. SPRR1A overexpression was reported to be closely related to the progression of some tumors, such as gastric cancer and colon cancer. However, the function of SPRR1A in lung adenocarcinoma (LUAD) has not been elucidated. Here, we first examined the expression pattern of SPRR1A in LUAD tissues, which indicated that the SPRR1A expression level was significantly elevated in LUAD tissues compared with normal lung tissues. High expression of SPRR1A was closely related to larger tumor size. LUAD patients with higher SPRR1A expression had poorer overall survival and SPRR1A was identified as an independent unfavorable prognosis factor. In addition, the effects of SPRR1A on lung cancer cells were tested through cellular experiments and the result demonstrated that knockdown of SPRR1A can suppress the proliferation and invasion capacities of tumor cells, while overexpressing SPRR1A exerted opposite effects. Finally, our findings were substantiated by the data obtained from in vivo xenografts using a mice model. In conclusion, LUAD patients with higher SPRR1A expression were more predisposed to poorer clinical outcomes and unfavorable prognoses, indicating the potential role of SPRR1A as a novel clinical biomarker and therapeutic target.

Modified cancer TNM classification for localized renal cell carcinoma based on the prognostic analysis of 3748 cases from a single center.

The optimal cutoff point for evaluating the prognosis of localized renal cell carcinoma (LRCC) remains unclear. This study aimed to verify the efficacy of tumor diameter in the 2010 American Joint Committee on Cancer (AJCC) TNM staging system and contribute to the modification of TNM staging on the prognosis of this disease. A total of 3748 patients with LRCC were enrolled and grouped according to the 2010 AJCC TNM staging system. COX analysis was used to stratify the prognosis. The optimal cutoff point of the tumor diameter in the T1 and T2 prognosis was explored. There were 3330 (88.9%) patients in stage T1 and 418 (11.1%) in stage T2. The cancer-specific mortality rate was 2.7% (100/3748). The mean follow-up was 49.8 months. A tumor diameter of 7 cm can determine the prognosis of patients at stages T1 and T2; however, 4.5 cm and 11 cm as the cutoff points for T1 and T2 sub-classification of patients with LRCC might show better recognition ability than 4 cm and 10 cm, respectively. The 2010 AJCC TNM stage can predict the prognosis of LRCC in stages T1 and T2. In addition, a tumor diameter of 4.5 cm and 11 cm might be the optimal cutoff points for the sub-classification of stages T1 and T2.

[Penile carcinoma: Practical issues, from the biopsy to surgery]. / Cancer du pénis : problèmes pratiques du quotidien, de la biopsie à la chirurgie.

The management of a penile carcinoma is complex, a collaboration between radiologist, pathologist and urologist is necessary to obtain a correct staging. In this review we try to demonstrate step by step how to achieve a complete pathology report, how to manage the patient (imaging, biopsy, fresh frozen section and surgery).

Predicting the probability of malignant pathological type of kidney cancer based on mass size: A retrospective study.

BACKGROUND: Different degrees of malignancy of renal cell carcinoma (RCC) correspond to dissimilar therapies, and the prediction of malignancy of kidney cancer based on tumor size is still not fully studied. METHODS: We evaluated a total of 50,776 patients with T1-T2, N0, M0 RCC diagnosed between 2004 to 2015 based on the Surveillance, Epidemiology, and End Results database. Three and four fuhrman grade clear cell RCC, three and four fuhrman grade papillary RCC, collecting duct RCC, sarcomatoid differentiation RCC and unclassified RCC were classified as aggressive RCC. The other RCC was classified as indolent RCC. The probability of aggressive and indolent was estimated according to tumor size using a logistic regression model. Differences in survival between subgroups were assessed using the Kaplan-Meier method. RESULTS: There were 38,003 cases of indolent tumor and 12,773 cases of aggressive tumor totally. As tumor size increases, the predicted probability of an aggressive tumor also increases. Concretely, kidney cancers of 2cm, 3cm and 4cm were estimated to be 19.6%, 21.6% and 23.7% more likely to be aggressive. And for the same tumor size, clear cell RCC in men is more likely to be invasive relative to women and other kidney cancer pathology types. In addition, both the overall and tumor-specific survival are longer for indolent tumors than for aggressive tumors. CONCLUSION: We evaluated the degree of malignancy of different sizes RCC in a retrospective study. This result may be helpful in the choice of initial therapy strategies for kidney cancer patients.

[The prognostic value of preoperative neutrophil-to-lymphocyte ratio in patients with non-metastatic renal cell carcinoma]. / Signification pronostique du rapport préopératoire neutrophiles-lymphocytes dans le cancer du rein non métastatique.

INTRODUCTION: The aim of this study was to investigate the prognostic significance of the preoperative neutrophil-to-lymphocyte ratio in non-metastatic renal cell carcinoma. PATIENTS AND METHODS: We retrospectively analyzed the records of patients with non-metastatic renal cell carcinoma who were operated between 2004 and 2020 at our institution. The Kaplan-Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox's proportional hazards regression models were utilized to analyze the association between neutrophil-to-lymphocyte ratio and oncological outcomes. RESULTS: We included 202 patients. Patients with higher neutrophil-to-lymphocyte ratio had larger tumors (P=0.03), higher ASA score (P=0.014), clinical symptoms (P=0.04), sarcomatoid differentiation (P=0.03) and tumor necrosis (P=0.02). The rates of recurrence-free survival and metastasis-free survival were significantly lower in patients with a high neutrophil-to-lymphocyte ratio than in those with a low ratio (P=0.017; P=0.036 respectively). Multivariate analysis identified the neutrophil-lymphocyte ratio as an independent predictor of recurrence-free and metastasis-free survival (P=0.021; P=0.001 respectively). CONCLUSION: A higher neutrophil-to-lymphocyte ratio has been associated with a symptomatic renal cancer with a significant prognostic factor for both recurrence-free and metastasis-free survival. LEVEL OF PROOF: 3.

[Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer]. / Recommandations du Comité de cancérologie de l'Association Française d'Urologie (CC-AFU) pour la bonne pratique des instillations intravésicales de mitomycine C, d'épirubicine et de BCG pour le traitement des tumeurs de la vessie n'infiltrant pas le muscle (TVNIM).

INTRODUCTION: Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration. METHODS: We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021. RESULTS: Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days. CONCLUSION: The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

[Sclerosing rhabdomyosarcoma of the parotid gland: Unusual location of a rare mesenchymal tumor]. / Rhabdomyosarcome sclérosant de la parotide : localisation inhabituelle d'une tumeur mésenchymateuse rare.

Rhabdomyosarcoma is a malignant mesenchymal tumour with skeletal muscle differentiation. Its sclerosing variant is a rare entity, which is described in the latest WHO edition of soft tissues in association with the spindle cell subtype, with which it shares clinical, morphological and cytogenetic features. Cytogenetic advances have allowed a prognostic approach to fusiform/sclerosing cell rhabdomyosarcoma by individualizing 3 different genomic prognostic groups. The parotid location of sclerosing rhabdomyosarcoma is exceptional with only two reported cases in the literature. It can pose a diagnostic challenge because of its rarity and histological similarities with other malignancies. We report the third case of sclerosing rhabdomyosarcoma of the parotid gland, which occurred in a 7-year old girl, who had consulted for a painless swelling of the parotid region of 4 months duration. Gross examination of the partial parotidectomy demonstrated an ill-circumscribed 35×30mm, firm and white glistening tumor. Histologically, it was composed of cords and trabeculae of small round cells, with ovoid and often irregular nuclei. Mitoses were numerous. The cytoplasm was scanty and cell margins were unclear. Tumor cells were set in a prominent hyalinized matrix. Scattered rhabdomyoblastic-like tumor cells were noted. The diagnosis of sclerosing rhabdomyosarcoma was performed after the positive immunostaining with desmin, myogenin and smooth muscle actin. No cytogenetic or molecular studies were performed. The patient underwent adjuvant chemo and radiotherapy, without recurrences or distant metastases during the 8-year follow-up.

[Hobnail variant of papillary thyroid carcinoma]. / Carcinome papillaire de la thyroïde à cellules en clous de tapissier.

We report the case of a hobnail variant of papillary thyroid carcinoma revealed by a cervical mass in a 67 years-old patient. This new entity in the 2017 WHO classification is rare. Histopathological diagnosis is based on four main criteria, present in≥30% of tumor cells: a discohesive tumor, micropapillary structures and loss of cell polarity and hobnail cells. This tumor expresses markers of thyroid differentiation. The most widely described molecular alteration is BRAF V600E mutation associated with other alterations, especially p53 mutations. This reflects the agressivness of this variant. It is important to recognize the hobnail variant of papillary thyroid carcinoma and to specify it in the pathological report because of its more pejorative prognosis, with local invasion, lymph node and distant metastasis, and deacreased survival. No specific management is recommended, but a close follow up seems necessary.

[Sexual and physical abuse during childhood; what is the impact on outcome in first episode psychosis patients?] / Traumatisme sexuel ou physique dans l'enfance : quel impact sur l'évolution d'un premier épisode psychotique ?

BACKGROUND: If exposure to childhood trauma increases the risk to later develop a psychotic disorder, the impact of such events on clinical presentation and outcome after a first psychotic episode deserves attention both in order to identify specific patients' needs and to develop adapted therapeutic interventions. METHODS: Three hundred and sixty-two patients treated at TIPP-Lausanne, a specialized program for the treatment of the early phase of psychotic disorders, were assessed prospectively, from baseline and every six months until the end of the 36 months of treatment. We compared characteristics of patients exposed to childhood sexual and/or physical abuse to those of non-exposed patients. RESULTS: One hundred and eight patients (29.8 %) were exposed to at least one episode of physical and/or sexual abuse during childhood. Exposed patients displayed higher levels of positive and depressive symptoms and had lower levels of functioning throughout the entire three year follow-up period. CONCLUSIONS: The prevalence of exposure to major traumatic events during childhood in early psychosis patients is very high, and it has an important impact on symptomatic and functional outcome. However, when clinical care is adapted, such patients seem to have a great potential for recovery. This justifies the implementation of specialized early psychosis programs and additional research in order to develop specific and adapted therapeutic strategies for such patients.

[Adjuvant radiotherapy after radical cystectomy for muscle-invasive bladder cancer]. / Place de la radiothérapie adjuvante après cystectomie pour les tumeurs de vessie infiltrant le muscle.

OBJECTIVES: Locoregional relapse (LRR) after cystectomy is a common early event associated with poor prognosis. The role of radiotherapy as an adjunct to radical cystectomy is not well-defined. The aim of this critical literature review is to provide an overview of the elements in favor of adjuvant radiation for patients treated for muscle-invasive bladder cancer. MATERIAL AND METHODS: An exhaustive review of the literature was carried out using the Pubmed search tool with the following keywords: "radiotherapy" [Mesh], "adjuvant" [Mesh], "local recurrence" [Mesh], "Bladder cancer" [Mesh]. RESULTS: Several recent publications have led to the development of a nomogram that predicts the risk of LRR, in order to identify patients for which adjuvant radiotherapy could be beneficial. Several randomized trials seem to suggest a benefit of radiotherapy, in particular when combined with chemotherapy, in terms of reducing LRR, and may even improve overall survival, with good safety profile. However, there are many biases and the interest of adjuvant radiotherapy in urothelial carcinomas remains debated. CONCLUSION: Prospective trials evaluating adjuvant radiotherapy with current techniques should be undertaken.

[Neurological sequels and follow-up of the child victim of non-accidental head trauma]. / Séquelles neurologiques et suivi de l'enfant victime.

Babies who suffer non-accidental head injuries systematically show sequels, whether they are neurological, cognitive or behavioural. Some of these disorders are immediately identified, such as neurological sequels, but others, such as cognitive or behavioural disorders, are revealed much later. Regular monitoring by a neuro-paediatrician is therefore essential in order to be able to adapt the child's care as closely as possible to his or her needs according to the sequels presented.

[Management of a patient with severe limb trauma]. / La prise en charge d'un patient victime d'un traumatisme sévère de membre.

The management of a patient with limb trauma begins with a rapid assessment of the lesions in order to prioritise the treatment of life-threatening lesions, primarily haemorrhage. Severe limb trauma is defined by the presence of specific severity criteria and requires the injured person to be referred to a specialised severe trauma centre. The prognosis is twofold, both vital and functional, based on the speed as well as the quality of immediate pre-hospital care, specific hospital care and the prevention of secondary complications.

Chondroitin polymerizing factor (CHPF) contributes to malignant proliferation and migration of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the human digestive system, and has been recognized as a serious threat to public health worldwide. This study explored the role of chondroitin polymerizing factor (CHPF) in the development and metastasis of HCC. Immunohistochemistry analysis was performed to detect CHPF expression in HCC tissues and para-carcinoma tissues. qRT-PCR and Western blot analysis were used to determine the mRNA and protein expression of CHPF. MTT assays, colony formation assays, and flow cytometry were used to evaluate the cell proliferation, colony formation, and cell apoptosis, respectively. Wound-healing and Transwell assays were performed to evaluate cell migration. The results show that CHPF was not only up-regulated in HCC tissues compared with para-carcinoma tissues, but was also related with more advanced stages of HCC. Further studies revealed that CHPF knockdown significantly inhibited cell proliferation and colony formation, and induce cell apoptosis of HCC cells. Moreover, suppressing the expression of CHPF reduced the migration and invasiveness of HCC cells. In conclusion, we demonstrated that CHPF plays important roles in the development and progression of HCC, and high expression levels of HCC may be related with poorer prognosis. The results from this study may provide a potential therapeutic target for HCC treatment.

[Study of epidemiological clinical and pathological characteristics of gastric adenocarcinoma in a Moroccan population]. / Étude des caractéristiques épidémiologiques cliniques et anatomopathologiques de l'adénocarcinome gastrique chez une population Marocaine.

Stomach cancer is essentially represented by gastric adenocarcinomas. It remains one of the world's top ten causes of death with a poor prognosis. The aim of our work is to describe the epidemiological characteristics of gastric adenocarcinoma through a retrospective, observational study over a period of one year. One hundred and twenty one cases were sent to the Pathology Laboratory of the IPM-Casablanca, 98 were selected for this study. There was a male predominance. Patients aged over 50 years represented the predominant age group (62%) (P-value=0.03). The average tumor size was 5,17±2,16cm, and most patients were diagnosed in the advanced TNM stage with a rate of 72.44%. In the absence of specific symptoms, gastric adenocarcinoma is a cancer of elderly, frequently diagnosed at a late stage, minimizing the chances of any curable treatment. The adoption of a screening policy in our area would probably be beneficial. Indeed, the benefit of annual screening at least among people aged over 50 years should be assessed.

[Study of the Human Papillomavirus (HPV) prevalence in head and neck carcinomas in a French monocentric cohort of 372 patients]. / Étude de la prévalence du papillomavirus (HPV) dans les cancers des voies aéro-digestives sur une cohorte unicentrique française de 372 patients.

INTRODUCTION: French data about HPV role in head and neck carcinomas are sparse, although French patients are mostly heavy smokers. In this series of oropharyngeal et non-oropharyngeal tumors, we aimed to determine what were the clinicopathological features associated with HPV and evaluate survival of patients according to HPV status. METHODS: Three hundred and seventy-two cases of head and neck squamous cell carcinomas were reviewed and clinicopathological data were detailed. For each case, we performed a HPV PCR and an immunostaining against p16 protein (paraffin embedded tissues). RESULTS: The series contained 90% of heavy smokers and 36% of tumors were located in oropharynx. HPV DNA was detected in 46% of oropharyngeal carcinomas and 16% of non-oropharyngeal carcinomas. Genotype 16 was the most frequently detected (84%). Clinicopathological features significantly associated with HPV DNA were: oropharyngeal location; absence of tobacco smoking; nodal involvement; poorly-differentiated non-keratinizing histology; positive p16 immunostaining. HPV infection was significantly associated with a longer survival for oropharyngeal carcinomas. It was not the case for non-oropharyngeal carcinomas. CONCLUSION: In this French series with lot of heavy smokers, under half of carcinomas are HPV induced. Clinicopathological features and survival data associated with HPV infection are the same as those classically described in literature.

[French ccAFU guidelines - update 2020-2022: retroperitoneal sarcoma]. / Recommandations françaises du Comité de cancérologie de l'AFU - actualisation 2020-2022 : sarcomes rétropéritonéaux.

OBJECTIVE: - To update French urological guidelines on retroperitoneal sarcoma. MATERIALS AND METHODS: - Comprehensive Medline search between 2018 and 2020 upon diagnosis, treatment and follow-up of retroperitoneal sarcoma. Level of evidence was evaluated. RESULTS: - Chest, abdomen and pelvis CT is mandatory to evaluate any suspected retroperitoneal sarcoma. MRI sometimes helps surgical planning. Before histological confirmation through biopsy, the patient must be registered in the French sarcoma pathology reference network. The biopsy standard should be an extraperitoneal coaxial percutaneous sampling before any retroperitoneal mass therapeutic decision. Surgery is retroperitoneal sarcoma cornerstone. The main objective is grossly negative margins and can be technically challenging. Multimodal treatment risks and benefits must be discussed in multidisciplinary teams. The relapse rate is related to tumor grade and surgical margins. Reported Negative margins rate thus encourage surgery in high-volume centers. CONCLUSION: - Retroperitoneal sarcoma prognosis is poor and closely related to the quality of initial management. Centralization through dedicated sarcoma pathology network in a high-volume center is mandatory.