Radiation Therapy of Head and Neck Paragangliomas: Experience from Radiotherapy Department at the National Institute of Oncology in Rabat (Morocco)

Background and Purpose: Paragangliomas are rare tumors of the head and neck. Their management remains problematic and varies considerably depending on the center. This study reported 14 years of experience in the management of head and neck paraganglioma (HNPGls). We aimed to assess the therapeutic results of these tumors in terms of local control and overall survival. Materials and Methods: We included 16 patients followed for HNPGls and treated by radiotherapy from January 2006 to June 2018 in the National Institute of Oncology in Rabat. Results: The median age was 44.5 years (15 - 67). 13 patients were female and three male with a sex ratio of 4.3. Cervical mass was the common sign (56.3%). All patients received radiation therapy. This radiation was exclusive in 43.7% of cases or adjuvant to partial surgical resection in 56.3%. The median dose of radiotherapy was 54 Gy (46 - 60) and it was delivered by a three-dimensional conformal radiotherapy technique in 15 patients and volumetric modulated arc therapy in one. There were few acute complications such as grade I and II mucositis and dermatitis. After a median follow-up of 5.6 years (2 - 13.4), local control, defined by radiological stability or regression, was obtained in 14 patients, two patients progressed and one died. Progression-free survival rates at 5 and 7 years were 93.8% and 78.1% respectively, and overall survival at 5 and 7 years was 92.3%. Conclusions: Surgery is the first-line treatment for HNPGls. When surgery is not possible or incomplete, radiotherapy has its place in the therapeutic strategy of this rare disease for long-term local control.

Chordoma Sociodemographic, Clinical and Therapeutic Aspects in National Institute of Oncology Rabat Morocco: A Report of 9 Cases

Introduction: Chordoma is a rare bone tumor, which develops mainly from the sacrum, the base of the skull, or the spine. Surgery + radiotherapy (if necessary) is the standard treatment. Data on chordoma are scarce in this region, and thus, here we summarized 9 patients with this tumor whom we treated in this institute. Material: Nine chordoma patients were summarized, who were treated in National Institute of Oncology in Rabat between 2013 and 2018. We retrieved data from medical charts and analyzed the clinical characteristics of this tumor. Results: The average age was 49 years (range: 29 - 72), with male: female of 3:6. The manifestation-diagnosis time was 4 months (range: 2 - 14). Regarding the tumor location, lumbosacral spine;5, the skull;4. Mass was evident in 6. Signs of locoregional compressions (paraparesis or tetraparesis) were observed in 3. As for treatment, a partial tumor excision was performed in 8, with 3 patients undergoing a wide excision. Radiotherapy was done;3 patients with a dose of 46 Gy, 3 patients with 66 Gy, 1 patient with 50 Gy, and 1 patient with a 16 Gy gamma radio-knife in a single session. 4 patients with a dose of 46 Gy, 2 patients with 60 Gy, and 1 patient with a 16 Gy gamma radio-knife in a single session. Of 9, 4 patients had good locoregional control whereas 5 patients had local recurrence. Conclusion: Chordoma is a predominantly local aggressive tumor with low metastatic potential. The surgical excision remains the main prognostic factor. Advances in radiotherapy may improve local control. These data are of use in management of this tumor in Rabat (Morocco).

Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment

Inflammatory myofibroblastic tumor(IMT)is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.Diagnostic challenges arise from the diverse pathological presentation,variable symptomatology,and lack of different imaging features.However,IMT is identified by the fusion of the anaplastic lymphoma kinase(ALK)gene,which is present in approximately 70%of cases,with various fusion partners,including ran-binding protein 2(RANBP2),which allows confirmation of the diagnosis.While surgery is the preferred approach for localized tumors,the optimal long-term treatment for advanced or metastatic disease is difficult to define.Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT.Crizotinib,an ALK tyrosine kinase inhibitor(TKI),was officially approved by the US Food and Drug Administration(FDA)in 2020 to treat IMT with ALK rearrangement.However,most patients face resistance and disease progression,requiring consideration of sequential treatments.Combining radiotherapy with targeted therapy appears to be beneficial in this indication.Early promising results have also been achieved with immunotherapy,indicating potential for combined therapy approaches.However,defined recommendations are still lacking.This review analyzes the available research on IMT,including genetic disorders and their impact on the course of the disease,data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication,as well as summarizing general knowledge about prognostic and predictive factors,also in terms of resistance to systemic therapy.

Quality assessment of surgery for colorectal cancer:Where do we stand?

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past decade.It has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units today.Total mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical societies.However,there are still ongoing discrepancies in outcomes largely based on surgeon performance.This is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume centers.Defining markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional level.With the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(i.e.arterial stumps)measured on postoperative scans as part of the routine cancer follow-up.There is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

Low-grade myofibrosarcoma of the maxillary sinus:Two case reports

BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is an extremely rare tumor characterized by the malignant proliferation of myofibroblasts.LGMS most commonly develops in adults,predominantly in males,in the head and neck region,oral cavity,especially on the tongue,mandible,and larynx.This article presents 2 cases of LGMS localized to the maxillary sinus and provides an overview of the available literature.CASE SUMMARY Two patients with LGMS located in the maxillary sinus underwent surgery at the Department of Head and Neck Surgery.Case 1:A 46-year-old patient was admitted to the clinic with suspected LGMS recurrence in the right maxillary sinus(rT4aN0M0),with symptoms of pain in the suborbital area,watering of the right eye,thick discharge from the right nostril,and augmented facial asymmetry.After open biopsy-confirmed LGMS,the patient underwent expanded maxillectomy of the right side with immediate palate reconstruction using a microvascular skin flap harvested surgically from the middle arm.The patient qualified for adjuvant radiotherapy for the postoperative bed,with an additional margin.Currently,the patient is under 1.5 years of observation with no evidence of disease.Case 2:A 45-year-old man was admitted to our clinic with facial asymmetry,strabismus,exophthalmos,and visual impairment in the right eye.Six months earlier,the patient had undergone partial jaw resection at another hospital for fibromatosis.A contrast-enhanced computed tomography scan revealed a tumor mass in the postoperative log after an earlier procedure.An open biopsy confirmed lowgrade fibrosarcoma(rT4aN0M0).The patient qualified for an extended total right maxillectomy with orbital excision and right hemimandibulectomy with immediate microvascular reconstruction using an anterolateral thigh flap.The patient subsequently underwent adjuvant radiotherapy to the postoperative area.After 9 months,recurrence occurred in the right mandibular arch below the irradiated area.The lesion infiltrated the base of the skull,which warranted the withdrawal of radiotherapy and salvage surgery.The patient qualified for palliative chemotherapy with a regimen of doxorubicin+dacarbazine+cyclophosphamide and palliative radiotherapy for bone metastases.The patient died 26 months after surgical treatment.The cases have been assessed and compared with cases in the literature.CONCLUSION No specific diagnostic criteria or treatment strategies have been developed for LGMS.The treatment used for LGMS is the same as that used for sinonasal cancer radical tumor excision;adjuvant radiotherapy or chemoradiotherapy should also be considered.They have low malignant potential but are highly invasive,tend to recur,and metastasize to distant sites.Patients should undergo regular follow-up examinations to detect recurrence or metastasis at an early stage.Patients should be treated and observed at the highest referral centers.

Role of immunotherapy in gastric cancer with liver metastasis

Gastric cancer continues to be a significant issue for public health,marked by its widespread occurrence and high mortality rates,even as the incidence of the disease shows a declining trend.The liver is the primary site for metastatic spread,with the peritoneum,lungs,and bones also being common targets.With the advent of biologic treatments and the introduction of immunotherapy for patients with metastatic conditions,the options to treat metastatic gastric cancer have expanded.This diversified therapeutic approach is designed to enhance patient quality of life and prolong survival,showcasing the progress in treatment modalities for individuals with gastric cancer and liver metastases.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer

Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival rates.In metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to 8.Several studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, respectively.In general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight cancer.These pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.

Systematic review of health-related quality of life after esophagectomy for esophageal cancer

This study is aimed to assess the long-term healthrelated quality of life （HRQL） of patients after esophagectomy for esophageal cancer in comparison with established norms, and to evaluate changes in HRQL during the different stages of follow-up after esophageal resection. A systematic review was performed by searching medical databases （Medline, Embase and the Cochrane Library） for potentially relevant studies that appeared between January 1975 and March 2011. Studies were included if they addressed the question of HRQL after esophageal resection for esophageal cancer. Two researchers independently performed the study selection, data extraction and analysis processes. Twenty-one observational studies were included with a total of 1282 （12-355） patients. Five studies were performed with short form-36 （SF-36） and 16 with European Organization for Research and Treatment of Cancer （EORTC） QLQ c30 （14 of them also utilized the disease-specific OESI8 or its previous version OES24）.The analysis of long-term generic HRQL with SF-36 showed pooled scores for physical, role and social function after esophagectomy similar to United States norms, but lower pooled scores for physical function, vitality and general health perception. The analysis of HRQL conducted using the Global EORTC C30 global scale during a 6-mo follow-up showed that global scale and physical function were better at the baseline. The symptom scales indicated worsened fatigue, dyspnea and diarrhea 6 mo after esophagectomy. In contrast, however, emotional function had significantly improved after 6 mo. In conclusion, short- and long-term HRQL is deeply affected after esophagectomy for cancer. The impairment of physical function may be a long-term consequence of esophagectomy involving either the respiratory system or the alimentary tract. The short- and long-term improvement in the emotional function of patients who have undergone successful operations may be attributed to the impression that they have survived a near-death experience.

Induction of apoptosis of human gastric carcinoma SGC-7901 cell line by 5,7-dihydroxy-8-nitrochrysin in vitro

AIM： To investigate the effect of 5, 7-dihydroxy-8- nitrochrysin （NOChR） on apoptosis of human gastric carcinoma SGC-7901 cell line.METHODS： SGC-7901 cells were cultured in vitro and the inhibitory effect of NOChR on proliferation of SGC-7901 cells was measured by using an Ml-r assay. NOChR-induced apoptosis rate of SGC-7901 cells was detected using flow cytometry （FCM） with PI staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of NOChR on the proxisome proliferator-activated receptor-γ （PPARγ）, Bcl-2 and Bax protein expression of SGC-7901 cells was analyzed by Western blot.RESULTS： MIF assay showed that NOChR markedly inhibited proliferation of SGC-7901 cells in a dose- dependent manner, and when ICso was 4.14 μmol/L, the potency of NOChR was 10 times than that of lead compound, chrysin （ChR, IC50 was 40.56 μmol/L）, and was similar to 5-fluorouracil （5-FU, IC50 was 4.51 μmol/L）. FCM with propidium iodide （PI） staining demonstrated that the apoptosis rates of SGC-7901 cells treated with 1.25, 5.00 and 20.00 μmol/L NOChR for 48 h were 9.8% 4- 0.2%, 36.8% 4- 1.9% and 45.5% 4- 3.5%, respectively, and were significantly higher when treated with 5.00 and 20.00 μmol/L NOChR than that with 20.00 μmol/L ChR （12.9% 4- 1.5%）. DNA agarose gel electrophoresis showed that treatment of SGC-7901 cells with 20.00 μmol/L NOChR for 48 h resulted in typical DNA ladder bands of DNA of SGC-7901 cells, which could be eliminated by treating with 10.00 μmol/L GW9662, a blocker of PPARy. Western blot analysis revealed that after 24 h of treatment with 20.00 μmol/L NOChR, PPARgamma and Bax protein expression of SGC-7901 cells increased but Bcl-2 expression decreased; however, pre-incubation with 10.00 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 20.00 μmol/L NOChR on Bax and Bcl-2 protein expression of SGC-7901 cells. CONCLUSION： NOChR induces apoptosis of SGO7901 cell lines by activating PPARy and decreasing ratio of Bcl-2 to Bax.

A prospective analysis of factors that influence weight loss in patients undergoing radiotherapy

Malnutrition occurs frequently in patients with cancer.Indeed,a variety of nutritional and tumorrelated factors must be taken into account in these patients.Recognizing this relationship,we aimed to prospectively evaluate the risk factors that influence weight loss in patients undergoing radiotherapy with oral nutritional supplementation and dietetic counseling.Weight loss of 74 patients during radiotherapy and 1 month after treatment was analyzed.Parameters such as age,gender,tumor location,tumor stage,Eastern Cooperative Oncology Group performance status(ECOG PS)score,and the use of chemotherapy were analyzed to evaluate their influence on weight loss.All patients underwent oral nutritional supplementation and dietetic counseling.Forty-six(65.7%)patients lost weight,with a mean weight loss of(4.73±3.91)kg,during radiotherapy.At 1 month after treatment,45(66.2%)patients lost weight,presenting a mean weight loss of(4.96±4.04)kg,corresponding to a(6.84±5.24)%net reduction from their baseline weight.Head and neck cancer patients had a mean weight loss of(3.25±5.30)kg,whereas the remaining patients had a mean weight loss of(0.64±2.39)kg(P=0.028)during radiotherapy.In the multivariate analysis,the head and neck tumor location(P=0.005),use of chemotherapy(P=0.011),and ECOG PS score of 2-3(P=0.026)were considered independent risk factors.Nutritional status and parameters,such as tumor location(especially the head and neck),the use of chemotherapy,and the ECOG PS score,should be evaluated before radiotherapy because these factors can influence weight loss during radiotherapy and 1 month after treatment.

Characteristics of common solid liver lesions and recommendations for diagnostic workup

Due to the widespread clinical use of imaging modalities such as ultrasonography,computed tomography and magnetic resonance imaging (MRI),previously unsuspected liver masses are increasingly being found in asymptomatic patients.This review discusses the various characteristics of the most common solid liver lesions and recommends a practical approach for diagnostic workup.Likely diagnoses include hepatocellular carcinoma (the most likely;a solid liver lesion in a cirrhotic liver) and hemangioma (generally presenting as a mass in a non-cirrhotic liver).Focal nodular hyperplasia and hepatic adenoma should be ruled out in young women.In 70% of cases,MRI with gadolinium differentiates between these lesions.Fine needle core biopsy or aspiration,or both,might be required in doubtful cases.If uncertainty persists as to the nature of the lesion,surgical resection is recommended.If the patient is known to have a primary malignancy and the lesion was found at tumor staging or follow up,histology is required only when the nature of the liver lesion is doubtful.

Advances in immunotherapy for treatment of lung cancer

Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.

Comethylation of p16 and MGMT genes in colorectal carcinoma:Correlation with clinicopathological features and prognostic value

AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.

Genetic changes of p53,K-ras,and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

AIM： To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS： We examined 42 cases of gallbladder carcinoma： 22 Japanese and 20 Hungarian cases, p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of flve-microsatellite markers （BAT-25, BAT-26, D2S123, DSS346, and D17S250）. RESULTS： Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases （11/22 vs 6/18, P = 0.348）. Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant （0/11 vs 2/6,P = 0.110）. K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 （42.1%） ]apanese cases were MSI-high （presence of novel peaks in more than one of the five loci analyzed）, whereas only 1 of 15 （6.7%） Hungarian cases was MSI-high （P = 0.047）. CONCLUSION： It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Role of MGMT as biomarker in colorectal cancer

O6-methylguanine DNA methyltransferase(MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients.

Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

Survival rates for metastatic lung cancer, including non-small cell lung cancer （NSCLC） and small cell lung cancer （SCLC）, are poor with S-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-- with its capacity for memory, exquisite specificity and central and universal role in human biology--immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences

Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.

Gastric cancer in a Caucasian population: Role of pepsinogen C genetic variants

AIM： To study the role of an insertion/deletion polymorphism in the pepsinogen C （PGC） gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions. METHODS： The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified： Allele 1 （510 bp）, Allele 2 （480 bp）, Allele 3/4 （450/460 bp）, Allele 5 （400 bp） and Allele 6 （310 bp）. RESULTS： Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion （OR = 0.34; P 〈 0.001）, non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia （OR = 0.28; P 〈 0.001） or invasive GC （OR = 0.39; P = 0.004）. CONCLUSION： Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.

De novo autoimmune hepatitis in liver transplant: State-of-the-art review

In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necroinflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of nonorgan specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management.