ABSTRACT
AIM: to determin the recurrence rate of benign recto-colonic polyps in a 5-year interval, and compare the development rate of intrapolypoid carcinomatous lesions in polypectomized versus nonpolypectomized subjects. MATERIAL AND METHOD: a group of 77 patients diagnosed with recto-colonic polypoid lesions during the period 2014-2019 underwent colonoscopy at the time of study initiation and then annually during a five-year interval. Results: The recurrence rate of polyps increased annually from 5 to 12.5%; the highest rate was noted in the last two years. The five-year cumulative risk of neoplastic lesions was 73% in patients without polypectomy and 20% among those with endoscopic resection (p 0.05). Comparing the recurrence rate of benign lesions (60%) in patients without neoplastic findings with the recurrence rate of adenomas in patients with benign lesions (40%), a higher risk of recurrence was found in the first category, and seemed to be influenced by the personal history of pre-existing adenomatous lesions. CONCLUSION: an increased risk of colorectal polyps recurrence was reported during five year follow up; moreover, during the first three years an increased risk of malignant transformation was observed among cases in which endoscopic resection was not feasible when compared to those in which complete excision was feasible.
Subject(s)
Colonic Polyps , Colorectal Neoplasms , Humans , Colonic Polyps/surgery , Colonic Polyps/diagnosis , Colonic Polyps/pathology , Treatment Outcome , Colonoscopy , Colon/pathology , Rectum/pathology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathologyABSTRACT
Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively.
Subject(s)
Hyponatremia , Ovarian Neoplasms , Humans , Female , Hyponatremia/complications , Hyponatremia/diagnosis , Prognosis , Treatment Outcome , Retrospective Studies , Ovarian Neoplasms/complications , Ovarian Neoplasms/surgery , Sodium , Postoperative Complications/etiologyABSTRACT
Intrahepatic cholangiocarcinomas represent rare and aggressive malignancies developing from the second order bile ducts to the smaller biliary branches. The aim of this narrative review is to discuss about the main diagnostic and therapeutic challenges in order to help medical and surgical oncologists to gain familiarity in regard to this subject. Articles discussing about epidemiology, histology, diagnostic, perioperative management and surgery which were published from January 2000 to September 2023 included in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar databases were reviewed. Articles reviewed in the current paper came to demonstrate that the main problem in such cases is related to the fact that most cases remain asymptomatic for a long period of time and therefore are diagnosed in advanced stages of the disease when curative procedures are feasible after performing extended visceral sacrifice or even worse, are no longer possible; however, the most efficient therapeutic strategy in order to improve the long term outcomes remains radical surgery. In this respect, attention was focused on improving the accuracy of the diagnostic tools and on identifying non-surgical therapeutic options which might increase the chances of achieving complete resection. Intrahepatic cholangiocarcinoma represent rare aggressive tumors with poor outcomes especially if radical surgery is not feasible.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Humans , Bile Ducts, Intrahepatic/surgery , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/epidemiology , Bile Duct Neoplasms/surgery , Treatment Outcome , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/epidemiology , Cholangiocarcinoma/surgeryABSTRACT
INTRODUCTION: This article presents a series of patients on which the transcervical approach was used to close a left-sided postpneumonectomy fistula. MATERIALS AND METHODS: The series comprises nine patients with a left pneumonectomy performed for a tuberculosis-related suppurative disease in five cases and for lung cancer in the remaining four. This procedure can be performed under certain conditions, the most important one being the length of the bronchial stump, which should be at least 1 cm, ideally 1.5 cm. The transcervical stump closure was successfully achieved in all patients, having been more technically demanding in cancer cases with previous lymphadenectomy. The postpneumonectomy infected cavity was subsequently treated. RESULTS: The follow-up continued for at least 1 year; one individual from the cancer patients group died from an uncontrolled sepsis during the postoperative period, another one died 17 months later from metastatic cancer and two of them are alive, with no signs of neoplastic or infectious relapse 15 and 37 months, respectively, after the cervical procedure. One patient from the suppurative disease group had a relapse of the fistula 2 months after surgery, requiring additional surgical procedures to deal with this issue; all the other patients are alive, with no signs of recurrence. CONCLUSIONS: The transcervical approach is a very suitable maneuver in selected patients with a bronchial stump at least 1 cm long, ideally 1.5 cm.
Subject(s)
Bronchial Fistula/surgery , Lung Neoplasms/surgery , Mediastinoscopy , Pneumonectomy/adverse effects , Tuberculosis, Pulmonary/surgery , Adult , Aged , Bronchial Fistula/diagnostic imaging , Bronchial Fistula/etiology , Bronchial Fistula/mortality , Female , Humans , Lung Neoplasms/mortality , Male , Mediastinoscopy/adverse effects , Mediastinoscopy/mortality , Middle Aged , Pneumonectomy/mortality , Risk Factors , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/mortality , Young AdultABSTRACT
Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Subject(s)
Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Smoking/adverse effects , Case-Control Studies , Gene-Environment Interaction , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study , Genotype , Humans , Polymorphism, Single Nucleotide , White PeopleABSTRACT
Gastric pull-up is the most commonly used procedure for esophageal replacement in both malignant and benign conditions. In our article we compare the differences in mortality and morbidity between thoracic anastomosis and cervical anastomosis during gastric pull-up. The study group comprised of 126 patients - 58 patients (56%) with cervical anastomosis and 68 patients (64%) with thoracic anastomosis. The overall mortality in the study group was 5.55% (7 patients), while the overall morbidity was higher at 28%. There were no significant differences between the two subgroups regarding mortality and morbidity, although the rate of anastomotic leakage was higher in the cervical subgroup (13.8% vs 1.5%). We recommend performing thoracic anastomosis during gastric pull-up whenever the location of the lesion allows it, since the procedure is safe, relatively easy to master and it shortens operating time by excluding the cervical approach.
Subject(s)
Anastomosis, Surgical , Esophagectomy , Esophagoplasty/methods , Stomach/transplantation , Aged , Anastomosis, Surgical/methods , Esophagectomy/methods , Female , Humans , Male , Middle Aged , Plastic Surgery Procedures/methods , Treatment OutcomeABSTRACT
Introduction: Postintubation tracheoesophageal fistula is a severe complication occurring under certain conditions in patients that require prolonged mechanical ventilation. MATERIAL AND METHODS: This article focuses on a sample of 11 patients with postintubation tracheoesophageal fistula, operated in our department between 2005 and 2015. The anterior approach with tracheal resection was performed in 10 of these patients, while an atypical surgical technique was preferred in a case involving a large-sized fistula. Three of these patients were subject to surgery while still on the ventilator, in order to help weaning them from mechanical ventilation. Two patients were operated following a relapse of the fistula, after attempts of closing it in other surgical units. Results: Two patients (of those who were still on mechanical ventilation) died from intubation-related complications that persisted after tracheal resection (anastomotic dehiscence with mediastinitis and tracheoarterial fistula in the brachiocephalic arterial trunk). The nine remaining patients improved, with their airways restored and having regained normal deglutition. Conclusions: The surgical approach of this pathology is successful in surgical units that are specialised in tracheal and oesophageal surgery. Adequately timing the surgery is crucial for a good outcome.
Subject(s)
Esophagus/surgery , Intubation, Intratracheal/adverse effects , Trachea/surgery , Tracheoesophageal Fistula/etiology , Tracheoesophageal Fistula/surgery , Adult , Anastomosis, Surgical/adverse effects , Esophagoplasty/methods , Female , Humans , Male , Middle Aged , Postoperative Complications , Prognosis , Plastic Surgery Procedures/methods , Recurrence , Retrospective Studies , Survival Rate , Tracheoesophageal Fistula/diagnosis , Tracheoesophageal Fistula/mortality , Treatment OutcomeABSTRACT
Background: Gallbladder cancer (GBC) is a rare entity with a poor prognosis, usually discovered late due to nonspecific symptoms; therefore, over the last years, attention has been focused on identifying the risk factors for developing this malignancy in order to provide an early diagnosis, as well as new prognostic factors in order to modulate the long-term evolution of such cases. The aim of this review is to discuss both major risk factors and prognostic factors in GBC for a better understanding and integration of relevant and currently available information. Methods: A literature search was performed using Cochrane Library, PubMed, Google Scholar, Elsevier, and Web of Science; studies published after the year of 2000, in English, were reviewed. Results: Over time, risk factors associated with the development of GBC have been identified, which outline the profile of patients with this disease. The most important prognostic factors in GBC remain TNM staging, safety margin, and R0 status, along with perineural invasion and lymphovascular invasion. Both the technique and experience of the surgeons and a pathological examination that ensures final staging are particularly important and increase the chances of survival of the patients. Conclusions: improvements in surgical techniques and pathological analyses might provide better and more consistent guidance for medical staff in the management of patients with GBC.
ABSTRACT
Ovarian cancer remains one of the most lethal gynaecological malignancies affecting women worldwide; therefore, attention has been focused on identifying new prognostic factors which might help the clinician to select cases who could benefit most from surgery versus cases in which neoadjuvant systemic therapy followed by interval debulking surgery should be performed. The aim of the current paper is to identify whether preoperative inflammation could serve as a prognostic factor for advanced-stage ovarian cancer. Material and methods: The data of 57 patients who underwent to surgery for advanced-stage ovarian cancer between 2014 and 2020 at the Cantacuzino Clinical Hospital were retrospectively reviewed. The receiver operating characteristic curve was used to determine the optimal cut-off value of different inflammatory markers for the overall survival analysis. The analysed parameters were the preoperative level of CA125, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII). Results: Baseline CA125 > 780 µ/mL, NLR ≥ 2.7, MLR > 0.25, PLR > 200 and a systemic immune inflammation index (SII, defined as platelet × neutrophil-lymphocyte ratio) ≥ 84,1000 were associated with significantly worse disease-free and overall survival in a univariate analysis. In a multivariate analysis, MLR and SII were significantly associated with higher values of overall survival (p < 0.0001 and p = 0.0124); meanwhile, preoperative values of CA125, PLR and MLR were not associated with the overall survival values (p = 0.5612, p = 0.6137 and p = 0.1982, respectively). In conclusion, patients presenting higher levels of MLR and SII preoperatively are expected to have a poorer outcome even if complete debulking surgery is performed and should be instead considered candidates for neoadjuvant systemic therapy followed by interval surgery.
ABSTRACT
Stress urinary incontinence (SUI) is a significant global health issue that particularly affects females, leads to notable societal and economic challenges and significantly affects the quality of life. This study focuses on the comparative analysis of two established surgical interventions, tension-free vaginal tape (TVT) and transobturator tape (TOT), at a single center and applied to 455 women suffering from SUI, with a mean follow-up period of 102 ± 30 months for TVT and 80.4 ± 13 months for TOT. Our findings indicate that, in comparison to TVT, the TOT procedure demonstrates fewer early and late post-operative complications in patient outcomes (1.41% vs. 17.64% and; 5.66% vs. 12.74%, both respectively). However, the TVT procedure shows a modestly favorable outcome in the risk of recurrence of SUI, compared to TOT (0% vs. 3.7%); the TOT procedure has also proven to be more effective in alleviating of urgency symptoms, although not at a statistically significant level (p = 0.072). Univariable and multivariable analysis of factors that predict late complications showed that only obesity can predict a worse outcome [OR]: 1.125 CI 95%: 1.105-1.533, p = 0.037), when adjustments are made for symptoms presented before surgery and procedure type. While both methods are safe and effective, the choice between them should be based on the specific characteristics of each case.
ABSTRACT
Acquired benign trachea-oesophageal fistula is a rare benign pathological entity with varying aetiologies that most often occurs post-intubation. This case report presents the case of a female patient, 31 years old, admitted to the emergency room with sepsis syndrome following bilateral aspiration pneumonia caused by a large trachea-oesophageal fistula. The fistula was the result of intra-tracheal migration of an oesophageal stent placed for post lye ingestion stenosis. Esophageal diversion and partial resection with oesophageal patch to repair the tracheal defect, under general anaesthesia with ventilation using rigid bronchoscopy and high frequency jet ventilation (HFJV), followed at a later date by esophageal replacement with colic graft were the procedures performed with a view to curing the patient. In conclusion, complex cases always require a tailored approach. It is important to note that HFJV may be applied for a longer period of time and the oesophagus can be used as patch for the posterior tracheal wall in selected cases. Staged surgery is also an option when the patients' poor health status does not permit major surgery.
ABSTRACT
In this study, we investigated the outcomes of laparoscopic approaches for adrenal tumor resection in 67 patients from a single center with a median age of 51 (range 40-79). Predominantly comprising women, the majority of patients were overweight or obese. Adrenal tumors larger than 6 cm were mostly treated using the laparoscopic transperitoneal method (p < 0.001). Our results revealed that patients subjected to the retroperitoneal approach exhibited quicker recovery, as evidenced by faster resumption of oral intake and ambulation, along with reduced intraoperative blood loss and shorter hospitalization (p-value < 0.05). In contrast, patients subjected to the transperitoneal approach experienced minimal complications, though not statistically significant, despite the technique's intricacy and slower recovery. These findings emphasize the significance of tailoring the surgical approach to individual patient characteristics, with particular emphasis on the tumor size. The choice between the retroperitoneal and transperitoneal methods should be informed by patient-specific attributes to optimize surgical outcomes. This study underscores the need for a comprehensive evaluation of factors such as tumor characteristics and postoperative recovery when determining the most suitable laparoscopic approach for adrenal tumor resection. Ultimately, the pursuit of individualized treatment strategies will contribute to improved patient outcomes in adrenal tumor surgery.
ABSTRACT
BACKGROUND/AIM: Thymic lipofibroadenoma is a benign growth of unknown etiology extremely rarely described in the literature, morphologically resembling lipofibroadenoma of the breast. The diagnosis is usually a postoperative surprise and is made by the anatomopathologist. Surgical resection is curative. CASE REPORT: The presented case is the first reported in a woman, to date. The patient was successfully submitted to surgery and complete resection of the giant intrathoracic tumor was performed. The histopathological and immunohistochemical studies came to demonstrated the presence of a thymic lipofibroadenoma while the postoperative outcomes were favorable. CONCLUSION: In cases presenting large intrathoracic tumors complete resection is able to provide a significant improvement of the general condition of the patient, as well as a chance for cure.
Subject(s)
Respiratory Tract Neoplasms , Thymoma , Thymus Neoplasms , Female , Humans , Postoperative Period , Thymus Neoplasms/diagnosis , Thymus Neoplasms/surgeryABSTRACT
BACKGROUND/AIM: Association between cervical cancer and uterine prolapse represents a scarce eventuality. This is a case series of 11 patients diagnosed with different stages of cervical cancer in association with uterine prolapse. PATIENTS AND METHODS: Between 2014 and 2020, 11 patients were diagnosed with cervical cancer on prolapsed uterine cervix. RESULTS: The mean age of patients at the time of uterine cervix diagnosis was 68 years. In six cases, the first intent treatment was surgery, while in the remaining five cases it consisted of radio-chemotherapy, followed by radical surgery. The perioperative and postoperative outcomes were compared to those reported in a similar series of patients diagnosed in similar stages of the disease, but in the absence of uterine prolapse, no significant differences being encountered. CONCLUSION: Although it represents an unusual situation, malignant transformation of the uterine cervix might be encountered even in cases presenting uterine prolapse. In such cases, the therapeutic strategy should be tailored according to the stage of the disease.
Subject(s)
Uterine Cervical Neoplasms , Uterine Prolapse , Aged , Female , Humans , Hysterectomy , Uterine Cervical Neoplasms/surgery , Uterine Prolapse/complications , Uterine Prolapse/diagnosis , Uterine Prolapse/surgeryABSTRACT
BACKGROUND/AIM: Gastroenteropancreatic neuro-endocrine carcinomas represent poorly differentiated neoplasms with a high capacity of spreading inducing the development of distant metastases. In such cases debulking surgery seems to offer a good chance for survival especially in well and moderately differentiated lesions. The aim of this study was to report the case of a 48-year-old patient submitted to surgery for moderately differentiated neuroendocrine gastric carcinoma with distant metastases. CASE REPORT: The patient was initially investigated for hematemesis and weight loss and was diagnosed with a lesser curvature gastric tumor in association with liver and peritoneal metastases. Due to the extent of the disease, the patient was initially submitted to neoadjuvant chemotherapy followed by surgery with radical intent. At the time of surgery subtotal gastrectomy en bloc with total omentectomy, peritonectomy, cholecystectomy and atypical liver resection were performed. Moreover, the two ovaries presented large tumoral masses so total hysterectomy with bilateral adnexectomy was performed. The histopathological studies confirmed the presence of a moderately differentiated neuroendocrine gastric carcinoma with negative resection margins. CONCLUSION: Multiple visceral resections might be needed in order to maximize the debulking effort in metastatic gastric neuroendocrine carcinomas.
Subject(s)
Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/surgery , Cytoreduction Surgical Procedures , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Humans , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Treatment OutcomeABSTRACT
BACKGROUND/AIM: The presence of "omental cake" has been considered since long as a negative prognostic factor in patients diagnosed with advanced-stage ovarian cancer. The aim of this paper was to study the impact of "omental cake" presence on the perioperative outcomes in advanced-stage ovarian cancer. PATIENTS AND METHODS: Between 2015 and 2020, 85 patients were submitted to surgery for advanced-stage ovarian cancer. RESULTS: Among cases diagnosed with "omental cake" the rate of complete cytoreduction was significantly diminished when compared to cases in which this entity was not revealed. In the meantime, the presence of omental cake among cases in which complete debulking was achievable was significantly associated with a higher number of digestive resections when compared to the other cases submitted to surgery and in which tumoral transformation of the omentum was encountered. CONCLUSION: The presence of "omental cake" is associated with a higher rate of incomplete resections. However, in cases in which complete debulking was achieved, the presence of omental cake was associated with a significantly higher number of digestive tract resections.
Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Female , Humans , Neoplasm Staging , Omentum/pathology , Omentum/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Retrospective StudiesABSTRACT
The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
ABSTRACT
Recent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (ORâ¯=â¯1.50; 95% CI: 1.31-1.72; pâ¯=â¯7.75â¯×â¯10-9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (pâ¯=â¯.03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.
Subject(s)
Adenocarcinoma/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lung Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Aged , Carcinoma, Non-Small-Cell Lung/pathology , DNA Methylation/genetics , Female , Gene Expression Regulation, Neoplastic , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.
Subject(s)
Chromosome Mapping , Genetic Predisposition to Disease/genetics , Lung Neoplasms/genetics , Major Histocompatibility Complex/genetics , Asian People/genetics , Female , Gene Frequency , Genetic Predisposition to Disease/ethnology , Genotype , HLA Antigens/genetics , Humans , Lung Neoplasms/ethnology , Male , Middle Aged , Peptides/genetics , Polymorphism, Single Nucleotide , White People/geneticsABSTRACT
AIM: Doege-Potter syndrome is a rare condition consisting of a mesenchymal tumor, either benign or malignant, accompanied by severe hypoglycemia. The syndrome was first described independently by two American physicians, Karl Walter Doege (1867-1932) and Roy Pilling Potter (1879-1968), in 1930, but it was not before 1988 that it was associated with non-islet cell tumor production of insulin growth factor (IGF) that induces hypoglycemia as a paraneoplastic syndrome. CASE PRESENTATION: We present the case of a 61-year-old woman with severe hypoglycemia that induced seizures. On the general check-up, a massive tumor occupying the lower part of left hemi-thorax was discovered. Initially, corticosteroids, glucose i.v. and high carbohydrate diet managed to prevent the severe blood glucose drop. Surgery exposed a massive well-defined pleural tumor. After surgical removal, blood glucose stabilized. Histological examination confirmed the fibrous tumor that proved to be malignant on immunochemistry. DISCUSSION: The authors discuss other cases reported in the literature of this rare condition and its pathogenic mechanisms, the presented case being the first reported in Romania. CONCLUSIONS: The clinician should be aware of the possible existence of a pleural tumor in a patient presenting an unexplained hypoglycemia because the surgical removal of the tumor can solve the clinical manifestations.