A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.

LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.

Mutations in five canonical Ras pathway genes (NF1, NRAS, KRAS, PTPN11 and CBL) are detected in nearly 90% of patients with juvenile myelomonocytic leukemia (JMML), a frequently fatal malignant neoplasm of early childhood. In this report, we describe seven patients diagnosed with SH2B3-mutated JMML, including five patients who were found to have initiating, loss of function mutations in the gene. SH2B3 encodes the adaptor protein LNK, a negative regulator of normal hematopoiesis upstream of the Ras pathway. These mutations were identified to be germline, somatic or a combination of both. Loss of function of LNK, which has been observed in other myeloid malignancies, results in abnormal proliferation of hematopoietic cells due to cytokine hypersensitivity and activation of the JAK/STAT signaling pathway. In vitro studies of induced pluripotent stem cell-derived JMML-like hematopoietic progenitor cells (HPCs) also demonstrated sensitivity of SH2B3- mutated HPCs to JAK inhibition. Lastly, we describe two patients with JMML and SH2B3 mutations who were treated with the JAK1/2 inhibitor ruxolitinib. This report expands the spectrum of initiating mutations in JMML and raises the possibility of targeting the JAK/STAT pathway in patients with SH2B3 mutations.

Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.

Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia.

BACKGROUND: Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT. PROCEDURE: Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing. RESULTS: Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy. CONCLUSIONS: Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.

Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia-ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic-ischemic encephalopathy with potential clinical application.

FoxO4 interacts with the sterol regulatory factor SREBP2 and the hypoxia inducible factor HIF2α at the CYP51 promoter.

The late steps of cholesterol biosynthesis are oxygen demanding, requiring eleven oxygen molecules per synthesized cholesterol molecule. A key enzymatic reaction, which occurs at the top of the Bloch and Kandutsch-Russell pathways, is the demethylation of lanosterol and dihydrolanosterol (DHL). This reaction is catalyzed by lanosterol 14α demethylase (CYP51) and requires three oxygen molecules. Thus, it is the first step in the distal pathway to be susceptible to oxygen deprivation. Having previously identified that the forkhead transcription factor 4 (FoxO4) represses CYP51 expression, we aimed to characterize its role at the CYP51 promoter. Hypoxia-treated 3T3L1 cells showed decreased cholesterol biosynthesis, accumulation of lanosterol/DHL, and stimulation of FoxO4 expression and its cytoplasmic translocation to the nucleus. Transfection assays with a CYP51 promoter reporter gene revealed that FoxO4 and sterol regulatory element binding protein (SREBP)2 exert a stimulatory effect, whereas FoxO4 and the hypoxia inducible factor (HIF)2α repress CYP51 promoter activity. Electromobility shift, chromatin immunoprecipitation, pull-down, and coimmunoprecipitation assays show that FoxO4 interacts with SREBP2 and HIF2α to modulate CYP51 promoter activity. We also show an inverse correlation between FoxO4 and CYP51 in adipose tissue of ob/ob mice and mouse fetal cortical neurons exposed to hypoxia. Overall, these studies demonstrate a role for FoxO4 in the regulation of CYP51 expression.

Parietal mass caused by a fish bone: case report.

It is a great challenge to distinguish the parietal inflammation, centered on the foreign body that pierced the digestive tract and remained in the wall before surgery, because of its atypical clinical nature. Ingestion of foreign bodies is not uncommon. Fish bones are particularly notorious culprits; however, most will pass through the gastrointestinal tract uneventfully. Patients and Methods: The authors report a case of a patient who presented with periumbilical abdominal pain and a computed tomography (CT) scan that revealed the presence of periumbilical fat infiltration on a foreign body admitted on the Department of Digestive Cancer Surgery and Liver Transplantation, Casablanca, Morocco. An exploratory laparotomy revealed a parietal mass centered by a fish bone. Results: Accidental ingestion of foreign bodies is common in clinical practice. However, perforation of the intestine by a foreign body is less common because the majority of foreign bodies pass without incident into the feces and only 1% of them (the sharpest and most elongated objects) will perforate the gastrointestinal tract, usually at the level of the ileum.CT, especially multidetector CT, is considered the method of choice for preoperative diagnoses of ingested foreign bodies and their complications due to its high-quality multiplanar capabilities and high resolution.Foreign body ingestion usually goes unnoticed, but the complications of this incident can be severe. Conclusion: This case report highlights the fact that intestinal perforation caused by an ingested foreign body is a difficult diagnosis that should always be suspected in an attack of abdominal pain. Frequently, the clinical diagnosis is difficult, and recourse to imaging is sometimes necessary. Most of the time, the treatment is only surgical.

Quantitative analysis of MGMT promoter methylation in glioblastoma suggests nonlinear prognostic effect.

Background: Epigenetic inhibition of the O6-methylguanine-DNA-methyltransferase (MGMT) gene has emerged as a clinically relevant prognostic marker in glioblastoma (GBM). Methylation of the MGMT promoter has been shown to increase chemotherapy efficacy. While traditionally reported as a binary marker, recent methodological advancements have led to quantitative methods of measuring promoter methylation, providing clearer insight into its functional relationship with survival. Methods: A CLIA assay and bisulfite sequencing was utilized to develop a quantitative, 17-point, MGMT promoter methylation index. GBMs of 240 newly diagnosed patients were sequenced and risk for mortality was assessed. Nonlinearities were captured by fitting splines to Cox proportional hazard models and plotting smoothed residuals. Covariates included age, Karnofsky performance status, IDH1 mutation, and extent of resection. Results: Median follow-up time and progression-free survival were 16 and 9 months, respectively. A total of 176 subjects experienced death. A one-unit increase in promoter CpG methylation resulted in a 4% reduction in hazard (95% CI 0.93-0.99, P < .005). GBM patients with low levels of promoter methylation (1-6 CpG sites) fared markedly worse (HR = 1.62, 95% CI 1.03-2.54, P < .036) than individuals who were unmethylated. Subjects with medium levels of promoter methylation (7-12 sites) had the greatest reduction in hazard (HR = 0.48, 95% CI 0.29-0.80, P < .004), followed by individuals in the highest promoter methylation tertile (HR = 0.62, 95% CI 0.40-0.97, P < .035). Conclusions: Our findings suggest that the relationship between the extent of MGMT promoter methylation and survival in GBM may be nonlinear. These findings challenge the current understanding of MGMT and underlines the clinical importance of determining its prognostic utility. Potential limitations include censoring, sample size, and extraneous mutations.

Epidemiology, incidence and treatment of rectal cancer in young women case serie about 11 cases (case series).

Introduction: Rectal cancer constitutes, by its frequency and its gravity, a real concern of the public health in the world, it represents the eighth most frequent cancer. Its incidence is increasing in young people and in particular in women, in whom it remains a rare disease known for its poor prognosis.The objective of our work is to highlight the epidemiological characteristics of rectal cancer in patients under 40 years of age, determine its incidence and outline the different therapeutic means. Materials and methods: Our work is a retrospective study with a descriptive aim on a series of 11 female patients aged less than 40 years, operated for rectal cancer in the department of digestive cancer surgery and liver transplantation Casablanca Morocco, over a period of 7 years from January 2013 to December 2019. Results: The average age of our patients was 34.8 years. The average diagnostic delay was 10 months. The most frequent clinical sign was rectorrhagia (90.9% of cases). On rectal examination, the tumor was inaccessible in 18.8% of cases and externalized in 9.09% of cases. It was located in the lower rectum in 36.36% of cases, the same for the middle rectum. Rectoscopy showed that the majority of tumors were circumferential (36.36%). The budding ulcerative aspect was the most frequently found with 7 cases or 63.63%. The histological study showed the predominance of lieberkühnian adenocarcinoma (63.63%). Thoracic-abdominal-pelvic CT scan showed liver metastases in only one patient (9.09%). Pelvic MRI showed invasion of the mesorectum in 5 cases (45.45%) and of the internal sphincter in 3 cases (27.27%). All our patients underwent laparotomy. Curative surgery was performed in 8 patients and 3 patients had palliative surgery. Preoperative radiotherapy was performed in 81.81% of cases. The evolution was marked by 27.27% of locoregional recurrences. The operative mortality was nil in our series. Conclusion: Detection of patients with precancerous conditions, screening for cancer in subjects at risk (familial recto-colic cancer, familial recto-colonic polyposis and ulcerative colitis), suspicion of cancer in the presence of any proctological sign, early diagnosis and curative surgical resection preceded by radiotherapy are the means that can improve the prognosis of rectal cancer in young women.

Solid pseudopapillary neoplasm of the head of the pancreas: A case report.

INTRODUCTION: and importance: Solid pseudopapillary tumor of the pancreas (SPN) or Frantz's tumor is a rare tumor of low malignant potential common in young women. The aim of this paper is to present and discuss a case of a solid pseudopapillary tumor of the pancreas occurring in a 19-year-old female. CASE PRESENTATION: A 19-year-old girl presented to our department with epigastric pain for two months, she had no clinical findings on physical examination. Abdominal Computed tomography scan (CT scan) showed the presence of a well-defined tumor arising from the pancreatic head measuring 9,1 × 8.1 × 8.5 cm, heterogeneous and with solid and necrosis components. The patient was subjected to surgery and histopathological examination confirmed the diagnosis of a pseudopapillary tumor of the pancreas. CLINICAL DISCUSSION: This is an interesting case report of a rare tumor, in so far as without any adjuvant chemotherapy Prognosis of the tumor is better than other pancreatic tumors. surgical resection seems to be the best strategy in the management of SPT. CONCLUSION: Close follow up is necessary for early detection of the recurrence and metastasis.

Postsurgical Diagnosis of an Unusual Case of Primary Hepatic Lymphoma Presenting as Liver Abscess with an Uncommon Complication: A Hepatogastric Fistula.

Primary hepatic lymphoma (PHL) is a very rare malignancy and constitutes 0.016% of all cases of non-Hodgkin's lymphoma and 0.4% of extranodal non-Hodgkin's lymphoma. We describe a rare case of primary hepatic lymphoma presenting as liver abscess which was complicated with the development of a hepatogastric fistula. A 58-year-old man presented with clinical signs of sepsis, high-grade fever, right upper abdominal pain, and weight loss which had progressed in the past 8 months. Noncontrast abdominal computed tomography (CT) revealed a heterogeneously hypodense lesion in the left lobe of the liver with multiple air foci within, which are seen to extend into the body of the stomach. The patient was initially misdiagnosed as a case of rupture of liver abscess into the stomach. Postoperative liver biopsy examination confirmed a diagnosis of diffuse large B-cell lymphoma. Systemic staging revealed no evidence of nodal or bone marrow involvement, so PHL was diagnosed. Chemotherapy was initiated, but discontinued due to the patient's general condition. Finally, the patient succumbed to neutropenic fever following chemotherapy. Here, we present the exceptional case of a primary hepatic lymphoma with an unusual complication, a hepatogastric fistula, and try through the existing literature to show the difficulties involved in diagnosis and treatment.

Helicobacter pylori co-infection with Epstein-Barr virus and the risk of developing gastric adenocarcinoma at an early age: Observational study infectious agents and cancer.

BACKGROUND: Gastric cancer (GC) is one of the leading causes of morbidity and mortality worldwide. The onset and progression of gastric cancer are attributed to numerous triggers, these triggers may be infection of the gastric epithelium by Helicobacter pylori (H. pylori), or by Epstein-Barr virus (EBV). Both agents can establish a lifelong persistent infection in the host, leading to chronic inflammation, which also contributes to cancer development. Objective: The objective of this study is to present the status of co-infection with H. pylori and EBV and the risk of developing adenocarcinoma at an early age in the population of Grand Casablanca. METHODS: In this study, 100 gastric tissue samples from patients with gastric cancer were examined for detection of H. pylori and EBV in tumor tissue using PCR techniques, and the clinical relevance was statistically analyzed. RESULTS: Results revealed an individual Epstein-Barr virus (EBV) infection observed in (40 %) of gastric carcinoma cases. Furthermore, the frequency of EBV infection was significantly different with intestinal and diffuse gastric cancer types [15 % vs. 85 %; <0.05]. The prevalence of individual H. pylori infections was 34 %, while the frequency of co-infection was 16 %. Moreover, no significant association was found between co-infection and sex, tumor grade, stage, and lymph node metastasis, but there was a significant association between co-infection and the age of GC patients. CONCLUSION: Thus understanding the status of co-infection could clarify the process of gastric carcinogenesis, and application of this knowledge for clinical purposes could facilitate diagnosis, risk management, and prevention.

Non-functional retroperitoneal paraganglioma: A report of case with literature review.

INTRODUCTION: Retroperitoneal paragangliomas are rare tumors, they arise from ganglia along the sympathetic and parasympathetic chain. We report a rare case of a non functional paraganglioma in whom surgical resection was performed. PRESENTATION OF CASE: A 35 years-old female presented with chronic abdominal pain, A contrast magnetic resonance imaging (MRI) of abdomen showed a well-defined Left latero-aortic cystic retro-peritoneal surgical resection using laparotomy was performed, The patiente recovered well and was discharged three days after surgery. Histological examination and immunohistochemical revealed a retroperitoneal paraganglioma. DISCUSSION AND CONCLUSION: Non-functioning retroperitoneal paragangliomas are rare and are most often Isolated. Radiological techniques including, Contrast-enhanced computed tomography (CT) and Magnetic resonance imaging (MRI) are useful for identifying and locating retroperitoneal paragangliomas. surgical excision is still the most effective treatment when it possible.

Retroperitoneal shwannoma: A case report.

INTRODUCTION: Schwannomas are tumors that arise from Schwann cells of the peripheral nerve sheath and rarely occur in the retroperitoneum (3% of all schwannomas). Patients are usually asymptomatic or have nonspecific symptoms, making accurate preoperative diagnosis difficult. Schwannomas are usually benign, but infrequently undergo malignant transformation. Herein, we report a case of retroperitoneal schwannoma and review the relevant literature. PRESENTATION OF CASE: A 25-year-old woman presented to our department with a 2-year history of abdominal pain that was localized in the right flank without radiation, constipation/diarrhea or externalized digestive hemorrhage. On physical examination, we found a painless palpable mass in the right hypochondrium extending to the right iliac fossa, measuring approximately 10 cm. The MRI and CT scan showed the presence of a large intra-abdominal oval formation in the right para-umbilical region. It was well limited, measuring 110*69mm with discrete irregular contours, thickened wall and heterogeneous content mostly fluid. They also showed the presence of a cystic formation in the right ovary measuring 84*52mm and extending over 76mm. The procedure consisted of resection of the retroperitoneal solid cystic mass, right ovariectomy and drainage of the right parietal-colic gutter by Salem sump tube. A laparotomy with a median incision above and below the umbilicus was performed. After the resection, the specimens were sent for anatomopathological examination which concluded that the retroperitoneal mass was a schwannoma and the ovarian mass was a serous cystadenoma. DISCUSSION: Retroperitoneal schwannomas are rare tumors and a pre-operative diagnosis is often difficult. The diagnosis is most often fortuitous and late, given the latency of the tumor's evolution, and the definitive diagnosis is based on histopathologic examination. Herein we presented a case of retroperitoneal schwannoma and studied the features of this phenomenon on the basis of the literature. CONCLUSION: Retroperitoneal schwannomas are rare. The diagnosis is often late at the stage of a large tumor. Radiologic findings are usually nondiagnostic. The treatment of choice is complete surgical excision. Prognosis is good but because of the risk of recurrence and malignant transformation, further follow-up is necessary.

Abdominal textiloma mimicking as gastrointestinal stromal tumor: A case report.

INTRODUCTION AND IMPORTANCE: Gossypiboma or textiloma is a mass comprising of cotton matrix within the body left accidentally during a surgical procedure. The body may react to this foreign body through an exudative inflammatory reaction or an aseptic fibrotic reaction in order to encapsulate the cotton material and result into a mass. CASE PRESENTATION: We report a case of 65-year-old female. She was referred to our department due to 2 episodes of nausea and vomiting. She had history of open cholecystetomy 29 years ago, then cure for eventration one year after. On exploratory laparotomy there was a mass measuring 6 cm axis at the expense of segment 3 of the liver coming into intimate contact with the duodenum. Atypical segmental hepatectomy of segment 3 of liver was performed, and the histological report confirmed necrotic textiloma. CLINICAL DISCUSSION: Textiloma represents a complication of all forms of surgery. It is a real, serious but preventable surgical complication, and could present with various complaints. Prevention of this condition can be achieved by meticulous count of surgical materials. CONCLUSION: The embarrassment faced by the surgeon and the medico legal implications of this iatrogenic complication are tremendous and all preventive measures should be taken to avoid this as no excuse is justifiable.

Chromophobe renal cell carcinoma: A case report and literature review.

INTRODUCTION: Chromophobe renal cell carcinoma, a distinct subtype of renal cell carcinoma (RCC) with characteristic light microscopic, histochemical, and ultrastructural features, typically has a favorable clinical course. PRESENTATION OF CASE: A 45-year-old femele presented with abdominal pain. A physical examination found a palpable mass in the left upper quadrant of the abdomen. A CT scan of the abdomen showed a heterogeneously enhancing mass, with necrosis and calcifications contents betwen the liver and the right kidney. she underwent surgical resection. Partial nephrectomy was performed. Pathological diagnosis was Chromophobe renal cell carcinoma. DISCUSSION AND CONCLUSION: Chromophobe RCC is a rare variety of kidney neoplasm that has recently been better characterized from a molecular and genetic perspective. Overall, it is considered to have a better prognosis, and is associated with earlier stage tumors and longer overall survival compared with clear cell RCC.

Spontaneous splenic rupture: A rare complication of acute myeloid leukemia. Report of a case.

INTRODUCTION: Spontaneous rupture of the spleen (SPR) is a rare and severe affection, difficult to diagnose, with multiple causes such as: Infectious and hematologic affections which represent more than half of the cases. Among this subset of patients, acute myeloid leukemia is one of the causes. PRESENTATION OF CASE: A 48-year-old man undergoing chemotherapy for acute myeloid leukemia presented with acute intense abdominal pain. Computed tomography showed Abdominal CT scan showed a splenic rupture with abundant hemoperitoneum and bilateral pleural effusion. The patient presented hemodynamic instability and was immediately operated, splenectomy were performed. DISCUSSION: Spontaneous rupture of the spleen usually presents as a severe abdominal syndrome, which may accompany non-specific symptoms.Two signs are suggestive of splenic rupture: Kehr's sign (left diaphragmatic irritation resulting in referred pain to the left shoulder) and Balance's sign (palpable tender mass in the left upper quadrant. Diagnostic methods of choice are computed tomography andultrasound. The prognosis is depending on the quality of care and the nature of the etiology. Splenectomy remains the cornerstone of the treatment of splenic rupture. It is important to include splenic rupture as a differential diagnosis for acute abdominal pain, especially in patients with hematologic malignancy, since early recognition and treatment increase patient survival and improve the prognosis. CONCLUSION: Even if spontaneous splenic rupture is rare, every clinician should have in mind the reflex to think of it, especially in patients with hematologic malignancies.

Retrorectal cystic hamartoma: A case report.

INTRODUCTION: and importance: Retrorectal cystic hamartoma (RCH) is a rare congenital lesion of the presacral space, which is part of the vestigial cystic tumors often benign and predominantly in women. Generally asymptomatic, the appearance of symptoms such as pain or neurological disorders should raise suspicion of degeneration. CASE PRESENTATION: We report an unusual observation of a 62-year-old patient admitted for perineal pain evolving for 2 months associated with tenesma and chronic constipation. The digital rectal examination found a posterior bulge at 4 cm from the anal margin, without intraluminal lesion. Rectosigmoidoscopy had noted posterior extrinsic compression but no rectal tumor. Pelvic CT and MRI had shown a solidocystic formation of the retro-rectal and presacral spaces, related to an enteric cyst. The operation was performed by abdominal approach and the surgical exploration had found a bilobed cystic formation. The cystic mass was removed and the anatomopathological examination concluded that it was a cystic hamartoma with no sign of malignancy. CLINICAL DISCUSSION: Retrorectal tumors develop in the space bounded anteriorly by the propria fascia of the rectum and posteriorly by the presacral fascia overlying the sacrum. Common in children and then often malignant, inversely, in adults, they are rare and most often benign tumors. They are generally asymptomatic with a predominance of females, unlike our observation where the patient was male with a symptomatology dominated by perineal pain and constipation. The discovery is incidental in the majority of cases, however, in some cases, these cysts may be revealed by complications. The lesion can be explored by transrectal or suprapubic ultrasound, MRI and CT scan. Rectoscopy and fistulography may complete the exploration in case of diagnostic doubt. The resection must be thorough and in monobloc because of the risk of recurrence and the approach depends on the location and the size of the lesion. CONCLUSION: RCH is a rare benign lesion whose morphological characteristics seem quite stereotyped. A detailed postoperative anatomopathological examination allows the diagnosis to be made and, above all, to look for a site of malignant transformation. This is why a complete surgical removal is necessary to prevent recurrence.

A gastrointestinal stromal tumor of stomach presenting with an intratumoral abscess: A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, GISTs of the stomach presenting as an intratumoral abscess are extremely rare, which necessitates emergency surgery, we report a case of a stomach GIST developing an intratumoral abscess, in whom emergency surgery was performed. PRESENTATION OF CASE: A 68-year-old man presented with severe abdominal pain and a fever. Laboratory data showed an elevated white blood cell count and C-reactive protein level. Computed to mography scan showed a 15 × 10 cm cystic mass adjacent to greater curvature of the stomach, which contained air. Emergency laparotomy revealed A giant cystic gastric mass was observed. Sleeve gastrectomy were performed. Immunohistochemically, the tumor was diagnosed as a Gastric high risk GIST,and imatinib mesylate was initiated, The patient had an uneventful postoperative course and remains well. DISCUSSION AND CONCLUSION: Such rare cases can be diagnosed and treated properly with careful clinical evaluation, surgical resection and adjuvant chemotherapy with imatinib mesylate is still the mainstay and most effective treatment for GISTs to date.

Effects of FoxO4 overexpression on cholesterol biosynthesis, triacylglycerol accumulation, and glucose uptake.

The Forkhead transcription factors FoxO1, FoxO3a, and FoxO4 play a prominent role in regulating cell survival and cell cycle. Whereas FOXO1 was shown to mediate insulin sensitivity and adipocyte differentiation, the role of the transcription factor FoxO4 in metabolism remains ill defined. To uncover the effects of FoxO4, we generated a cellular model of stable FoxO4 overexpression and subjected it to microarray-based gene expression profiling. While pathway analysis revealed a disruption of cholesterol biosynthesis gene expression, biochemical studies revealed an inhibition of cholesterol biosynthesis, which was coupled with decreased mRNA levels of lanosterol 14alpha demethylase (CYP51). FoxO4-mediated repression of CYP51 led to the accumulation of 24,25 dihydrolano-sterol (DHL), which independently and unlike lanosterol inhibited cholesterol biosynthesis. Furthermore, FoxO4-overexpressing cells accumulated lipid droplets and triacylglycerols and had an increase in basal glucose uptake. Recapitulation of these effects was obtained following treatment with CYP51 inhibitors, which also induce DHL buildup. Moreover, DHL but not lanosterol strongly stimulated liver X receptor alpha (LXRalpha) activity, suggesting that DHL and LXRalpha mediate the downstream effects initiated by FoxO4. Together, these studies suggest that FoxO4 acts on CYP51 to regulate the late steps of cholesterol biosynthesis.