Prevalence and patterns of mutations in RAS/RAF/MEK/ERK/MAPK signaling pathway in colorectal cancer in North Africa.

BACKGROUND: Our review discuss (i) the findings from analyzed data that have examined KRAS, NRAS and BRAF mutations in patients with colorectal cancer (CRC) in North Africa and to compare its prevalence with that shown in other populations and (ii) the possible role of dietary and lifestyle factors with CRC risk.  METHODS: Using electronic databases, a systematic literature search was performed for the KRAS, NRAS, and BRAF mutations in CRC patients from Morocco, Tunisia, Algeria and Lybia.  RESULTS: Seventeen studies were identified through electronic searches with six studies conducted in Morocco, eight in Tunisia, two in Algeria, and one in Libya. A total of 1843 CRC patients were included 576 (31.3%) in Morocco, 641 (34.8%) in Tunisia, 592 (32.1%) in Algeria, and 34 (1.8%) in Libya. Overall, the average age of patients was 52.7 years old. Patients were predominantly male (56.6%). The mutation rates of KRAS, NRAS and BRAF were 46.4%, 3.2% and 3.5% of all patients, respectively. A broad range of reported KRAS mutation frequencies have been reported in North Africa countries. The KRAS mutation frequency was 23.9% to 51% in Morocco, 23.1% to 68.2% in Tunisia, 31.4% to 50% in Algeria, and 38.2% in Libya. The G12D was the most frequently identified KRAS exon 2 mutations (31.6%), followed by G12V (25.4%), G13D (15.5%), G12C (10.2%), G12A (6.9%), and G12S (6.4%). G12R, G13V, G13C and G13R are less than 5%. There are important differences among North Africa countries. In Morocco and Tunisia, there is a higher prevalence of G12D mutation in KRAS exon 2 (≈50%). The most frequently mutation type in KRAS exon 3 was Q61L (40%). A59T and Q61E mutations were also found. In KRAS exon 4, the most common mutation was A146T (50%), followed by K117N (33.3%), A146P (8.3%) and A146V (8.3%). CONCLUSION: KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Intestinal intussusception in a young women: unusual cause and specific management.

BACKGROUND: Intussusception in adults is a rare cause of abdominal pain that is often associated with organic pathology. We describe a case of ileocolic intussusception revealing a cecal adenocarcinoma in a young woman successfully managed by laparoscopic-assisted surgery adhering to oncological principles. CASE PRESENTATION: A 30-year-old woman with a family history of colon adenocarcinoma in a young brother presented to our emergency department with a 2-month history of intermittent colicky abdominal pain accompanied by nausea and vomiting. Physical examination showed a palpable mass in the right lower quadrant of the abdomen. Computed tomography showed a 3-layered structure giving the characteristic target-shaped appearance in the ascending colon, highly suggestive for an ileocolic intussusception associated with right colic parietal thickening and an adjacent lymphadenopathy. Patient was planned for laparoscopic exploration and eventually definitive surgery. Intra-operatively, we found an ileocolic intussusception with thickening of the colic wall and slight proximal intestinal dilation. Multiple lymphadenopathies along the ileocecal artery were observed. Laparoscopic right hemicolectomy was performed following strict oncologic principles with "en bloc resection" and lymphadenectomy given the risk of an underlying malignancy. Considering this risk, previous reduction of the invaginated segments was not attempted and primary extracorporeal anastomosis was performed using manual sutures. Macroscopic examination of the resected specimen revealed a tumor mass of the caecal wall .The histological analysis identified a moderately differentiated tubular adenocarcinoma invading the serosa (T3) without permeation of the lymphatic or venous capillaries. No lymphatic metastasis of 28 nodes removed was seen. Postoperative course was uneventful and patient was discharged 5 days after surgery. Postoperative chest, abdomen, and pelvis CT scan were normal. Therefore, tumor is classified as stage II A (T3N0 M0).There was loss of MLH2 and MSH6 protein expression on immunohistochemistry findings reflecting a microsatellite instability phenotype, and the patient was followed up without adjuvant chemotherapy. CONCLUSION: Ileocolic intussusception rarely revealed a cancer in young adults. Laparoscopic surgery has a special interest in the diagnosis and treatment in this pathology. Oncogenetic consultation should be required in malignant lesion.

Long recurrence-free survival of localized rectal melanoma after abdominoperineal resection in comparison to partial excision and highlighting the place of immunotherapy: A case report.

Rectal malignant melanomas (RMM) are remarkably uncommon, the rectal location represents less than one percent of all rectal cancer. Because of its low global survival rate, the surgical strategy is a subject of controversy for attaining a r0 resection. the palliative treatment is also debateable, but recently; radiotherapy and immunotherapy became the preferred treatment and offer the best outcome. to ensure r0 resection, abdominoperineal resection (apr) is considered the main surgical option, but because of its morbidity and functional limitations, local excision techniques such as endoscopic mucosal resection (emr) combined with chemoradiotherapy are being increasingly performed to preserve the quality of life and reduce local recurrence rate. In this report, we evaluate the place that apr still keeps as surgical procedure in comparison to partial excision. we report a case of a 72 years old patient, who presented rectal syndrome with rectorrhagia for 2 months, the diagnosis of localized rectal melanoma was confirmed by endoscopy, magnetic resonance imaging, histological analysis tissue with immunohistochemistry. the procedure strategy was a surgical treatment with apr. After a long recurrence-free survival period, the patient develops local recurrence and immunotherapy-resistant metastasis.

Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively.We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

Case note: retroperitoneal nonfunctioning paraganglioma.

Paragangliomas are extra-adrenal chromaffin tumours that develop at the expense of neuroectodermal cells of the autonomous nervous system. Retroperitoneal and nonfunctioning forms are very rare. They are often asymptomatic and can reach a substantial size. Treatment usually involves surgery with the goal of total excision. We report the case of a patient who presented with indistinct abdominal pain. This case demonstrates how the diagnosis of retroperitoneal nonfunctioning paragangliomas relies mostly on histological results.

Sacral hemangiopericytoma involving the retrorectal space: report of a case.

A primary hemangiopericytoma (HP) of the bone is rare, because the vast majority of these tumors arise in soft tissue. This report presents a case of a hemangiopericytoma in the sacrum (S1-S2) with extension to the retrorectal space. Only a few cases of osseous hemangiopericytomas in the sacrum and involving the retrorectal space have so far been reported. The difficult diagnosis of HP and the surgical strategy was chosen according to the location of the lesion in the sacrum and retrorectal space. A local excision was indicated. A sacral resection should be considered for tumors below S4. This report demonstrated the safety of this strategy. Adjuvant radiotherapy is useful in HP. The value of chemotherapy is still doubtful, although patients with high-grade tumors or metastatic spread seem to gain substantial benefit. Due to the often unpredictable behavior of this neoplasm, extended follow-up is strongly recommended.

[Role of splenectomy in the treatment of non-cirrhotic portal hypertension: about 3 cases]. / Place de la splénectomie dans la prise en charge de l'hypertension portale non cirrhotique: à propos de 3 cas.

Non-cirrhotic portal hypertension was first described by Guido BANTI in 1898 as a condition characterized by the association of portal hypertension with splenomegaly, anemia and healthy liver. The diagnosis was based on abdominal ultrasound, splenoportography and liver biopsy. Our study aimed to evaluate the role of splenectomy in non-cirrhotic portal hypertension. We conducted a retrospective study of 3 patients (2 women and 1 man) treated by our staff over the period January 2010 -September 2016. The diagnosis of idiopathic portal hypertension was based on the following criteria: portal hypertension, the presence of oesophageal varices associated with splenomegaly, the absence of cirrhosis or of other liver disorders responsible of portal hypertension. All patients underwent splenectomy. Outcome after splenectomy was marked by the standardization of clinical, radiological and biological signs of this disease associated with the absence of oesophageal varices recurrence. Splenectomy associated with ligation of oesophageal varices may be sufficient to treat this syndrome and especially its consequences without using splenorenal bypass.

[Parietal-scar endometriosis after cesarean section: a rare entity]. / L'endométriose pariétale cicatricielle après césarienne: une entité rare.

Wall endometriosis is a rare clinical entity whose pathophysiology remains unclear. It occurs most frequently after gynecologic or obstetric surgery. We report the case of a patient with cyclic pain at the caesarean section scar. Clinical examination showed a 5 cm mass in the right iliac fossa. Tomodensitometry revealed a tissue density mass (45mm on the major axis). Hence, the decision to perform a wide excision of the lesion. Anatomo-pathological examination confirmed the diagnosis of parietal endometriosis. Postoperative sequelae were simple with a follow-up period of 20 months with no recurrence of the mass or of the pain. Our study highlights the characteristics of this disease to allow the health practitioner to understand the importance of diagnosis, of early treatment of this disease as well as of the possibility to prevent it during each gynecologic or obstetric surgery.

An exceptional collision tumor: gastric calcified stromal tumor and pancreatic adenocarcinoma.

The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen.

Analysis of prognostic factors affecting mortality in Fournier's gangrene: A study of 72 cases.

INTRODUCTION: Fournier's gangrene is a rapidly progressing necrotizing fasciitis of the perineum and genital area associated with a high mortality rate. We presented our experience in managing this entity and identified prognostic factors affecting mortality. METHODS: We carried out a retrospective study of 72 patients treated for Fournier's gangrene at our institution between January 2005 and December 2014. Patients were divided into survivors and non-survivors and potential prognostic factors were analyzed. RESULTS: Of the 72 patients, 64 were males (89%) and 8 females (11%), with a mean age of 51 years. The most common predisposing factor was diabetes mellitus (38%). The mortality rate was 17% (12 patients died). Statistically significant differences were not found in age, gender, and predisposing factors, except in heart disease (p = 0.038). Individual laboratory parameters significantly correlating with mortality included hemoglobin (p = 0.023), hematocrit (p = 0.019), serum urea (p = 0.009), creatinine (p = 0.042), and potassium (p = 0.026). Severe sepsis on admission and the extent of affected surface area also predicted higher mortality. Others factors, such as duration of symptoms before admission, number of surgical debridement, diverting colostomy and length of hospital stay, did not show significant differences. The median Fournier's Gangrene Severity Index (FGSI) was significantly higher in non-survivors (p = 0.002). CONCLUSION: Fournier's gangrene is a severe surgical emergency requiring early diagnosis and aggressive therapy. Identification of prognostic factors is essential to establish an optimal treatment and to improve outcome. The FGSI is a simple and valid method for predicting disease severity and patient survival.

An unusual localization of retroperitoneal paraganglioma: a case report.

Paragangliomas are rare tumors arising from extra-adrenal chromaffine tissues. The diagnosis of non-functional retroperitoneal paraganglioma and its surgical management can be difficult. We report a case of a retroperitoneal paragangliomaof an unusual localization that renders the surgery more challenging. A 40 year-old woman presented to our department with a four-month history of upper quadrant pain with no vomiting, no fever, nor jaundice. Physical examination was normal. Ultrasonography showed a retro duodenal homogenous mass and computed tomographyscan showed a well-circumscribed round mass of heterogeneous density, which was in close contact with the aorta and the left kidney vein. Laboratory tests were normal. The patient underwent surgical management. The surgical exploration found a retroperitoneal tumor that was encapsulated and showing intimate contact with the abdominal aorta. We performed a complete resection of the tumor. Histological examination of the surgical specimen revealed a paraganglioma. The post operative course was uneventful. Paragangliomas are rare tumors. They can be asymptomatic for a long time and thus be diagnosed at late stage. A follow-up of patients is then essential. Surgical treatment is the only radical treatment and should be performed even in paragangliomas in close contact with the great vessels.

Perineal approach for surgical treatment in a patient with retro-rectal tumor: a case report and review of the literature.

BACKGROUND: Retrorectal tumors in adults are very rare and little known condition. These tumors, often misdiagnosed or mistreated, should be completely excised because of the potential for malignancy or infection. A suitable operative approach is the key to the successful surgical management. CASE PRESENTATION: We report the case of a 45-year-old Arab male who presented with chronic pelvic pain accompanied by straining to defecate and dysuria. The clinical examination showed a painless mass in the left perineal area. Pelvic magnetic resonance imaging and computed tomography scan demonstrated a huge and well-limited pelvic mass causing displacement and compression of the rectum and bladder. Although the large size of the mass (>7 cm in the greater diameter), it was successfully and completely excised through only perineal approach without undertaking coccygectomy or sacrectomy. The histopathological study revealed a low-grade leiomyosarcoma. The patient is currently in 4-years follow-up with no signs of recurrence or metastasis. CONCLUSION: Even large retro-rectal tumors may be successfully excised by the perineal approach especially in carefully selected patients, but require extensive knowledge of pelvic anatomy and expertise in pelvic surgery.

Long-standing insulinoma: two case reports and review of the literature.

BACKGROUND: Insulinomas are rare pancreatic endocrine tumors. Most are benign and solitary. However, the nonspecific symptoms and small size of these tumors led to difficulties of diagnosis and localization. CASE PRESENTATION: We present two Arab patients with pancreatic long-standing insulinoma. Both patients presented episodic hypoglycemic symptoms respectively during 10 and 2 years. Biochemical and morphological workup detected localized pancreatic insulinoma. Open procedure surgery was done for the two patients and insulinomas were successfully removed by enucleation. CONCLUSION: Insulinoma remains a diagnostic challenge to practitioners. Diagnosis of suspected cases is easily confirmed by standard endocrine tests, especially the supervised fasting test. Accurate preoperative localization is essential for more effective and safest surgery.

Successful surgical treatment of extrahepatic biliary papillomatosis diagnosed with endoscopic retrograde cholangiopancreatography: a case report.

INTRODUCTION: Biliary papillomatosis is a condition characterized by multiple papillary tumors of variable distribution and extent within the biliary tract. Papillary carcinoma can develop in these lesions. It is a rare biliary pathological entity and its clinical features and outcome are not well known. CASE PRESENTATION: We experienced a case of biliary papillomatosis in a 51-year-old North African man who presented with obstructive jaundice. Laboratory tests showed elevated bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase levels. Imaging (ultrasound and magnetic resonance imaging) was suggestive of Klatskin tumor associated to common bile duct stones. After endoscopic retrograde cholangiopancreatography, a balloon sweep retrieved friable tissue from his bile ducts. Histology demonstrated papillary adenomatous proliferation showing high-grade dysplasia and he was referred for surgical management. CONCLUSIONS: Although biliary papillomatosis is rare, it is a premalignant condition that should be well known and considered in all diagnoses of obstructive jaundice. We report a new case of biliary papillomatosis and highlight the contribution of endoscopic retrograde cholangiopancreatography in the diagnosis of this condition.