RAS Mutations Predict Recurrence-Free Survival and Recurrence Patterns in Colon Cancer: A Unicenter Study in Morocco.

PURPOSE: To date, only a few studies have investigated the role of molecular alterations in cancer recurrence. This exploratory study aimed to evaluate the impact of molecular alterations on the time and site of recurrence in patients with stage I-IV CRC and to identify the risk factors predicting recurrence-free survival in colon cancer. METHODS: A total of 270 patients were retrospectively included. We assessed the full RAS status using Sanger and pyrosequencing. MSI status was determined by immunohistochemical analysis. Molecular alterations were correlated with recurrence timing (early or late), recurrence patterns, and recurrence-free survival. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: Of the 270 patients, 85 (31%) experienced recurrence, among whom 53% had mutant full RAS status, 48% had KRAS mutations, and 31.4% had KRAS p. G12V mutation subtype. Compared with those with late recurrence, patients with early recurrence were significantly older (P = 0.02) and more likely to have poorly differentiated tumors, a higher rate of positive lymph nodes, KRAS mutations, and especially KRAS p. G12V mutation variant. RAS mutation status, KRAS mutations, and rare mutations are more common in patients with lung cancer recurrence. Multivariate logistic regression analysis revealed that differentiation, perineural invasion, full RAS mutation status, and KRAS codon 13 mutations were independent factors for recurrence-free survival in colon cancer. CONCLUSION: In this cohort, the timing and patterns of recurrence appeared to be associated with the patient's molecular profile. KRAS codon 12 mutations were the worst predictors of recurrence-free survival at all stages in our population.

Left-Sided Colon Cancer and Right-Sided Colon Cancer: Are They the Same Cancer or Two Different Entities?

Background Colon cancer is one of the most common cancers in the world and one of the main causes of cancer-related deaths. In Morocco, it occupies the first place among digestive cancers. Right-sided and left-sided colon cancers have different embryological, epidemiological, pathological, genetic, and clinical characteristics. This distinction leads to differences in the evolution and prognosis of the disease. This study aimed to identify epidemiological factors and clinical and pathological characteristics that can influence perioperative and prognostic outcomes in patients with right-sided colon cancer compared to those with left-sided colon cancer. Methodology We conducted a retrospective cohort study over a period of nine years from January 2012 until December 2020. We included 277 patients divided into two groups, namely, right colon cancer (group 1) (n = 99) and left colon cancer (group 2) (n = 178). Results The average age of our series was 57.4 years, with extremes ranging from 19 to 89 years old (SD = ±13.6451 years). The average age in the right colon group was 55.97 (SD = ±13.341 years). The average age in the left colon group was 58.18 (SD = ±13.69 years). The male gender had a predominance, with a sex ratio of 1.3 for both groups. Among the patients in group 2, 65% showed lymph node involvement on the CT scan, whereas only 34% of patients in group 1 displayed the same condition. The recurrence rate in the right-sided colon cancer group was 22.2% compared to 24.9% in the left-sided group. The five-year overall survival was estimated for the right-sided and left-sided colon cancer groups at 87% and 96.5%, respectively. In patients with stage III and IV cancer, overall survival was better for those who underwent surgery for left-sided colon cancer compared to those who underwent surgery for right-sided colon cancer (p = 0.029). In the case of vascular emboli or involvement of the perineural sheath, there was no significant difference in overall survival (p = 0.446 and p = 0.655, respectively). The three-month survival without recurrence was almost identical in both groups (31% for right-sided colon cancers and 30.9% for left-sided colon cancers). Age over 61 years was a predictive factor of poor prognosis in recurrence-free survival (hazard ratio = 3.245; p = 0.023). Conclusions We identified factors that can influence perioperative outcomes and prognosis in patients with right-sided colon cancer compared to those with left-sided colon cancer. Our findings suggest that age and lymph node involvement along with other factors play a role in the overall survival and recurrence outcomes of these patients. Further research is necessary to explore these differences and develop personalized treatment plans for patients with colon cancer.

Impact of Resident Post-Graduate Year on Laparoscopic Cholecystectomy Outcomes.

Introduction Laparoscopic cholecystectomy is a minimal access procedure in which the gallbladder is removed by laparoscopic techniques. Effective training for laparoscopic surgery should focus on not only understanding the anatomy and procedural steps but also acquiring the specific gestures and techniques of this type of surgery that may differ from those used in traditional open surgery. The aim of our study was to analyze whether the laparoscopic cholecystectomy performed by surgeons in training is a safe procedure. Material and methods This is a retrospective review of 433 patients who were divided into two groups: laparoscopic cholecystectomies performed by trainees and those performed by senior surgeons. Results Around 66% of surgeries were performed by resident surgeons. There was no demographic difference between residents and senior surgeons. Operative time was significantly longer in the residents' group compared to senior surgeons' group (96 minutes vs 61 minutes; p<0.001). The overall intra- and post-operative complication rates were 3.1% and 2.5%, respectively, with no significant difference between the two groups (p=0.368 and p=0.223). Conversion to open laparotomy was required in 8% of cases in each group (p=0.538). The mean length of hospital stay after surgery was significantly longer in patients operated by residents (p<0.001). We did not notice any case of mortality in both groups.

Rectosigmoid adenocarcinoma revealed by metastatic anal fistula. The visible part of the iceberg: a report of two cases with literature review.

Colonic adenocarcinoma revealed by metastatic anorectal fistula is rare, with few cases in the literature. Such lesions can be taken for the more common manifestation of a benign perianal abscess or fistula. Once diagnosed, the management of such conditions remains controversial. We herein report two cases with perianal fistula that were subsequently found to have developed perianal adenocarcinoma on biopsy. Further colonic investigation revealed a rectosigmoid adenocarcinoma. Histology and immunohistochemical staining was identical in both primary and metastatic tumors. Preoperative chemoradiation with further rectal low anterior resection and local excision of metastatic anal fistula was performed. There is no recurrence after 3 years of follow-up.

Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients.

BACKGROUND: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. METHODS: We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. RESULTS: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P < 0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation (P=0.007). In all stages, high tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. CONCLUSIONS: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

Small bowel carcinoid tumor causing intestinal ischemia: A case report with review of the literature.

Background: Intestinal carcinoid tumors are well-differentiated neuroendocrine tumors that are capable of secreting bioactive hormones and/or amines; These tumors are uncommon but are the most common primary tumors of the small intestine. Case presentation: We report the case of an 80-year-old woman who presented with a long history (about 14 years ago) of atypical digestive symptoms such as vague abdominal pain, alternating diarrhea, and constipation, treated as functional colopathy without improvement, until the day when she presented with worsening pain that prompted her consultation. CT scan revealed typical manifestations of a carcinoid tumor associated with signs of subacute small bowel ischemia. Despite the surgery being considered a gold standard treatment, it was rejected due to the extent of tumor mesenteric involvement, therefore, the patient received only somatostatin treatment. Conclusion: Small bowel carcinoid tumors are rare, with typical imaging features based on cross-sectional imaging (CE CT/MRI). Intestinal ischemia is a well-known complication that can be a factor in mortality.

Lymph Nodes With Germinal Centers Are Not Associated With Tumor Response After Neoadjuvant Treatment in Locally Advanced Rectal Cancer.

In patients with locally advanced rectal cancer, neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision as a standard of care. We aimed to explore the number, size, germinal centers, extracapsular invasion of lymph nodes (LN), and their impact on overall survival and disease free survival. Furthermore we also investigated the characteristics of lymph nodes in patients who received neoadjuvant therapy and those who underwent surgery between 2011 and 2018. The count and measurement of lymph nodes was assessed by careful visual inspection and manual palpation. The predictive cut-off value of the lymph node ratio (LNR) was determined based on the receiver operating characteristic (ROC), method and the survival outcomes based on Kaplan-Meier curves. We found that the size and the number of lymph nodes decreased significantly after neoadjuvant treatment. The mean LN for patients who received neoadjuvant therapy was 12.68 ± 6.69 and for patients who did not receive neoadjuvant therapy was 16.29 ± 5.61 (P = .012). The average size for patients who received neoadjuvant therapy followed by surgery was 3.30 ± 1.10 versus 4.22 ± 1.18 mm for control group (surgery only) (P < .001), an LNR of 0.13 (sensitivity: 86%, specificity: 47%, AUC: 60%, 95% CI, 0.41%-0.76%) predicted recurrence and metastasis. Presence of lymph nodes with germinal centers was significantly associated with absence of vascular invasion, nodal tumor deposits, distant metastasis, and lower age group (<50 years). However there was no association seen between overall survival and relapse free, total number of lymph nodes enlarged and extracapsular invasion in positive nodes. Finally there is no association between lymph nodes with germinal centers and tumor response after neoadjuvant treatment in locally advanced rectal cancer.

Mutation status and prognostic value of KRAS and NRAS mutations in Moroccan colon cancer patients: A first report.

This study aimed to estimate the incidence of KRAS, NRAS, and BRAF mutations in the Moroccan population, and investigate the associations of KRAS and NRAS gene mutations with clinicopathological characteristics and their prognosis value. To achieve these objectives, we reviewed medical and pathology reports for 210 patients. RAS testing was investigated by Sanger sequencing and Pyrosequencing technology. BRAF (exon 15) status was analyzed by the Sanger method. The expression of MMR proteins was evaluated by Immunohistochemistry. KRAS and NRAS mutations were found in 36.7% and 2.9% of 210 patients, respectively. KRAS exon 2 mutations were identified in 76.5% of the cases. RAS-mutated colon cancers were significantly associated with female gender, presence of vascular invasion, classical adenocarcinoma, moderately differentiated tumors, advanced TNM stage III-IV, left colon site, higher incidence of distant metastases at the time of diagnostic, microsatellite stable phenotype, lower number of total lymph nodes, and higher means of positive lymph nodes and lymph node ratio. KRAS exon 2-mutated colon cancers, compared with KRAS wild-type colon cancers were associated with the same clinicopathological features of RAS-mutated colon cancers. NRAS-mutated patients were associated with lower total lymph node rate and the presence of positive lymph node. Rare RAS-mutated tumors, compared with wild-type tumors were more frequently moderately differentiated and associated with lower lymph node rate. We found that KRAS codon 13-mutated, tumors compared to codon 12-mutated tumors were significantly correlated with a higher death cases number, a lower rate of positive lymph, lower follow-up time, and poor overall survival. Our findings show that KRAS and NRAS mutations have distinct clinicopathological features. KRAS codon 13-mutated status was the worst predictor of prognosis at all stages in our population.

[Epiploic appendagitis: a rare cause of acute abdomen]. / Appendagite épiploïque: cause rare d'abdomen aigu.

Epiploic appendagitis is a rare cause of acute abdomen. It can mimic other inflammatory processes such as diverticulitis or appendicitis. Diagnosis is based on CT scan. Medical management is the approach of choice in the absence of complications.

The Effect of Lymph Nodes' Histologic Response on Survival Outcomes in Moroccan Patients with Rectal Cancer.

Prognosis for patients with locally advanced rectal cancer remains controversial. The purpose of this study was to elucidate possible association between therapeutic effect on lymph nodes (LNs) and patient prognosis. Overall, 149 patients with rectal cancer received preoperative radiotherapy in concomitance with chemotherapy or exclusive radiotherapy before rectal excision. Microscopic examination of formalin-fixed lymph nodes was assessed for therapeutic effect. The establishment of groups combined reaction tissue types of fibrosis, colloid, and necrosis after neoadjuvant treatment was assigned. The average age was 56.38 years, ranged between 22 and 88 years, 53% were female, and 47% were men, with a sex ratio of 1 : 12. In the present study, we noticed that after a median follow-up time of 40.67 months (0-83; SD: 21.1), overall survival was statistically significant depending on age groups. Kaplan-Meier analysis showed significant differences in the rate of patients with an age under 65 years (70.64%) versus those with an age over 85 years (36.5%) (p < 0.001). Also, the OS was statistically significant depending on therapeutic effect groups composed of 0TE (No Therapeutic effect), C+ (presence of only colloidal effect), F+ (presence of only fibrosis tissue), and ME+ (mixture of 2 or 3 types of therapeutic effect) group. Indeed, we observed a significantly higher OS rate in the ME + group (86%) compared with the OS rate of LNs group with no therapeutic effect (57%) (p=0.028). Additionally, there was a significant association between the presence of fibrosis on LNs and an extended delay of more than 8 weeks to neoadjuvant treatment completion and surgery. Our study indicates that the best patient prognosis could be predicted based on tumor presenting a best pathologic effect on lymph nodes, and that delaying surgery for more than 8 weeks to neoadjuvant treatment completion improves therapeutic response on LNs.

Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population.

Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen's data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p = 0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p = 0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p = 0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p = 0.016, r = 0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.

[Voluminous colorectal foreign bodies inserted voluntarily: about a case]. / Volumineux corps étranger colorectal introduit volontairement: à propos d'un cas.

Insertion of foreign bodies is a curiosity and a taboo in our country. It is characterized by the severity of possible complications and the different therapeutic opportunities. We report the case of a patient with rectal incarceration of a vouminous object introduced voluntarily. He underwent manual extraction. Extraction, when possible, allow to avoid surgery that is necessary in the case of failure or complications.

Transverse colon volvulus presenting as bowel obstruction: a case report.

BACKGROUND: Transverse colon volvulus is an uncommon cause of bowel obstruction. The total number of cases reported in the literature is 100. It constitutes a surgical emergency since it can lead to bowel infarction, peritonitis, and death if not diagnosed at once. It seemed appropriate to report this case that was treated at the Department of Visceral Surgery A, University Hospital Center Hassan II of Fez in Morocco. CASE PRESENTATION: We report a rare case of transverse colon volvulus in a 42-year-old Arabic man, with no particular history, who presented to our emergency department with a 5-day history of constipation, progressive abdominal pain, nausea, and vomiting. His last bowel movement had been 3 days ago. Abdominal radiography showed a large bowel obstruction with a "U-shaped" loop in the left upper abdomen. Abdominal computed tomography was not performed because of impaired renal function. He was operated on urgently after conditioning and the diagnosis of a transverse colon volvulus was done intraoperatively. Rotated in a 360° clockwise direction on its mesentery, the bowel was intact without signs of ischemia. An extended right hemicolectomy was carried out with end-to-side ileocolic anastomosis. Through this case, we will try to discuss its physiopathology, etiologies, diagnosis, and management in emergencies. CONCLUSION: This case is unusual because no etiological factor has been found. Its diagnosis can be difficult and management effectiveness remains controversial. It is important to highlight this case and those of the literature, as many surgeons may have never seen a case of transverse colon volvulus. Volvulus of the transverse colon may therefore not be considered in the differential diagnosis of recurrent intermittent abdominal pain or acute intestinal obstruction. Prompt recognition with emergency intervention constitutes the key to a successful outcome.

[Acute intestinal intussusception revealing intestinal T-cell lymphoma in adults]. / Invagination intestinale aiguë révélant un lymphome T digestif chez l'adulte: à propos d'un cas.

Acute intestinal intussusception occurs primarily in infants and young children. It uncommonly occurs in adults. It can have various causes. In the vast majority of cases, it is secondary to a benign or malignant tumor. Intestinal T-cell lymphoma revealed by intestinal intussusception is very rare. We report the case of a 43-year old patient admitted with intestinal occlusion to the Emergency Department at the University Hospital Hassan II, Fes, Morocco. Abdominal CT scan showed acute intestinal intussusception associated with incarcerated bowel loop with bowel wall thickening. Treatment was based on open carcinological resection. Anatomopathological and immunohistochemical examination of the surgical specimen showed large T-cell anaplastic lymphoma. After surgery, chemotherapy was indicated to improve prognosis and to avoid a potential relapse. Intestinal intussusception rarely occurs in adults. It most often leads to the detection of an organic cause such as a tumor. This study and literature review aim to highlight the clinical and diagnostic features as well as the therapeutic approaches for this rare disease.

[Internal hernia through the falciform ligament: a rare cause of intestinal obstruction]. / Hernie interne du ligament falciforme: une cause rare d'occlusion intestinale.

Internal hernias are a rare cause of acute intestinal obstruction. Hernias through the falciform ligament is uncommon. Diagnosis is often made intraoperatively. Abdominal CT scan, performed in an emergency situation, can enable preoperative diagnosis and guide the therapeutic approach. In this respect, we here report a case whose data were collected in the Department of Visceral Surgery at the University Hospital Hassan II in Fez. The study involved a 48-year old patient, with no particular previous history, admitted to the Emergency Department with occlusion evolving over 4 days. Abdominal x-ray without treatment objectified multiple hydroaeric levels in small bowel some of which projected towards the hepatic region as well as the presence of a flat intestinal loop in continuity with distended intestinal segment. Abdominal CT scan was not performed due to altered renal function. The patient then underwent emergency surgery after stabilization of his condition and the diagnosis of internal hernias through the falciform ligament was made intraoperatively. In adults, internal hernia through the falciform ligament is a rare cause of acute intestinal obstruction in our daily practice. The diagnosis is most often made intraoperatively. It is necessary to suspect it in young patients with no history of abdominal surgery or intraperitoneal infectious process and with hydroaeric levels in the right upper quadrant.

Implication of Microsatellite Instability Pathway in Outcome of Colon Cancer in Moroccan Population.

BACKGROUND: Tumors with microsatellite instability (MSI tumors) have distinct clinicopathological features. However, the relation between these tumor subtypes and survival in colon cancer remains controversial. The aim of this study was to evaluate the overall survival (OS) in patients with MSI phenotype, in FES population. METHODS: The expression of MMR proteins was evaluated by immunohistochemistry for 330 patients. BRAF, KRAS, and NRAS mutations were examined by Sanger sequencing and pyrosequencing methods. The association of MSI status with a patient's survival was assessed by the Kaplan-Meier method and log-rank test. RESULTS: The mean age was 54.6 years (range of 19-90 years). The MSI status was found in 11.2% of our population. MSI tumors were significantly associated with male gender, younger patients, stage I-II, right localization, and a lower rate of lymph node and distant metastasis. The OS tends to be longer in MSI tumors than MSS tumors (109.71 versus 74.08), with a difference close to significance (P = 0.05). CONCLUSION: Our study demonstrates that MSI tumors have a particular clinicopathological features. The results of survival analysis indicate that the MSI status was not predictive of improved overall survival in our context with a lower statistical significance (P = 0.05) after multivariate analysis.

Squamous cell carcinoma associated anal fistulas in Crohn's disease unique case report with literature review.

Squamous cell carcinoma arising from perineal fistula in patients with Crohn's disease (CD) is a rare entity, with few reported cases in the literature making its clinical characterization troublesome. The outcome is poor following operative treatment as the malignancy of chronic perineal fistula in Crohn's disease is usually overlooked and tardily diagnosed. We present a unique case of a 47-year-old man with a 20-year history of chronic perineal fistula that was diagnosed with extensive perineal squamous cell carcinoma extending down to the right thigh. Computer tomography showed locally advanced disease with inguinal and lung metastasis. Treatment was consisted of diverting colostomy and palliative care. The patient died 3 months later. The clinical data and clinicopathological features of reported cases in the literature were reviewed.

Anorectal avulsion: an exceptional rectal trauma.

Anorectal avulsion is an exceptional rectal trauma in which the anus and sphincter no longer join the perineum and are pulled upward. As a result, they ventrally follow levator ani muscles. We present a rare case of a 29-years old patient who was admitted in a pelvic trauma context; presenting a complete complex anorectal avulsion. The treatment included a primary repair of the rectum and a diverting colostomy so as to prevent sepsis. Closure of the protective sigmoidostomy was performed seven months after the accident and the evolution was marked by an anal stenosis requiring iterative dilatations.

A case report of acute acalculous cholecystitis due to Salmonella Paratyphi B complicated by biliary peritonitis.

Non-typhoidal salmonella are a rare case of acute acalculouscholecystitis (AAC). Salmonella Paratyphi B, which accounts for one of the less invasive NTS serotypes, has rarely been reported to cause cholecystitis. We describe a case of 65-year old previously healthy man, who present with signs of acute abdomen, due to biliary peritonitis as a complication of acute acalculouscholecystitis caused by Salmonella paratyphi B. Our case illustrates the potential severity of infection with Salmonella Paratyphi B especially in older patient. High index of awarenessshould be considered in endemic areas.

Benign cystic mesothelioma of the peritoneum: a case report and literature review.

Benign cystic mesothelioma of the peritoneum (BCM) is an uncommon lesion with some 130 cases reported since the first case described by Smith and Mennenmeyer in 1979. It is a rare intra abdominal tumor occurring predominantly in women of reproductive age. Due to the rarity of this tumor, similarity of patient presentation, and comparable features on imaging, the diagnosis of this pathology is difficult, and is based on histological findings. This tumor is known for local recurrence. It's agreed that surgery is the only effective treatment, but there are no evidence-based treatment strategies for BCM.