Clinico-pathological associations and concomitant mutations of the RAS/RAF pathway in metastatic colorectal cancer.

BACKGROUND: Over the past few years, next-generation sequencing (NGS) has become reliable and cost-effective, and its use in clinical practice has become a reality. A relevant role for NGS is the prediction of response to anti-EGFR agents in metastatic colorectal cancer (mCRC), where multiple exons from KRAS, NRAS, and BRAF must be sequenced simultaneously. METHODS: We optimized a 14-amplicon NGS panel to assess, in a consecutive cohort of 219 patients affected by mCRC, the presence and clinico-pathological associations of mutations in the KRAS, NRAS, BRAF, and PIK3CA genes from formalin-fixed, paraffin-embedded specimens collected for diagnostics and research at the time of diagnosis. RESULTS: We observed a statistically significant association of RAS mutations with sex, young age, and tumor site. We demonstrated that concomitant mutations in the RAS/RAF pathway are not infrequent in mCRC, and as anticipated by whole-genome studies, RAS and PIK3CA tend to be concurrently mutated. We corroborated the association of BRAF mutations in right mCRC tumors with microsatellite instability. We established tumor side as prognostic parameter independently of mutational status. CONCLUSIONS: To our knowledge, this is the first monocentric, consecutively accrued clinical mCRC cancer cohort tested by NGS in a real-world context for KRAS, NRAS, BRAF, and PIK3CA. Our study has highlighted in clinical practice findings such as the concomitance of mutations in the RAS/RAF pathway, the presence of multiple mutations in single gene, the co-occurrence of RAS and PIK3CA mutations, the prognostic value of tumor side and possible associations of sex with specific mutations.

The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer.

BACKGROUND: Adequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters. METHODS: A total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation. RESULTS: One-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 - 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0-39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006).Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes. CONCLUSION: In TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression.

Primary omental torsion: A case report.

A patient presented with an acute abdomen at the Emergency Department. The patient, a 69-year-old man, was admitted and underwent surgery with a provisional diagnosis of acute appendicitis. During surgery, omental torsion was diagnosed and the involved omentum was removed. The patient had no previous surgical history. Omental torsion is a rare cause of acute abdomen in children and adults who may present with various signs and symptoms; a preoperative diagnosis may therefore be difficult and can usually only be established during surgery.

Factors that influence 12 or more harvested lymph nodes in resective R0 colorectal cancer.

BACKGROUND/AIMS: The number of lymph nodes required for accurate staging is a critical component in colorectal cancer (CRC). Current guidelines demand at least 12 lymph nodes to be retrieved. Results of previous studies were contradictory in factors, which influenced the number of harvested lymph nodes. This study was designed to determine the factors that influence the number of harvested lymph nodes (> or = 12) in resective R0 early-stage CRC in a single institution. METHODOLOGY: Between July 2005 and December 2008, data on 225 patients who underwent surgery for CRC were retrospectively evaluated. Data for a total of 139 R0-surgery patients were collected and all the tumor-bearing specimens were fixed with node identification performed. Several possible factors that influence 12 or more harvested lymph nodes were investigated and classified into four aspects: (1) operating surgeon, (2) examining pathologist, (3) patient (age, sex, and body mass index) and (4) disease (tumor localization, tumor cell differentiation, tumor stage, type of resection). RESULTS: A total of 100 patients (71.9%) with 12 or more harvested lymph nodes and 39 patients (28.1%) with < 12 lymph nodes were analyzed. The results demonstrate that within a single institution, tumor localization, depth of tumor invasion according to Dukes stage and grading were independent influencing factors of 12 or more harvested lymph nodes. Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. CONCLUSIONS: The number of harvested lymph nodes was highly variable in patients who underwent resection of R0 CRC. Neither the operating surgeon nor the examining pathologist had significant influence over the number of harvested lymph nodes. Therefore, from the viewpoint of the surgeons, disease itself is the most important factor influencing the number of harvested lymph nodes.

Colon and rectal surgery for cancer without mechanical bowel preparation: one-center randomized prospective trial.

BACKGROUND: Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. The aim of the study was to assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation. METHODS: Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications. RESULTS: Two hundred forty four patients were included in the study, 120 in group A and 124 in group B. Demographic characteristics, type of surgical procedure and type of anastomosis did not significantly differ between the two groups. There was no difference in the rate of surgical infectious complications between the two groups but the overall infectious complications rate was 20.0% in group A and 11.3% in group B (p .05). Wound infection (p = 0.18), anastomotic leak (p = 0.52), and intra-abdominal abscess (p = 0.36) occurred in 9.2%, 5.8%, and 5.0% versus 4.8%, 4.0%, and 2.4%, respectively. No mechanical bowel preparation seems to be safe also in rectal surgery. CONCLUSIONS: These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.

Urachal tumour: case report of a poorly understood carcinoma.

BACKGROUND: Urachal carcinoma is an uncommon neoplasm associated with poor prognosis. CASE PRESENTATION: A 45-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. TC-scan revealed a 11 x 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. The tumor was removed surgically. Histological examination detected poor-differentiated adenocarcinoma, which had invaded the urinary bladder. The patient has been followed up without recurrence for 6 months. CONCLUSION: The urachus is the embryological remnant of urogenital sinus and allantois. Involution usually happens before birth and urachus is present as a median umbilical ligament. The pathogenesis of urachal tumours is not fully understood. Surgery is the treatment of choice and role of adjuvant treatment is not clearly understood.

Complicated small-bowel diverticulosis: a case report and review of the literature.

Here we report a case of a 60 years old woman who came to the Emergency Department of San Martino Hospital suffering from abdominal pain for about a week with high fever in the last 24 hours. The final histological examination led to the diagnosis of ileal diverticulosis associated with perforation and peritonitis with a fibrotic reaction involving the last ileal loop, the caecum and the appendix.

Small bowel metastasis from primary neuroendocrine small cell lung carcinoma.

Small bowel metastases from a primary lung carcinoma are rare. We report a case of a 76-year-old male with a primary neuroendocrine small cell carcinoma of the lung, treated by chemotherapy, who developed fever and bowel symptoms (subocclusion and pain). On CT examination, he was found to have a tumour in the small bowel. The patient then underwent abdominal surgery. At operation we found small bowel occlusion by neoplasia and we therefore resected 15 cm of ileum with a side-to-side anastomosis. Early recognition of this rare condition is important due to the fact that complicated intestinal metastases from lung carcinoma can lead to high mortality rates and poor short-term outcomes. With advances in chemotherapy and palliative care, patients with metastatic lung carcinoma can sometimes survive more than a year with a reasonable quality of life.