Alessio Manaresi

Can elderly patients with colorectal cancer tolerate planned surgical treatment? A practical approach to a common dilemma

Aim  Analysing the effectiveness of a surgical procedure is mandatory in every modern health‐care system. The aging of the population stresses the need for a good standard of care. This study tests the hypothesis that porthsmouth‐physiologic operative severity score for enumeration of morbidity and mortality (P‐POSSUM) and colorectal‐POSSUM (CR‐POSSUM) would be useful clinical auditing tools in colorectal cancer surgery for aged patients.

The EGFR R521K polymorphism influences the risk to develop colorectal cancer.

Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been extensively investigated for its possible involvement in cancer development and progression. In colorectal cancer (CRC) EGFR family has been found frequently over-expressed, thus therapy targeting EGFR has been developed. Interestingly, it has been observed that genetic variants in these receptors may alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in members of the EGFR family could influence different biologic activities, such as ligands affinity, dimerization efficiency, kinase activity, expression levels, with a consequent impact in signalling pathways and cell behaviour. This study aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family members could represent susceptibility factors able to influence the risk to develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3 common non-synonymous SNPs. Genetic association tests were performed to verify a possible relationship with CRC. Evidence of genotype association was found for the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031). Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to develop CRC.

Diffuse cavernous haemangioma of the rectum and anus: an unusual case of rectal bleeding with challenging management

Diffuse cavernous haemangioma of the rectum (DCHR) is an uncommon vascular pathology usually diagnosed in younger patients (5–25 years old) with painless, recurrent rectal bleeding. Here, an unusual case of an older patient with sigmoid adenocarcinoma and concomitant diffuse DCHR from the rectum to the distal edge of the anal canal is reported. The purpose of this article is to report this unusual case and to discuss pitfalls in diagnosis, preoperative assessment and treatment of DCHR.

Prepouch ileitis, myth or reality? The first case with acute abdomen

To the Editor: Restorative proctocolectomy with ileo pouch–anal anastomosis (IPAA) is a well-established procedure for ulcerative colitis (UC) in selected patients. Pouchitis is a common condition in many patients after restorative proctocolectomy. A similar condition, termed prepouch ileitis, characterized by inflammation proximal to the pouch, has also been recently described. This condition is poorly understood and generally considered of little clinical relevance. We describe the first case of a potential life-threatening complication from perforated ileitis of the new terminal ileum 2 years after restorative proctocolectomy for a nonresponder UC. In May 2004 a 62-year-old man with a history of UC nonresponding to medical treatment was referred for surgery. Restorative proctocolectomy (RPC) with IPAA and diverting loopileostomy was performed. The postoperative course was uneventful and 3 months later the patient underwent ileostomy closure with side-to-side mechanical anastomosis. In January 2006 the patient was diagnosed with rheumatic polymyalgia and uveitis and treated with immunosuppressants. In September 2006 he was admitted to the Emergency Department complaining of nausea, vomiting, fever, abdominal pain, and hematic diarrhea. Chest and abdominal x-rays were within normal limits. Pouchoscopy with biopsies was performed and he was treated for acute pouchitis with antibiotics and mesalazine with little improvement. Two weeks later he was transferred to our surgical unit with signs of peritonitis. The laboratory data were within normal limits. A double contrast computed tomography (CT) scan (intravenous and transanal) was performed: a copious amount of free abdominal air was detected and minimal leakage of the transanal contrast was found in the new terminal ileum (NTI); the pouch was regular (Fig. 1). A significant amount of purulententeric fluid was detected in the abdomen with clear signs of diffuse peritonitis (fluid culture was positive for E. coli and Enterococcus faecium). A double perforation was detected at the site of the side-to-side anastomosis (previously made for the ileostomy closure) located about 30 cm above the IPAA. Ileal resection, closure of the distal ileal stump, and end-ileostomy was performed. The postoperative period was complicated by prolonged septic status in the intensive care unit. Twenty-five days after surgery he was discharged in good condition. Two years later the patient is in good health. Laboratory analysis, pouchgram, pouchoscopy, and enteric magnetic resonance imaging (MRI) are all within normal limits. The macroscopic appearance of the specimen showed a severe ulcerating mucosa with 2 full-thickness discontinuities through the bowel (Fig. 2a). Villous atrophy alternated with pseudopolypoid lesions; mucosal chronic inflammatory cell infiltrate accompanied by neutrophils in the lamina propria were detected (Fig. 2b,c). Granuloma was not seen in any section. A second analysis of the previously resected colon and rectum excluded Crohn’s disease (CD) or indeterminate colitis (IC). A diagnosis of prepouch Ileitis (PI) was made according to the histopathological features reported by Bell et al. Pouchitis is a common condition after restorative proctocolectomy. Bell et al recently reported a series of 15 patients (2.6% of 571), with inflammation of the NTI after RPC with IPAA for pathologically confirmed UC. They describe this pathologic condition as a distinct disease called PI. Clinical and histochemical characteristics seem to overlap with pouchitis. PI seems to have a distinct etiopathogenesis and can occur independently of pouchitis, CD, or IC. Coexistent pouchitis was reported only in 7/15 patients (47%). Other authors have described this condition, which is often associated with chronic refractory pouchitis and mucosal changes that lessen in severity at the more proximal end. What we describe here is a case of acute abdomen following perforation of the NTI 2 years after RPC and IPAA. Terminal ileitis was not found to be associated with CD or IC. This is the first reported case of perforated PI. Endoscopic evaluation of the NTI should become mandatory for patients after proctocolectomy and IPAA who present with clinical symptoms of pouchitis, even in the absence of any direct evidence of pouch inflammation. Although nowadays no relation is identified with any risk factor, nevertheless a side-to-side ileostomy closure could be a circumstance predisposing for fecal stasis resulting in mucosal irritation and inflammation. This aspect should be considered in further analysis of the phenomenon. Despite the limited clinical magnitude, clinicians should be aware that perforation of the NTI can occur. This life-threatening complication should be included in the differential diagnosis of patients with abdominal pain after RPC.

The R521K polymorphism of EGFR influences the risk of colorectal cancer

In colorectal cancer (CRC) epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been found frequently over-expressed. New therapies directed against EGFR have been developed in many human cancers. Unexpectedly, EGFR alterations could be good prognostic indicators, like in lung cancer, where an EGFR variant in non-smoker female patients is associated with higher survival after surgery and increases the efficiency of therapy based on EGFR inhibitors. The role of the genetic polymorphisms of the EGFR family members in colorectal cancer development has not been completely explored. In our preliminary study, three missense polymorphisms mapping in EGFR family members have been investigated in the peripheral blood of a small Italian sample size of 70 patients and 72 controls to verify if they could be considered CRC susceptibility factors. For the first time, the evidence of genotype association was found for the R521K EGFR polymorphism: the protective effect for this variant allele has been found to reduce the risk for colon cancer onset.

A preliminary audit experience of surgery for rectal cancer after neoadjuvant chemoradiation therapy

AIMS AND BACKGROUND A surgical audit is a systematic critical analysis of surgical performance, with the goal to improve the quality of patient care. Rectal cancer surgery is one of the most delicate procedures in the field of surgical oncology, with significant variations in terms of complications from center to center. Neoadjuvant chemoradiation therapy leads to a significant reduction in local recurrences in patients with locally advanced lower and medium rectal cancer. The aim of the study was to evaluate the influence of neoadjuvant chemoradiation therapy on postoperative morbidity and mortality in patients with rectal cancer. METHODS AND STUDY DESIGN From January 1, 2003, to December 31, 2007, patients who underwent elective surgical resection for lower and medium rectal cancer in our Surgical Unit were prospectively analyzed. Patients (n=42) were divided into two groups: (1) those treated with neoadjuvant chemotherapy and consequent surgical resection (19/42); (2) those treated with primary surgical treatment (23/42). P-POSSUM (Portsmouth Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity) and CR-POSSUM (ColoRectal-POSSUM) scores were calculated for each patient group. Thirty-day mortality and morbidity rates were prospectively collected in a comprehensive data base. Data were evaluated by comparing the predictions of the two scoring systems in both study groups with clinically observed mortality and morbidity rates. RESULTS In group 1, no death was registered (0/19). The P-POSSUM and CR-POSSUM expected mortality was 2.43% and 4.52%, respectively (P > 0.05). In group 2, a single death was documented (1/23, 4.35%). The P-POSSUM and CR-POSSUM expected mortality was 2.1% and 4.94%, respectively. The postoperative complications rate for group 1 was 10.52% (2/19) compared to 34.88% as expected from the P-POSSUM score (P < 0.05). In group 2, a postoperative complication rate of 39.13% (9/23) was observed compared to 34.26% as expected from the P-POSSUM score (P > 0.05). CONCLUSIONS No significant influence on morbidity or mortality was detected in patients who underwent neoadjuvant radio-chemotherapy.