Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial.

BACKGROUND: Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAFV600E status in stage III CC patients. METHODS: All stage III CC patients from the PETACC-8 randomized trial tested for MSI, RAS and BRAFV600E status were included. The site and characteristics of recurrence were analyzed according to molecular status. Survival after recurrence (SAR) was analyzed. RESULTS: A total of 1650 patients were included. Recurrence occurred in 434 patients (26.3%). Microsatellite stable (MSS) patients had a significantly higher recurrence rate (27.2% vs. 18.7%, P = 0.02) with a trend to more pulmonary recurrence (28.8% vs. 12.9%, P = 0.06) when compared to MSI patients. MSI patients experienced more regional lymph nodes compared to MSS (12.9% vs. 4%, P = 0.046). In the MSS population, the recurrence rate was significantly higher in RAS (32.2%) or BRAF (32.3%) patients when compared to double wild-type patients (19.9%) (p < 0.001); no preferential site of recurrence was observed according to RAS and BRAFV600E mutations. Finally, decreased SAR was observed in the case of peritoneal recurrence or more than two recurrence sites. CONCLUSIONS: Microsatellite, RAS and BRAFV600E status influences recurrence rates in stage III CC patients. However, only microsatellite status seems to be associated with specific recurrence patterns. More than two recurrence sites and recurrence in the peritoneum were associated with poorer SAR.

Role of transanal irrigation in the treatment of anterior resection syndrome.

BACKGROUND: Transanal irrigation(TAI) has been reported to be an inexpensive and effective treatment for low anterior resection syndrome(LARS). The aim of the present prospective study was to evaluate the use of TAI in patients with significant LARS symptoms at a single medical center. METHODS: Patients who had low anterior resection for rectal cancer between April 2015 and May 2016 at the Careggi University Hospital were assessed for LARS using the LARS and the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI) questionnaires 30-40 days after  surgery or ileostomy closure (if this was done). Quality of life was evaluated using a visual analog scale and the Short Form-36 Health Survey. All patients with LARS score of 30 or higher were included (early LARS) as were all patients with a LARS score of 30 or higher referred 6 months or longer after surgery performed elsewhere (chronic LARS) in the same study period. Study participants were trained to perform TAI using the Peristeen™ System for 6 months, followed by 3 months of enema therapy following a similar protocol. RESULTS: Thirty-three patients were enrolled in the study. Six patients stopped the treatment. The 27 patients (19 early LARS and 8 chronic LARS) who completed the study had a significant decrease in the number of median daily bowel movements [baseline 7 (range 0-14); 6 months 1 (range 0-4); 9 months 4 (range 0-13)]. The median LARS Score fell from 35.1 (range 30-42) (baseline) to 12.2 (range 0-21) after 6 months (p < 0.0001) and then rose to 27 (range 5-39) after 3 months of enema therapy. There was no difference in LARS score decrease at 6 months between the patients with early and chronic LARS (22.5 and 23.9 respectively; p=0.7) and there were no predictors of score decrease. Four components of the SF-36 significantly improved during the TAI period. The MSKCC BFI score significantly improved in several domains. Twenty-three patients (85%) asked to continue the treatment with TAI after the study ended. CONCLUSIONS: TAI appears to be an effective treatment for LARS and results in a marked improvement of continence and quality of life.  Patients may be assessed and treated for LARS early after surgery since the treatment benefit is similar to that observed in patients with LARS diagnosed  6 months or longer after surgery. The potential rehabilitative role of TAI for LARS is promising and should be further investigated.

Gastric Antral Vascular Ectasia (GAVE) a case report, review of the literature and update of techniques.

INTRODUCTION AND IMPORTANCE: Gastric Antral Vascular Ectasia is a rare disorder that causes up to 4 % of severe acute gastrointestinal bleeding. It affects elderly females with iron deficiency anemia due to chronic blood loss as a common presenting sign. CASE PRESENTATION: We report the case of a 70-year-old man admitted to the Urgency Department for severe asthenia associated with abdominal pain and severe anemia. An urgent upper endoscopic examination showed antral hyperemic streaks and vascular ectasias extending from the pyloric ring to the gastric body as well as signs of recent bleeding. Histological results demonstrated the pathognomonic features of GAVE. CLINICAL DISCUSSION: The first line treatment is considered argon plasma coagulation (APC), given its wider availability, safety, efficacy and cost-effectiveness. In current literature, other therapies and different types of endoscopic treatments have been proposed, such as EBL, RFA and Yag: laser. To date, there is no specific recommendation that privileges one method over another in the treatment of GAVE, although APC has proven effective and even better in terms of complications and costs than the other techniques. CONCLUSION: In our experience, endoscopic coagulation with APC probes is a relatively easy-to-use technique with low cost, minimal invasiveness and provides immediate results. On the other hand, a standardized algorithm is also required concerning to the different subtypes to give the best treatment in every case.

A unique presentation of a renal clear cell carcinoma with atypical metastases.

INTRODUCTION: Renal cancer is a relatively common neoplasia with renal clear cell carcinoma being the most frequent histological type. This tumor has a strong tendency to metastasize virtually to all organs. Today, new diagnostic tools allow physicians to distinguish between those patients with "incidental findings" and those with advanced metastatic disease. PRESENTATION OF CASE: A 70-year-old male with multiple indolent subcutaneous masses underwent colonoscopy after a positive fecal screening test for colorectal carcinoma. A rectal lesion was discovered but biopsy was negative. CT scan revealed advanced renal cancer involving the peritoneal cavity, retroperitoneum and lung. Biopsy of subcutaneous masses confirmed the suspected metastases. The patient underwent surgery (an open left nephrectomy with rectosigmoid resection and metastases debulking) because of a high risk of bowel obstruction and increasing anemia. After three years of multi-targeted therapy and follow-up, the patient is still asymptomatic and in good general condition. DISCUSSION: Treatment of metastatic renal cancer is still controversial even if more than 30% of patients have metastasis at the time of diagnosis. Recently introduced targeted therapies are encouraging but still present problems with side effects and an unlimited period of efficacy. Although there is no consensus, several studies and guidelines consider metastasectomy to be a valid option. CONCLUSION: Recent series highlight surgery as a key-point in the management of advanced renal clear cell carcinoma. Our case demonstrates the validity of a surgical strategy supported by a multidisciplinary approach.

Analysis of the optical properties of bile.

Invasive bile determination is very useful in the diagnosis of many gastric pathologies. At the moment, this measurement is performed with Bilitec 2000, an optical fiber sensor, that is based on absorption by bilirubin. Nevertheless, erroneous evaluations are possible, due to the different configurations which the bilirubin molecule can adopt. The optical behavior of human samples of pure bile and bile+gastric juice has been examined using an optical fiber spectrophotometer and two suitably modified Bilitec 2000 units. A protocol has been established for the treatment of biological fluids, in order to make it possible to study the behavior of their optical properties as a function of pH and concentration without causing any alteration in the samples. The analysis of pH dependence evidenced the presence of different calibration curves at different pH values: the self-aggregation of the bilirubin molecules observed in pure bile samples was almost totally absent in the gastric samples. Measurements carried out on Bilitec 2000 showed that the most appropriate wavelength for bilirubin detection in the stomach should be 470 nm.

Marked variation of thymidylate synthase and folylpolyglutamate synthetase gene expression in human colorectal tumors.

Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.

Microsatellite instability in a population of sporadic colorectal cancers: correlation between genetic and pathological profiles.

BACKGROUND: Tumours with high-frequency microsatellite instability exhibit unique genotype and phenotype features, whereas the difference between low-frequency microsatellite instability and apparently stable tumours is far from being clear. AIMS: To identify distinctive genetic and pathological characteristics of low-frequency microsatellite instability tumours. METHODS: Microsatellite instability status of 57 sporadic colorectal cancers and its correlation with genetic, pathological and clinical features was analysed. RESULTS: High frequency microsatellite instability and low-frequency microsatellite instability and apparently stable cancers were different in terms of tumour localisation (p=0.015), frequency of APC mutations (p=0.012), occurrence of Crohn's-like/lymphoid reaction (p=0.0353) and morphological evidence of origin from an adenoma (p=0.0338). Specifically, in low-frequency microsatellite instability cancers, APC mutations were very frequent (76.9%, 10/13) and a Crohn's-like/lymphoid reaction was common (38.5%, 5/13). High-frequency microsatellite instability tumours were preferentially located in the right colon and exhibited a higher frequency of loss of heterozygosity at the FHIT locus compared with low-frequency microsatellite instability and apparently stable cases (p=0.0243). Dukes' stage (p=0.0021), tumour localisation (p=0.0410) and pattern of cancer growth (p=0.0374), were the only factors affecting patient survival. However, a borderline improvement was noted in overall survival in high-frequency microsatellite instability and low-frequency microsatellite instability cancer patients (p=0.062). CONCLUSIONS: These results indicate that low-frequency microsatellite instability tumours have different genetics and histological features and suggest that they are a distinct group of colorectal cancers.