Carlo Rossetti

Surgical treatment of locally recurrent rectal carcinoma

PURPOSE: This study was performed to analyze the outcomes of patients with local (pelvic) recurrence (following radical surgery for rectal cancer) who subsequently underwent a new operation. METHODS: Forty-five patients (19 percent of 213 local recurrences) were explored surgically because the disease was deemed to be confined to the pelvis with a limited extension and, therefore, amenable to surgical cure. RESULTS: Only 21 of the 45 patients who underwent surgical exploration had an oncologically radical operation (RO). In the remaining 24 patients, either a simple exploration or palliation or a nonradical procedure (R1-R2) was performed. In the RO group, there was a 19 percent five-year survival ratevs.a 0 percent rate in the R1-R2 group (median survival, 4 months). Site of recurrence (anastomosisvs.other sites) was statistically associated with a higher chance of long-term survival for those who underwent an RO operation. CONCLUSIONS: The prognosis of locally recurrent rectal cancer is dismal; less than 10 percent of all patients who underwent surgical treatment benefit from reoperation with an overall survival for five years. On the basis of these results, we no longer consider the surgical approach as the primary option for treating locally recurrent rectal cancer.

Phase I-II study of hypofractionated simultaneous integrated boost using volumetric modulated arc therapy for adjuvant radiation therapy in breast cancer patients: a report of feasibility and early toxicity results in the first 50 treatments

BackgroundTo report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery.MethodsBetween September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor.ResultsThe median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up.ConclusionsThe 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes.

Fourteen Italian families affected with hereditary nonpolyposis colorectal cancer (HNPCC) were screened for germline mutations at three DNA mismatch repair (MMR) genes, MSH2, MLH1, and GTBP, by using a combination of different methods that included an in vitro synthesized protein assay, single‐strand conformation polymorphism analysis, and direct sequencing. DNA alterations were observed in six instances, including a single base deletion in MSH2 exon 14, an A‐to‐G transition in the splice donor site of MLH1 exon 6, and two missense mutations in MLH1 exons 5 and 9. A previously reported common mutation affecting the splice donor site of MSH2 exon 5 was identified in two families. No mutations were detected in the GTBP gene. In total, eight of 16 Italian HNPCC families (50%), including two previously reported kindreds, were found to carry a mutation in MMR genes. We compared the mean age of colorectal cancer onset in the index cases (three patients for each family) between the two groups of kindreds, those with identified mutation vs. those without, and found that the first had a significantly lower value (43.0 vs. 53.7 years, P = 0.014). This finding suggests that HNPCC families with a more advanced age of tumor onset are less likely to be associated with known MMR genes. Genes Chromsom. Cancer 19:135–142, 1997.

COLORECTAL CANCER: WHAT HAS CHANGED IN DIAGNOSIS AND TREATMENT OVER THE LAST 50 YEARS?

Aims and background This overview focuses on what has changed in the diagnosis and treatment of colorectal cancer over the last 50 years. Methods The most important international registers (SEER, European and Italian) as well as the literature have been consulted. Furthermore, many prognostic factors are analyzed with the aim to understand the reasons why 5-year survival has improved over the last two decades. Results Since the biologic characteristics of the tumor cannot be changed, improved survival must be supported by concomitant multiple factors, such as earlier diagnosis (as given by a more informed educational behavior and the advent of screening) as well as the wide use of colonoscopy and the technical improvement of surgical and medical treatment. However, it seems that the greatest improvement in survival is limited to 5-year controls, whereas long-term survival does not appear to show any significant improvement. Conclusions We can hypothesize that our efforts have just delayed the inevitable end: death. Nevertheless, further research should be done to confirm this hypothesis, perhaps in the field of molecular biology, which may also be the right approach to understanding the biologic aggressiveness of each tumor.

Clinical aspects and management of hereditary non-polyposis colorectal cancer (HNPCC)

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomical dominant trasmitted disease phenotypically defined according to the “Amsterdam criteria” as follows: at least 3 affected relatives, one of whom first degree relative of other two, at least two successive generations affected. Important cardinal features are: 1 prevalent proximal location of cancers (above splenic flexure); 2 multiple synchronous or methachronous large bowel cancers; 3 early age of onset (<50 years); 4 presence of extracolonic cancers (endometrium, stomach, urinary tract, skin). The treatment is essentially surgical and total colectomy with ileo-rectum anastomosis is already proposed as standard procedure with annual endoscopic examination of retained rectum. The screening of individuals at risk, so determined by the analysis of pedigree or the results of molecular tests, must be performed every 1-2 years by colonoscopy starting around the age of 25 years. In this review are described and analysed the spectrum of the disease with particular attention to the frequency and characteristics of extracolonic cancers. Moreover, the guidelines of the surveillance and screening are reported following the data of the literature and as proposed by the International Collaborative Group (ICG-HNPCC).

Different expressivity of two adjacent mutations of the APC gene.

Aims and background The phenotypic expression of different APC mutations in familial adenomatous polyposis (FAP) is variable: two to three variants of the disease have been defined based on the severity of colonic manifestations. Age of onset and number of polypectomies per person-year of postsurgical follow-up were compared in two FAP families with very close mutation sites in the APC gene, in order to ascertain mutation-specific variation of expressivity. Families and APC mutations Family A (5 patients) carried a newly characterized mutation, a four bp deletion at codon 843. Family B (5 patients) carried a previously identified mutation at codon 835. Results Mean age of onset was 49.7 years in family A and 30.5 years in family B; number of polypectomies per person-year of follow-up was 1.05 for family A and 10.1 for family B (P <0.001). Conclusions There is significant variation of expressivity (allelic heterogeneity) in FAP between two mutations separated by only eight codons, located at the 5’ extremity of APC gene exon 15.

NEUTROPENIC ENTEROCOLITIS: IS THERE A RIGHT TIMING FOR SURGERY? ASSESSMENT OF A CLINICAL CASE

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.

Abnormal pattern of mucin secretion at the resection margin of colorectal carcinomas.

In a retrospective study, we investigated 56 consecutive patients who had undergone radical intestinal resection for colorectal adenocarcinoma and who had developed local or distant recurrences of the disease. We found that the presence of a predominant sialomucin pattern at the margins of resection of the surgical specimen was correlated with a high percentage of local, endoluminal recurrence in the anastomotic mucosa. In contrast, no correlation could be found when the recurrences occurred in the outer tissues around the anastomosis or at some distance from it.