Small bowel carcinoma revealing HNPCC syndrome.

Small bowel adenocarcinoma is a rare condition with poor prognosis. Like colorectal cancer, small bowel carcinoma may be a part of genetic syndromes with carcinogenetic pathways different from sporadic forms. We report a case of 41-year-old man with small bowel carcinoma revealing hereditary non polyposis colorectal cancer (HNPCC) syndrome. This report supports the systematic study of the MSI status in every patient with a small bowel carcinoma below 60-year-old of age in order to screen for HNPCC syndrome even in the absence of a family history of related cancers.

[Single-center cohort study of elderly patients with surgically removed colorectal cancers]. / Patients agés opérés et pris en charge pour un cancer colorectal: etude d'une cohorte monocentrique.

Incidence of colorectal cancers (CRCs) increases with age. The surgical and medical management of elderly patients needs to be improved. Until recently, these patients were not included into controlled clinical trials. Between 2004 and 2007, 88 patients (median age 79) had surgery for CRC in our hospital. In half the cases, patients had an emergency surgery (40/88). Twenty patients had dementia, with no relationships between dementia and emergency surgery (50% vs. 45% for patients without dementia), nor between dementia and median length of hospital stay (16 days vs. 22 days). In metastatic setting (20 patients), chemotherapy was omitted in 10 cases, usually patients with dementia (5 patients; p = 0.002) Standard therapy was hardly applicable because many patients were frail. In the future, usefulness of participation to the staffs of a geriatrist will be assessed prospectively.

[Colorectal cancer in elderly patients]. / Cancer colorectal et sujets âgés: y a-t-il une spécificité de prise en charge?

Colorectal cancer (CRC) is predominantly a disease of the elderly. The increase of life expectancy will no doubt lead to an increase of these cancers. Few studies have been specially designed for older patients treated for CRC. In general, publications consisted of small phase II studies or retrospective analyses of the subpopulation of elderly patients (from large phase III) -- patients over the age of 65 as compared with younger patients. Therefore we now need to offer specific treatment combining oncologist and geriatric physicians to better codify and adapt treatments to the physiological age of the patient. This is a review of the different stages of care for elderly patients with colorectal cancer in the light of recent publications.

[Bone metastases pain in the elderly]. / Douleurs des métastases osseuses chez le patient âgé.

Every year in Europe and in USA, more than 60% of new cases of cancer are diagnosed at the patient's of more than 65 years with a mortality of more than 70%. Pain, is a major symptom which often accompanies cancer. It is always painful and intolerable, notably when pain is linked to bone metastases to elderly patients often poly pathological. In 1/3 of cases pain is present at the time of diagnosis of cancer and in 2/3 of cases at the advanced diseases. The bone metastases occupy the third place after the pulmonary and liver metastases. They are in order of frequency linked in breast cancer, the kidney and the prostate cancer. Bone metastases are at the origin of the loss of the elderly autonomy, with for consequence an impairment of quality of life. Validated tools are at now available to assess this pain. The different treatments offered in bone metastases pain are: the chemotherapy, the surgery, radiotherapy, bisphosphonates and analgesic treatment.

Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation.

Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP). We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.

Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer.

BACKGROUND: Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer. PATIENTS AND METHODS: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria. RESULTS: Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients. CONCLUSION: No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.

[Sunitinib and hypothyroidism]. / Sunitinib et hypothyroïdie.

Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.

[Gefitinib treatment for carcinomatous meningitis in non-small cell lung cancer]. / Géfitinib et méningite carcinomateuse d'un carcinome bronchique non à petites cellules (CBNPC).

BACKGROUND: Carcinomatous meningitis is a major complication in Non Small Cell Lung Cancer (NSCLC). Despite treatment with radiotherapy alone or in combination with intrathecal and systemic chemotherapy, its prognosis remains poor. OBSERVATION: We report a case of a female non-smoker with adenocarcinoma with bronchoalveolar features presenting with carcinomatous meningitis three years after the diagnosis of her primary tumour. Gefitinib treatment was proposed because of the persistence of meningitic symptoms despite cranial irradiation. Clinical response was observed within 3 weeks and lasted for 9 months. CONCLUSION: Gefitinib may be effective in treating carcinomatous meningitis complicating NSCLC and should be considered in this situation given the absence of effective alternatives.

[Biotherapy in colorectal cancer]. / Biothérapies dans le traitement des cancers colorectaux.

Strategies for the treatment of metastatic colorectal cancer must take into account the contribution of monoclonal antibodies. A group of new efficient tools in oncology, these drugs target tumor antigens. Bevacizumab recognizes VEGF. Vascular endothelial growth factor (VEGF) is a key mediator in angiogenesis. This antibody combined with chemotherapy increases the survival of patients treated for metastatic colorectal cancer. Median survival of patients treated with antibodies and chemotherapy is 20 months, compared with only 15 months for patients treated with chemotherapy alone. Cetuximab is a monoclonal antibody that binds competitively and with high affinity to the EGF receptor. Cetuximab is currently approved for use in patients with pretreated colorectal cancer. EGF is a major cell growth factor. The side effects of these new biotherapies are different from chemotherapy: bevacizumab affects vascular elements and the most common side effect of anti-EGFR treatment is acneiform skin rash.

Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicentre study.

BACKGROUND: A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup. PATIENTS AND METHODS: This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses. RESULTS: We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P<0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P<0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002). CONCLUSIONS: Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

[Local recurrence after conservative therapy of breast cancer: risk factors, site of recurrence, evolution]. / Récidives mammaires après traitement conservateur du cancer du sein: facteurs de risque, topographie des récidives, évolution.

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

[At last, an effective therapy for non-differentiated GI sarcomas (gastro intestinal stromal tumor)]. / Enfin un traitement efficace dans les sarcomes digestifs indifférenciés (tumeurs stromales).

Gastrointestinal stromal tumors (GISTs) are non differentiated sarcoma of the gastrointestinal tract and have for a long time been confused with well differentiated tumors and classified as leiomyosarcoma. These tumors are characterized immunohistochemically by CD 117 staining. This marker represents the expression of c-kit which is a receptor for growth factor with enzymatic activity (tyrosine kinase). Recent studies have found that an inhibitor of specific tyrosine kinase is effective in the treatment of GIST with an estimated response rate of more than 60%. This new drug could significantly improve the prognosis of these aggressive chemoresistant tumors.

[Micrometastases in colonic cancers: diagnostic methods and prognostic elements]. / Les micrométastases dans les cancers coliques: méthodes diagnostiques et éléments pronostiques.

Micrometastasis are defined by the existence of cells or groups of cells in target organs. In the particular cas of colon cancers, although lymph node involvement is frequent, metastatic medullary involvement (while rarely at the origin of identified metastasis) can also be observed. Furthermore, micrometastatics cells can be identified in the circulating blood. This research relies on recent technics of immunocytochemistry with image analysis or molecular biology technics (generally PCR or RT-PCR). It is essential to have a specific reliable marker of metastatic cells. The prognostic value of identifying micrometastasis in organs also remains to be defined.

Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX.

BACKGROUND: Colorectal cancer (CRC) patients whose tumours have microsatellite instability (MSI) do not benefit from adjuvant 5-fluorouracil. However, the predictive value of MSI is not known for FOLFOX, now recommended in adjuvant setting. PATIENTS AND METHODS: MSI phenotype was assessed by the pentaplex method. Three-year relapse and disease-free survival (DFS) of patients treated for CRC with FOLFOX 4 in an adjuvant setting were compared according to MSI phenotype. RESULTS: A total of 105 patients (19 MSI, 86 microsatellite stable, MSS) were included. Stage II patients more frequently exhibited MSI (58%) than MSS (21%); (p=0.002). Patients with MSI relapsed significantly less than those with MSS (10.5% vs. 35.0%; p=0.04). DFS was similar for MSI and MSS (p=0.1). In univariate analysis, stage (p=0.0006) and MSI status (p=0.017) were significant predictors of DFS. CONCLUSION: MSI status was associated with significantly fewer relapses and a better prognosis. FOLFOX4 did not alter survival of patients with MSI and can be administered to them.