Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study.

BACKGROUND: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS: A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS: In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION: In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.

The Frequency of Germline BRCA and Non-BRCA HR-Gene-Variants in a Cohort of Pancreatic Cancer Patients.

Germline DNA alterations affecting homologous recombination pathway genes have been associated with pancreatic cancer (PC) risk. BRCA2 is the most studied gene and affects the management of PC patients and their families. Even though recent reports have suggested a similar role of germline ATM pathogenic variants (PV) in familial PC, there is still a disagreement between experts on how it could affect patient management given the lack of proper PC risk estimates. We retrospectively analyzed the germline data of 257 PC patients among whom nearly 50% were sporadic cases. We showed similar frequencies of BRCA2 (4.9%) and ATM (4.4%) PV or likely pathogenic variants, which were not related to familial history. Based on our findings and that of the literature, we suggest including ATM gene among the panel of genes analyzed in PC patients pending the publication of prospective studies.

Is intra-arterial hepatic chemotherapy painful?

BACKGROUND: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration. This pain is related to extrahepatic infusion and gastroduodenal ulceration. However, intense abdominal pain was observed under oxaliplatin IAHC specifically without any extrahepatic infusion. METHOD: We retrospectively reviewed the charts of 68 patients who received IAHC in our center between 2011 and 2015. Patient's demographics and disease characteristics were collected. Other variables such as the type, duration, and dosage of the chemotherapy administered, as well as the usage of painkillers before, during, or after intra-arterial administration, were also registered. RESULTS: The mean age of the patients was 59 years. 61.7% were male (n = 42). The mean dose of oxaliplatin administered was 162 mg per cure over 6.7-h course. Fifty percent were diagnosed with a left colon cancer, and 85.2% had synchronous liver metastasis. While 47% of patients received IAHC as a third-line therapy, the main chemotherapeutic drug was oxaliplatin (85.2% of cases; n = 58), then OPTILIV protocol (5FU, irinotecan, oxaliplatin) (13.3%; n = 9), and mitomycin C (1.5%; n = 1). A dose reduction of 23.6% had been noted in 58.8% (n = 40) cases due to adverse effects. Among patients who received opioids during IAHC (n = 40), 20% required opioids in intercure. Before, during, and after IAHC administration, patients complained of abdominal pain in 8.8%, 58.8%, and 19.1%, and opioids were used in 10.2%, 57.3%, and 19.1%, respectively. The main onset of pain occurs during the third cycle of chemotherapy. Among our patients, 11.7% and 22% had ulcer and extrahepatic perfusion, respectively, while 7.3% of them were asymptomatic. The mean occurrence of these signs was during the fourth cycle of IAHC. 33.8% and 52.9% of patients had abdominal pain while an extended and short infusion time, respectively. CONCLUSION: Lengthening of the infusion time did not prevent the occurrence of abdominal pain significantly but was nonetheless decreased compared with patients undergoing short infusion durations. Pain was more common in patients who did not have a dose reduction and who presented with ulcer and extrahepatic perfusion. Abdominal pain occurred on average one cycle before ulcer or extrahepatic perfusion diagnosis. In current practice, pain should be an alarming indicator in patients receiving IAHC, as it may be associated with ulcer or extrahepatic perfusion and thus requiring opioids.

Prognostic factors for progression-free and overall survival in advanced biliary tract cancer.

BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.

FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort.

BACKGROUND: First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA). PATIENTS AND METHODS: From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center's multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery. RESULTS: Seventy-seven patients were enrolled. They received a median number of five cycles (1-30). Grade 3-4 toxicities were neutropenia (11 %), nausea (9 %), diarrhea (6 %), fatigue (6 %), and anemia (1 %). Grade 2-3 sensory neuropathy occurred in 25 % of patients. No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28 % of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70 % had radiotherapy and 36 % underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77 % (95 % CI 65-86) and 1-year progression-free survival rate was 59 % (95 % CI 46-70). CONCLUSION: First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial.

Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer.

BACKGROUND: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients. METHODS: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models. RESULTS: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs -, ≤2 cells per spot) and CD68 (+, >0 vs -, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. CONCLUSION: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.

Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.

Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial.

BACKGROUND: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). PATIENTS AND METHODS: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. RESULTS: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively. CONCLUSION: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. EUDRA CT NO: 2007-007029-38.

Efficacy and tolerance of cetuximab in combination with 5 FU plus irinotecan based chemotherapy in metastatic squamous cell anal carcinoma.

BACKGROUND: Squamous cell anal carcinoma (SCAC) is an uncommon neoplasia often cured by surgery and/or chemo-adiation therapy at the localized stage. Although the first-line treatment for metastatic anal canal cancer is now better codified with two validated treatment regimens, carboplatin-paclitaxel and modified docetaxel-cisplatin-5FU (DCF), there is little data and no consensus regarding subsequent lines [1-5]. In this study, we report the safety and efficacy of cetuximab (an epidermal growth factor receptor inhibitor) in combination with 5-FU plus irinotecan based chemotherapy. METHOD: A retrospective analysis of patients with metastatic SCAC (mSCAC), who failed on at least one prior line of treatment, before being treated with the combination FOLFIRI and cetuximab between March 2015 and February 2022 at Gustave Roussy cancer center, was performed. RESULTS: A total of 33 patients with a pre-treated mSCAC were analyzed. The combination of FOLFIRI and cetuximab provided a disease control rate (DCR) of 73%, and response rate of 30%. With a median follow-up of 38 months, the median progression free survival was 5.5 months, and the median overall survival was 13.7 months. Fourteen patients (42%) experienced grade III/IV adverse events that remained manageable. CONCLUSION: Our study suggests that FOLFIRI and cetuximab is a promising combination in the management of mSCAC with a very good DCR and a manageable toxicity profile. Further prospective trials would be needed to confirm our results.

Long term activity of vemurafenib in cancers with BRAF mutations: the ACSE basket study for advanced cancers other than BRAFV600-mutated melanoma.

BACKGROUND: BRAF inhibitors are approved in BRAFV600-mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAFV600-mutated melanoma and NSCLC. PATIENTS AND METHODS: Patients with advanced tumours other than BRAFV600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. RESULTS: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAFV600 mutations and 10 with BRAFnonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib. CONCLUSION: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers.

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

BACKGROUND: We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. RESULTS: By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CONCLUSION: CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.

Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.

Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis.

PURPOSE: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). PATIENTS AND METHODS: From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). RESULTS: PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). CONCLUSION: Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study.

BACKGROUND: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. PATIENTS AND METHODS: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. RESULTS: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. CONCLUSIONS: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.

Lymph road mapping obtained via blue sentinel node detection to avoid middle colic artery resection for highly selected colon cancer cases: proof of a concept?

BACKGROUND: In theory, perioperative detection of lymph nodes with the injection of isosulfan blue dye should provide lymph road mapping (LRM) able to direct the resection. However, there is no supporting evidence for this theory in cases of colon cancer. We reanalysed all operative reports using the sentinel lymph node technique with blue dye injection. MATERIALS AND METHODS: The retrospective study included 140 patients who underwent the sentinel lymph node (SLN) procedure between February 2001 and November 2007, including 70 cases in which the in vivo technique was used. In 8 cases (11%), LRM was used by the surgeon to determine the extent of resection. RESULTS: In 5 cases, including limited or extended resection, the final pathological stage was II at the end of the follow-up period, and the patients had no recurrent disease. However, findings for 3 cases of stage III cancer were more relevant to the aims of this study. In these 3 patients, one with cancer (T3N1(3/22)) located at the hepatic flexure, and 2 with cancers (T3N2(7/41) and T2N2 (4/15)) at the splenic flexure, the middle colic artery was conserved as a result of LRM information. Of these 3 patients, 1 was alive without disease at 6-year follow-up and 2 at 5-year follow-up. CONCLUSION: LRM obtained via blue sentinel node detection makes it possible to avoid middle colic artery resection for selected colon cancer cases. LRM seems particularly suitable in cases of colonic flexure location or prior colon surgery.

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors.

BACKGROUND: Acute and subacute cutaneous side-effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. Much less is known about the chronic cutaneous effects of these drugs and about their potential psychosocial impact on patients. OBJECTIVES: We performed a retrospective study of patients treated with EGFRIs for more than 6 months. METHODS: All patients had a detailed dermatological examination. The primary cancer, associated chemotherapies, skin treatment, evolution of skin symptoms and their impact on quality of life (QoL) as evaluated by the Dermatology Life Quality Index (DLQI) were noted. RESULTS: Seven men and nine women were identified. The mean length of EGFRI treatment was 10 months (range 6-27). At the time of examination, all patients (100%) had cutaneous side-effects. Grade I or II folliculitis was found in 37.5% of the patients. Additional skin manifestations were xerosis (100%), mucositis (69%), hair abnormalities (87.5%), eyelash trichomegaly (62.5%), facial hypertrichosis (56%), painful paronychia (56%) and onycholysis (44%). Dose reduction or EGFRI discontinuation for skin toxicity were needed in six patients (37.5%). DLQI evaluation showed a moderate to strong impact on QoL in four patients (25%). CONCLUSIONS: Cutaneous side-effects are found in 100% of patients treated with EGFRIs for more than 6 months and have a significant effect on patients' QoL. The clinical spectrum of skin manifestation varies over time. As the use of EGFRIs rapidly increases, it is critical for us to improve our knowledge in the understanding and managment of these skin manifestations.

Prediction and diagnosis of bone metastases in well-differentiated gastro-entero-pancreatic endocrine cancer: a prospective comparison of whole body magnetic resonance imaging and somatostatin receptor scintigraphy.

PURPOSE: Our purpose was to compare the sensitivity of whole body (WB) magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS) for the diagnosis of bone metastases (BMs) in patients with well-differentiated gastro-entero-pancreatic endocrine cancer (WD-GEP-EC) and to determine predictive factors of BM. PATIENTS AND METHODS: WB-MRI and SRS were prospectively performed in 79 patients with bronchial (11), thymic (five), gastric (two), duodeno-pancreatic (24), ileal (26), colic (one), or unknown primary (10) WD-GEP-EC. RESULTS: A total of 36 patients (46%) had 333 BMs involving 119 skeletal segments. WB-MRI and SRS were equally sensitive for detecting patients with BM (86 vs. 81%; P = 0.56), with 33% of the patients diagnosed with only one procedure. WB-MRI detected more BMs than SRS (80 vs. 57%; P = 0.017). Compared with SRS, WB-MRI detected more spine BMs (96 vs. 45%; P < 0.001) and tended to detect more pelvic and lower limb BMs (P = 0.054 and P = 0.06, respectively). Compared with WB-MRI, SRS detected more skull BMs (100 vs. 0%; P < 0.001) and tended to detect more rib BMs (P = 0.08). Sternal and upper-limb BMs were equally detected with WB-MRI and SRS (P = 0.32 and P = 0.46, respectively). Bone staging with SRS and spine MRI rather than WB-MRI would have detected 92% of the patients with BMs and 83% of all BMs. The extent of liver involvement and bronchial-thymic primary tumors were independent predictive factors for BM. CONCLUSIONS: We recommend bone staging with SRS and spine MRI in all patients with bronchial-thymic or unknown primary WD-GEP-EC. In case of duodeno-pancreatic or ileal primary, bone imaging may be restricted to patients with liver metastases.

Functional results and quality of life for patients with very low rectal cancer undergoing coloanal anastomosis or perineal colostomy with colonic muscular graft.

BACKGROUND: The aim of this study was to compare functional results and quality of life (QoL) of two salvage techniques: coloanal anastomosis (CAA) or perineal reconstruction after abdominoperineal resection for very low rectal cancer. METHODS: Between 1991 and 2001, 50 patients were operated for a very low rectal adenocarcinoma and analyzed after a follow-up greater than one year and because there was no relapse or no treatment, they were included in the analysis. Thirty-eight patients had a CAA, including: straight anastomosis (n=23), J pouch (n=10), coloplasty (n=2) and intersphincteric resection (n=3). Twelve patients underwent a PC. RESULTS: Vaizey's incontinence score was equivalent for the two groups: CAA 12 (0-22) versus PC 11 (8-13). The only differences were more frequent fractioned stools for the CAA group and increased pad soiling for the PC group. Overall QoL scores (QLQ C-30) were equivalent for CAA and PC. CONCLUSIONS: For very low rectal tumors, the choice of surgical technique must be based on oncologic rather than future functional or QoL criteria, because both approaches seem to provide similar results.

Acute pancreatitis following segmental pancreatic resection associated with portal vein thrombosis and aneurysm of the spleno-mesenteric venous confluence.

Vascular abnormalities associated with acute pancreatitis are well-known and reported in the literature in up to 50% of the patients with acute necrotizing pancreatitis. Most reported vascular abnormalities are superior mesenteric and/or portal vein thromboses and arterial pseudo-aneurysms. Portal vein aneurysm and/or spleno-mesenteric venous aneurysm are rare entities. Furthermore, portal vein aneurysm can be complicated by portal vein thrombosis. We report a case of spleno-mesenteric vein aneurysm that unusually followed portal vein thrombosis and was secondary to postoperative pancreatitis following segmental pancreatic resection for a well-differentiated endocrine carcinoma. The patient was treated successfully with conservative treatment, although he developed a hepatic abscess two months after his treatment.