Unresectable metastatic colorectal cancer patient cured with cetuximab-based chemotherapy: a case report with new molecular insights.

Here we report the case of a 20-year-old patient who was diagnosed in 2002 with a metastatic colorectal cancer (CRC). He achieved a complete response under cetuximab-based therapy and remains without disease recurrence until now while chemotherapy was discontinued in 2009. The tumor exhibited high level of epidermal growth factor receptor (EGFR) amplification, no mutation in KRAS, NRAS or BRAF genes and a microsatellite-stable (MSS) phenotype. Intriguingly this young patient was carrying a monoallelic germline mutation of MUTYH that was associated with an inactivation of the second allele by loss of heterozygosity on tumor DNA. Moreover, this mutation was associated with a specific mutational signature on tumor level characterized by C > A single base substitutions and a higher mutational load than usually observed in MSS neoplasms. This case report paves the way for further researches on MUTYH-associated cancers' sensitivity to anticancer therapies.

Prophylactic laparoscopic cholecystectomy in adult sickle cell disease patients with cholelithiasis: A prospective cohort study.

INTRODUCTION: Prophylactic laparoscopic cholecystectomy remains controversial and has been discussed for selected subgroups of patients with asymptomatic cholelithiasis who are at high risk of developing complications such as chronic haemolytic conditions. Cholelithiasis is a frequent condition for patients with sickle cell disease (SCD). Complications from cholelithiasis may dramatically increase morbidity for these patients. Our objective was to evaluate the effectiveness of prophylactic cholecystectomy in SCD patients with asymptomatic gallbladder stones. METHODS: From January 2000 to June 2014, we performed 103 laparoscopic cholecystectomies on SCD patients. Fifty-two patients had asymptomatic cholelithiasis. The asymptomatic patients were prospectively enrolled in this study, and all underwent a prophylactic cholecystectomy with an intraoperative cholangiography. The symptomatic patients were retrospectively studied. Upon admission, all patients were administered specific perioperative management including intravenous hydration, antibiotic prophylaxis, oxygenation, and intravenous painkillers, as well as the subcutaneous administration of low-molecular-weight heparin. During the same period, 51 patients with SCD underwent a cholecystectomy for symptomatic cholelithiasis. We compared these 2 groups in terms of postoperative mortality, morbidity, and hospital stay. RESULTS: There were no postoperative deaths or injuries to the bile ducts in either group. In the asymptomatic group, we observed 6 postoperative complications (11.5%), and in the symptomatic group, there were 13 (25.5%) postoperative complications. DISCUSSION: Regarding the SCD complications, we observed 1 case (2%) of acute chest syndrome in an asymptomatic cholelithiasis patient, while there were 3 cases (6%) in the symptomatic group. Vaso-occlusive crisis was observed in 1 patient (2%) with asymptomatic cholelithiasis, and in 4 patients (8%) in the other group. The mean hospital stay averaged 5.8 (4-17) days for prophylactic cholecystectomy and 7.96 (4-18) days for the comparative symptomatic group. CONCLUSIONS: Postoperative complications related to SCD were less frequent for asymptomatic patients who had a laparoscopic prophylactic cholecystectomy. This intervention, if performed with perioperative specific management, is safe and helps avoid emergency operations for acute complications including cholecystitis, choledocholithiasis, and cholangitis. For SCD patients, a prophylactic cholecystectomy reduces hospital stays.

Abdominal tuberculosis: utility of laparoscopy in the correct diagnosis.

INTRODUCTION: Abdominal tuberculosis is one of the most prevalent form of extra-pulmonary disease, and the diagnosis is difficult because of non-specific clinical features. METHOD: We presented a case of a Tunisian woman with cough, nausea, decreased appetite and pelvic-abdominal pain. CT scan showed peritoneal thickening, peritoneal tiny nodules and enlarged mesenteric lymph nodes ascitic fluid. Sputum analysis was negative. Abdominal paracentesis was performed, and no malignant cell was detected. The Ziehl staining revealed a negativity for acid-fast bacilli. RESULTS: Diagnostic laparoscopy was performed. Biopsy specimens of peritoneum, liver, omentum and diaphragm showed omental epithelioid granulomas with a centrale caseous necrosis and Langhans giant cells. The patient received anti-tubercular treatment. CONCLUSIONS: In case of suspicion of tuberculosis, when bacteriologic and cytologic analysis is negative, laparoscopy with biopsies is helpful for correct diagnosis and appropriate management.

Neoadjuvant chemotherapy or primary surgery for stage III/IV ovarian cancer: contribution of diagnostic laparoscopy.

BACKGROUND: The aims of this retrospective study were to evaluate laparoscopic triage of patients with advanced ovarian cancer towards primary surgery or neoadjuvant chemotherapy, and to analyze outcome according to the treatment. METHODS: Between January 2001 and December 2006, 55 patients with stage III - IV ovarian cancer underwent diagnostic laparoscopy. Primary surgery was performed when complete cytoreduction was considered feasible, while the other patients received neoadjuvant chemotherapy (platinum-based combination with taxanes) and interval surgery. All the patients received adjuvant chemotherapy. RESULTS: Patients treated with neoadjuvant chemotherapy (n = 29) had a higher mean body mass index (P = 0.048), higher serum CA 125 levels (P = 0.026), and more metastases (P = 0.045) than patients treated with primary surgery (n = 26). In patients treated with primary surgery, complete cytoreduction and a residual tumour size

Stage II colon cancer prognosis prediction by tumor gene expression profiling.

PURPOSE: This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated. PATIENTS AND METHODS: Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes. RESULTS: The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy. CONCLUSION: Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.

[Rehabilitation after abdominal surgery]. / Réhabilitation après chirurgie viscérale.

A combined strategy of anesthetic and surgical care defines postoperative rehabilitation, which aims to accelerate recovery from surgery, shorten convalescence, and reduce postoperative morbidity. Preoperative and early postoperative oral feeding, a relatively "dry" fluid regimen, and the avoidance of or early removal of drains, gastric tubes and bladder catheters all contribute to decreasing postoperative morbidity after abdominal surgery. Postoperative pain control, prevention of nausea and vomiting, shortening the duration of postoperative ileus, and early ambulation can also help to decrease postoperative morbidity. The use of multimodal fast-track clinical rehabilitation programs should improve outcomes and quality of life, reduce hospital stays, and save money.

Peritoneal carcinomatosis after laparoscopic radical hysterectomy for early-stage cervical adenocarcinoma.

BACKGROUND: The risk of wound metastasis after laparoscopic management of early-stage cervical cancer is well known, but there are few data on peritoneal carcinomatosis of cervical adenocarcinoma. CASE: We report the first case of peritoneal carcinomatosis occurring in a woman with FIGO stage Ib1 cervical adenocarcinoma who underwent laparoscopic type III radical hysterectomy and bilateral pelvic lymphadenectomy (sentinel node procedure) followed by vaginal brachytherapy. A peritoneal recurrence was diagnosed 16 months after surgery and was treated with chemotherapy and laparotomy. CONCLUSION: Laparoscopy for cervical adenocarcinoma may carry a risk of peritoneal dissemination.

Gene expression profiling of nonneoplastic mucosa may predict clinical outcome of colon cancer patients.

PURPOSE: This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in Stage II and III colon cancer patients. METHODS: Tumor and nonneoplastic mucosa mRNA samples from 12 colon cancer patients were profiled using the Affymetrix HGU133A GeneChip. Six of 12 patients experienced a metachronous metastasis, whereas the 6 others remained disease-free for more than five years. Three datasets were constituted, including, respectively, the gene expression measures in tumor samples (T), in adjacent nonneoplastic mucosa samples (A), and the log-ratio of the gene expression measures (L). The step-down procedure of Westfall and Young and the k-nearest neighbor class prediction method were applied on T, A, and L. Leave-one-out cross-validation was used to estimate the generalization error of predictors based on different numbers of genes and neighbors. RESULTS: The most frequent results were one false prediction with the A-based predictors (95 percent) and two false predictions with the T- and L: -based predictors (65 and 60 percent, respectively). A-based predictors were more stable (i.e., less sensitive to changes of parameters, such as numbers of genes and neighbors) than T- and L: -based predictors. Informative genes in A-based predictors included genes involved in the oxidative and phosphorylative mitochondrial metabolism and genes involved in cell-signaling pathways and their receptors. CONCLUSIONS: This study suggests that one can build a prognosis predictor for Stage II and III colon cancer patients, based on microarray gene expression measures, and suggests the potential usefulness of nonneoplastic mucosa for this purpose.

Impact of CT and 18F-deoxyglucose positron emission tomography image fusion for conformal radiotherapy in esophageal carcinoma.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiotherapy planning for esophageal carcinoma patients. METHODS AND MATERIALS: Thirty-four esophageal carcinoma patients were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same treatment position. PET images were coregistered using five fiducial markers. Target delineation was initially performed on CT images, and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: (18)F-fluorodeoxy-D-glucose-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative conformal radiotherapy. The gross tumor volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and increased in 7 patients (21%). The GTV reduction was > or =25% in 4 patients owing to a reduction in the length of the esophageal tumor. The GTV increase was > or =25% with FDG-PET in 2 patients owing to the detection of occult mediastinal lymph node involvement in 1 patient and an increased length of the esophageal tumor in 1 patient. Modifications of the GTV affected the planning treatment volume in 18 patients. Modifications of the delineation of the GTV and displacement of the isocenter of the planning treatment volume by FDG-PET also affected the percentage of total lung volume receiving >20 Gy in 25 patients (74%), with a dose reduction in 12 patients and dose increase in 13. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of esophageal carcinoma. The affect on treatment outcome remains to be demonstrated.

Colon cancer prognosis prediction by gene expression profiling.

This study assessed the possibility to build a prognosis predictor, based on microarray gene expression measures, in stage II and III colon cancer patients. Tumour (T) and non-neoplastic mucosa (NM) mRNA samples from 18 patients (nine with a recurrence, nine with no recurrence) were profiled using the Affymetrix HGU133A GeneChip. The k-nearest neighbour method was used for prognosis prediction using T and NM gene expression measures. Six-fold cross-validation was applied to select the number of neighbours and the number of informative genes to include in the predictors. Based on this information, one T-based and one NM-based predictor were proposed and their accuracies were estimated by double cross-validation. In six-fold cross-validation, the lowest numbers of informative genes giving the lowest numbers of false predictions (two out of 18) were 30 and 70 with the T and NM gene expression measures, respectively. A 30-gene T-based predictor and a 70-gene NM-based predictor were then built, with estimated accuracies of 78 and 83%, respectively. This study suggests that one can build an accurate prognosis predictor for stage II and III colon cancer patients, based on gene expression measures, and one can use either tumour or non-neoplastic mucosa for this purpose.

Cardio-esophageal cancer. Is 18Fluorodeoxyglucose positron emission tomography worthwhile?

BACKGROUND/AIMS: 18Fluorodeoxyglucose positron emission tomography has been proposed for the preoperative staging of carcinomas of the esophagus and gastric cardia. The aim of this study was to assess its diagnostic value and its influence on therapeutical decisions. METHODOLOGY: Twenty-eight patients with a cancer of the esophagus or gastric cardia underwent a 18Fluorodeoxyglucose positron emission tomography on a gamma camera with coincidence detection electronics, in addition to our standard preoperative procedures (barium swallow, liver ultrasonography, chest X-ray). Four types of lesions were searched for: primary tumor, abdominal and mediastinal lymph nodes, and distant metastases. Results of 18Fluorodeoxyglucose positron emission tomography were compared to pathological findings. RESULTS: Sensitivity for the primary tumor was 86%. Sensitivity for mediastinal and abdominal lymph nodes was 75 and 54%, respectively, whereas specificity was 100%. Distant metastases were detected in 4 patients: liver metastasis in 2 patients and bone metastasis in 2 patients. Results of 18Fluorodeoxyglucose positron emission tomography influenced therapeutical decisions for 2 patients. CONCLUSIONS: 18Fluorodeoxyglucose positron emission tomography seems to be worthwhile in the preoperative staging of carcinomas of the esophagus and gastric cardia, mainly because it may detect distant metastases.

Los tumores quísticos del páncreas. Cistoadenomas y cistoadenocarcinomas: diagnóstico y actitud práctica / Cystic tumors of the pancreas. Cystadenomas and cystadenocarcinomas: diagnosis and practice

Los autores reportan 16 casos de tumores quísticos del páncreas (TQP), 5 cistoadenomas serosos (CS), 6 cistoadenomas mucinosos (CM) y cinco cistoadenocarcinomas (CC). Estos se trataron de 11 mujeres y 5 hombres. La edad media fue de 63 años (extremos 44 a 89 años). Cuatro enfermos fueron asintomáticos, 6 enfermos habían adelgazado de 3 a 10 kg. Un enfermo con un CC tuvo una ictericia. Los TQP fueron diagnosticados por ecografía o tomografía computada. Los TQP se topografaron diez veces a nivel de la cabeza del páncreas, dos veces en el cuerpo y 4 veces en la cola. Al término de las exploraciones preoperatorias el diagnóstico de TQP no fue reconocido en cuatro casos. El diagnóstico exacto de la naturaleza del tumor fue hecho en el preoperatorio en cinco casos: dos CS, un CM y dos CC. El diagnóstico de certeza fue hecho por el estudio histológico de la pieza quirúrgica en once casos, por punción quirúrgica en dos casos, por la existencia de metástasis hepáticas en un caso, y por citopunción bajo tomografía en el resto, un enfermo se negó a operarse. Trece enfermos fueron operados: a cuatro se les realizó una duodenopancreatectomía cefálica (un CS y tres CC), a cinco se les realizó una exéresis tumoral (un CS y cuatro CM), a dos se les realizó una pancreactetomía distal (un CM y un CC) y a dos se les realizó una punción quirúrgica (dos CS). Los CS asintomáticos pueden ser no operados bajo vigilancia si el diagnóstico es certero. Los otros tumores quísticos deben ser resecados, ya sea porque exista duda sobre su naturaleza, ya sea porque se trate de un CS sintomático, o un CM o un CC. En este último caso, el pronóstico es mejor que en los casos de cáncer de páncreas exócrino no metastásico.

Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal.

PURPOSE: To evaluate our data concerning the prognostic factors for locoregional control, survival, late complications, and sphincter conservation in a series of epidermoid cancers of the anal canal without clinical evidence of metastasis. METHODS AND MATERIALS: Between June 1972 and January 1997, 305 patients were treated with curative-intent radiotherapy (RT). The T stage according to the 1987 International Union Against Cancer classification was T1 in 26, T2 in 141, T3 in 104, and T4 in 34. Forty-nine patients had nodal involvement at presentation. The pretreatment anal function score, according to our in-house system, was 0 for 22 patients, 1 for 182, 2 for 74, 3 for 7, and 4 for 11 patients; for 9 patients, scores were unavailable. The treatment started with external beam radiotherapy (EBRT) in 303 patients (median dose 45 Gy). After a rest period of 4-6 weeks, a boost of 20 Gy was delivered by EBRT in 279 patients and by interstitial (192)Ir brachytherapy in 17 patients. Seven patients received only one course of EBRT (mean dose 49.5 Gy), and 2 patients were treated with interstitial (192)Ir brachytherapy alone (55 Gy and 60 Gy). Concomitant chemotherapy (5-fluorouracil and either mitomycin C or cisplatin) was delivered to 19 patients. The mean follow-up was 103 months (median 84). RESULTS: At the end of RT, the local tumor clinical complete response rate was 96% for T1, 87% for T2, 79% for T3, and 44% for T4. Of the 61 locally progressive tumors, 27 (44%) were salvaged with abdominoperineal resection. The rate of local tumor relapse was 12%. Among 37 local tumor relapses, 20 (54%) were salvaged with abdominoperineal resection and one with interstitial (192)Ir brachytherapy. The overall local control rate (with or without salvage local therapy) was 84%. The local control rate with good anal function (score 0 or 1) was 56.5%. Of 181 available patients with their anus preserved, 94% had good anal function. For a subgroup of 15 patients with a tumor length of <2 cm and without nodal involvement, the clinical complete response rate after RT completion was 100%, the local control rate with or without local salvage treatment was 100%, and among 13 available patients with their anus preserved, the anal function score was good in 12 patients (92%). The 10-year disease-free survival rate was 74%. After multivariate analysis, three independent predictive factors significantly influenced disease-free survival: the interval between the two courses of RT (>38 days vs. < or =38 days, p = 0.0025), pretreatment anal function score (0 vs. 1 vs. 2 vs. 3 vs. 4, p = 4.4.10(-6)), and clinical complete response after RT completion (no complete response vs. complete response, p = 2.5.10(-14)). CONCLUSION: We confirm the excellent results with RT in T1 and T2 lesions. However, to improve survival without colostomy with good anal sphincter function, chemoradiotherapy should be preferred for tumors > or =2 cm in length and for locally advanced tumors.

Rectal cancer surgery in patients more than 80 years of age.

BACKGROUND: This retrospective study aimed to compare the prognosis for rectal cancer in patients more than 80 years old with that observed in younger patients. METHODS: Patients operated on for a rectal adenocarcinoma, from 1980 to 1998, were divided into two groups: group 1 (>80 years, n = 92); group 2 (<80 years, n = 276). RESULTS: There were significant differences between the two groups with regard to the sex ratio, the American Society of Anesthesiologists (ASA) classification, the emergency presentation, and the curative operation rate. The operative mortality rate was 8% in group 1, 4% in group 2 (P = 0.26). The overall 5-year survival rate was 35% in group 1, 53% in group 2 (P = 0.0004). In patients operated on for cure, the cancer-specific 5-year survival rate was 50% in group 1, 59% in group 2 (P = 0.08). CONCLUSIONS: The prognosis for rectal cancer in patients over 80 years is not significantly different from that of younger patients. Surgery should not be restricted on the basis of age.

[18 F-fluorodeoxyglucose positron emission tomography for characterization and initial staging of pancreatic tumors]. / Tomographie par émission de positons au (18 F)fluorodésoxyglucose dans l'évaluation initiale des tumeurs du pancréas.

AIM: To evaluate positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) for characterizing and initial staging of pancreatic tumors and to determine its impact on therapeutic strategy. PATIENTS AND METHODS: This study included 24 patients with pancreatic tumor who underwent PET before treatment. Twenty-two patients had a malignant tumor and two had a benign tumor. The PET scan was performed after intravenous injection of FDG with a gamma camera. PET findings were compared with histology of the pancreatic tumor (n=24), liver metastases (n=5), peritoneal metastases (n=5), and lymph node metastases (n=5). Absence of metastasis or lymph node involvement was determined by surgery or by CT scan, ultrasonography, magnetic resonance imaging and at least two months follow-up. RESULTS: The sensitivity of the PET scans to identify pancreatic carcinoma was 64% (95% confidence interval 44-84%). PET scans could not be interpreted for lymph node involvement adjacent to the tumor. For liver metastases, the PET scan was positive in 3 out of 5 patients. For peritoneal metastases, the PET scan was positive in 4 out of 5 patients but was doubtful in one. There were two false positives. Among the 4 cystic tumors, the PET scan was positive for 2 malignant tumors and negative for 2 benign tumors. Surgical strategy was modified in only one of the 24 patients on the basis of PET findings. CONCLUSION: The sensitivity of PET for the diagnosis of primary malignant pancreatic tumor was found to be low. The contribution of FDG-PET to the surgical decision appears to be limited to the detection of metastases or lymph node involvement distant from the tumor, contraindicating surgery. Nevertheless, the sensitivity of FDG-PET is lower than that of laparoscopy for peritoneal metastases. Indications for PET should be included in an evaluation of therapeutic decision making and cost analysis.