Stauffer syndrome : a rare paraneoplastic complication of renal cell carcinoma to be kept in mind. Case report and literature survey.

The authors report the case of a 74-years-old woman treated by immunotherapy for a metastatic renal cell carcinoma and having developed an important cholestasis with thrombocytosis, increased CRP, leucocytosis and hypoalbuminemia. Liver remained free of metastases at medical imaging. The diagnosis of a Stauffer syndrome was confirmed by the hepatic biopsy. A complete response of liver disorders was obtained after nephrectomy. From literature survey, Stauffer syndrome should be kept in mind in cancer patients, especially those suffering from a renal cell carcinoma, presenting with cholestasis with no underlying cause.

Patient management after primary rectal cancer diagnosis. Special focus on surgical treatment for non-metastatic disease.

Background: Rectal cancer is a public health priority. Primary objectives of this study were to evaluate the quality of care for non-metastatic rectal cancer using process and outcome indicators. Delay of management, length of stay and readmission rate, sphincter preservation, morbidity, number of examined lymph nodes, mortality, overall and disease-free survivals were evaluated. Secondary objectives were to estimate the relationship between possible predictive parameters for (1) anastomotic leakage (logistic regression), (2) overall or disease-free survivals (cox regression).Methods: We performed a retrospective study on 312 consecutive patients diagnosed with primary rectal cancer between 2016 and 2019. We focused on the 163 patients treated by surgery for non-metastatic cancer.Results: The treatment began within 33 days (range 0-264) after incidence, resection rate was 67%. Digestive continuity rate in lower, middle and upper rectum was 30%, 87% and 96%. Median of 14 lymph nodes (range 1-46) was analyzed. Length of stay and readmission rate were 11 days (range 3-56) and 4%, respectively. Within 90 postoperative days, clinical anastomotic leakage occurred in 9.2% of cases, major morbidity rate was 17%, mortality 1.2%. Multivariate analysis revealed that stoma decreased the risk of anastomotic leakage [hazard ratio: 0.16; 95% confidence intervals: 0.04-0.63; p = 0.008]. The 5-year overall survival after surgery was 85 ± 4%, disease-free survival 83 ± 4%. Patients with major complications, male gender and R1/R2 resection margin had a poorer prognosis.Conclusion: This work showed encouraging results in rectal cancer treatment in our institution, our results were in line with recommendations at the time.

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

[Demons-Meigs syndrome secondary to an ovarian Brenner tumour. Case report and literature survey]. / Syndrome de Demons-Meigs secondaire à une tumeur de Brenner. Présentation d'un cas clinique et revue de la littérature.

A 65-year old woman presents with a Demons-Meigs syndrome characterized by dyspnea resulting from a transsudative pleural effusion, an important unilateral right ovarian mass and ascites. The diagnosis of a Brenner type histology was obtained after complete surgical removal of ovarian tumor. After discharge the patient entered in a sustained complete response and thus potential cure. Brenner tumor is a rare and often benign ovarian affection. The clinical signs aren't generally much specific: pelvic pain or heaviness, metrorrhagia and menstrual irregularity may be observed. Brenner tumor may exceptionally induce a Demons-Meigs's syndrome. This syndrome associates one or more benign tumors of the female reproductive tract with pleural and peritoneal effusions. This could depict a rich but disturbing clinical picture. The prognosis and the regression of the symptomatology are nevertheless excellent after tumor surgical resection.

Les auteurs rapportent le cas d'une patiente de 65 ans admise pour un syndrome de Demons-Meigs caractérisé par une dyspnée sur épanchement pleural transsudatif, une masse ovarienne unilatérale volumineuse et de l'ascite. La résection complète de la masse tumorale permettra le diagnostic de tumeur de Brenner de l'ovaire droit et sera soldée par la disparition de tout signe clinique et, a priori, la guérison de la patiente. La tumeur de Brenner est une affection ovarienne rare et généralement bénigne. Les signes cliniques sont généralement peu spécifiques : douleurs ou pesanteurs pelviennes, métrorragies ou encore une irrégularité du cycle menstruel peuvent être observées. La tumeur de Brenner peut, exceptionnellement, s'inscrire dans un syndrome de Demons-Meigs. Ce syndrome, associant une ou plusieurs tumeurs bénignes de l'appareil génital féminin à un épanchement pleural et péritonéal, peut donner un tableau clinique plus riche, mais aussi plus alarmant. Le pronostic, avec la régression de la symptomatologie, est cependant excellent après exérèse chirurgicale de la tumeur.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

A Belgian Survey on Geriatric Assessment in Oncology Focusing on Large-Scale Implementation and Related Barriers and Facilitators.

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.

Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV.

BACKGROUND: Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in ∼15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. PATIENTS AND METHODS: Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m(2)), oxaliplatin (85 mg/m(2)) and 5-fluorouracil (2800 mg/m(2)) were delivered via an implanted HAI access port and combined with i.v. cetuximab (500 mg/m(2)) every 14 days. Multidisciplinary decisions to resect LM were taken after every three courses. The rate of macroscopic complete resections (R0 + R1) of LM, progression-free survival (PFS) and overall survival (OS) were computed according to intent to treat. RESULTS: The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extrahepatic lesions of <1 cm were found in 41% of the patients. A median of six courses was delivered. The primary end point was met, with R0-R1 hepatectomy for 19 of the 64 previously treated patients, 29.7% (95% confidence interval 18.5-40.9). Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%) and diarrhea (16.4%) were frequent. Objective response rate was 40.6% (28.6-52.3). Median PFS and OS reached 9.3 (7.8-10.9) and 25.5 months (18.8-32.1) respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months (32.6-37.8), with 37.4% (23.6-51.2) alive at 4 years. CONCLUSION: The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing. PROTOCOL NUMBERS: EUDRACT 2007-004632-24, NCT00852228.

[Cancer recurrence or sarcoidosis: the essential contribution of pathology]. / Récidive tumorale ou sarcoïdose: un rendez-vous en anatomo-pathologie à ne pas manquer.

The development of pulmonary nodules or lymph nodes in the course of a malignancy, in particular breast cancer, can sometimes correspond to the onset of sarcoidosis. Osteolytic lesions can simultaneously occur which further strengthens the impression of a metastatic disease. No particular test, biological markers or imaging technique, has a satisfactory discriminating power and a biopsy is needed to establish the correct diagnosis and decide on the adequate treatment. The concomitance of sarcoidosis and cancer raises the possibility of a granolumatous disease.

[A trans-hospital pilot programme for onco-geriatry. The experience of the CHC-Liege]. / Programme pilote trans-hospitalier d'onco-gériatrie.

The authors offered to 296 consecutive cancer patients aged > or = 70 to undergo a joint comprehensive geriatric and oncological assessment. After pluridisciplinary discussion, several reflections have emerged: the need in 15 - 32% of cases to reinforce the role of the paramedical staff; the correlation between age, low clinical indices, alteration of renal function as well as geriatric characteristics; 67% of evaluated cases presented a significant geriatric profile; recommendations for patients' management in relation to their pattern of frailty and health aging (standard, adapted or palliative treatment).

[Chronotherapy with 5-fluorouracil folinic acid and oxaliplatin delivered over 48 hours every second week in colorectal cancer. The CHC-Liège experience (Belgium)]. / Chronochimiothérapie à base de 5-fluorouracil, acide folinique et oxaliplatine administrée en deux jours toutes les deux semaines pour le cancer colorectal. L'expérience du CHC-Liège (Belgique).

One hundred and ten consecutive patients suffering from a colorectal cancer received chronotherapy infused over two days every two weeks. Each course comported 5 FU 3g/m(2), folinic acid (600 mg/m(2) - l. form or 1200 mg/m(2)--racemic form) and oxaliplatin (85/mg/m(2)--adjuvant indication or 100mg/m(2)--palliative indication). According to chronobiological concepts, 5 FU and folinic acid were infused from 10 pm to 10 am with a peak at 4 am while oxaliplatin was delivered from 10 am to 10 pm with a peak at 4 pm. The overall tolerance was excellent with a maximum of 17% patients experiencing a grade 3 toxicity. The toxicity was higher in women, in older patients (>=70) or in case of flat infusion. In adjuvant situation (60 cases), progression free and overall survivals established respectively at 76% (42+months) and 88% (45+months). Fifty-two percent response rate were recorded within the palliative group (50 cases) with an overall 68% disease control. Median progression free survival was seven months but median survival was not attained at 31+ months. Thirty percent patients could benefit from a curative surgery after chemotherapy. Older patients (>=70) experienced worsened survival. In conclusion, we think that our chrono-FOLFOX 2-12 should be proposed as standard treatment for colorectal cancer patients.

Phase I - II study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid, carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study.

Thirty-six metastatic colorectal cancer patients received every 2 weeks, as first- (17) or second-line (19) treatment a combined chronotherapy with CPT-11 (infused at day 1 from 2 to 8 a.m.; peak at 5 a.m.), given with 5FU (700 mg/m(2) per day; days 2-5) and folinic acid (300 mg/m(2) per day; days 2-5) both infused from 10 p.m. to 10 a.m. with a peak at 4 a.m., and carboplatin (40 mg/m(2) per day; days 2-5; infused from 10 a.m. to 10 p.m.; peak at 4 p.m.). The doses of CPT11 could be easily pushed from 120 to 180 mg/m(2) in successive cohorts in the phase I part of the study (11 cases). Twenty-five patients were then treated in the phase II of the trial. The overall toxicity was mild leading to dose-reductions in only 11-13% courses. The tumoral activity was interesting with 81% responses and 94% tumour control. Also prolonged survivals were recorded with 8.8 months of progression free and 15.6 months overall survivals. More prolonged survivals were observed in chemotherapy naive patients. Seven patients (19%) could be reoperated from their residual disease.

Evaluation of biological rhythms in elderly cancer patients. A complementary translational research within the frame of the trans-hospital pilot program of oncogeriatrics launched at CHC-Liège.

Thanks to the sponsoring of Belgian Cancer Plan, we have launched a trans-hospital project of oncogeriatrics implying any concerned actors from medical (oncology, geriatrics, various specialties) and paramedical staffs (nurses, physiotherapists, ergotherapists, dieteticians, social workers, psychologists…). We aim to recruit 300 consecutive patients aged over 70 and presenting with a new diagnosed cancer. They will benefit from both detailed Comprehensive Geriatrical (CGA) and Oncological (COA) assessments. A multidisciplinary concertation will try to define for each patient an individualized treatment planning taking into account CGA, CGO, co-morbidities, predictive indexes of chemotherapy toxicity (MAX2, i.e.). Detailed records will be obtained in collaboration with the data-management staff. Furthermore, a complementary translational research will include patients for a simple evaluation of their circadian rhythmicities through cortisol titration at 8a.m. and 4p.m. and actometry recordings of the rest-activity rhythms. Future steps could be developed aiming at the restoration of circadian structure disturbances with revalidation (physical exercise, tai-chi, yoga) and resynchronization (melatonin, hydrocortisone, bright light…) programs.

Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer: a meta-analysis.

BACKGROUND: Molecular circadian clocks can modify cancer chemotherapy effects, with a possible moderation according to sex differences. We investigated whether sex determine the optimal delivery schedule of chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: A meta-analysis was performed using individual data from three international Phase III trials comparing 5-fluorouracil, leucovorin and oxaliplatin administered in chronomodulated (chronoFLO) or conventional (CONV) infusions. The data from 345 females and 497 males were updated at 9 years. The main end point was survival. RESULTS: Overall survival was improved in males on chronoFLO when compared with CONV (P = 0.009), with respective median values of 20.8 (95% CL, 18.7 to 22.9) and 17.5 months (16.1 to 18.8). Conversely, median survival was 16.6 months (13.9 to 19.3) on chronoFLO and 18.4 months (16.6 to 20.2) on CONV in females (P = 0.012). The sex versus schedule interaction was a strong predictive factor of optimal treatment schedule, with a hazard ratio of 1.59 (1.30 to 1.75) for overall survival (P = 0.002) in multivariate analysis. CONCLUSIONS: Males lived significantly longer on chronomodulated chemotherapy rather than on conventional chemotherapy. The current chronoFLO schedule deserves prospective assessment as a safe and more effective first-line treatment option than conventional delivery for male patients.

[Hemolytic uremic syndrome induced by gemcitabine. A poorly recognized complication?]. / Syndrome hémolytique et urémique induit par la gemcitabine. Une complication méconnue?

This report is concerned with the development of an hemolytic uremic syndrome (HUS) in 6 patients (3 males, 3 females, aged 53 to 73) suffering from an advanced cancer and treated by protracted (>= 4 months) infusions of gemcitabine. Over 4 to 14 months, the patients received 13-34 infusions delivering a cumulative dose oscillating between 9 and 29 g/m2. A progressive alteration of renal function preceeded the acute syndrome. After interruption of gemcitabine and symptomatic treatment, the evolution of haemolytic anemia was generally favourable. This was not the case for renal dysfunction: 2 complete and 1 partial resolution of renal insufficiency were noted, but 1 case required chronic dialysis. Based on the authors experience, the frequency of an HUS complication after protracted gemcitabine treatment could be as high as 2.7 %.

Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer.

The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) > or =5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III-IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of > or =5 months after an objective response to taxanes. Furthermore, toxicity was significant.

[Esthesioneuroblastoma: a case report and literature review]. / Esthésioneuroblastome: à propos d'un cas et revue de la littérature.

Esthesioneuroblastoma (ENB) or olfactive neuroblastoma is a rare cancer arising from the neuroepithelium of the olfactory epithelium of the nasal cavity. Sinusal, orbital and intracranial expansions are common. The anatomopathological diagnosis will frequently require immuno-histochemical tests and sometimes electron-microscopy as well as genetic testing. Medical imaging with CT scan and MRI is essential for the stadification. Treatment will generally associate debulking or curative surgery (with combined rhino-neurosurgical accesses) and conformal stereo-tactic radiotherapy. Chemotherapy was generally reserved for palliative cases; it can be now proposed as neoadjuvant treatment. Most patients will relapse; thus the follow-up will remain ad vitam.

[Chemotherapy for human gastric cancer: a review]. / Qu'attendre de la chimiothérapie dans le cancer de l'estomac en 2008?

The authors review the actual position of medical treatment for human gastric cancer. Chemotherapy has been evaluated first in palliative situation, then as adjuvant post-surgical approach either through systemic or intraperitoneal route. Now chemotherapy may also be proposed as neoadjuvant (before surgery) treatment as part of an integrated global pluridisciplinary approach. New hopes to improve the prognosis come then from both neoadjuvant and adjuvant chemotherapy (+/- radiotherapy) and further from less toxic infusional therapies (chronomodulation), new schedules with proved active molecules (docetaxel, oxaliplatin, irinotecan, pemetrexed) as well as from new targeted treatments (against ie, EGF-receptor and angiogenesis).

[Cancer associated retinopathy (CAR). Two clinical cases and review of the literature]. / Cancer associated retinopathy (CAR). Présentation de deux cas cliniques et revue de la littérature.

The cancer associated retinopathy (CAR) is a paraneoplasic retinopathy in which an antigen-antibody reaction, due to retinal antigens, also expressed in tumours, leads to degeneration of retinal photoreceptor cells. We observed in CHL-Luxembourg, 2 clinical cases of non-Hodgkin's lymphoma with severe prognosis in whom we described the presence of anti-recoverin antibodies. The CAR is most frequently associated with small cell lung and ovarian carcinomas. Clinical symptoms (phosphenes, progressive loss of eyesight) sometimes, occur before the diagnostics of primary cancer. Retinal degeneration may be assessed by electroretinogram, visual field, fundus oculi. A crossed reactivity between tumour and retinal antigens may initiate an antigen-antibody reaction, that implicates optic lesions. Different antigenic proteins have been evidenced, the most frequent being the recoverin. This protein plays a role in the adaptation to light and darkness. It is expressed in more than 50% of different types of neoplastic cells and would play a role in tumour proliferation. The antigen-antibody reaction leads to death by apoptosis of photoreceptor and bipolar retinal cells. These antirecoverin antibodies are also observed in other retinal degenerative diseases. The diagnosis is confirmed by titration of antibodies in the serum by Western Blot, Elisa and immunohistochemical methods. However, this diagnosis is by exclusion (vs. brain metastasis, drug toxicity, demyelinating diseases, autoimmune non paraneoplastic retinopathies). Corticosteroids are the only therapy that can bring some benefit. There is no value in starting a therapy if the retinal degeneration has reached an advanced stage. Note that the CAR must be distinguished from the Melanoma Associated Retinopathy (MAR) which is a similar paraneoplastic syndrome, but with rapid evolution of its symptoms and different etio-pathogenesis.

[Circadian behaviour of host versus tumour outcome. A review]. / Importance du comportement circadien de l'hôte pour la genèse et l'évolution des cancers. Une revue.

The authors reviewed experimental and clinical data emphasizing the importance for host to keep a reference circadian rythmicity. This assessment seems true both in the cancerogenesis phase, as well in the active phase of tumoural disease.