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.

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

[Case report: Muir-Torre syndrome diagnosed from a sebaceoma mimicking an ulcerated breast cancer]. / Syndrome de Muir-Torre. À propos d'un cas diagnostiqué suite à l'apparition d'un sébacéome mimant un cancer ulcéré du sein gauche.

On the basis of a case report, we conducted a search through the literature concerning Muir-Torre syndrome. This syndrome is considered to be a phenotypic variant of Lynch syndrome (or Human Non Polyposis Colorectal Cancer). Muir-Torre syndrome is a familial cancer syndrome defined as the association of an internal malignancy with cutaneous sebaceous tumors. It is a rare disease. In our knowledge, this case is the first reported skin lesion related to Muir-Torre syndrome, located on the breast and mimicking ulcerated breast cancer. Genetic counselling obviously has an important place in the management of this pathology.

[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.

[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 %.

Diagnostic pitfalls in digestive neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) represent a rare and highly heterogeneous entity that often is revealed by vague and non-specific symptoms, leading to a delayed diagnosis. Here we will review some of the most regularly observed false positive and false negative cases and provide clues to recognize and manage them properly. Particularly, the value of chromogranin-A as a serum tumour marker and Somatostatin receptor scintigraphy as an imaging test, are reviewed. Indeed, chromogranin-A and other hormones, such as gastrin, as well as urinary 5-hydroxy-indolic acetic acid (5-HIAA) are often tested to diagnose NET without appraising the clinical situation, leading to extensive work-up on false bases. On the other hand, some tests are performed in situations where they do not add additional information (e.g. 5-HIAA in pancreatic or rectal NET) because invariably negative. Somatostatin receptor scintigraphy is an expensive examination, still not reimbursed in Belgium, for which indications must be carefully assessed, knowing its specificity and sensitivity.

Carcinoid heart disease--a hidden complication of neuroendocrine tumours.

Carcinoid heart disease (CHD) develops in serotonin-producing neuroendocrine tumours (NET) due to fibrotic endocardial plaques with associated valve dysfunction leading most often to right-sided heart failure. The classical carcinoid syndrome usually occurs when serotonin-producing NET metastasize to the liver. Up to 50% of those patients will exhibit carcinoid heart disease. The pathophysiological process is not yet completely understood: serotonin is considered to be a major initiator of the fibrotic process, but other tumour secreted factors may contribute to the pathogenesis. Histopathology reveals intact valvular cusps with superimposed fibrotic plaques, leading to thickening and retraction of the valves, causing valvular dysfunction. A high index of clinical suspicion to diagnose CHD is needed since symptoms can be rather non-specific. Transthoracic echocardiography is the gold standard for diagnosis and should probably be performed at the time of diagnosing serotonin-producing NET and then repeated annually. On the other hand, when diagnosing right-heart failure, the presence of CHD and underlying serotonin-producing NET should be taken into account. Therapeutic options include pharmacotherapy for heart failure, control of the systemic carcinoid disease and in selected individuals cardiac valve replacement. The elucidation of the pathologic process is necessary to develop targeted antifibrotic therapeutic agents since CHD seems to be irreversible and associated with poor prognosis.

Locoregional and radioisotopic targeted treatment of neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) are a heterogeneous group of proliferative disorders whose management dramatically relies on tumour biology. For well-differentiated, low-proliferative index tumours, locoregional treatment and targeted radioisotopic therapies offer an attractive and seemingly efficient alternative to palliative surgical resections. Lack of well-designed, prospective, randomized multicentric studies hinders a balanced evaluation of available locoregional treatment methods: embolization, chemo-embolization, radio-embolization. According to available datas, all techniques achieve a 50-60% radiological response rate and almost 80% of symptomatic relieve for the patients, while their impact on progression-free and overall survival remains not assessable. Same conclusions can be drawn for radiolabeled targeted therapies like MetaiodoBenzylGuanidine (MIBG) and Peptide Receptor Radionuclide Therapy (PRRT), which, provided that their target is expressed by tumour cells, can deliver therapeutic doses of radiation to neoplastic tissues. 131I-MIBG has been associated with a 50% symptomatic response rate and mainly haematological toxicities. PRRT with 111In-DiethyleneTriamineentaacetic Acid-Octreotide, [90Y-DOTA0-Tyr3]-Octreotide, or [177Lu-DOTA0-Tyr3]-Octreotate seem to alleviate symptoms in 50% of patients and obtain a radiological response in 30-38%. Renal toxicity, partially preventable, is more frequent than previously thought and result in an annual decrease in glomerular function by 4 to 8% per year. Forthcoming research in GEP NET should by a majority be designed in randomized, prospective and multicentric fashion. Locoregional disease trials must focus on clinical outcome differences between embolization techniques (embolization, chemoembolization and radioembolization) and surgery. In disseminated disease, studies should assess radiolabeled targeted therapies efficiency when administered along with and compared to new biological and older chemotherapeutic agents.

The antiproliferative effect of somatostatin analogs: clinical relevance in patients with neuroendocrine gastro-entero-pancreatic tumours.

Somatostatin analogs (SSAs) have an important role in the management of patients with neuroendocrine tumours of the gastrointestinal tract and pancreas (GEP NETs). These compounds can control the symptoms induced by the production of hormones and peptides. The antiproliferative effects of SSAs and especially tumour shrinkage are less obvious in patients with GEP NETs than in those with acromegaly. However, based upon phase II experience there is a strong suggestion of a disease stabilizing effect of SSAs in selected patients. Those patients with a progressive, non-functional GEP NET, positive octreotide scintigraphy, a low proliferation index and in the absence of surgical options may benefit from a first-line medical therapy with SSAs. The exploration of the mechanisms of this effect are unclear and hampered by the lack of suitable preclinical models. The better understanding of the tumour biology of GEP NETs, together with the development of new SSAs with better affinity on all somatostatin receptors, represent an unmet medical need.

The potential role of targeted therapies in the management of neuroendocrine tumours.

The management of gastro-entero-pancreatic neuroendocrine tumours is evolving thanks to new TNM-classification, diagnostic and staging procedures and new therapeutic options. Targeting new pathways, mostly angiogenesis, development of novel agents is under way and opens new perspectives in controlling the evolution of these tumours and possibly changing their management. In parallel, new functional imaging techniques and biomolecular markers will be developed to provide adequate tools for the assessment of tumor response according to therapeutic intervention on angiogenesis, proliferation and apoptosis. This paper reviews the potential role of new investigational targeted agents which will likely become the backbone of future therapy of neuroendocrine tumors.

Role of chemotherapy in gastro-entero-pancreatic neuroendocrine tumors: the end of a story?

Gastroenteropancreatic Neuroendocrine Tumours (GEP NET) are heterogeneous and rare malignancies although their prevalence is increasing. Multiple therapeutic approaches are available to date for their management, including surgery, hormonal and immune radionucleide therapies and chemotherapy. The purpose of this review is to collect, examine, and analyze data available regarding contemporary chemotherapeutic management of GEP NET in order to determine whether or not chemotherapy still takes place in the therapeutic arsenal of GEP NET. We therefore performed a systematic search of all the English-spoken literature regarding GEP NET. Anthracyclins, 5-fluorouracil (5-FU), DTIC and streptozotocin are amongst the most commonly used chemotherapeutic agents, usually prescribed in combination. Their efficiency in reducing tumor burden is not always associated with better survival, perhaps due to severe toxicity. Chemotherapy in GEP NET is mainly devoted to poorly differentiated tumours, but also in well differentiated carcinomas either not eligible or resistant to other therapies. Chemotherapy remains therefore useful in specific cases of GEP NET management. However, a new era of antitumoral agents, such as targeted therapies, could eventually replace these old recipes in the near future.

The role of surgery and transplantation in neuroendocrine tumours.

Surgery represents the only chance of cure for a patient with a neuroendocrine tumour (NET). The main indications for surgery lie in the risk of developing metastatic disease with increasing tumour diameter and for a functioning NET also in control of the hormonal syndrome. However, only a small minority of patients presents with a potentially resectable primary NET without metastatic disease. An R0-resection is mandatory, which may be achieved in selected cases by tissue sparing surgical techniques. Most patients unfortunately present with a locally advanced or metastatic disease. For patients with an advanced functioning NET, control of the hormonal syndrome may also represent a surgical indication. Various cytoreductive techniques or, in highly selected cases, liver transplantation can be applied. For locally advanced non-functioning tumours, there is an indication for surgery in large tumours which tend to create local complications because of bleeding or bowel obstruction. Especially in ileal NETs aggressive surgical therapy is recommended because of prevention of long-term complications, which may improve survival.

[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).

[Interest of chronotherapy in multidisciplinary management of oesophageal and gastric cancers]. / Intérêt de la chronothérapie dans le traitement pluridisciplinaire des cancers de l'oesophage et de l'estomac.

The authors evaluated the impact of a chronotherapy with 5-FU, folinic acid and carboplatine (chronomodulated infusions by ambulatory pumps; 5/21 days) for the management of oesophagus (52 cases) and gastric (56 cases) cancer patients. The overall tolerance of treatment was gauged excellent (grade 3-4; % patients: mucitis: 11-23%; leucopenia 6-19%; thrombopenia 18-50%; almost no digestive disturbances nor alopecia). Also tumor outcome was considered interesting with major responses rate in 61% (gastric) to 79% (oesophagus) of patients. The median survival of oesophageal cancer was limited to 9.2 months; the one of disseminated gastric cancer was 12.7 months but 72% of curatively resected patients were alive at 5+ years.

Tumour necrosis factor (TNF) gene polymorphism in Crohn's disease (CD): influence on disease behaviour?

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level.

[Polyarteritis nodosa related to hepatitis b virus infection]. / Périartérite noueuse en relation avec une hépatite B.

A 66-year-old man was hospitalized for asthenia, weight loss, fever and chills. A polyarteritis nodosa associated with hepatitis B virus infection in a replicative phase was diagnosed. Etiology, physiopathology, and clinical characteristics of hepatitis B virus-related polyarteritis nodosa will be reviewed, as well as the effectiveness of therapy combining corticosteroïds, interferon alpha and plasma exchanges.