[A case of systemic sclerosis]. / U ne rémission « en peau de chagrin ¼.

In systemic sclerosis, the presence of an anti-RNA polymerase III antibody (ARNpol3) is associated with an increased risk of cancer. The characteristic picture of this serotype includes severe diffuse cutaneous involvement, a high risk of renal scleroderma crisis and a 10 year survival of only around 30%. Pulmonary involvement is less common. We report the case of a woman initially treated for drug-induced acute interstitial lung disease revealing chronic interstitial pneumonia with autoimmune features. The disease evolved in three stages with the occurrence of a rapidly progressive diffuse skin sclerosis with anti-ARNPol3 antibodies in the context of ovarian cancer remission.

The effect of environmental factors on the incidence of perforated appendicitis.

BACKGROUND: Acute appendicitis is the most common abdominal emergency. Its etiopathogenesis appears to be multifactorial. Several studies suggested a relationship between the development of acute appendicitis and some environmental factors. Air pollution predisposes some people to develop perforated appendicitis. However, data are relatively scarce and the results still controversial. AIM: Determine the seasonal variation of acute appendicitis and study the association between perforated appendicitis and short-term exposure to climatic factors and to air pollutants. METHODS: A cross-sectional study was conducted including patients hospitalized in the general surgery department of Farhat Hached University Hospital in Sousse for acute appendicitis between January 1st and December 31st, 2014. Climatic conditions were collected from the National Institute of Meteorology. Data on air pollution were given by the National Agency for the Protection of the Environment and obtained by the modeling of the atmospheric pollution. For statistical analysis, we used mean concentrations of each environmental factor corresponding to the day of hospital admission and lagged by the 7 previous days. These factors were compared between the group of patients with perforated appendicitis and patients with nonperforated appendicitis. RESULTS: We collected 246 cases of acute appendicitis. Perforated appendicitis was reported in 15.2% of the cases. The incidence of acute appendicitis was higher during summer. Compared to nonperforated appendicitis, perforated appendicitis was significantly associated with the mean relative humidity of the 5 day lag (p = 0.046), rainfall of the 7 day lag (p = 0.043), and consultation delay (p <10-3). Furthermore, perforated appendicitis was significantly associated with the daily mean concentration of carbon dioxide (p = 0.042), the 2- day lag mean concentration of particulate matter less than 10 µ (PM10 ) (p = 0.016), and the 2-day lag mean concentration of ozone (p = 0.048). After multivariate statistical analysis, predictive factors for perforated appendicitis were the consultation delay (OR: 1.621, 95% CI [1.288 - 2.039]; p<10-3) and the 2 day lag mean concentration of PM10 (OR: 1.066, 95% CI [1.007- 1.130]; p = 0.029). CONCLUSION: Short-term exposure to particulate matter was associated with perforated appendicitis. Further large-scale studies are needed to support this conclusion. KEY WORDS: Air pollution, Appendicitis, perforated appendicitis, Climateparticulate matter.

Incidence of salivary side effects after radioiodine treatment using a new specifically-designed questionnaire.

Sialadenitis is one of the common complications of radioiodine treatment for thyroid malignancy. The aim of this study was to evaluate the prevalence of radioiodine-induced sialadenitis and other side effects by using a self-administered questionnaire. From 1 January 2011 to 31 December 2012 all consecutive patients with a newly-established diagnosis of thyroid cancer who were treated with adjuvant radioiodine at La Timone University Hospital were sent a self-administered questionnaire on salivary complaints that had been specifically designed for this study. A total of 413 patients sent the questionnaire back, of whom 100 (24%) had experienced pain, 116 (28%) discomfort or swelling, and 147 (36%) dry mouth or xerostomia. This survey has highlighted the number of side effects of radioiodine treatment in a large group of patients and corroborates previous observations. Our new self-administered questionnaire may be useful to others for follow-up and research.

IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas.

PURPOSE: The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and 18F-FDOPA uptake on PET in newly diagnosed gliomas. METHODS: A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone 18F-FDOPA PET at an initial stage before surgery and histological diagnosis. 18F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). RESULTS: Patients with IDH mutation showed higher 18F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). CONCLUSION: This study showed paradoxically higher 18F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of 18F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.

Morphological and functional imaging of neck paragangliomas.

OBJECTIVE: To review the optimal techniques for localization and characterization of neck paragangliomas (PGL). MATERIAL AND METHODS: Systematic review of the literature from the PubMed/Medline database. RESULTS: Neck PGL are hypervascular tumours essentially arising from paraganglionic tissue situated at the carotid bifurcation (carotid body) and along the vagus nerve. Morphological and functional imaging are indicated to confirm the diagnosis, identify multifocal disease and for local and regional staging. MR angiography is the noninvasive technique of choice. CT scan and especially CT angiography are excellent alternatives for diagnosis and staging. Conventional arteriography remains useful preoperatively for embolization and occlusion tests. Functional imaging allows localization and characterization of PGLs. Somatostatin receptor scintigraphy (SRS) was the reference imaging technique for staging of sporadic PGLs. The indications for PET imaging have been extended over recent years in parallel with the development of new tracers such as [18F]-FDOPA PET or 68Gallium-labelled DOTA peptides. 68Gallium-labelled DOTA peptides has become the first-line imaging modality in the evaluation of cervical PGLs, regardless of the genetic background. CONCLUSION: Morphological and functional imaging is essential for the staging of neck PGL.

Adrenocortical carcinoma surgery-surgical extent and approach.

PURPOSE: Adequate tumour resection is the gold standard of care for adrenocortical carcinoma (ACC). However, the optimal surgical strategy remains debatable. In our opinion, the extent of surgery (adequate tumour resection) is the primary concern, rather than the surgical approach (laparoscopic or open). We propose that both surgical approaches have a role in the management of ACC provided the extent of resection is selected based on patient and tumour characteristics and accurate pre-operative investigations. METHODS: A review of 25 curative intent resections for ACC between 2002 and 2013 was done. Group A (16 patients-64 %) included all patients who underwent planned radical adrenalectomy without any other resection and group B (9 patients-36 %) included all patients who underwent a planned extensive resection based on pre-operative investigations. RESULTS: Of 471 adrenalectomies, 25 were performed for ACC with curative intent. Tumours were significantly larger in group B with mean size of 119.6 versus 62.4 mm in group A (p = 0.002). Tumours in group B also had higher WEISS scores (mean score 7 vs 5.2, p = 0.033) and almost always required multi-organ resection. The recurrence rate was 37.5 % (n = 6) for group A and 44.4 % for group B (n = 4), p = 1.00. Poor prognosis was associated with significantly higher WEISS scores (p = 0.016) and a trend towards more advanced ENSAT disease stage (p = 0.06). Estimated overall survival was 74.17 months (group A 67.3 vs group B 70.1, p = 0.244). CONCLUSIONS: Accurate pre-operative staging is critical to select a tailored surgical strategy. Multi-organ resection remains the preferred approach for large and potentially invasive ACC. Some patients presenting with smaller ACC may benefit from a more extensive resection.

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits <5% significant recurrence after 10 years of follow-up and normal glucocorticoid function in more than 50% of the cases. Therefore, cortical sparing adrenal surgery should be systematically considered in the management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2.

Differentiated thyroid cancer with liver metastases: lessons learned from managing a series of 14 patients.

Liver metastases from differentiated thyroid carcinoma (LMDTC) are rare and usually occur in disseminated metastatic disease. The aim of this study was to review the diagnosis and management of LMDTC. Between 1995 and 2011, 14 patients with a mean age of 59.7 years (+/-10.2) were treated for LMDTC. Data were retrospectively reviewed and analyzed. Seven patients had distant metastases at diagnosis, including 2 with synchronous liver lesions. The average time of onset of LMDTC from initial diagnosis was 52.2 months (+/49.5). All LMDTC were discovered during routine radiologic monitoring. Histologic analysis confirmed LMDTC in 5 patients. Eight patients received tyrosine kinase inhibitors, 1 patient underwent resection of their LMDTC after chemotherapy. Six patients (disseminated metastases, significant comorbidities) did not receive any specific treatment. The median survival after diagnosis of LMDTC was 17.4 months (+/-3.3): 23.6 months (+/-2.9) for patients who underwent chemotherapy versus 3.9 months (+/-0.9) for patients who did not receive any specific treatment (P < 0.001). Developing DTC liver metastasis is a very poor prognostic sign. Chemotherapy by TKIs, especially, hold promise in the cure of LMDTC for selected patients.

Retrostyloid parapharyngeal space tumors: a clinician and imaging perspective.

Although tumors of the parapharyngeal space are rare, they represent a formidable diagnostic and treatment challenge. The differentiation of a retrostyloid lesion from a prestyloid lesion is critical for guiding the differential diagnosis. The majority of lesions involving the retrostyloid parapharyngeal space are either peripheral nerve sheath tumors, head & neck paragangliomas or metastatic lymph node metastases. This article provides insights into the many currently available radiological and radionuclide imaging procedures and guides clinicians toward their appropriate use. In the near future, many patients might also benefit from new diagnostic approaches such as high resolution integrated PET/MRI and new tracers that enable "in vivo" assessment of these tumors at molecular level.

[Prognostic value of sentinel lymph node in Merkel cell carcinoma of the head and neck]. / Intérêt pronostique du ganglion sentinelle dans les carcinomes a cellules de Merkel de la tête et du cou.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor. The aim of our study was to analyze the prognosis of patients operated on for CCM and having no lymph node involvement after analysis of sentinel lymph node (SLN). MATERIAL AND METHOD: This was a retrospective study of 10 cases of CCM stage I or II who received the SLN technique in our institution between 2003 and 2010. RESULTS Among the 10 patients, 7 had an identification of at least one SLN, among which the node could be surgically removed in 6 cases. In cases of failure of SLN technique, a neck dissection +/- parotidectomy was performed. No lymph node metastasis was found in our series. Mean follow-up was 38 months. The overall survival rate was 100% at 2 years and 50% at 5 years. The Disease-free survival was 85% at 2 and 5 years. CONCLUSION: Our results show that the technique of sentinel lymph node is a reliable tool for evaluating nodal status of patients with CCM and that pN0 patients have a good prognosis.

(18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic tool but not of prognostic value.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. (18)F-FDG PET ((18)F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, (18)F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative (18)F-FDG PET based on SUVs assessments has a prognostic value in ACC patients. METHODS: A retrospective analysis was performed in patients who underwent (18)F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; (18)F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All (18)F-FDG PET/CT procedures were reinterpreted in a blind fashion. RESULTS: Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)(max) = 11 (range: 3-56) and a tumor/liver SUV(max) ratio = 4.2 (range: 1.3-15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. (18)F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis. CONCLUSIONS: At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.

Radioiodine thyroid ablation in graves' hyperthyroidism: merits and pitfalls.

Ablative approaches using radioiodine are increasingly proposed for the treatment of Graves' disease (GD) but their ophthalmologic and biological autoimmune responses remain controversial and data concerning clinical and biochemical outcomes are limited. The aim of this study was to evaluate thyroid function, TSH-receptor antibodies (TRAb) and Graves' ophthalmopathy (GO) occurrence after radioiodine thyroid ablation in GD. We reviewed 162 patients treated for GD by iodine-131 ((131)I) with doses ranging from 370 to 740 MBq, adjusted to thyroid uptake and sex, over a 6-year period in a tertiary referral center. Collected data were compared for outcomes, including effectiveness of radioiodine therapy (RIT) as primary endpoint, evolution of TRAb, and occurrence of GO as secondary endpoints. The success rate was 88.3% within the first 6 months after the treatment. The RIT failure was increased in the presence of goiter (adjusted odds ratio = 4.1, 95% confidence interval 1.4-12.0, P = 0.010). The TRAb values regressed with time (r = -0.147; P = 0.042) and patients with a favorable outcome had a lower TRAb value (6.5 ± 16.4 U/L) than those with treatment failure (23.7 ± 24.2 U/L, P < 0.001). At the final status, 48.1% of patients achieved normalization of serum TRAb. GO occurred for the first time in 5 patients (3.7%) who were successfully cured for hyperthyroidism but developed early and prolonged period of hypothyroidism in the context of antithyroid drugs (ATD) intolerance (P = 0.003) and high TRAb level (P = 0.012). On the basis the results of this study we conclude that ablative RIT is effective in eradicating Graves' hyperthyroidism but may be accompanied by GO occurrence, particularly in patients with early hypothyroidism and high pretreatment TRAb and/or ATD intolerance. In these patients, we recommend an early introduction of LT4 to reduce the duration and the degree of the radioiodine-induced hypothyroidism.

A retroperitoneal bronchogenic cyst.

Bronchogenic cysts are benign congenital malformations usually. A retroperitoneal location is extremely uncommon. We reported a case of bronchogenic cyst occurred in the retroperitoneum in a 60-year-old patient. An abdominal CT for a prostatic adenocarcinoma staging has reported this incidental lesion. Biological, radiological and histological assessment confirmed the bronchogenic cyst diagnosis. The treatment of choice for most authors is surgical excision. However, because of a low malignant transformation risk, we have chosen a follow-up with abdominal computerized tomography every 6 months. During 3 years, biological and radiological assessments have shown a stable lesion. Therefore, it seems reasonable to propose a simple radiological monitoring for bronchogenic cysts in selected patients.

Current and future anatomical and functional imaging approaches to pheochromocytoma and paraganglioma.

After establishing a biochemical diagnosis, pheochromocytomas and extra-adrenal paragangliomas (PPGLs) can be localized using different anatomical and functional imaging modalities. These include computed tomography, magnetic resonance imaging, single-photon emission computed tomography (SPECT) using 123I-metaiodobenzylguanidine or 111In-DTPA-pentetreotide, and positron emission tomography (PET) using 6-[18F]-fluorodopamine (18F-FDA), 6-[18F]-fluoro-l-3,4-dihydroxyphenylalanine (18F-DOPA), and 2-[18F]-fluoro-2-deoxy-d-glucose. We review the currently available data on the performance of anatomical imaging, SPECT, and PET for the detection of (metastatic) PPGL as well as parasympathetic head and neck paragangliomas. We show that there appears to be no 'gold-standard' imaging technique for all patients with (suspected) PPGL. A tailor-made approach is warranted, guided by clinical, biochemical, and genetic characteristics. In the current era of a growing number of PET tracers, PPGL imaging has moved beyond tumor localization towards functional characterization of tumors.

OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer.

Despite many advances in oncology, almost all patients with pancreatic cancer (PC) die of the disease. Molecularly targeted agents are offering hope for their potential role in helping translate the improved activity of combination chemotherapy into improved survival. Heat shock protein 27 (Hsp27) is a chaperone implicated in several pathological processes such as cancer. Further, Hsp27 expression becomes highly upregulated in cancer cells after chemotherapy. Recently, a modified antisense oligonucleotide that is complementary to Hsp27 (OGX-427) has been developed, which inhibits Hsp27 expression and enhances drug efficacy in cancer xenograft models. Phase II clinical trials using OGX-427 in different cancers like breast, ovarian, bladder, prostate and lung are in progress in the United States and Canada. In this study, we demonstrate using TMA of 181 patients that Hsp27 expression and phosphorylation levels increase in moderately differentiated tumors to become uniformly highly expressed in metastatic samples. Using MiaPaCa-2 cells grown both in vitro and xenografted in mice, we demonstrate that OGX-427 inhibits proliferation, induces apoptosis and also enhances gemcitabine chemosensitivity via a mechanism involving the eukaryotic translation initiation factor 4E. Collectively, these findings suggest that the combination of Hsp27 knockdown with OGX-427 and chemotherapeutic agents such as gemcitabine can be a novel strategy to inhibit the progression of pancreas cancer.

Modern PET imaging for paragangliomas: relation to genetic mutations.

AIM AND METHODS: Paragangliomas (PGL) are neural crest-derived tumours that are found along the autonomic neural network throughout the body and can be multiple and/or metastatic. Nuclear medicine imaging in combination with conventional imaging is required to fully delineate the extent of the disease. The performance of molecular imaging modalities is widely dependent on tumour biology. RESULTS: In the present paper we discuss the recent publications focused on the role of positron emission tomography (PET) imaging and the relationship between tracer uptake patterns and genetic mutations associated with the disease. CONCLUSION: Recent advances in genetic and molecular pathogenesis of PGL have allowed for the identification of new molecular diagnostic and therapeutic radiopharmaceuticals tailored to genetic abnormalities. However, the optimal diagnostic imaging algorithm remains to be determined.

Comparison of [¹¹¹In]pentetreotide-SPECT and [¹8F]FDOPA-PET in the localization of extra-adrenal paragangliomas: the case for a patient-tailored use of nuclear imaging modalities.

AIMS AND METHODS: The aim of this prospective study was to compare the diagnostic value of [¹8F]FDOPA-PET and [¹¹¹In]pentetreotide-SPECT somatostatin receptor scintigraphy (SRS) in patients with nonmetastatic extra-adrenal paragangliomas (PGLs). Twenty-five consecutive unrelated patients who were known or suspected of having nonmetastatic extra-adrenal PGLs were prospectively evaluated with SRS and [¹8F]FDOPA-PET. ¹³¹I-MIBG and [¹8F]FDG-PET were added to the work-up in patients with a personal or familial history of PGL, predisposing mutations, abdominal PGLs, metanephrine hypersecretion and abdominal foci on SRS and/or [¹8F]FDOPA-PET. RESULTS: SRS correctly detected 23/45 lesions of which 20 were head or neck lesions (H&N) and 3 were abdominal lesions. [¹8F]FDOPA-PET detected significantly more lesions than SRS (39/45, P < 0·001). Both SRS and ¹8F-DOPA-PET detected significantly more H&N than abdominal lesions (66·7% vs 20%, P = 0·003 and 96·7% vs 67%, P = 0·012, respectively). In two patients with the succinate dehydrogenase D (SDHD) mutation, [¹8F]FDOPA-PET missed five abdominal PGLs which were detected by the combination of SRS, [¹³¹I]MIBG and [¹8F]FDG-PET. A lesion-based analysis using a forward stepwise logistic regression model demonstrates that size ≤ 10 mm (P = 0·002) and abdominal lesions (P = 0·031) were independently associated with "[¹8F]FDOPA-PET diagnosis only". In turn, a previous history of surgery and/or the presence of germline mutation was associated with lower lesion size (P = 0·001). CONCLUSIONS: The sensitivity of SRS for localizing parasympathetic PGLs is lower than originally reported, and [¹8F]FDOPA-PET is better than SRS for localizing small lesions. SRS should be replaced by [¹8F]FDOPA-PET as the first-line imaging procedure in H&N PGL, especially in patients at risk of multifocal disease (predisposing mutations and or previous history of surgery).

Iodine biokinetics and radioiodine exposure after recombinant human thyrotropin-assisted remnant ablation in comparison with thyroid hormone withdrawal.

CONTEXT: A few prospective studies have evaluated the use of recombinant human TSH (rhTSH) for radioiodine remnant ablation. OBJECTIVE: Our objective was to compare the effects of the both TSH regimens on iodine biokinetics in the thyroid remnant, dosimetry, and radiation protection. DESIGN: We conducted a prospective randomized study. MATERIALS AND METHODS: Eighty-eight patients were enrolled for radioiodine ablation to either the hypothyroid or rhTSH arms. A whole-body scan was performed at 48 and 144 h after therapy. Dose rates were assessed at 24, 48, and 144 h. Urinary samples were obtained during the first 48 h. Thyroglobulin was assessed before and after therapy. Iodine biokinetics in the remnants were calculated from gamma-count rates. Radiation-absorbed dose was calculated using OLINDA software. Exposure estimation was based on a validated model. RESULTS: The effective half-life in the remnant thyroid tissue was significantly longer after rhTSH than during hypothyroidism (P = 0.01), whereas 48-h (131)I uptakes and residence times were similar. After therapy, thyroglobulin release (a marker of cell damage) was lower in the rhTSH arm. The mean total-body effective half-life and residence time were shorter in patients treated after rhTSH. Residence time was also lower for the colon and stomach. Absorbed dose estimates were lower in the rhTSH arm for the lower large intestine, breasts, ovaries, and the bone marrow. Dose rates at the time of discharge were lower in the rhTSH group with a reduction in cumulative radiation exposure to contact persons. CONCLUSIONS: In comparison with thyroid hormone withdrawal, rhTSH is associated with longer remnant half-life of radioactive iodine while also reducing radiation exposure to the rest of the body and also to the general public who come in contact with such patients.