Hypertension in a Patient With Polycystic Kidney Disease Complicated by Concomitant Pheochromocytoma.

Background: Due to the high prevalence of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD) and advanced chronic kidney disease, diagnosing secondary hypertension poses challenges. We present a rare case of pheochromocytoma in an ADPKD patient to highlight the diagnostic difficulties in identifying secondary hypertension due to pheochromocytoma/paraganglioma (PPGL) in end-stage renal disease (ESRD) patients. Case Report: A 48-year-old female with ADPKD and ESRD experienced recurrent hypertensive crises (up to 220/135 mmHg) accompanied by palpitations and tremors that recurred over the past 2 years. Introduction of a betablocker to the antihypertensive therapy aggravated her symptoms. The initial documentation of elevated urinary metanephrines was interpreted as false positive finding due to renal failure. Subsequent measurements of free plasma metanephrines revealed significant elevations raising suspicion of PPGL. Magnetic resonance imaging identified a 29 mm right adrenal mass. The patient underwent right adrenalectomy resulting in resolution of the hypertensive crises. Discussion: The diagnosis of PPGLs can present significant challenges and is further complicated in ESRD due to nonspecific clinical symptoms and diagnostic pitfalls. Less than 20 PPGL cases have been reported in patients with ESRD. The intolerance of beta-blocker therapy, as well as the use of a scoring system for the likelihood of PPGL should have raised suspicion. Conclusion: PPGL should be considered in all patients with uncontrolled hypertension and beta-blockers intolerance, even in the presence of other etiologic mechanisms such as ESRD. Measuring free plasma metanephrines provides the most reliable biochemical screening in the context of impaired renal function.

Peripheral lymphadenopathy of unknown origin in adults: a diagnostic approach emphasizing the malignancy hypothesis.

The term lymphadenopathy refers to an abnormality in size, consistency or morphological aspect of one or several lymph nodes. Although lymphadenopathies are commonly observed in everyday clinical practice, the difficulty of differentiating benign and malignant disease may delay therapeutic approaches. The present review aims to update diagnostic algorithms in different clinical situations based on the currently available literature. A literature review was performed to assess current knowledge of and to update the diagnostic approach. A short clinical vignette was used as an example of a typical clinical presentation. This case of metastatic lymphadenopathy with incomplete patient history demonstrates how misleading such lymphadenopathy may be, leading to a delayed diagnosis and even a fatal outcome. Any lymphadenopathy persisting for more than 2 weeks should be considered suspicious and deserves further investigation. Precise clinical examination, meticulous history-taking and a search for associated symptomatology are still cornerstones for diagnosing the origin of the condition. The next diagnostic step depends on the anatomical region and the specific patient's situation. Imaging starts with ultrasound, while computed tomography (CT) and magnetic resonance imaging (MRI) allow assessment of the surrounding structures. If the diagnosis remains uncertain, tissue sampling and histological analyses should be performed. Except for head and neck loco-regional lymphadenopathy, there are no methodical guidelines for persistent lymphadenopathy. The present review clarifies several confusing and complex situations. The accuracy of fine needle aspiration cytology could be increased by using core needle biopsy with immunocytologic and flow cytometric methods. Notably, except in the head and neck area, open biopsy remains the best option when lymphoma is suspected or when inconclusive results of previous fine needle aspiration cytology or core needle biopsy are obtained. The incidence of malignant lymphadenopathy varies with its location and the various diagnostic strategies. In metastatic lymphadenopathy of unknown primary origin, European Society for Medical Oncology (ESMO) guidelines and modern methods like next-generation sequencing (NGS) may help to manage such complex cases.

Assessing the perioperative gain of weight (Δweight) as a determinant of morbidity after kidney transplantation: a retrospective exploratory study.

Kidney transplantation (KT) is associated with a substantial risk of postoperative complications (POC) for which performant predictors are lacking. Data showed that a perioperative gain of weight (ΔWeight) was associated with higher risk of POC, but it remains unexplored in KT. This retrospective study aimed to investigate the association between ΔWeight and POC after KT. ΔWeight was calculated on postoperative day (POD) 2. POC were graded according to the Dindo-Clavien classification. Primary endpoint was overall POC. A total of 242 patients were included and 174 (71.9%) complications were reported. Patients showed a rapid gain of weight after KT. Mean ΔWeight was 7.83 kg (± 3.20) compared to 5.3 kg (± 3.56) in patients with and without complication, respectively (p = 0.0005). ΔWeight showed an accuracy of 0.74 for overall POC. A cut-off of 8.5 kg was determined. ΔWeight ≥ 8.5 kg was identified as an independent predictor of overall POC on multivariable analysis (OR 2.04; 95% CI 1.08-3.84; p = 0.025). ΔWeight ≥ 8.5 kg appeared as an independent predictor of POC after KT. These results stress the need to monitor weight in KT and to further investigate this surrogate with future studies assessing its clinical relevance.

[Surgical treatment for primary aldosteronism]. / Rôle de la chirurgie dans l'hyperaldostéronisme primaire.

Primary aldosteronism is the most common cause of secondary hypertension in the middle-aged population. A high level of suspicion is required, due to the higher morbidity and mortality associated with damage to target organs (heart, brain, vessels, kidneys) than with essential hypertension. Screening involves 3 phases: detection, confirmation and detection of lateralization if surgery is an option. The choice of treatment will depend on the cause and the patient's wishes and may be either medical (mineralocorticoid receptor antagonists) or surgical (unilateral adrenalectomy). Both treatment options reduce the risk of cardiovascular morbidity and mortality if blood pressure is well controlled.

L'hyperaldostéronisme primaire est la cause la plus fréquente d'hypertension artérielle secondaire dans la population d'âge moyen. Un haut niveau de suspicion doit être de mise en raison d'une morbimortalité liée aux atteintes d'organes cibles (cœur, cerveau, vaisseaux, reins) plus élevée que lors d'hypertension artérielle essentielle. Le dépistage se fait en 3 phases : détection, confirmation et recherche de latéralisation si une chirurgie est envisageable. Le choix du traitement va dépendre de la cause et des désirs du patient et peut être médicamenteux (antagonistes des récepteurs des minéralocorticoïdes) ou chirurgical (surrénalectomie unilatérale). Les deux options thérapeutiques diminuent le risque de morbimortalité cardiovasculaire si la tension artérielle est bien contrôlée.

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Response to tumor-infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+ T-myeloid cell networks in melanoma.

Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell-intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor-reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network-based biomarkers that could improve patient selection and guide the design of ACT clinical trials.

Surgical site infections after kidney transplantation are independently associated with graft loss.

Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.

Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Feasibility and Performance of Free-Hand Single-Photon Computed Tomography/Ultrasonography for Preoperative Parathyroid Adenoma Localization: A Pilot Study.

The aim of this prospective pilot study was to evaluate the feasibility of a new hybrid imaging modality, free-hand single-photon computed tomography/ultrasonography (fhSPECT/US), for preoperative localization of parathyroid adenomas and to compare its performance with conventional ultrasonography and SPECT/CT. Twelve patients diagnosed with primary hyperparathyroidism underwent sequentially US and parathyroid scintigraphy, including SPECT/CT, followed by fhSPECT/US, allowing for real-time fusion between US and freehand-generated gamma-camera images. The fhSPECT/US detection rates were correlated with histopathology, when available, or with the imaging modality showing the most lesions. Based on a per patient analysis, the detection rate was significantly different when comparing SPECT/CT to fhSPECT/US (p = 0.03), and not significantly different when comparing SPECT/CT to US (p = 0.16) and US to fhSPECT/US (p = 0.08). Based on a per-lesion analysis, the detection rate of SPECT/CT was significantly higher than that of US (p = 0.01) and fhSEPCT/US (p = 0.003), and there was no significant difference in detection rate when comparing US to fhSPECT/US (p = 0.08). The main perceived limitations of fhSPECT/US in lesion detection were: (i) lesions localized at a depth ≥4.5 cm; (ii) imperfect image fusion due to tissue compression; (iii) limited spatial manipulation ability of the SPECT mobile camera handheld probe; and (iv) a wide spread of detected activity. In conclusion, clinical use of fhSPECT/US for localization of parathyroid adenomas is feasible, but shows lower sensitivity than conventional modalities and requires technical improvements.

[Surgical management of primary hyperparathyroidism]. / Prise en charge chirurgicale de l'hyperparathyroïdie primaire.

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia due to inappropriate parathyroid hormone (PTH) secretion mostly caused by a single adenoma. Clinical manifestations vary and include bone loss (osteopenia, osteoporosis), kidney stones, asthenia and psychiatric disorders. In 80 % of cases PHPT is asymptomatic. Secondary causes of elevated PTH such as renal insufficiency and/or vitamin D deficiency should be excluded, and 24-hour calciuria should be measured to rule out familial hyocalciuric hypercalcemia. Surgery requires radiological tests: a cervical ultrasound to exclude concomitant thyroid pathology and a functional examination (Sestamibi scintigraphy or F-choline PET scan). Management should be discussed in a multidisciplinary team. Treatment is surgical and can also be offered to asymptomatic patients.

L'hyperparathyroïdie primaire (HPTP) est caractérisée par une hypercalcémie causée par une sécrétion inappropriée de parathormone (PTH) due, dans la majorité des cas, à un adénome parathyroïdien unique. Les manifestations cliniques sont variées, comme la perte osseuse (ostéopénie, ostéoporose), les calculs rénaux, l'asthénie et les troubles psychiatriques. Dans 80 % des cas, l'HPTP est asymptomatique. Il faut exclure une cause secondaire d'élévation de la PTH sur une insuffisance rénale ou un déficit en vitamine D et doser la calciurie sur 24 heures pour exclure une hypercalcémie hypocalciurique familiale. La chirurgie nécessite des examens de radiologie au préalable : un ultrason cervical pour exclure une pathologie thyroïdienne concomitante et un examen fonctionnel (scintigraphie au Sestamibi ou PET-scan à la F-choline). Il est important de discuter de la prise en charge de façon multidisciplinaire. Le traitement curatif est chirurgical et peut aussi être proposé aux patients asymptomatiques.

Parathyroid Imaging.

Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid adenomas. 1° HPT causing hypercalcemia, kidney stones and/or osteoporosis should be treated whenever possible by parathyroidectomy. Accurate preoperative location of parathyroid adenomas is crucial for surgery planning, mostly when performing minimally invasive surgery. Cervical ultrasonography (US) is usually performed to localize parathyroid adenomas as a first intention, followed by 99mTc- sestamibi scintigraphy with SPECT/CT whenever possible. 4D-CT is a possible alternative to 99mTc- sestamibi scintigraphy. Recently, 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has made its way in the clinics as it is the most sensitive method for parathyroid adenoma detection. It can eventually be combined to 4D-CT to increase its diagnostic performance, although this results in higher dose exposure to the patient. Other forms of hyperparathyroidism consist in secondary (2° HPT) and tertiary hyperparathyroidism (3° HPT). As parathyroidectomy is not usually part of the management of patients with 2° HPT, parathyroid imaging is not routinely performed in these patients. In patients with 3° HPT, total or subtotal parathyroidectomy is often performed. Localization of hyperfunctional glands is an important aid to surgery planning. As 18F-FCH PET/CT is the most sensitive modality in multigland disease, it is the preferred imaging technic in 3° HPT patients, although its cost and availability may limit its widespread use in this setting.

Incidence, Risk Factors, and Management of Incisional Hernias After Kidney Transplant: A 20-Year Single Center Experience.

BACKGROUND: Incisional hernias (IH) constitute a complication after kidney transplant (KT). Patients may be particularly at risk because of comorbidities and immunosuppression. The study aim was to assess the incidence, risk factors, and treatment of IH in patients undergoing KT. METHODS: This retrospective cohort study included consecutive patients who underwent KT between January 1998 and December 2018. Patient demographics, comorbidities, perioperative parameters, and IH repair characteristics were assessed. Postoperative outcomes included morbidity, mortality, need for reoperation, and length of stay (LOS). Patients who developed IH were compared with those who did not develop one. RESULTS: Forty-seven patients (6.4%) developed an IH after a median delay of 14 months (IQR, 6-52 months) in 737 KTs. On uni- and multivariate analyses, body mass index (odds ratio [OR], 1.080; P = .020), pulmonary diseases (OR, 2.415; P = .012), postoperative lymphoceles (OR, 2.362; P = .018), and LOS (OR, 1.013; P = .044) were independent risk factors. Thirty-eight patients (81%) underwent operative IH repair, and 37 (97%) were treated with a mesh. The median LOS was 8 days (IQR, 6-11 days). Three patients (8%) developed surgical site infections, and 2 patients (5%) presented hematomas requiring surgical revision. After IH repair, 3 patients (8%) had a recurrence. CONCLUSIONS: The incidence of IH after KT seems rather low. Overweight, pulmonary comorbidities, lymphoceles, and LOS were identified as independent risk factors. Strategies focusing on the modifiable patient-related risk factors and early detection and treatment of lymphoceles may help to decrease the risk of IH formation after KT.

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma.

Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.

Neuroblastic Tumors of the Adrenal Gland in Elderly Patients: A Case Report and Review of the Literature.

Background: Neuroblastic neoplasms (NN) include ganglioneuromas (GN), ganglioneuroblastomas (GNB), and neuroblastomas (NB). They generally arise in childhood from primitive sympathetic ganglion cells. Their incidence in adults, especially among elderly, is extremely low. Case Presentation: This is the case of a 74-year-old woman with history of abdominal pain, weakness and night sweating since several months. Blood pressure was normal. CT-scan showed a 10 cm left adrenal mass, without other pathologic findings. An open left-sided adrenalectomy was performed. Recovery was uneventful with hospital length of stay of 8 days. Based on morphological, immunohistochemical, and molecular features the diagnosis was a nodular GNB. A positron emission tomography (PET) performed 6 weeks after the resection did not show any residual tumor or distant metastases. The patient was followed-up with annual clinical and radiological exams. Conclusion: This case presentation, associated with a review of the literature, illustrates the importance to include NN in the preoperative differential diagnosis of adrenal tumors in adults and highlights the need for multidisciplinary patient work-up and management.

Case Report: Tyrosine Kinase Inhibitors Induced Lymphadenopathy in Desmoid Tumor Patients.

Tyrosine kinase inhibitors (TKIs) are nowadays a valuable treatment of desmoid tumors, a rare mesenchymal neoplasm. Although many side effects of imatinib and pazopanib, commonly or rarely occurring, have been described, reactional lymphadenopathy has not yet been reported. In this publication, we report two cases of patients with desmoid tumors, treated with pazopanib and imatinib, who developed reactional lymphadenopathy. As this side effect is presented as a newly formed mass, it can result in new diagnostic questions and added imaging tests and can even lead to discontinuation of the treatment. This report may help the clinicians facing similar problems adopt a "watch and wait" approach.