Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin's lymphoma patients-the Polish Lymphoma Research Group (PLRG) Observational Study.

BACKGROUND: Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin's lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. PATIENTS AND METHODS: Consecutive patients with newly diagnosed classical Hodgkin's lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (-) (DS 1-3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3-5 underwent iPET2. RESULTS: About 106 early (I-IIA) and 204 advanced (IIB-IV) patients were enrolled between January 2008 and October 2014. iPET1 was (-) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (-) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2-90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(-) remained iPET2(-) (fast responders), 41/82 with IPET1(+) became iPET2(-) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. CONCLUSION: The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Renal involvement in systemic amyloidosis: an Italian collaborative study on survival and renal outcome.

BACKGROUND: Few data are available from large population-based studies on survival and renal outcome of patients with renal involvement and different types of systemic amyloidosis. METHODS: Two hundred and ninety of over 373 patients affected from systemic amyloidosis with renal involvement diagnosed in Italy between January 1995 and December 2000 were followed from diagnosis to death or until the last available clinical control. Eighty-three patients were excluded from analysis either because the amyloid type remained undetermined or they were lost at follow-up. Clinical and laboratory information was collected according to the different types of amyloidosis using a specific form which included renal function with 24 h proteinuria at diagnosis and at the end of follow-up, the type and the date of onset of dialysis and the kind of treatment they underwent. RESULTS: The median time of follow-up was 24 months in primary (AL) amyloidosis (range: 1-88 months), 16 months in AL with associated multiple myeloma (MM + AL: range 1-76 months), 30 months in reactive (AA) amyloidosis (range: 1-99 months) and 52 months in patients with familial forms (AF: range 14-82 months). Patients with AL showed a significantly shorter survival than AA. Despite no significant differences of renal outcome or survival on dialysis being observed between the two groups, a lower renal survival with a higher number of patients who progressed to end-stage renal disease (ESRD) was observed in patients with AA. Overall survival was markedly improved in patients with AL who underwent a specific therapy (conventional chemotherapy or autologous stem cell transplantation (ASCT)) even in the absence of a positive kidney response. Multivariate analysis showed cardiac involvement and specific therapy to significantly influence survival in AL whereas age, serum creatinine (sCr) and heart involvement significantly affected survival in AA. In both groups, sCr and heart involvement were the most relevant predictors for renal outcome, together with urinary protein excretion, in patients with AA. CONCLUSIONS: Our results show a worse survival in AL due to the higher prevalence of heart involvement in this group and emphasize that a specific therapy significantly prolongs survival and slows the progression of renal disease in patients with AL. We suggest that a late nephrological referral is likely the cause of the higher sCr found at presentation in patients with AA and probably accounts for the lower renal survival observed in the short term in these patients. At the time being, renal transplantation and ASCT are still rare therapeutic options for renal patients affected from systemic amyloidosis.

Nodular macroglossia with combined light chain and beta-2 microglobulin deposition in a long-term dialysis patient.

We describe a case in which nodular macroglossia, a very rare type of tongue involvement, was associated with the co-deposition of lambda light chain and beta-2 microglobulin fibrils in the tongue. The combined presence of two different amyloid fibrils did not lead to a more unfavourable clinical outcome. We believe that both these features often remain underdiagnosed and are in fact more frequent than reported. A careful clinical examination of the tongue together with serum immunofixation should be routine in all patients with dialysis-related amyloidosis in order to investigate the prevalence and type of tongue involvement and to rule out other types of amyloidosis. In all cases of suspected mixed amyloidosis, immunohistochemical characterization of fibrils should be carried out by electron microscopy.

Total antioxidant capacity (TAC): is it an effective method to evaluate the oxidative stress in uraemia?

Lipoprotein abnormalities are common in uraemia and are considered important factors for development of atherosclerosis and progression of renal disease. Reduction of total antioxidant capacity (TAC) and lipid peroxidation (LP) probably play a major role in both processes. The aim of this study was to assess the effect of renal function, dietary manipulation and lipids on TAC of uraemic patients with different chronic renal failure (CRF). Sixty patients (36M, 24F), aged 60 +/- 12 years were divided into five groups according to serum creatinine levels (sCr,mg/dl)--CRFI, 1.5-3; CRFII, > 3-5.5; CRFIII, > 5.5; CRFIV, > 3 on vegetarian supplemented diet (SD); CRFV haemodialysis patients (HD)- and investigated for TAC by enhanced chemiluminescent assay, autoantibodies against oxidized LDL (oxLDLAb), lipids, apolipoprotein AI, B, Lp(a) and uric acid (UA). The results were compared to a control group of 19 people (8M, 11F), aged 52 +/- 11 years with sCr < 1.5. TAC increased significantly with the progression of CRF and was strongly related to both sCr and UA. Lipids and SD did not show any influence on TAC. Unexpectedly, lipid peroxidation did not correlate to TAC, neither to sCr or UA. HD accounted for a mild reduction of both TAC and LP. Patients on SD showed a marked reduction of LP as compared to patients with a similar degree of renal failure (CRF-III) but on conventional diet. Our results suggest that elevated TAC in uraemia is likely to be dependent on increased UA levels and does not seem to induce an effective protection in vivo from oxidative stress. In conclusion, TAC does not appear to be a reliable method for assessing the oxidative susceptibility of CRF patients.

Familial AL-amyloidosis in three Italian siblings.

BACKGROUND AND METHODS: Familial occurrence of immunoglobulin-related (AL) amyloidosis has occasionally been reported. In this work we describe the concomitance of systemic amyloidosis and monoclonal gammopathy (one case of Waldenström's macroglobulinemia and two cases without multiple myeloma or related diseases) in three Italian siblings, two males and one female. RESULTS AND CONCLUSIONS: All of them showed a common pattern of polyneuropathy to different degrees; two presented a sicca syndrome and one also suffered from nephropathy. Two of them showed the same HLA typing with the same light chain type (k), but had different presenting symptoms. Polyneuropathy and a history of peptic disease in two cases was suggestive of type III familial amyloidotic polyneuropathy (FAP) occurring in the setting of a familial monoclonal component. However, immunohistochemical studies on different tissue specimens using anti-apolipoprotein A1 and anti-transthyretin antibodies were negative. Further screening of DNA samples for transthyretin (TTR) gene mutations was also negative. Clinical and laboratory investigations ruled out reactive or senile amyloidosis and immunohistochemical studies with anti-light chain antibodies on amyloidotic tissue specimens were positive. As a consequence, this family represents a new case of familial AL-amyloidosis.

AL-amyloidosis in monoclonal gammopathies.

Sixty-two patients affected by MGUS underwent fat tissue aspirate examination for diagnosis of AL amyloidosis. Nine out of the 62 were found to be Congo red positive. MGUS had already been diagnosed for quite a long time in about 60% of these patients, while this prevalence decreased to 24% among the Congo red negative patients. The follow-up of the positive patients is reported.

Are lipid abnormalities reliable cardiovascular risk factors in dialysis patients?

Patients on chronic hemodialysis often present both hyperlipidemia and a high incidence of cardiovascular disease (CVD). Uremic hyperlipidemia has usually been regarded as one of the most important cardiovascular risk factors (CVRF) in these patients. In order to study whether the "uremia-induced" lipid abnormalities are actually associated with evidence of uremic CVD, and consequently may be considered reliable CVRF, 123 patients on chronic dialysis were reviewed for the presence of CVD and, at the same time, examined for their lipoprotein pattern and other clinical and biochemical variables. Lipids and lipoproteins did not prove helpful in our study in identifying patients with CVD. Despite the fact that they had been on dialysis for a shorter time, CVD patients were significantly older and had higher blood pressure than patients without CVD. Our data suggest that the uremia-induced lipid abnormalities are not reliable markers of CVD in dialysis patients, and support the hypothesis that dialysis per se does not accelerate the atherosclerotic process in uremic patients.

Renal involvement in IgD myeloma.

Nine patients affected from IgD myeloma were studied retrospectively in order to elucidate the incidence and peculiar traits of related nephropathy. Eight patients developed chronic renal failure, and as many as 5 were already suffering from renal failure since first admission to the hospital. In 3 cases acute renal failure was the major presenting symptom of the disease. Five patients underwent a regular dialytic treatment. We suggest that the high incidence of renal involvement found in IgD myeloma is related to the high incidence of Bence-Jones proteinuria observed in this disease. Presenting atypical symptoms, among which renal failure is the most important, are misleading and characteristic of the disease. Survival time seems to be negatively influenced by the presence of renal failure at the time of diagnosis.

La duodenopancreatectomia cefálica en el tratamiento del cáncer de cabeza de pancreas, papila y duodeno periampular / Cephalic duodenopancreatectomy in the treatment of head of the pancreas, papilla and periampullary duodenum

Se presentan 25 casos de duodeno-pancreatectomías cefálicas realizadas en 15 carcinomas de cabeza de páncreas, 5 carcinomas de papila de Vater y 5 carcinomas de segunda porción de duodeno. Se analizan aspectos diagnósticos y terapéuticos, sin intentar hacer un estudio comparativo de las tres patologías

Hepaticoyeyunostomia intraparenquimatosa a lo Champeau con hepatectomia segmentaria. / Hepatico-jejunostomy according to Champeau's technic with segmentary hepatectomy

Se presentan dos casos de estenosis alta del hepatico comun, iatrogenicas, tratadas con una hepaticoyeyunostomia con reseccion hepatica a lo Champeau. La evolucion alejada ha sido excelente