Laparoscopic Left Side Duodenum Adenocarcinoma Resection (III-IV Segment): A Step-By-Step Surgical Technique.

INTRODUCTION: Nonampullary duodenal adenocarcinoma (NDA) accounts for approximately 5% of all gastrointestinal cancers. Complete surgical resection (R0) with regional draining lymph node removal is mandatory as treatment to potentially cure nonampullary duodenal cancer or to achieve long-term survival. METHODS: According to existing literature, minimally invasive surgery has been reported to be safe and oncologically equivalent in pancreaticoduodenectomy for pancreatic and duodenal cancer. We describe a fully laparoscopic approach for the left-side adenocarcinoma of the duodenum "left-side" is defined with reference to the mesenteric vessels (III-IV segment). RESULTS: For the first time in literature, this multimedia paper describes a fully laparoscopic complete resection (R0) of the left side of the duodenum (III-IV segment) with locoregional lymph node resection. The main steps of the procedure are described using the concept of the critical view of safety. Reconstruction of intestinal continuity was ensured by full intracorporeal anastomosis. CONCLUSIONS: Through the tips and indications presented in this article, we supply a guide to the minimally invasive approach and increase operating surgeons' familiarity with such a complex procedure.

Cardiac amyloidosis detection by early bisphosphonate (99mTc-HMDP) scintigraphy.

OBJECTIVE: To determine one or more indexes able to detect the presence of cardiac amyloidosis (CA) from planar scintigraphy images after injection of 99mTc-HMDP tracer and to identify the earliest acquisition time able to ensure an accurate diagnosis of amyloid transthyretin CA. METHODS AND RESULTS: A total of 38 patients were included: 18 subjects with a final diagnosis of ATTR-CA and 20 controls. Dynamic planar images of the anterior thorax were acquired, starting at intravenous injection of ≈ 700 MBq of 99mTc-HMDP. From time/activity curves (TAC) of regions of interest such as heart, vascular region, right ribcage, and soft tissues, several indices were considered. From the analysis, it resulted that both TACHeart/Bone(t) and RIheart-bone(t), for t > 6 minutes, well distinguish ATTR-CA patients from controls subjects. This is confirmed by the area under curves (AUC) analysis giving AUC values =.9 at t ≅ 6 minutes and AUC ≅ 1 for t > 10 minutes. CONCLUSIONS: The method proposed allows determining the presence of ATTR-CA, in an inexpensive manner both in terms of examination costs and time spent.

Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.

OBJECTIVE: To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes. METHODS AND RESULTS: Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients. CONCLUSION: Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.

Porcine coronary arteries: immunohistochemical profile of TNF-alpha, IL-1beta, TGF-beta1 and ICAM-1.

BACKGROUND: In our study we used immunohistochemical technique to demonstrate the presence of the cytokines tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL-1ß), transforming growth factor beta1 (TGF-ß1) and intercellular adhesion molecule-1 (ICAM-1) in porcine coronaries even in physiological conditions. MATERIALS AND METHODS: Inflammatory cytokines are polypeptide mediators which act as a communication signal between immune system cells and other types of cellsin different organs and tissues, both in human and pig coronary circulation. RESULTS: Our results show that pro-inflammatory cytokines TNF-α, IL-1ß, TGF-ß1 and ICAM-1 are also present in the medium tunica of the coronary arteries under physiological conditions. These results may be compared with those found in coronary atherosclerosis, where the increase in TNF-α has a dramatic effect on the function of the left ventricle, and the high value of IL-1 correlates directly with the extent of myocardial necrosis. In our study we observe the damage and activation of endothelial cells; this induces endothelial dysfunction by accumulation and oxidation of low density lipoproteins (LDL). The formation of oxidized LDL could play a central role in the amplification of the inflammatory response causing an increased expression of pro-inflammatory cytokines which promotes leukocyte recruitment in the intimal layer. These leukocytes, after the adhesion to the endothelium, penetrate the intimate tunic. CONCLUSIONS: Therefore inflammatory processes promote the onset and evolution of atheroma and the development of thrombotic complications.

The role of congenital malformations of the thoracic outlet in the development of the syndrome.

BACKGROUND: Thoracic outlet syndrome (TOS) represents a clinical condition caused by compression of the neurovascular structures that cross the thoracic outlet. TOS can be classified in: 1) neurogenic TOS (NTOS), 2) venous TOS (VTOS), 3) arterial TOS (ATOS). Many different causes can determine the syndrome: congenital malformations, traumas, and functional impairments. MATERIALS AND METHODS: This manuscript reviews how the congenital malformations play an important role in adult age; however, TOS also affects patients of all ages. RESULTS: Radiological imaging like X-ray (radiography), magnetic resonance and computed tomography can provide useful information to assess TOS causes and decide a potential surgery. 79% of the patients included in the first two stages of nerve, artery, vein (NAV) staging experienced excellent results with kinesiotherapy; whereas patients included in the third and fourth stage of NAV staging were subject to surgery. CONCLUSIONS: The treatment of acute forms of TOS involves thrombolysis and anticoagulant therapy; surgery is appropriate for true NTOS, vascular TOS and in some cases when conservative treatment fails.

Imaging Techniques as an Aid in the Early Detection of Cardiac Amyloidosis.

The idea that performing a proper succession of imaging tests and techniques allows an accurate and early diagnosis of cardiac amyloidosis, avoiding the need to perform the myocardial biopsy, is becoming increasingly popular. Furthermore, being imaging techniques non-invasive, it is possible to perform the follow-up of the pathology through repeated image acquisitions. In the present review, the various innovative imaging methodologies are presented, and it is discussed how they have been applied for early diagnosis of cardiac amyloidosis (CA), also to distinguish the two most frequent subtypes in CA: immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR); this allows to perform the therapy in a targeted and rapid manner.

Arthrogenic human synovial cysts: immunohistochemical profile of interleukin-1beta, interleukin-6, tumour necrosis factor-alpha.

BACKGROUND: Synovial cysts are currently classified as degenerative lesions affecting the joint capsule or adjacent structures. MATERIALS AND METHODS: In our study we describe the results obtained in an immunohistochemical study comprising 18 patients with synovial cysts, performed to evaluate the pathophysiological role of some inflammatory cytokines such as: interleukin (IL)-1ß, IL-6 and tumour necrosis factor-alpha (TNF-α). RESULTS: Results showed an over-expression of TNF-α, IL-1ß and IL-6 which appears to be involved in the onset and progression of the disease. At the present time it is not possible to affirm that these molecules play a direct role also due to the absence of further and more specific investigations. The authors therefore hypothesize that inhibition of inflammation may have a significant role in the pathogenesis and regression of synovial cysts. CONCLUSIONS: Hence, these inflammatory cytokines may be considered potential therapeutic targets. The development of synthetic inhibitors of these inflammatory factors could lead to a reduction in the intensity of inflammation, thus inhibiting the onset and development of the disease.

Noise correlations and SNR in phased-array MRS.

The acquisition of magnetic resonance spectroscopy (MRS) signals by multiple receiver coils can improve the signal-to-noise ratio (SNR) or alternatively can reduce the scan time maintaining a reliable SNR. However, using phased array coils in MRS studies requires efficient data processing and data combination techniques in order to exploit the sensitivity improvement of the phased array coil acquisition method. This paper describes a novel method for the combination of MRS signals acquired by phased array coils, even in presence of correlated noise between the acquisition channels. In fact, although it has been shown that electric and magnetic coupling mechanisms produce correlated noise in the coils, previous algorithms developed for MRS data combination have ignored this effect. The proposed approach takes advantage of a noise decorrelation stage to maximize the SNR of the combined spectra. In particular Principal Component Analysis (PCA) was exploited to project the acquired spectra in a subspace where the noise vectors are orthogonal. In this subspace the SNR weighting method will provide the optimal overall SNR. Performance evaluation of the proposed method is carried out on simulated (1)H-MRS signals and experimental results are obtained on phantom (1)H-MR spectra using a commercially available 8-element phased array coil. Noise correlations between elements were generally low due to the optimal coil design, leading to a fair SNR gain (about 0.5%) in the center of the field of view (FOV). A greater SNR improvement was found in the peripheral FOV regions.

Natural whey starter for Parmigiano Reggiano: culture-independent approach.

AIMS: The aim of this work was to obtain a deeper insight into the knowledge of microbial composition of Parmigiano Reggiano natural whey starters through different culture-independent methods. METHODS AND RESULTS: Eighteen different Parmigiano Reggiano natural whey starters sampled from three different provinces of this cheese production area and the nonacidified wheys from which they arose have been studied by length heterogeneity polymerase chain reaction (LH-PCR) and fluorescent in situ hybridization (FISH). A high microbial composition variability between different samples has been observed. CONCLUSIONS: Revealing different images of the same community, LH-PCR and FISH have given a more accurate view of the not well-known Parmigiano Reggiano whey starter ecosystem. SIGNIFICANCE AND IMPACT OF THE STUDY: New lights have been shed on Parmigiano Reggiano natural whey starters microbial composition, highlighting how culture-independent approach could be used and improved to study this and other food ecosystems.

"Shades of Gray" in pancreatic ductal adenocarcinoma: Reappraisals on resectability criteria: Debated indications for surgery in pancreatic cancer.

Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related deaths and, currently, surgery is the only curative treatment. Patients with borderline resectable pancreatic cancer (BRPC) can benefit from a multidisciplinary approach and R0 resection, and can achieve the same outcome as resectable patients treated with upfront surgery. However, the definition of BRPC changes according to different classifications with a heterogeneous distribution of patients, and it is thus difficult to compare clinical evidence. We performed a literature review to assess the most suitable classification of BRPC. Our review was conducted using the PubMed database. Only articles containing more than ten patients classified according to NCCN, MDACC or AHPBA/SSAT/SSO classifications were selected. A total of 16 studies were included in our analysis, and were grouped according to one of these three classifications. The total resection rate was 61.4%, with considerable differences between the groups (68.4% for NCCN, 54.9% for MDACC and 53.2% for AHPBA/SSO/SSAT). The total R0 resection rate was 90.1% (89.1% for NCCN, 92.5% for MDACC and 84% for AHPBA/SSO/SSAT). Of the three classifications, NCCN limits the use of confusing terms and uses restrictive criteria to define the most appropriate treatment for each subgroup. However, several reports have suggested that, even in the case of a limited disease, biological and clinical factors should be considered in order to classify patients as resectable. NCCN classification appears to be the classification that allows the highest percentage of patients with BRPC to achieve resection without reducing the R0 resection rate. The choice of therapy should not only be based on imaging results, but also on a wider clinical multidisciplinary evaluation.

Whey starter for Grana Padano cheese: effect of technological parameters on viability and composition of the microbial community.

This work aimed to investigate the effects of thermal treatments and yeast extract addition on the composition of the microbial community of natural whey starters for Grana Padano cheese. Different natural whey starter samples were held at 4 degrees C for 24 h (cooling treatment), or at -20 degrees C for 24 h (freezing treatment) to evaluate the possibility of conservation, or at 54 degrees C for 1 h (heat treatment) to evaluate the effect of the temperature commonly used during curd cooking. Separately, another set of samples was enriched with 0.3, 0.5, and 1.0% (wt/vol) of yeast extract to study its effect on the growth of lactic acid bacteria (LAB) in the starter. The new approach in this study is the use of 2 culture-independent methods: length heterogeneity (LH)-reverse transcription (RT)-PCR and fluorescence microscopy. These techniques allowed us to easily, quickly, and reproducibly assess metabolically active LAB in the control and treated samples. The LH-RT-PCR technique distinguished microorganisms based on natural variations in the length of 16S rRNA amplified by RT-PCR, as analyzed by using an automatic gene sequencer. Fluorescence microscopy counts were performed by using a Live/Dead BacLight bacterial viability kit. The repeatability of LH-RT-PCR showed that this technique has great potential to reveal changes in the microbial community of natural whey starters for Grana Padano cheese. All species showed low sensitivity to cold (4 degrees C). However, after the freezing (-20 degrees C) and heating (54 degrees C) treatments, different behaviors of the species were reported, with significant changes in their viability and relative composition. Heating treatment during curd cooking profoundly affected the viability and composition of the community that remained in the cheese and that consequently modified the microbial population. At the same time, this treatment produced the selection of LAB in whey and could be considered as the first step in natural whey starter production. Addition of yeast extract stimulated the growth of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. lactis to the detriment of Lactobacillus helveticus species. Because the yeast extract altered the microflora balance, whey starter conservation at -20 degrees C and yeast extract addition cannot be suggested as technological innovations.

Independent component analysis applied to the removal of motion artifacts from electrocardiographic signals.

Electrocardiographic (ECG) signals are affected by several kinds of artifacts that may hide vital signs of interest. In this study we apply independent component analysis (ICA) to isolate motion artifacts. Standard or instantaneous ICA, which is currently the most addressed ICA model within the context of artifact removal, is compared to two other ICA techniques. The first technique is a frequency domain approach to convolutive mixture separation. The second is based on temporally constrained ICA, which enables the estimation of only one component close to a particular reference signal. Performance indexes evaluate ECG complex enhancement and relevant heart rate errors. Our results show that both convolutive and constrained ICA implementations perform better than standard ICA, thus opening up a new field of application for these two methods. Moreover, statistical analysis reveals that constrained ICA and convolutive ICA do not significantly differ concerning heart rate estimation, even though the latter overcomes the former in ECG morphology recovery.

Identification of time point to best define 'sub-optimal response' following intravitreal ranibizumab therapy for diabetic macular edema based on real-life data.

PurposeTo determine the average time-point at which it is best to define 'sub-optimal response' after ranibizumab treatment for diabetic macular edema (DME) based on the data obtained from real-life clinical practice.MethodsIn this retrospective observational study, 322 consecutive treatment naïve eyes with DME were treated with three loading doses of intravitreal ranibizumab followed by re-treatment based on decision of the treating physician on a case-by-case basis. The demographic data, clinic-based visual acuity measurements and central subfield thickness (CST) assessed on spectral domain optical coherence tomography (OCT) were evaluated at baseline (month 0), 1, 2, 3, 6, and 12 months.ResultsOn an average, the improvement in visual acuity and CST was first seen after the loading dose. However, the maximal response in terms of proportion of patients with improvement in visual acuity and/ or CST in this cohort was observed at 12 months. Patients who presented with low visual acuity at baseline (<37 ETDRS letters) were unlikely to attain driving vision with ranibizumab therapy.ConclusionsOn an average, a 'sub-optimal response' after ranibizumab therapy is best defined at month 12 as patients may continue to improve with treatment.

Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease.

A total of 277 patients with untreated Hodgkin's disease, clinical stages I-II, were randomized to cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP) alone for 6 monthly cycles or to CVPP plus radiation therapy (RT), 3,000 rad, to involved areas (CVPP plus RT). One or more of the following factors were considered as unfavorable prognosis: age greater than 45 years, more than two lymph node areas involved, or bulky disease. In the favorable group, disease-free survival (77% vs. 70%) or overall survival (92% vs. 91%) at 84 months for CVPP versus RT plus CVPP was similar. Patients with unfavorable prognosis treated with RT plus CVPP had longer disease-free survival (75% vs. 34%) (P = .001) and overall survival (84% vs. 66%) than patients treated with CVPP alone.

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.

PURPOSE: In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. PATIENTS AND METHODS: Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. RESULTS: Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. CONCLUSION: We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.

An update of the results of intensive therapy in children with acute lymphoblastic leukemia.

On January 1984 a protocol for newly diagnosed children with acute lymphoblastic leukemia started in a multiinstitutional setting in Argentina, Costa Rica and Cuba. The protocol was based on the BFM 76/79 study. It consisted in 8 drug 8 weeks induction-consolidation regimen with a delayed intensification regimen followed by maintenance with 6-mercaptopurine-methotrexate and pulses with vincristine-prednisone for 36 months. CNS prophylaxis with IT therapy, age based schedule was given. Only patients with greater than 50000 WBC counts received cranial irradiation. A total of 720 patients were registered up to June 1987, 703 of them were eligible. Six hundred an twenty six (89%) of the patients achieved complete remission, 7 partial remission, 8 failed to respond and 62 (9%) had drug or disease related death before completing induction therapy. At 72 months 50% remained in complete remission, 45% and 58% of all the patients remained disease-free and alive respectively. Sites of relapse were bone marrow 21%, CNS 10%, testis 2%, combined 4% and 8% died in complete remission. No difference in response was observed among the three prognostic groups, however the disease-free survival at 72 months was 52% for good prognosis compared to 42% for intermediate and poor prognosis (P = 0.0009). This results showed a marked improvement over previous studies of our group and, that, intensive and large clinical trials can be performed in Latinamerica.

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.