GEMTUZUMAB OZOGAMICIN COMBINED WITH INDUCTION CHEMOTHERAPY IN YOUNG ADULTS WITH ACUTE MYELOID LEUKEMIA: REVIEW AND PERSPECTIVES.

Progress in treatment of acute myeloid leukemia (AML) is slow. Many new agents have been tested, but few were approved. Gemtuzumab Ozogamicin (GO) is a new AML-targeted drug that is composed by a monoclonal antibody targeting a surface antigen of myeloid leukemic cells (CD33) combined with a potent cytotoxic (calicheamicin). We review here the studies of GO in AML, including an update of the Italian studies, and we trace back the story of a drug that was developed 15 years ago and, regrettably, is no longer available for the treatment of AML, with the exception of Japan. GO was approved by the US FDA for the second-line treatment of AML in the elderly, and was shown by several European large prospective and randomized studies to be active also in first line, both alone, but particularly in combination with standard chemotherapy. Regrettably, a registration study that was performed in US could not confirm the superiority of GO and chemotherapy on chemotherapy alone, and the drug was withdrawn. The differences among the US and the European studies are discussed. The profile of the AML patients who are expected to benefit more by the reintroduction of GO is proposed: first-line, less than 60 years old, CD33 expressed in more than 20% leukemic cells, low/intermediate cytogenetic risk, and low expression of the PGP multidrug resistance protein

An investigation of performance limits of conventional and tunneling graphene-based transistors

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Necrobiosis Lipoidica Affecting the Leg: What Is the Best Treatment in a Patient with Very High Aesthetic Demand?

Summary: Necrobiosis Lipoidica (NL) is a rare necrotising disorder of the skin characterized by collagen degeneration, thickening of blood vessels, and granulomatous inflammatory process. Its main clinical features are brownish-red papules and yellowish plaques with atrophic central areas. NL affects 0.3% -1.2% of the diabetic population, mostly women (female/male ratio is 3:1). Management of NL is challenging, especially for large lesions refractory to medical therapy, thus requiring surgical excision as an alternative option. Due to the rare occurrence of this condition no treatment guidelines exist and individualized treatment mostly depends on the severity of the lesion, location and patient's expectations. A case of a 30-year-old diabetic woman with very high aesthetic expectations was succesfully treated with staged resections of a giant NL to the leg and reconstruction with dermal template and full thickness skin grafts. Grafts were taken from the groin region bilaterally and from the lower abdomen after a cosmetic mini-abdominoplasty procedure. This approach allowed for a stable and very satisfactory aesthetic result with no donor site exposed scars

The New Transverse-Facial Artery Musculomucosal Flap for Intraoral Reconstructions

Head/neck cancer resections often require reconstruction to restore form and function. Small-to-medium size intraoral defects can be successfully reconstructed by local pedicled flaps, such as the facial artery musculomucosal (FAMM) flap,1 which encompasses different layers: cheek mucosa and submucosa, the underlying layer of the buccinator muscle, a portion of the orbicularis oris close to the labial commissure, and the facial artery.2 The flap is usually outlined longitudinally over the facial artery course, and average size is 5 × 2.5 cm. We describe here an innovative flap design and dissection, apt to treat larger defects than the usual ones. Go to: METHODS In a 50-year-old patient with squamous carcinoma of the soft palate involving also surrounding oral soft tissue, after oncological resection, we designed on the cheek mucosa an 8 × 3 cm flap with a squamous carcinoma orientation. The flap axis was crossing about 90 degrees the projection of the facial vessels. Dissection was carried out in anteroposterior direction and the facial artery skeletonized in continuity 3.5 cm superiorly and inferiorly the flap entrance (Fig. ​(Fig.1).1). Once the vascular pedicles had been mobilized and the labial artery ligated, the transverse (t)-FAMM flap was transposed superoposteriorly and sutured to the residual mucosa of the hard palate. A contralateral t-FAMM flap was harvested and transposed. The whole soft palate was then reconstructed by suturing the 2 flaps together

Laparoscopically assisted transperineal approach in the management of a giant pelvic lipoma

Giant lipomas affecting the retroperitoneum and pelvis are quite rare. The surgical management of these lesions may be technically demanding and controversies exist with respect to diagnosis, competences being involved, type of surgical approach, radicality, and timing. A unique case presentation of a giant lipoma occupying the whole pelvis and the gluteal region is presented. Due to its size, many anatomical areas are involved, requiring the expertise of multiple specialists to treat. After multidisciplinary counseling, the lesion is radically resected in one stage by using a new videolaparoscopically assisted transperineal access to the pelvis. This type of surgical approach may be of interest for resecting pelvic tumors in women and men

Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC. Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration. Results: APE1's cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1's mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix. Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA

Contemporaneous Portal-Arterial Reperfusion during Liver Transplantation: Preliminary Results

We prospectively compared sequential portal-arterial revascularization (SPAr, group 1 no. 19) versus contemporaneous portal-hepatic artery revascularization (CPAr, group 2 no. 21) in 40 consecutive liver transplantation (LT). There were no differences in the demographics characteristics, MELD score, indication to LT, and donor's parameters between the two groups. CPAr had longer warm ischemia 66 ± 8 versus 37 ± 7 min (P < .001), while SPAr had longer arterial ischemia 103 ± 42 min (P = .0004). One-year patient's and graft survival were, respectively, 89% and 95% versus 94% and 100% (P = .29). At median followup of 13 ± 6 versus 14 ± 7 months biliary complications were anastomotic stenosis in 15% versus 19% (P = .78), and intrahepatic nonanastomotic biliary strictures in 26% versus none (P = .01), respectively, in SPAr and CPAr. CPAr reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia

Ileocecal Fistula Caused by Multiple Foreign Magnetic Bodies Ingestion

The incidence of accidental foreign body (FBs) ingestion is 100,000 cases/year in the US, with over than 80% of cases occurring in children below 5 years of age. Although a single FB may pass spontaneously and uneventfully through the digestive tract, the ingestion of multiple magnetics can cause serious morbidity due to proximate attraction through the intestinal wall. Morbidity and mortality depend on a prompt and correct diagnosis which is often difficult and delayed due to the patient's age and because the accidental ingestion may go unnoticed. We report our experience in the treatment of an 11-year-old child who presented to the emergency department with increasing abdominal pain, vomiting, diarrhea, and fever. Surgery evidenced an ileocecal fistula secondary to multiple magnetic FB ingestion with attraction by both sides of the intestinal wall. A 5-centimeter ileal resection was performed, and the cecal fistula was closed with a longitudinal manual suture. The child was discharged at postoperative day 8. After one year, the patient's clinical condition was good