Pathological implications of metabolic reprogramming and its therapeutic potential in medulloblastoma.

Tumor-specific alterations in metabolism have been recognized to sustain the production of ATP and macromolecules needed for cell growth, division and survival in many cancer types. However, metabolic heterogeneity poses a challenge for the establishment of effective anticancer therapies that exploit metabolic vulnerabilities. Medulloblastoma (MB) is one of the most heterogeneous malignant pediatric brain tumors, divided into four molecular subgroups (Wingless, Sonic Hedgehog, Group 3 and Group 4). Recent progresses in genomics, single-cell sequencing, and novel tumor models have updated the classification and stratification of MB, highlighting the complex intratumoral cellular diversity of this cancer. In this review, we emphasize the mechanisms through which MB cells rewire their metabolism and energy production networks to support and empower rapid growth, survival under stressful conditions, invasion, metastasis, and resistance to therapy. Additionally, we discuss the potential clinical benefits of currently available drugs that could target energy metabolism to suppress MB progression and increase the efficacy of the current MB therapies.

A Recurrent Pathogenic Variant of INPP5K Underlies Autosomal Recessive Congenital Muscular Dystrophy With Cataracts and Intellectual Disability: Evidence for a Founder Effect in Southern Italy.

Inositol polyphosphate-5-phosphatase K [INPP5K (MIM: 607875)] acts as a PIP3 5-phosphatase and regulates actin cytoskeleton, insulin, and cell migration. Biallelic pathogenic variants in INPP5K have recently been reported in patients affected by a form of muscular dystrophy with childhood onset. Affected patients have limb girdle muscle weakness, often associated with bilateral cataracts, short stature, and intellectual disability. Here we report four patients affected by INPP5K-related muscle dystrophy, who were apparently unrelated but originated from the same geographical area in South Italy. These patients manifest a recognizable phenotype characterized by early onset muscular dystrophy associated with short stature and intellectual disability. All affected subjects were homozygous or compound heterozygous for the c.67G > A (p.Val23Met) missense change and shared a common haplotype, indicating the occurrence of a founder effect.

[Main points of vertical banded gastroplasty technique in open surgery]. / Punti chiave di tecnica della gastroplastica verticale con bendaggio per via laparotomica.

VGP represents the single more diffuse bariatric operation among the others restrictive ones, proposed and used from Mason since 1970. Other restrictive operations followed, introduced in the surgical armamentarium, but the Mason-like procedure remained the reference one, although with variations introduced by the single surgeon. On a basis of a personal experience of 163 patients operated with VGP, the Authors report the personal modifications of the procedure, in search of safety and better results.

[A possible late complication of Mason's vertical gastroplasty: the erosion of the vertical band]. / Possibile complicanza tardiva della gastroplastica verticale secondo Mason: il decubito della benderella.

AIM: To evaluate possible adverse consequences and complications following the procedure of Mason-McLeans Vertical Banded Gastroplasty (VBG), and in those cases the possibility to be related to a surgical mistake. PERSONAL EXPERIENCE: It is based on a casuistic of more than 180 patients, submitted to this restrictive bariatric surgery in the same institution since 2001. Controls of the prescribed postop follow up revealed a very low rate of complications, as only in three cases, all of them with spontaneous presentation, there was a complication related to the banding. RESULTS: All the observed complications were related to a late postoperative inadequate alimentation for excess of meals, after the immediate orthodox behaviour of the first months. DISCUSSION: From the comparative evaluation of all the patients submitted to the Mason-McLean procedure it seems of the utmost evidence the importance of a correct alimentation, mainly to the low bulk of the single meal, to avoid complications and obtain the best EWL%. CONCLUSIONS: Adherence to the guidelines for the post op alimentation in such patients is the key to obtain the best results from the operation avoiding the side effects and complications here described.

Diaphragmatic relaxation: pathophysiological alterations and current possibilities of surgical repair.

Diaphragmatic relaxation is a pathology not frequently observed because it is generally oligosymptomatic. The development of modern technology has induced an important contribution to the diagnosis and treatment of the disease which can find a possibility of restoration in surgery. A 63-year-old patient with a light syndrome of respiration deficiency and an altered relaxed profile of the right cupola was subjected to surgical treatment with the technique of diaphragmatic plicature without any adverse implication during and after the operation. After a brief recovery, the patient was discharged and after 9 years he affirmed still absence of dyspnoea from limited labor and absence of respiration problems. The selected surgical technique for the restoration of the altered muscle is the diaphragmatic plicature without incision or excision of the altered part of the muscle. The preferable access way today is that of laparotomy which is devoid of problems of thoracotomy and generally it permits quite easily the restoration of all diaphragmatic defects. Diaphragmatic plicature is a simple, effective and long-lasting intervention but we cannot determine the complete recovery of the normal contractile function of the muscle. There is no morbidity and mortality directly related to this technique, the latter incidentally associated with complications of general anesthesia.

Inflammatory breast cancer.

The very original definition of carcinomatous mastitis suggests the main diagnostic difficulty of this onchologic condition. Actually it is more correctly appointed as inflammatory breast cancer, because notwithstanding the inflammatory appearance, it is a true systemic breast cancer, for which surgery represents an only marginal treatment resource. If is now well known that radical mastectomy is ineffective and only a combination of CT and RT offers survival results of some value. But the actual correct multi modal treatment cannot be undertaken if not after a correct diagnostic confirmation, avoiding an anti-inflammatory therapeutic attempt that is time consuming and possibly deceptive. Surgery and histology can be the only means of a correct diagnosis when FNAB is falsely negative, but the lymph nodes must be the preferential tissue to examinate to avoid long lasting drainage from the breast parenchyma after a biopsy, that delays the beginning of the true treatment.