Pasquale Petronella

Dipeptidyl Peptidase 4 Inhibition May Facilitate Healing of Chronic Foot Ulcers in Patients with Type 2 Diabetes

The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19–35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.

Peri-procedural tight glycemic control during early percutaneous coronary intervention is associated with a lower rate of in-stent restenosis in patients with acute ST-elevation myocardial infarction.

OBJECTIVE We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI). RESEARCH DESIGN AND METHODS A total of 165 hyperglycemic patients (glucose ≥ 140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy. Coronary angiography was performed at study entry and at 6-month follow-up. Blood samples for glycemia, hemoglobin A1c, inflammatory markers (C-reactive protein and TNF-α), monocyte chemoattractant-protein-1, and oxidative stress (nitrotyrosine) were collected immediately before and 24 h, 30 and 180 d after PCI. RESULTS After insulin infusion, mean plasma glucose during the peri-procedural period was greater in the CGC group than in the IGC group (CGC, 191 ± 15 mg/dl; IGC, 145 ± 35 mg/dl; P < 0.001). After the insulin infusion period, the levels of markers of oxidative stress (nitrotyrosine), inflammation (C-reactive protein, TNF-α), and monocyte chemoattractant-protein-1 were significantly higher in CGC patients compared with IGC patients. Moreover, ICG during PCI reduces restenosis by half (48 and 24%) at 6 months. During follow-up, there was no difference in mortality rates, glucose, inflammatory and oxidative stress markers among the groups. In-stent restenosis was positively associated with mean plasma glucose levels as well as oxidative stress and inflammatory markers during the insulin infusion period. CONCLUSIONS In hyperglycemic patients with STEMI, optimal peri-procedural glycemic control by reducing oxidative stress and inflammation may improve the outcome after PCI.

Primary thyroid angiosarcoma: an unusual localization

The finding of thyroid nodules is a very common occurrence in routine clinical practice. Approximately 5% to 7% of the entire population have thyroid nodules. Vascular lesions are one of the most controversial issues in thyroid pathology. These include benign lesions such as hemangiomas and, rarely, malignant tumors such as angiosarcomas or undifferentiated angiosarcomatoid carcinomas. In particular, angiosarcoma of the thyroid gland is a rare, highly aggressive malignant vascular tumor and in Italy the greatest geographical incidence of this lesion is witnessed near the Alps. Here, a case of thyroid angiosarcoma in a 71-year-old man with a history of goiter for about 20 years is described. The unusual localization of this lesion, the difficulties in reaching a definitive diagnosis for this particular histological type of primary tumor and a history of long-standing multinodular goiter in thyroid of an older man from outside the Alpine region prompted us to report this case of thyroid angiosarcoma mainly to discuss surgical, histopathological and immunohistochemical features.

Hyperglycemia in streptozotocin-induced diabetes leads to persistent inflammation and tissue damage following uveitis due to reduced levels of ciliary body heme oxygenase-1.

This study investigated the heme oxygenase-1 (HO-1) and the endotoxin-induced uveitis (EIU) in diabetic streptozotocin (STZ)-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1β and CXCL8. Subsequent EIU further and significantly (P < .01) increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

Involvement of the Ubiquitin-Proteasome System in the Formation of Experimental Postsurgical Peritoneal Adhesions

We investigated the Ubiquitin-Proteasome System (UPS), major nonlysosomal intracellular protein degradation system, in the genesis of experimental postsurgical peritoneal adhesions. We assayed the levels of UPS within the adhered tissue along with the development of peritoneal adhesions and used the specific UPS inhibitor bortezomib in order to assess the effect of the UPS blockade on the peritoneal adhesions. We found a number of severe postsurgical peritoneal adhesions at day 5 after surgery increasing until day 10. In the adhered tissue an increased values of ubiquitin and the 20S proteasome subunit, NFkB, IL-6, TNF-α and decreased values of IkB-beta were found. In contrast, bortezomib-treated rats showed a decreased number of peritoneal adhesions, decreased values of ubiquitin and the 20S proteasome, NFkB, IL-6, TNF-α, and increased levels of IkB-beta in the adhered peritoneal tissue. The UPS system, therefore, is primarily involved in the formation of post-surgical peritoneal adhesions in rats.

Prostaglandin E1 versus lumbar sympathectomy in the treatment of peripheral arterial occlusive disease: randomised study of 86 patients.

BACKGROUND AND AIM The aim of this study was to compare the effects of a pharmacological and a surgical vasodilatatory therapy in the treatment of chronic arterial diseases of the lower limbs. METHODS AND RESULTS After giving their informed consent, 40 patients were randomised to receive a slow (approximately 2-hour) infusion of 40 microg of prostaglandin E1 twice daily for 28 days (group A), and 46 were randomised to undergo lumbar sympathectomy, including the second and third ganglion. Twenty-four (60%) of the patients in group A experienced complete remission, seven (17.5%) were partial responders, and nine (22.5%) failed to respond. Of the 46 patients in group B, 29 (63%) experienced complete remission, seven (15.2%) were partial responders, and 10 (21.7%) failed to respond. CONCLUSIONS Broadly similar results were obtained with the two types of treatment, both of which are indicated mainly in Fontaine stages IIB and III (non-advanced), particularly when revascularising therapy is impossible or excessively risky. The two strategies can be advantageously combined with direct revascularisation surgery and may therefore constitute a first-line approach favouring subsequent therapy.

Angiosarcoma of the thyroid in an old man

Background The angiosarcoma of the thyroid gland is a primary malignant highly aggressive tumor. It is classified as a malignant vascular thyroid lesion of mesenchymal origin. In addition to the neck and head, the majority of angiosarcomas also originate from the skin and soft tissues, or limbs of patients with lymphedema. Angiosarcoma of the thyroid is rare and the greatest incidence is witnessed near the Alps. It constitutes only 2-10% of malignant thyroid tumors in Switzerland, Austria and Northern Italy. The prevalence in the Alpine regions can be due probably to iodine deficiency with a long history of endemic goiter. It strikes in old age. There are cases in which the tumor occurs without a history of goiter, and it the occurrence is very unusual in non-alpine areas, so it seemed interesting to present a case involving this type. Due to the increase of the thyroid volume, often occurring in a short time, dyspnea is a frequent symptom, associated with deviation of the tracheal axis. From the macroscopic point of view, this tumor typically appears to be with big dimensions, with large areas of necrosis and hemorrhage. Microscopically, freely anastomosed channels are often associated with a papillary configuration having a pattern of predominant intraluminal growth; the nuclei of the epithelioid endothelial cells are large, vesicular, smooth-contoured, with a large basophilic or amphophylic nucleolus connected by chromatin strands to the nuclear membrane. Typical and atypical mitosis were found in large numbers; the growth pattern is usually highly invasive and tumor necrosis is very strong. Of fundamental importance is the peculiarity that tumor cells express vascular markers such as Factor VIII, CD 31 and CD 34. The distinction between angiosarcoma and anaplastic sarcomatoid carcinoma is difficult and the same expression of the angiosarcoma has been subject to dispute. Clinical history: most of these tumors appear as a poorly encapsulated and infiltrating mass, which tends to grow in the absence of pain. Local recurrence, even after complete excision, and metastasis are common. After diagnosis, patients often die quickly. This type of cancer typically metastasizes in the first instance at the level of regional lymph nodes and lung, in the late stages in the bone marrow. Multimodal treatment, a widely accepted approach, envisages surgery, radiotherapy and chemotherapy. The study was inspired by the observation of a case of thyroid hemangiosarcoma in a 71-year-old man with a history of goiter for twenty years, who decided to undergo an operation for the worsening of the dyspnea.

Outcome of surgical treatment of carcinoma of the pancreas.

Aims and background Pancreatic resections for neoplastic diseases have a high risk of severe intra- and postoperative complications and are associated with high mortality rates. They should be performed as a rule in centers specializing in this type of surgery. However, it is becoming increasingly likely that such tumors may have to be treated in surgery units which are not specifically dedicated to pancreatic surgery. The aim of this study was to assess the improvements in clinical results in a non-specialized general surgery setting in the light of the most recent progress in surgical techniques, drug treatments and nutritional support. Methods and study design We analyzed 48 patients with pancreatic cancer treated in our institution over the period from 1980 to 1998: 36 had cancer of the head of the pancreas, 5 of the ampulla, 1 in the second duodenal portion, and 6 of the body-tail. The operations performed consisted of 13 Whipple pancreaticoduodenectomies with cutting and stapling of the distal pancreatic stump at the level of the isthmus, 4 left pancreasectomies, 2 local resections of the ampulla, 21 palliative operations, and 2 exploratory laparotomies. Results and conclusions The patients were submitted to follow-up including clinical examinations, blood-chemistry tests, and instrumental investigations. The mean survival was 18 months in the cases where radical surgery was performed, compared to 11 months after palliative surgery. We conclude that an improved prognosis can obtain after pancreatic resection. This is attributable to a more accurate preoperative staging and to the aid of the various forms of nutritional support and pharmacological prophylaxis currently available.

Wound bed preparation with NPWT in diabetic foot ulcers: case report

Background Negative Pressure Wound Therapy (NPWT) is primarily used for very complex chronic wounds. The surgical treatment of the diabetic wounds with loss of soft tissue usually consists of closure using split-thickness skin grafts or transposition flaps. However, the first step consists of standard wound care with moist gauze dressing with the aim to prepare the wound bed for final closure. Clinical and experimental studies reported that negative pressure increases local blood flow and decreases bacterial colonization. Localized negative pressure removes fluids from the wound and promotes the granulation tissue, which is required for wound closure.

SOLID-CYSTIC PSEUDOPAPILLARY TUMOR OF PANCREAS: DESCRIPTION OF TWO CASES AND LITERATURE REVIEW

The authors report the cases of two young female patients aged 17 and 27 years who underwent surgery for a rare tumor of the pancreas, Frantzs tumor or solid-cystic pseudopapillary tumor. Solid-cystic pseudopapillary tumor of the pancreas is a rare tumor, accounting for 2.7% of pancreatic exocrine tumors. About 90% of these tumors occur in young women and they can reach very large dimensions. Due to their rareness and behavior, they are often associated with diagnostic and therapeutic problems. In most cases surgical treatment is curative and neither chemotherapy nor radiotherapy should be added. In the few cases where surgery is not possible, radiotherapy can be used because these tumors appear to be radiosensitive.