Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes.

PURPOSE: Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

An overlooked sibling of the fruit-piercing moth Eudocima phalonia (Linnaeus, 1763) from Africa (Lepidoptera, Erebidae, Calpinae).

In recent years, we have been investigating the tropical calpine genus Eudocima Billberg, 1920 (Lepidoptera, Erebidae, Calpinae) with the intent of producing a generic revision. There are a number of undescribed species and here we describe as new a closely related species to the widespread and economically important fruit-piercer Eudocima phalonia (Linnaeus, 1763) (= fullonia Clerck, 1764), with which it has long been confused. Study material came from the private collection of Vernon Antoine Brou collection (VAB) and the Natural History Museum, London (NHM).

Chylous reflux pathologies: diagnosis and microsurgical treatment.

BACKGROUND: This article aims to make a contribution to the present knowledge of the diagnosis and therapy of chylous reflux pathologies, based largely on the authors' clinical experience in the microsurgical treatment of these disorders. METHODS: In 47 patients affected by chylostatic disorders the diagnosis was based on the clinical history, physical examination, lymphoscintigraphy, lymphography, ultrasound, CT scanning and lymphangio-MR. In cases of chylous reflux towards the external genitalia or the lower limbs, the puncture of one of the lymphostatic verrucae which may be part of the symptomatology, can be sufficient for the clinical diagnosis. If patients suffer from hypoproteinaemia and/or an intestinal malabsorption syndrome, this should be dealt with to ensure them at least temporary metabolic compensation before surgical treatment, if any. In patients affected by chylous ascites, antigravitational ligatures of incompetent collectors, sometimes associated with lymphovenous shunts, can be a therapeutic solution. RESULTS: We have found that CO2 laser irradiation at very low power achieved full section closure of lymphatic and chylous vessels as complete as if they had been tied. In the case of chyloedema of the external genitalia and of/or the lower limbs, reductive plastic treatment completes the result after antigravitational ligatures and derivative microsurgery. CONCLUSIONS: A laser-microsurgical technique used to manage chylous reflux pathologies achieved positive and permanent results, especially after an accurate preoperative diagnostic study to determine the site and nature of the lymphatic and chylous leakage and associated disorders.

[Lymphedema secondary to breast cancer treatment: possibility of diagnostic and therapeutic prevention]. / Linfedema secondario al trattamento del cancro mammario: possibilità di prevenzione diagnostica e terapeutica.

We performed a prospective randomized study upon 50 patients who had undergone a breast cancer treatment, considering particularly the possibility of appearance of arm secondary lymphedema. The patients were divided in two groups of 25 patients each. In the 1st group, we performed only a clinical follow-up, whilst in the 2nd one, we used also lymphoscintigraphy. The aim of the study was to compare the incidence of arm secondary lymphedema in the two groups, and relate the data with those of the international literature, in order to identify diagnostic procedures indicative of the risk of development of lymphedema and find proper therapeutic preventive measures. It is certainty complex to foresee the appearance of arm lymphedema due to breast cancer treatment. No specific preventive therapeutic methods based upon particular diagnostic investigations were ever reported. Patients had undergone surgery and radiation for breast cancer in the period between April 1992 and June 1994, and controlled at over 5 years after operation. Upper limb lymphoscintigraphy was performed only in one of the two groups of 25 patients, before operation and, furthermore, after 1-3-6 months and 1-3 years from the treatment. Patients who presented lymphoscintigraphic alterations (dermal back flow, diffused or delayed transit of the tracer, etc.), before edema appeared clinically, underwent physical and rehabilitative therapy (bandages, manual lymphatic drainage, mechanical lymph drainage, elastic garments, etc.) and microsurgery (lymphatic-venous anastomoses at the arm), performed early (stages Ib and II) in patients not responsive to physical therapy. In the first group followed only clinically, secondary arm lymphedema occurred in 9 cases (36%), and appeared after a period variable from 1 week to 2 years (3-6 months averagely). In the second group, lymphoscintigraphy, performed preoperatively, permitted to find lymphatic impairment (absence of deltoid way, reduced axillary lymph nodal tracer uptake, delayed transit of the tracer) at the upper limb in 4 patients (15%). After breast cancer surgery, lymphoscintigraphy pointed out alterations of lymphatic circulation in 5 patients (20%) after 1 month, in other 6 cases (56%) at 6 months, other 5 (76%) after 1 year and 3 (88%) at 3 and 5 years. Physical preventive therapy performed in patients with positive lymphoscintigraphy, even before the clinical appearance of edema, allowed to find a clinically evident lymphedema only in 2 cases (8%). The last two patients underwent early (at stage Ib and II) microsurgical operation of lymphatic-venous anastomoses, with complete regression of edema and improved lymphatic drainage of the arm controlled by lymphoscintigraphy (appearance of preferential lymphatic pathways, absence of dermal back flow). Secondary arm lymphedema due to breast cancer treatment appears in 20-25% of cases till 35% when surgery is associated with radiotherapy. Lymphoscintigraphy allows to pointout alterations of lymphatic drainage before the clinical appearance of edema. Preventive physical and rehabilitative measures allows to reduce the clinical appearance of lymphedema significantly. Microsurgical operation performed precociously, at the early stages of the disease, permits to obtain the complete regression of the pathology thanks to the repair of preferential lymphatic pathways before of fibrosclerotic tissural alterations occur, which cause progressive worsening of clinical conditions, together with recurrent attacks of acute lymphangitis.

Is there a role for microsurgery in the prevention of arm lymphedema secondary to breast cancer treatment?

The secondary lymphedema of the upper limb (post-mastectomy lymphedema) has an incidence, in patients who underwent axillary lymphadenectomy for breast cancer, between 5 to 25%, up to 40% after radiotherapic treatment. We studied 50 patients treated for breast cancer. The patients were divided in two groups of 25 each, comparable for age, sex, pathology and treatment and followed up to 5 years after operation for breast. One group of 25 patients was controlled only clinically (physical examination, water volumetry) at 1-3-6 months and 1-3-5 years from breast cancer treatment. The other group of 25 patients was followed also by lymphatic scintigraphy performed pre-operatively and after 1-3-6 months and 1-3-5 years from operation. In the first group, followed only clinically, lymphedema appeared in 9 patients after a period variable from 1 week to 2 years, with highest incidence between 3 and 6 months. In the second group of 25 patients, the preventive therapeutic protocol allowed to have a clinically evident arm lymphedema only in 2 patients. The comparison of the two groups of 25 patients proved a statistically significant difference in the appearance of arm secondary lymphedema (p = 0.01, using Fisher's exact test). The diagnostic and therapeutic preventive procedures allow to reduce the incidence rate of lymphedema significantly, in comparison with patients who did not undergo this protocol of prevention.

Lymphatic microsurgery for the treatment of lymphedema.

One of the main problems of microsurgery for lymphedema consists of the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphoedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic study and surgical outcome have not been adequately documented. Over the past 25 years, more than 1000 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic micro-vascular procedures has today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). For those cases where a venous disease is associated to more or less latent or manifest lymphostatic pathology of such severity to contraindicate a lymphatic-venous shunt, reconstructive lymphatic microsurgery techniques have been developed (autologous venous grafts or lymphatic-venous-Iymphatic-plasty - LVLA). Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume. Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed earlier at the very first stages of lymphedema.

Long-term results after lymphatic-venous anastomoses for the treatment of obstructive lymphedema.

Over the past 25 years, 665 patients with obstructive lymphedema have been treated with microsurgical lymphatic-venous anastomoses; of these, 446 patients were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Lymphangioscintigraphy, lymphangiography (in patients with gravitational reflux pathology), and echo-Doppler were used preoperatively. Subjective improvement was noted in 578 patients (87%). Objectively, volume changes showed a significant improvement in 552 patients (83%), with an average reduction of 67% of the excess volume. Of those patients followed up, 379 patients (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. In those patients who improved, drainage resulted in increased softness of the limbs. Peripheral edema (hand and foot) diminished considerably in most patients. These long-term results indicate that lymphatic-venous anastomoses have a place in the treatment of obstructive lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with earlier operations because patients referred earlier usually have fewer lymphatic alterations.

The use of vein grafts in the treatment of peripheral lymphedemas: long-term results.

This study evaluates long-term results of the treatment of peripheral lymphedemas by the microsurgical reconstructive technique of interposed vein grafts. The technique consists of the use of autologous vein grafts to reconstruct lymphatic pathways where there is a block to the lymphatic circulation of the limb, whether of congenital or acquired etiology. The venous segment represents a sort of "bridge" between afferent and efferent lymphatic collectors (lymphatic-venous-lymphatic plasty [LVLA]). The results also proved to have positive long-term effects after microsurgical operation. Follow-up evaluation was performed clinically by water volumetry and instrumentally by lymphangioscintigraphy. With this LVLA technique, peripheral lymphedemas can be treated when derivative lymphovenous shunts cannot be used because of impaired venous circulation in the same lymphedematous limb. The new aspect of the study is that we report long-term clinical and instrumental results.