Clinico-pathological features, treatments and survival of malignant insulinomas: a multicenter study.

INTRODUCTION: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. AIM OF THE STUDY: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. MATERIALS AND METHODS: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. RESULTS: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. CONCLUSIONS: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.

Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients.

Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Moreover, several recent reports showed a direct association between the onset of IAS and the consumption of dietary supplements containing alpha-lipoic acid (LA). Insulinoma remains the most prevalent cause of hypersulinaemic hypoglycaemia in Caucasians. Consequently, primary investigation in these patients is generally focused on localisation of the pancreatic tumour, often with invasive procedures followed by surgery. We described a case of an Italian woman presenting to us with severe recurrent hypoglycaemia associated with high insulin and C-peptide levels and no evidence of pancreatic lesions at imaging diagnostic procedures. She had taken LA until 2 weeks before hospitalisation. After an evaluation of her drug history, an autoimmune form of hypoglycaemia was suspected and the titre of insulin autoantibodies was found to be markedly elevated. This allowed us to diagnose LA-related IAS, thus preventing any unnecessary surgery and avoiding invasive diagnostic interventions. Learning points: IAS is a rare cause of hyperinsulinaemic hypoglycaemia that typically affects Asian population, but it has been increasingly recognised in Caucasian patients. It should be considered among the differential diagnosis of hyperinsulinaemic hypoglycaemia to avoid unnecessary diagnostic investigations and surgery. It should be suspected in the presence of very high serum insulin levels (100-10 000 µU/mL) associated with high C-peptide levels. There is a strong association with administration of drugs containing sulphydryl groups included LA, a dietary supplement commonly used in Western countries to treat peripheral neuropathy.

[Liver haemangioma: current surgical indications. Our experience]. / Gli angiomi epatici: attuali indicazioni al trattamento chirurgico. Revisione casistica.

Hemangiomas are the more frequent benign liver tumours. Therapeutic approach at these neoplasms is changed in the last years because has resulted that massive haemoperitoneum from a spontaneous rupture of the hemangiomas is a rare occurrence. From a personal review of 124 liver resection performed for traumatic and organic, benign and malignant, pathologies, the Authors present two cases of symptomatic liver haemangioma surgically treated Excluding emergency induced by tumour hemorrhage, actually indications to surgical treatment are controversial. In all patients the right approach is choice by the integrated evaluation of general conditions of the patient, liver functionality and from anatomical location of the neoplasm.

[Appendicectomy: laparoscopic versus open treatment. A case survey]. / Appendicectomia: laparoscopica versus laparotomica. Analisi della casistica.

AIM: Laparoscopy is actually the gold standard approach in many surgical procedures: this consideration is still controversial as to appendectomy. METHODS: From 2000 to 2004 we have performed 257 appendectomies: 51 (20%) in laparoscopic approach. Preoperative diagnosis has been formulated on blood parameters, abdominal or, sometimes, transvaginal ultrasonography. RESULTS: Two hundred and fifty-seven surgical operations, 62 laparoscopic, have been performed for suspicious appendicitis. In the laparoscopic procedures, 11 revealed various diseases without appendicitis. In the remaining 51 cases, appendectomy has been performed totally intra-abdominal and none case turned to laparotomic conversion. Operative times were between 27 and 105 min in the laparoscopic appendectomies (LA) and between 18 and 46 min in the laparotomic appendectomies (OA). In 7.3% of OA and in 3.9% of LA wall infections occurred, as well as abdominal abscesses in 1% of OA and in 4% of LA. Postoperative discharge was after 3.3 days and bowel canalization appeared at 10-18 hours from the surgery, in OA and in LA. CONCLUSIONS: On the basis of these results, the conclusion is drawn that, although discordant opinions in the literature, the advantages of the laparoscopic approach compared to laparotomic approach is still to be demonstrated, both in advantages for the patient and in costs. Laparoscopy is the better surgical technique when the preoperative diagnosis is not clear, particularly in young women or in elderly, in whom a colic neoplasm may be suspected.

[Malignant carcinoid of the last ileal ansa. Report on 2 consecutive clinical cases]. / Il carcinoide maligno dell'ultima ansa ileale. Presentazione di due casi clinici consecutivi.

Carcinoid tumors are very rare neoplasms, arising from enterochromaffin cells, classified in Apud system, exhibiting an intermediate malignancy, because of their long lasting clinical silence and low evolution to advanced stage. At the same time, these features unfortunately cause a high incidence of lymphatic and liver metastases, visible at first diagnostic approach, which are also determined by aspecific symptoms and signs, especially involving jejunal and ileal carcinoids, as the two cases described, and by very frequent absence, in current clinical practice, of pathognomonic carcinoid syndrome. Two carcinoids located into the distal ileal ansa, strictly adjacent to the ileocecal valve, are reported; the first tumor, accompanied by lymphonodal positivity, the second by a solitary hepatic metastasis, requiring segmentectomy of the liver, in addition to right hemicolectomy.

[Common bile duct injuries during videolaparocholecystectomy]. / Le lesioni della via biliare principale in corso di videolaparocolecistectomia.

In the years an increase of last biliary injuries during laparoscopic cholecystectomy was observed. At present this occurrence rate is 0.1-3.4% of laparoscopic procedures. Probably this is to be related to less contraindications to cholecystectomy by laparoscopic procedures, with increase of more difficult operations. The intraoperative biliary injuries are due to anatomical anomalies of the local structures, mistakes of technique, flogosis of the cholecisto-choledocal region. Factors preventing iatrogenic injuries are accurate and standardized operative technique, adoption of modern instruments, intraoperative cholangiography. The Authors have reviewed their experience based on 1236 laparoscopic cholecysectomies performed in six years (1992-1998) in their own structure. Four lesions of the biliary tract (0.3%) have occurred: three Bismuth I-II and one Bismuth IV. They have always performed intraoperative cholangiography, without false negative, in contrast with present literature. They conclude underlining the need of the routine contrastrographic study of the biliary tract in all cholecysectomies as well as of an adequate training in radiological imagines interpretation.

[Metabolic preparation for surgical operations and the problem of chronic shock]. / La preparazione metabolica all'intervento chirurgico e il problema dello shock cronico.

Surgical patients with a chronic energy deficit display a particulare metabolic situation known as chronic shock, marked by deficient utilisation of energy. The picture is related to functional disorders of the cell enzymes, following incomplete resynthesis due to the lack of substrates. The main features are: a) lactic metabolic acidosis due to anaerobic oxidation, usually with insufficiency of the Krebs cycle; b) exaggerated protein catabolism, due to utilisation of amino acids as the energy substrate; c) incomplete utilisation of the (mostly endogenous) substrates available, with lactacidaemia, aminoacidaemia, and increased lipidaemia. A rational form of treatment is proposed after careful analysis of these features and their corresponding clinical phenomena.