Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry.

BACKGROUND: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. METHODS: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 , instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. RESULTS: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). CONCLUSIONS: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.

Crohn's disease and Takayasu's arteritis: is this association difficult to find out?

Takayasu's arteritis is rarely reported associated with Crohn's disease in the English world literature. A case of Takayasu's arteritis type V in a young female affected by Crohn's disease is presented and the pathophysiology mechanism, and the clinical and diagnostic aspects are underlined. Surgical strategy is discussed.

Influence of age and menopausal status on pathologic and biologic features of breast cancer.

The distribution of the main prognostic factors in different age groups was evaluated in 1226 patients operated on for primary breast cancer, in order to identify those influenced by age and/or menopausal status. Patients were divided into the following groups: 1) 40 years of age and under; 2) premenopausal over 40 years of age; 3) postmenopausal under 75 years of age and 4) 75 years of age and over. Our findings showed that the youngest patients had the worst prognostic pattern, which improves as age increases and is the best in patients over 75 years of age. Some of the parameters investigated (tumour size, histologic and nuclear grade, tumour infiltrating lymphocytes, p53 and Ki 67) were found to be influenced by age, some (necrosis and oestrogen receptors) were influenced by menopausal status and/or age, some (vascular invasion, ploidy, S-phase and progesterone receptors) showed significant differences in different age groups but there was no consistent relation with patient age or menopausal status, and others (node status, ErbB2/Neu and Cathepsin D) were not influenced by age or menopause.

Immunoenzymatic assay of erbB2 protein in cancer and non-malignant breast tissue. Relationships with clinical and biochemical parameters.

The erbB2-encoded protein p185 was determined in 130 breast cancer specimens and in 29 non-malignant breast tissues using a recently available ELISA method. The assay showed good characteristics of precision and accuracy. In the non-malignant tissue p185 concentrations were normally distributed and directly correlated with estrogen receptors (ER) and progesterone receptors (PR). In cancer tissue p185 showed higher concentrations than in non-malignant tissue. No relationships were found between p185 and the main clinical and pathological parameters, except that a direct association with nuclear grade was found. We have categorized the breast cancer samples according to p185 concentrations as p185-negative (concentrations lower than the higher non-malignant tissue) and p185-positive. Our data suggested a different behaviour of p185 in samples with low or high p185 concentrations. Indeed, in p185-negative samples the concentrations were directly correlated with both ER and PR. Conversely, p185-positive samples were directly associated with node status and pT, and inversely associated with ER and PR.

A new approach to tumour marker assessment by perioperative determination in breast and colorectal cancer.

Preoperative serum tumour markers are currently classified as positive or negative according to a predetermined cut-off point. In the present study we examined the dynamic variation of marker levels after radical surgery of breast and colorectal cancer. CEA and CA15.3 were measured in 93 patients with breast cancer, CEA and CA19.9 in 97 patients with colorectal carcinoma before and 30 days after radical surgery. Any variation higher than 3-fold the analytical coefficient of variation of the assay was considered significant. In patients with negative preoperative marker levels a significant decrease was noted after surgery in 15.6% of cases for CEA and 27.8% for CA15.3 in breast cancer and in 46.8% for CEA and 25.7% for CA19.9 in colorectal cancer. Using both cut-off-based and dynamic criteria, we found an overall positivity rate of 19.6% for CEA and 33.3% for CA15.3 in breast cancer; 60.0% for CEA and 37.1% for CA19.9 in colorectal cancer. From the present findings we conclude that the dynamic study of perioperative variations of tumour markers is a sensitive method additional to cut-off-based criteria for the assessment of the phenotypic expression of the marker by the tumour.

The association between abdominal aortic aneurysms and chronic leg ischaemia. Prevalence in 125 consecutive patients.

A study was carried out to see if in patients with atherosclerotic lesions of the lower limbs the percentage of abdominal aneurysms is higher than in the general population. One hundred twenty five consecutive patients were studied in two different hospitals and compared with a control group. In the two groups with peripheral vascular diseases the patients had a prevalence of aneurysms of 12%, while in the control group the prevalence was of 3%. All patients were operated on successfully except two of them who are now in follow up with regular ultrasound assessment, one with an aortic aneurysm of 3.2 cm and the other with an aortic diameter of 4 cm and moderate liver failure.

Acute ischemia of the lower limb in a case of persistence of the primitive sciatic artery.

A rare case of persistent primitive sciatic artery with a small aneurysm in its proximal part is reported. The occlusion of this artery caused extensive lower limb ischemia which called for amputation. The diagnostic difficulties are stressed out.

Critical evaluation of limb salvage concept and indication for infrapopliteal reconstructive surgery.

A large number of surgical procedures aimed at revascularizing the popliteal and infrapopliteal arteries has been reported in patients affected by rest pain or gangrene of the extremities as well as intermittent claudication. In consideration of the high incidence of early and late unsuccessful results following this type of surgery as reported in the literature, we believe that peripheral reconstructions should be restricted to those patients presenting a clinical picture of such severity that major amputation is unavoidable in the short run. In these patients our choice of the appropriate surgical procedure is strictly related to the patency or not of the popliteal artery. The role of the above knee femoropopliteal bypass is discussed. A series of patients that we have operated upon according to these criteria is analyzed. The low number of cases in our group of patients and the high rate of postoperative failures reflect our policy on this matter.

Atherosclerotic aortic-bisiliac aneurysms in two monocorial twins.

Two cases of aorto-bisiliac aneurysms in monocorial twins in their sixties were observed. We report experimental and clinical data from the literature about genetic involvement in the formation of aneurysms, especially when associated with other risk factors. In addition to the genetic factors in the twins we studied, we also found other risk factors, such as hypertension and smoking, which took a long time to affect the patients before the aneurysms were detected.

[Diagnostic algorithms. Analysis of the factors conditioning their definition. An illustrative case (bilio-pancreatic pathology)]. / Algoritmi diagnostici. Analisi dei fattori condizionanti la loro definizione. Caso esemplificativo (patologia bilio-pancreatica).

A case of biliopancreatic pathology studied with traditional (the old algorithm) and the latest (new algorithm) diagnostic techniques is examined. A comparative analysis reveals the second to be simpler, less expensive and less dangerous to the patient. The hope is expressed that doctors will become better informed of the diagnostic criteria to employ for the purpose of cost reduction.

[Cervico-mediastinal goiter]. / Il gozzo cervico-mediastinico.

The descent of a cervical goiter below the plain of the thoracic inlet to become substernal in location, is fairly rare, but not exceptional, with an incidence, derived from several large series of operated patients, ranging from 1.7% to 13.1%. The importance of this particular location of the goiter is chiefly due to the fact that the thyroid is growing in a limited space with many surrounding structures, that unavoidably, sooner or later, will be compressed or strained. This provokes respiratory symptoms (such as cough, dyspnea, stridor) or difficulty in swallowing or determines a superior vena cava syndrome with venous stasis in the neck and in the upper thorax, and with facial oedema. The substernal location, that already constitutes a complication of the basic thyropathy, is further aggravated by the incidental malignant transformation of the substernal goiter or by the development of a thyrotoxicosis due to hyper-functioning intra-thoracic thyroid tissue. For all these reasons the presence of a substernal goiter represents in and of itself a precise indication for a surgical treatment. This study is aimed at examining the series of 19 substernal goiters observed at the Institution of General and Cardiovascular Surgery, University of Milan, from 1967 to 1987, particularly analyzing the progresses in the diagnostic procedures, the adopted surgical therapy and the observed complications.

[Screening and follow-up of patients with arteriopathies of the lower limbs using the test proposed by Laing]. / Screening e follow-up dei pazienti con arteriopatia agli arti inferiori con l'impiego del test proposto da Laing.

The Authors tested a standard exercise suggested by Laing in 1980 for the screening and the follow-up of patients with atherosclerotic lesions of the arteries of the lower limbs. Were included in this study 44 patients with monolateral symptoms and was studied the asymptomatic limb. The results were compared with the ones obtained by the traditional exercise proposed by Strandness and with the ones of a control group studied with the two tests. The excellent correlation of the data gives us the opportunity to reaffirm the utility of the Laing's standard exercise in the clinical investigation of potentially arteriopathic patients.

[Our experiences in the surgical treatment of post-phlebitis syndrome of the lower extremities]. / La nostra esperienza nel trattamento chirurgico della sindrome post flebitica degli arti inferiori.

One to ten year follow-up of 90 patients with post-phlebitis syndromes in various stages is reported. Stress is laid on the fact that treatment of the post-phlebitic limb has not yet been clearly defined, and that various medical and surgical measures are adopted from one case to another. A personal preference for surgical management, restricted to the superficial circulation and the "projected" interruption of incompetent communicating vessels, is expressed, though if considerable trophic lesions are present their regression by means of medical treatment only is regarded as an essential prerequisite to surgery. "Restricted" surgical management gave results that were more than satisfactory in 72.7% of cases, as in other series in the literature.

[An unusual case of atherosclerotic aneurysm of the trunk of the superior mesenteric artery, successfully treated with surgery]. / Di un caso non comune di aneurisma aterosclerotico del tronco dell'arteria mesenterica superiore, operato con successo.

A case of atherosclerotic aneurysm of the superior mesenteric artery is reported. This was located about 15 cm from its origin and immediately distal to the middle colic artery in a patient who had been operated on 4 years previously with aorto-iliac substitution for aneurysm of the same nature with ligature and section of the inferior mesenteric artery at the origin. Interruption of the latter created further technical problems solved with a serie of anastomoses that permitted the introduction of a good direct flow from the superior mesenteric respectively to the right colic and into an ileal branch which became a bridge or, rather, a "new mesenteric" assuring excellent pulsed flow into the underlying ileal branches, one of which anastomized at the ileocolic. This enabled direct, valid, pulsed flow to be resumed.

[Nosocomial infections. State of the art]. / Le infezioni nosocomiali. Stato dell'arte.

Little information exists up till now about the prevalence of nosocomial and community acquired infections in Italian hospitals. Little is known about the effects of thorough cleaning in today's hospitals. This review examines the common microorganisms associated with hospital acquired infections and their ability to survive in the hospital environment. The most frequent site of hospital acquired infections is the urinary tract, followed by surgical wounds and the upper respiratory tract. Analysis of North America and European data shows that the increase in length of stay for infected patients is the most striking of all examined costs. Improving standards of hygiene in hospitals would be a safe method to control hospital-acquired infections and their costs.

[The physiopathology and therapy of esophageal diverticula]. / Fisiopatologia e terapia dei diverticoli esofagei.

The authors report their experience in the management of 14 patients affected by esophageal diverticula and surgically treated (9 had cervical diverticula, 2 had epibronchial diverticula and 3 had epiphrenic diverticula). All these patients underwent a diverticulectomy: in 3 cases the diverticulectomy was associated with a subdiverticular myotomy. In the last three cases the resection of the diverticulum was performed using an automatic stapler. The follow-up of these patients was prolonged for a period of 5 years with clinical, radiographic and endoscopic evaluations performed at 6 monthly intervals. The most recently operated patient has a minimum follow-up of 22 months. There were no operative deaths and none of the patients complained of recurrence of the diverticulum or of the preoperative symptomatology. No significant complications were observed in the postoperative period in the patients who underwent a simple diverticulectomy or in the cases in which a subdiverticular myotomy was associated. The scant number of observed patients does not allow us to draw any conclusion about the necessity maintained by most authors of an associated myotomy. It is however evident that this adjunctive procedure doesn't cause any further difficulty and is not loaded with an increased risk of complications. Finally the authors believe in the usefulness of performing the diverticulectomy with an automatic stapler, these devices allow in fact a considerable reduction of the surgical time and prevent dangerous contaminations of the operative field.

[Personal experience in the treatment of intestinal carcinoids]. / Nostra esperienza nel trattamento dei carcinoidi intestinali.

The authors report 7 cases of intestinal carcinoids. They examine the clinical aspects and describe and discuss both surgical and medical treatment strategies. They also critically evaluate the value of monitoring some oncological markers and their prognostic significance. Each patient underwent an in-depth evaluation of tumour evolution (CAT, ultrasonography, NMR, angiography) and urinary 5HIAA and platelet 5HT were monitored. Surgery took the form of ileal or ileocolic resection, gastric resection, exeresis of the tumour using a transanal route, ligature of the right branch of the hepatic artery afferent to the metastasised lobe of the liver. Five patients were treated using chemotherapy and three, also suffering from carcinoid syndrome, with octreotide. On the basis of their personal experience the authors underline the limited value of the study of 5HT and 5HIAA tumour markers in the diagnosis of small carcinoid tumours. This is compensated by the outstanding role of these markers in the diagnosis of the hepatic and/or lymphoglandular diffusion of the tumour. These markers were not influenced by octreotide treatment in cases in which longastatin was successfully used to combat carcinoid syndrome. Their behaviour allowed useful information to be acquired regarding the tumour evolution following surgery.

[Heterotopia of the gastric fundus wall in bilobate gallbladder associated with dilatation of the main bile duct. Description of a case]. / Eterotopia di parete gastrica fundica in colecisti bilobata associata a dilatazione della via biliare principale. Descrizione di un caso.

On the basis of a recent case of fundic gastric heterotopia in the gallbladder, the principal, possible embryogenetic hypotheses of the malformation are described and discussed. The possibility that acid secretion of the gastric glands contained in the ectopic fundic mucosa determined part of the symptomatological and clinical picture accompanying signs of lithiasic cholecystopathy is also evaluated.

[Problems of diagnostic origin in tumors of the small intestine developing in the smooth muscle. Report on 7 cases]. / Problemi di origine diagnostica nei tumori dell'intestino tenue ad origine dalla muscolatura liscia. Osservazioni su 7 casi.

The smooth muscle tumors of the small intestine are particularly interesting for the difficulty and the delay of their diagnosis. This usually happened for the poor and indefinite symptomatology and the problematic exploration of the organ. Starting up from the observation of 7 patients between 1986 and 1989 the Authors critically examined the literature about this problem to value the diagnostic opportunities of the principal clinical exams, suggesting as resolutive investigation, if indicated, the angiographic selective study of the visceral abdominal arteries.

[Importance of Staphylococcus epidermidis in the bacterial colonization of abdominal drains in surgical patients]. / Rilevanza dello Staphylococcus epidermidis nella colonizzazione batterica dei drenaggi addominali in pazienti chirurgici.

Bacterial adherence to biomaterials as an element of clinical relevance is a well-known factor in the pathogenesis of sepsis. Drainages, intravascular catheters, surgical prostheses and other devices are susceptible to bacterial colonization with clinical consequences. In the last few years attention has been paid to coagulase-negative Staphylococcus (S. epidermidis), mainly to some strains able to produce a highly adhesive polysaccharide substance, called glycocalix or slime. This promotes adherence either interbacterial either between bacteria and biologic tissues or synthetic materials acting as a pathogenetic factor in sepsis being able to increase bacterial resistance to phagocytes and antibiotics. Bacterial contamination of 40 abdominal drainage tubes in patients operated in elective and in emergency surgery for various pathology has been evaluated. Sonication of the tip of the drainage was utilized in order to promote the detachment of adherent colonies and its effectiveness was compared to that of microcentrifugation. Culture of 25 drainages (62.5%) showed no bacterial contamination; 7 drainages (17.5%) have proved to be colonized by S. epidermidis, in 4 cases the isolated strains were also methicillin-resistant, 2 of which slime-producing. Out of the 7 drainages colonized by S. epidermidis, 4 were removed from patients operated in emergency: none of the isolated strains was slime-producing. Six drainages (15%) were colonized by Gram+ bacteria (S. fecalis, P-sensible cocci, rods), 1 (2.5%) by E. coli and 1 (2.5%) by P. aeruginosa, S. epidermidis appears to be the chief contaminant of abdominal drainages, especially in emergency surgery; slime production has always been observed in methicillin-resistant strains: this confirms the hypothesis that slime production is typical of specialized, virulent strains.(ABSTRACT TRUNCATED AT 250 WORDS)