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Hürthle cell neoplasms of the thyroid gland are uncommon but potentially lethal lesions, the treatment of which is controversial because of a lack of information about their biological and clinical behaviour. Based on histological criteria Hürthle cell tumours cannot always be separated accurately into benign and malignant. Unexpected evolutions with malignant late recurrence of an adenoma previously labelled as benign have been reported. The authors reviewed the clinical and pathological features of 32 patients with Hürthle cell adenomas. The results suggest that total thyroidectomy 'de principe' is not necessary and that some electron microscopy criteria are useful to understand the nature and to predict the biological deportment of Hürthle cell adenomas.

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.

We report the use of a colony-stimulating granulocyte-macrophage factor (GM/CSF) and erythropoietin (EPO) combination as salvage treatment in four heavily-pretreated patients with refractory/recurrent B-CLL. Induction therapy was subcutaneous GM-CSF 2.5 μg/kg, and EPO, 150 units/kg both daily for the first 14 d. Maintenance therapy was GM-CSF on days 1, 3 and 5 and Epo on days 2, 4 and 6 at the same doses with weekly recycling. All the patients responded favourably. A significant reduction of lymphocytosis, lymphoadenomegaly, and organomegaly was obtained within one month of therapy. The number of infections and transfusional requirement decreased dramatically. The hemoglobin increased to over 11 g/dl in 3 out of 4 patients. With a median follow-up of 11 months (range 5–13) we observed 4 partial responses (NCI/IWCLL) and only one progression after a 10-month partial response. This combination regimen seems very active, safe and easy to administer. It may represent a promising therapeutical option in heavily pretreated patients. Further clinical and biological studies on a larger cohort of patients are needed to confirm these preliminary data, to clarify the hypothetical interactions between these cytokines and B-CLL cell proliferation pathways, and to establish if this therapy may have an impact on survival.

A simple and precise high-performance liquid procedure has been developed for the determination of Ofloxacin (DL-8280), a new oxazine derivative in human serum, urine and bile using Norfloxacin as internal standard. The work-up procedure involves a chemical extraction step followed by isocratic chromatography on a anion-exchange analytical column, with ultraviolet detection. The run time for the assay was 11.5 minutes.

// Stefano Guadagni 1 , Giammaria Fiorentini 2 , Andrea Mambrini 3 , Francesco Masedu 1 , Marco Valenti 1 , Andrew Reay Mackay 1 , Donatella Sarti 2 , Enrico Ricevuto 1 , 4 , Marco Clementi 1 , Marco Catarci 5 , Gianni Lazzarin 1 and Gemma Bruera 1 , 4 1 Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila, Italy 2 Department of Oncology and Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro, Italy 3 Oncology Unit, Azienda USL Toscana Nord Ovest, Massa Carrara, Italy 4 Oncology Territorial Care S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy 5 General Surgery Unit, “C. e G. Mazzoni” Hospital, Ascoli Piceno, Italy Correspondence to: Stefano Guadagni, email: stefano.guadagni@univaq.it Keywords: hypoxic pelvic perfusion with mitomycin C and oxaliplatin; unresectable recurrent rectal cancer; retrospective cohort study Received: April 04, 2019 Accepted: May 05, 2019 Published: June 11, 2019 ABSTRACT Background Innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have been proposed for unresectable recurrent rectal cancer (URRC). Regorafenib and trifluridine-tipiracil reported significantly increased PFS 1.9-2.0 months, OS 6.4-7.1 months vs placebo, respectively. Present study evaluated safety and efficacy of mitomycin/oxaliplatin HPP associated to intravenous cetuximab, and of third line systemic therapy in clinical practice. Methods HPP consisted of: isolation, perfusion, chemofiltration. Patients received mitomycin 25 mg/m 2 and oxaliplatin 80 mg/m 2 during HPP; from days 21 to 28, cetuximab 250 mg/m 2 /week. In case of partial response or stable disease, HPPs were repeated every 8 weeks. In control group, systemic third and further lines of therapy were defined in clinical practice according to clinical (age, comorbidities, performance status), biological parameters ( KRAS , NRAS , BRAF genotype). Results From 2005 to 2018, 49 URRC patients were enrolled; 33 in HPP/target-therapy, 16 in systemic therapy control group. No HPP related complications were reported. Most common adverse events were skin, bone marrow toxicities. In HPP/target-therapy group, ORR and DCR were 36.4 and 100%; in systemic therapy control group, 18.7 and 31.25%, respectively. In HPP/target-therapy compared with systemic therapy group, respectively, DCR seemed significantly favourable ( P = 0.001), as PFS 8 vs 4 months ( P = 0.018), and OS 15 vs 8 months ( P = 0.044). Conclusions Present data showed that integration of HPP/target-therapy may be effective in local control, and efficacy as third line treatment of URCC patients. This therapeutic strategy deserves further prospective randomized trials to be compared to conventional systemic treatments.

Adenocarcinoma of the small bowel is uncommon. Due to the paucity and lack of specificity of symptoms, patients are usually seen late in the course of their illness when curative therapy, mainly represented by wide surgical resection, is unlikely. The authors report a case of primary adenocarcinoma arising in the jejunal limb transposed for a Roux-en-Y esophagojejunostomy reconstruction eight years after a total gastrectomy performed for an advanced gastric cancer (pT2N1M0), with mixed histological pattern (tubular-mucinous) and negative CEA staining of cancer cells. Evidence for excluding the possibility of a recurrence of the primitive gastric cancer was based on the different histologic pattern, positive CEA staining of cancer cells and other features of the second neoplasm. Early diagnosis of the neoplasm was made possible by its favorable anatomic location and the early onset of symptoms, which prompted effective surgical therapy (wide resection). The authors, furthermore, analyze and discuss the possible pathogenesis of the neoplasm, based on the evidence of slow jejunal limb emptying, elevated concentration of N-Nitroso compounds and contamination by N-nitrosating bacteria in the jejunal limb juice, suggesting that each of these factors could have had a role to play in the development of the jejunal malignancy.

Lesions of the colon are generally considered to be sequelae of pancreatitis. They include: localized paralytic ileus (colon cutoff sign), necrosis, fistulae, stenosis and varices. On the basis of an extensive review of the literature (332 cases), it is suggested that the real incidence of these lesions is significant. The anatomic relationship of the large bowel to the pancreas is an important factor in the genesis and localization of the lesions. Enzymatic-inflammatory and ischemic processes are involved in the most highly supported theories. Each complication shows different diagnostic and clinical patterns. In this paper, six cases of such lesions are presented, including 2 cases of necrosis, 2 of stenosis, 1 of fistula and 1 case of localized paralytic ileus.

A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).

Gastric lipomas are uncommon lesions, usually single and located in the antrum. Common symptoms include upper digestive bleeding, anemia, and intestinal obstruction. Alternatively, they may remain asymptomatic, and detectable only at autopsy. A case of a 72-year-old man, who died of myocardial infarction, was found at autopsy to have multiple gastric lipomas of the corpus and antrum, with a single lesion measuring 10 x 6.5 x 3 cm.

Aims and Background The optimal salvage therapy for recurrent ovarian carcinoma has not been clearly established. Response to second-line chemotherapy is low, with a short median survival (8.8-15 months). We investigated the effect of an aggressive approach consisting of surgery followed by intraperitoneal drug delivery and local hyperthermia. Patients and Methods In a phase II clinical study, 27 patients with advanced/recurrent ovarian carcinoma were treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Median patient age was 53 years (range, 30-67) and mean follow-up was 17.4 months (range, 0.3-36.0). Patients had been surgically staged and heavily pretreated with cisplatin-based, taxol-based or taxol/platinum-containing regimens. Nineteen (70%) patients were cytoreduced to minimal residual disease 2/L) + mitomycin C (3.3 mg/m2/L) through a heart-lung pump (mean flow of 700 mL/min) for 60 min in the hyperthermic phase (42.5 °C). Results Two-year overall survival was 55%. Median times to overall progression and local progression were 16 months and 21.8 months, respectively. Variables that affected the overall survival or time to progression were as follows: residual disease (P = 0.00025), patient age (P = 0.04), and lag time between diagnosis and cytoreductive surgery + intraperitoneal hyperthermic perfusion (P = 0.04). Treatment-related morbidity, mortality and acute toxicity (grade II-III) rates were 11%, 4% and 11%, respectively. Eight (89%) of 9 patients had ascites resolution. Conclusion Our results suggest that cytoreductive surgery + intraperitoneal hyperthermic perfusion is a well-tolerated, feasible and promising alternative in the management of selected patients with recurrent ovarian cancer, but further randomized controlled studies are needed in order to confirm our findings.

This study was undertaken to determine the survival of patients with unresectable and refractory non small cell lung cancer (NSCLC) submitted to thoracic stop-flow perfusion (TSP). Forty-five patients with NSCLC confined to thoracic region entered the study. All 45 patients had been pretreated with some form of chemotherapy and had progression of disease. The cytostatic regimen was mitomycin 10 mg/m 2 , navelbine 25 mg/m 2 and cisplatin 60 mg/m 2 . In 39/45 patients, immediately after TSP, hemofiltration was performed to reduce systemic side effects There were 16/45 responses to the first TSP (CR 0; PR 16): a response rate of 35.6%. Median time to progression was 4 months. Median survival was 7.5 months.1-year survival rate was 36.4%, 2-year survival rate was 14%, and 3-year survival rate was 5.7%.

CH-40 is a suspension of activated carbon particles that was developed in Japan to carry anticancer drugs to regional nodes and peritoneal seedings of gastric cancer.Forty-five consecutive patients who had surgical resection and D2 lymph node dissection for gastric cancer over a 2-year period were randomly assigned to preoperative endoscopic submucosal injection of CH-40 (group A) or no staining (group B). A total of 21 patients in group A and 24 in group B were available for analysis.The number of resected nodes per patient was significantly higher (t = 6.06; 40 df; P.0001) in group A (mean+/-S.E. = 35.3+/-1.24) than in group B (mean+/-S.E. = 25.5+/-1.02). The rate of metastatic nodes resected was significantly higher (chi2 = 6.903 ; 1 df; P = .009) in stained (22.5%) than in non-stained (14.7%) nodes of group A and also (chi2 = 6.906; 1 df; P = .009) in stained nodes of group A than in group B (15.8%).Preoperative endoscopic vital staining with CH-40 proved to be rapid, safe, and effective in all cases in this series. Its use allowed surgeons to resect a higher number of lymph nodes. and to identify and examine more metastatic nodes. It also permitted identification of nodal micrometastases on routine histopathologic examination.

Hepatic arterial infusion (HAI) chemotherapy is accepted to be an option in patients with non-resectable metastases from colorectal cancer confined to the liver. In a multi-istitutional trial, 76 patients were randomly assigned to receive HAI versus HAI plus systemic bolus 5-fluorouracil and leucovorin. The primary endpoint was survival, followed by response, recurrence and toxicity. Survival was longer for HAI plus systemic chemotherapy (HAI+SYC) than HAI (median, 20 vs. 14 months; p = 0.0033), as were responses (47.5% and 41.7%; p = 0.09) and time to hepatic progression (12 vs. 8 months; p = 0.039). Side effects included haematological toxicity that was mostly mild and reversible in 432 cases. Neutropenia grade 3 occurred in four patients in the HAI+SYC arm and one in the HAI arm. Diarrhoea occurred in 20% and 7% of patients and stomatitis occurred in 18% and 2%, respectively. On the contrary biliary toxicity was significant; twelve patients had evidence of bilirubin elevations of more than 3 mg/dl (six in each arm), and two had asymptomatic arterial biliary-tree fistulae: one in the HAI+SYC arm and one in the HAI arm. Grade 3 elevation in alkaline phosphatase and aminotransferase levels occurred in 26% and 24%, respectively. In conclusion, the combination of HAI+SYC is active and safe showing a clinical advantage with respect to simple HAI, increasing overall survival, response rate and time to progression.

Aims and background The advantage of delivering chemotherapy by hepatic arterial infusion is the acquisition of a high concentration of the drug in the target. Irinotecan (CPT-11) is active for the treatment of advanced colorectal cancer. In phase I studies, doses of 20 mg/m2/d for 5 days given every 4 weeks as continuous infusion or 200 mg/m2 as a short 30-min infusion given every 3 weeks is recommended for phase II studies. Methods and study design Twelve patients with a median liver substitution of 30% (20-50%) were enrolled, 6 progressed after a FOLFOX-induced partial response and 6 progressed after 5-fluorouracil and folinic acid. All patients had a surgically (n = 6) or angiographically placed port (n = 6). They received hepatic arterial infusion chemotherapy with CPT-11 (200 mg/m2) on an outpatient basis, every 3 weeks as a short 30-min infusion for six cycles. Results Four partial responses were observed (33%) lasting 24, 15, 12 and 8+ weeks, 3 stable disease (25%) lasting more than 12 weeks, and 5 progressions (41%). Six patients (50%) presented a >30% reduction in CEA. Toxicity was G2 diarrhea in 5 patients (41%) and G2 myelosuppression in 6 (50%); one patient had abdominal right upper quadrant pain requiring analgesics. Conclusions CPT-11 is active as hepatic arterial infusion chemotherapy in liver metastases from colorectal cancer and can rescue systemically pretreated patients. Our schedule seems safe, feasible and well accepted on an outpatient basis.