Entropy-controlled selectivity in the vinylation of a cyclic chiral nitrone. An efficient route to enantiopure polyhydroxylated pyrrolidines.

A short synthesis of 1,4-dideoxy-1,4-imino-L-arabinitol (LAB1) (4) and of 1,4-dideoxy-1,4-imino-D-galactitol (5), two azasugars active as enzymatic inhibitors, is reported. The key reaction is the addition of vinylmagnesium chloride to (3S,4S)-3,4-bis(benzyloxy)-3,4-dihydro-2H-pyrrole 1-oxide (3), a nitrone easily available from L-tartaric acid. Unexpectedly, the reaction affords the corresponding (2S,3S,4S)-1-hydroxy-2-ethenyl-3,4-bis(benzyloxy)pyrrolidine (9) in very good yield and in 93/7 diastereomeric ratio (dr) independently of the reaction temperature, thus representing a unique case of entropy-controlled reaction in a 100 K interval (from +20 degrees C to -80 degrees C). The trans intermediate 9 is converted in two steps (reduction, N-protection) into the common intermediate (2S,3S,4S)-1-(benzyloxycarbonyl)-3,4-bis(benzyloxy)-2-ethenylpyrrolidine (11). Double bond oxidation followed by reductive debenzylation opens a route to the target pyrrolidine azasugars 4 and 5.

Adjuvant chemotherapy after gastric resection in node-positive cancer patients: a multicentre randomised study.

After curative resection for gastric adenocarcinoma, 103 patients, all with positive nodes, were randomised so that 48 received adjuvant chemotherapy of epidoxorubicin (EPI) 75 mg m-2 on day 1, leucovorin (LV) 200 mg m-2 on days 1-3 and 5-fluorouracil (5-FU) 450 mg m-2 on days 1-3, every 21 days for 7 months, whereas the remaining 55 did not. During the first year of observation, 21 control patients (38%) and five treated patients had recurrences. After a follow-up period of 36 months, 12 of the treated patients (25%) and only seven controls (13%) were still alive. At that point, the median survival was 13.6 months for the 55 untreated patients and 20.4 months for the 48 treated patients, a significant difference. We found a survival advantage for patients treated with the EPI-LV-5-FU regimen and a consistent delay in the appearance of recurrent or metastatic cancer. Acute toxicity was mild and treatment was well accepted by all patients. There was no long-term toxicity or any cardiac toxicity. We conclude that this particular chemotherapy, administered shortly after gastric resection, improves survival rate in node-positive gastric cancer patients, even although final assessment of this particular adjuvant approach must await completion of the trial.

Epidoxorubicin and high dose leucovorin plus 5-fluorouracil in advanced gastric cancer: a phase II study.

We conducted a multicentric phase II study on advanced gastric cancer to determine the efficacy and toxicity of treatment with epidoxorubicin (EPI) plus high doses of leucovorin (LV) and 5-fluorouracil (5-FU). Thirty-seven patients with measurable disease were enrolled into the trial and treated with EPI 75 mg/m2 on day 1 and LV 200 mg/m2 plus 5-FU 450 mg/m2 from day 1 to 3, the cycle being repeated every 3-4 weeks from a median of five cycles per patients. The response rate was 49% in 35 evaluable patients, with two complete remissions and 15 partial responses. Median response duration was 12.4 months; median survival for responding patients was 17.3 months, which was significantly longer than 8.7 months for non-responding patients. General toxicity was usually mild, myelotoxicity was moderate and there was no evidence of cardiac toxicity. These results show that EPI-LV-5-FU is an effective regimen for advanced gastric carcinoma. The efficacy of this combination should now be tested as an adjuvant therapy in resectable gastric cancer.

[Role of surgery for non-Hodgkin lymphoma of the gastrointestinal tract]. / Ruolo della chirurgia nei linfomi non-Hodgkin del tratto gastroenterico.

From January 1974 to December 1990, 619 patients were submitted to surgical treatment for gastrointestinal carcinoma: 10 cases (1.61%) of non-Hodgkin's lymphomas were observed (4 of the stomach, 3 of the small intestine, 1 of the colon, 2 of the rectum). There were 5 men and 5 women, mean age 57.1 years (range 34-80). In 6 patients the diagnosis was performed with radiological investigations, in 4 with ultrasonography too. Endoscopy biopsy was unfit for diagnosis in the gastric localizations, while it was positive in both rectal localizations. Seven patients were operated and no postoperative morbidity or mortality was observed. The role of surgery is discussed, diagnosis for staging and therapy alone or associated with chemotherapy and/or radiotherapy.

[Hemorrhagic pseudocyst of the adrenal gland. Presentation of a case]. / Pseudocisti emorragica del surrene. Presentazione di un caso.

The Authors report a case of voluminous hemorrhagic pseudocyst of the left suprarenal gland. The anatomo-pathological classification of adrenal cysts is described, in particular with reference to the etiopathogenetic hypotheses regarding the formation of hemorrhagic pseudocysts. Lastly, the importance of using instrumental tests for a correct diagnosis is underlined and the surgical indications of accidentally discovered asymptomatic cysts are discussed.

Thyroxine and triiodothyronine levels in thyroid vein blood and in thyroid tissue of patients with autonomous adenomas.

Thyroxine (T4) and triiodothyronine (T3) concentrations were measured in peripheral and thyroid vein blood and in nodular and extranodular thyroid tissue from twenty-four patients with autonomous thyroid nodules (AFTN); fifteen of these patients showed clinical signs of hyperthyroidism and nine were euthyroid. Thirteen patients with solitary non-functioning thyroid adenomas who were clinically euthyroid, served as controls; samples of thyroid vein blood and normal thyroid tissue being obtained from the contralateral lobe. T4 (189.4 +/- 27.2 nmol/l) and T3 (7.05 +/- 2.03 nmol/l) concentrations were significantly higher in the thyroid vein blood of patients with AFTN compared with controls (T4 = 119 +/- 9.1 nmol/l, P less than 0.05; T3 = 2.3 +/- 0.21 nmol/l, P less than 0.01) whereas peripheral levels in the two groups were similar. The T3 concentrations (10.56 +/- 4.12 nmol/g wet tissue) in autonomously-functioning thyroid nodular tissue were significantly higher than those of extranodular (1.9 +/- 0.62 nmol/g wet tissue, P less than 0.01) and normal thyroid tissue (2.63 +/- 0.43 nmol/g wet tissue, P less than 0.05). The T4 levels were not different in the tissues examined. The concentrations of T4 and T3 in thyroid vein blood did not show any significant correlation with the hormone levels in thyroid tissue.