General surgery in haemophiliac patients.

With improvements in medical technology, more and larger surgical procedures are performed in haemophiliac patients, but rarely reported in the surgical literature. A retrospective study from a 10 year period from one referral centre identified a total of 68 operations performed in haemophiliac patients. The levels of the defective factors were carefully monitored preoperatively and postoperatively, and replaced according to a standard formula. Special caution was taken to avoid any postoperative medication or procedures that could provoke haemorrhagic complications.Two patients suffered postoperative bleeding complications that were managed conservatively. Inhibitory factors were detected preoperatively in one case, and postoperatively in another, and were managed with aggressive replacement therapy. There was no mortality, and the overall morbidity rate was 6%. With adequate preoperative and postoperative monitoring of the clotting factors, meticulous haemostasis during surgery, careful postoperative nursing, and timely replacement therapy, haemophiliac patients can be operated with good results. Postoperative bleeding complications are rare, and usually amenable to conservative management.

Polypoid hamartoma of Brunner's gland of the duodenum.

BACKGROUND/AIMS: Brunner's gland adenoma is an extremely rare but important entity. Controversy exists over its etiology and pathogenesis, but the present view is that it is a duodenal hamartoma with a predominance of Brunner's gland elements. METHODS: A case of a 76-year-old woman with a reddish pedunculated polyp prolapsing between the bulb and the second part of the duodenum seen at endoscopy and removed surgically through a longitudinal duodenotomy is presented. RESULTS: The cut surface of the tumor had a grayish color, revealing multiple cystic spaces which on microscopic examination proved to be enlarged Brunner's glands. The hyperplastic glands formed lobules which were surrounded by bundles of fibromuscular and connective tissue. In the adjacent duodenum, large numbers of lobules of well-differentiated Brunner's glands with mucus-secreting epithelial cells were seen. CONCLUSION: The reported case supports the theory that Brunner's gland adenomas are duodenal hamartomas with a predominance of Brunner's gland elements and further shows that a continuity exists in Brunner's glands of the tumor and those of the adjacent duodenum.

5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial.

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.

A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer.

Combination chemotherapy (CT) has, in some groups of patients with gastric cancer (GC), who are at a high risk for relapse, resulted in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting. Based on the above data, we studied adjuvant CT with FEM (5-fluorouracil (5-FU), epirubicin, mitomycin C) in a randomized study of patients with completely resected stage III GC and patients with stages T1-3 with a low histologic grade. CT was started 2-3 weeks after surgery. From August 1988 until February 1994, 84 patients with completely resected tumors and lymph nodes were randomized to either group A (FEM) or group B (no treatment). Patients were eligible for randomization if they had a Karnofsky score > 60, no postoperative evidence of residual tumor, and normal cardiac, hepatic and renal functions. Forty-two patients were randomized to each group, with no significant differences regarding: age distribution, group A 53 years (41-65), group B 57 years (35-66); sex, group A 32/10, group B 25/17 (men/women); site of primary tumor, group A 22/20, group B 25/17 (pylorus/antrum); histologic grade, group A 0/19/23, group B 0/25/17 (grades I/II/III); lymph node metastases, group A 30, group B 32, and surgical procedure, group A 33/9/6, group B 35/7/9 (total gastrectomy/partial gastrectomy/splenectomy). Group A received 5-FU 600 mg/m2/day i.v. on days 1, 8, 29 and 36, epirubicin 45 mg/m2/day i.v. on days 1 and 29, and mitomycin C 10 mg/m2 i.v. on day 1. The schedule was repeated every 56 days for 3 cycles. Group B received no treatment odd was only subjected to the regular follow-up. At the last follow-up at 66 months, 27/42 patients in group A (64%) had relapsed or died, compared to 34/42 patients in group B (81%). The differences in the relapse and the disease-free and the overall survival rates were not statistically significant. Only the subgroup of patients with histologic grade III tumors receiving adjuvant FEM demonstrated a trend towards improved survival (p = 0.085). Main therapy-related toxicities for the treatment group were grade I-II anemia, neutropenia, and throbocytopenia in 16, 45, and 22% of patients, respectively, and grade I-II nausea and vomiting in 29% of patients. Based on the present findings and those of previous studies, even if one considers the difference reaching statistical significance in the latter for histologic grade III tumors, it becomes evident that with current therapeutic modalities adjuvant therapy has no established role in the management of resectable GC. Studies of new-generation regimens, such as FAMTX (5-FU, Adriamycin and methotrexate) as well as ELF (etoposide, Leucoverin, and 5-FU), should be conducted in the adjuvant therapy setting with a nontherapy control group, in order to clarify the issue of adjuvant CT in resectable GC.