Quantitative analysis of luciferase activity of viral and hybrid promoters in bovine preimplantation embryos

OBJECTIVE: The aim of the study was to determine if ACH given after NCH followed by RH could decrease the incidence of distant metastases in patients with locally advanced carcinoma of cervix uteri. MATERIAL: 56 pts (34 Ib, 18 IIb, 4 IIIb) with confirmed diagnosis of squamous cervical cancer were enrolled in this phase II trial. The methodology used was: 1) Figo clinical staging; 2) Ultrasonographic determination of tumor volume in < or > 4 cms; 3) V.B.P. scheme: cis-platinum 50 mg/m2/day 1; vincristine 1 mg/m2/day 1; bleomycin 25 mg/m2/days 1-2-3 (3 courses with 10 days interval); 4) Clinical and sonographic tumor response evaluation following U.I.C.C. response criteria; 5) Radical hysterectomy; 6) Pathological risk factor evaluation; 7) ACH with P.M.C. (cis-platinum 50 mg/m2, methotrexate 30 mg/m2, cyclophosphamide 500 mg/m2) 3 courses every 21 days; 8) Comparison and location of recurrences with a neoadjuvant group (NCH + RH + RT to whole pelvis), and with a control group treated with conventional radiotherapy were done. For statistical analysis the Chi-Square was used and D.F.S. and overall survival (O.S.) were calculated according to the Kaplan Meier and Log Rank Test. RESULTS: After a median follow-up of 75 months (range 42-108), O. S. for stage Ib was 88%, Stage IIb 78%, and 50% for IIIb. The recurrences were 12% (4/34) for Stage Ib (3 local and 1 distant); 28% for IIb (5/18) (4 pelvic and 1 distant); 50% (2/4) for IIIb (2 pelvic recurrences). When residual tumor volume was < 2 cm in the surgical specimen (n=39) there were 4 recurrences (3 pelvic and 1 distant), and 7 (6 pelvic and 1 distant) for tumors > 2 cm. (p<0.01 for pelvic recurrences). For the stage Ib with residual tumor <2 cm (n=14) there were no pelvic recurrences and only 1 distant. Comparing for Stage Ib with previous tumor volume >4 cm of the ACH Group (n=17) with a classical NCH (n=51) and control (n=51) groups, there were observed 2 (11.7%) pelvic and 1 (5,8%) distant relapses for the 1st Group, 3 (5.9%) pelvic and 3 (5.9%) distant relapses for the 2nd, and 11 (21.6%) pelvic and 5 (9.8%) distant relapses for the 3rd Group. From the comparison of locally advanced tumors (Stages IIb + IIIb) of ACH group (n=22), with a Stage IIIb surgically removed of classical NCH group (n=38) and with a control group of conventional RT (n=51), there were observed 6 (27%) pelvic and 1 (4.5%) distant relapses for the 1st Group, 4 (11%) pelvic and 7 (18.4%) distant relapses for the 2nd, and 31 (60.7%) pelvic and 5 (9.8%) distant for the 3rd one. CONCLUSION: ACH after NCH + RH could be used for stage Ib with tumor volume > 4 cm, with complete clinical response or residual tumor < 2 cm. The results of this group of tumors suggest the importance of going on phase III trials comparing NCH+RH alone vs. NCH+RH+ACH. ACH could also be used to try to obtain better control of distant metastases in Stages IIb and IIIb. In these cases radiotherapy to the whole pelvis must not be excluded.     

Factors associated with exposure in Occupational Safety and Health Administration data

PURPOSE: To identify clinical and pathologic differences between nonadvanced (resectable by cholecystectomy) gallbladder adenocarcinomas (GBA) and advanced (nonresectable) GBA. PATIENTS AND METHODS: Twenty-nine cases of GBA were divided into two groups. Patients in group A (n = 15) underwent complete tumor resection by cholecystectomy, and those in group B (n = 14), incomplete or no resection of the tumor. Clinical (age, sex, pain, jaundice, weight loss, abdominal mass, fever), biological (anemia, hypoalbuminemia, cholestasis-cytolysis), diagnostic (ultrasound, intraoperative, postoperative) and pathologic (tumor size and differentiation status) aspects were compared in the two groups. RESULTS: Clinical and biological factors showed no significant differences between the two groups. Overall effectiveness of GC diagnosis before the postoperative pathologic examination was 6.7% in group A and 57.1% in group B (p < 0.001). Advanced tumors (T3-T4) were found in group B, and nonadvanced tumors in group A (T1-T2, 66.7%). In group B well-differentiated tumors (10 cases) predominated, whereas poorly-differentiated tumors predominated in group A (19 cases, p < 0.01). CONCLUSIONS: The preoperative diagnosis of GBA is difficult, except in advanced cases. No clinical differences exist between completely resected and nonresectable tumors. Resected tumors are usually a postoperative pathologic finding, and are usually nonadvanced and well differentiated.     

Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 +/- 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 +/- 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.     

Bispecific antibody-mediated lysis of placental and germ cell alkaline phosphatase targeted solid tumors in immunocompetent mice

Recently, an immunocompetent in vivo mouse model was developed based on germ cell alkaline phosphatase (GCAP) transgenic (FVB/N x C3H) mice in which both placental alkaline phosphatase (PLAP)+ and GCAP+ solid MO4 tumors develop. A bispecific anti-PLAP/GCAP anti-mouse CD3 antibody (Ab) 7E8 x 7D6, previously shown to induce efficient dose-dependent T-cell proliferation and PLAP+ tumor cell lysis in the presence of recombinant IL-2 and the anti-mouse CD3 Ab 7D6, was used in this report in in vivo lysis experiments targeting GCAP+ tumors grown in GCAP+ transgenic mice. Mice received injections i.v. twice a week with PBS (group 1) or with 10 micrograms of the bispecific Ab 7E8 x 7D6, either alone (group 2) or combined with 1 microgram of the anti-CD3 Ab 7D6 (group 3), starting 7 days after the tumor inoculation. A fourth group received a local treatment with mouse splenocytes precoated with 10 micrograms 7E8 x 7D6 and 1 microgram 7D6. In between Ab injections, groups 2, 3, and 4 received 10(4) units recombinant IL-2 (i.v.) every day. Two weeks of treatment with the bispecific Ab either alone or combined with 7D6 resulted in a significant decrease of GCAP+ tumor cells in groups 2 and 3 (4 +/- 3% and 10 +/- 11% GCAP+ cells/tumor) as compared to the nontreated tumors (95 +/- 5% GCAP+ cells), although tumor volumes were not significantly different (12 +/- 15 cm3 and 14 +/- 11 cm3 versus 16 +/- 7 cm3). Apparently, the elimination of GCAP+ cells from the tumor seemed to favor conditions enabling the outgrowth of the few GCAP- cells originally present in the tumor inoculate. In contrast, tumor volumes in group 4 (local treatment) were significantly smaller (P < 0.03; 5 +/- 10 cm3, 8 +/- 11% GCAP+ cells) as compared to the nontreated group, probably due to the presence of higher amounts of Ab and infiltrated activated T cells (567 +/- 322 CD5+ cells/mm2) capable of secreting cytostatic cytokines like tumor necrosis factor alpha and IFN-gamma as compared to groups 2 and 3 (266 +/- 135 and 198 +/- 86 CD5+ cells/mm2, respectively). In summary, this study clearly demonstrated that bispecific antibodies specifically concentrate cytotoxic T cells into a solid tumor in vivo, with subsequent elimination of the targeted tumor cell.     

Discharge planning in a community hospital--a multidisciplinary approach

OBJECTIVES: Osteoporosis is common in subjects over 70 years of age. Likewise, the incidence of monogammapathies of undetermined signification (MGUS) increases with age. We conducted this study to determine whether the biological and histomorphometric characteristics of osteoporosis in patients with MGUS are different from those in primary osteoporosis and to ascertain whether any cause and effect relationships could exist between MGUS and osteoporosis, excluding signs of active myeloma. PATIENTS AND METHODS: Serum and urinary phosphorus and calcium, histomorphometric measurements, hormone levels and serum cytokines (IL1, IL6 and TNF alpha) were determined in 7 patients (mean age 71.8 years, 2 men and 5 women) with MGUS associated with osteoporosis with vertebral fractures (OP) and compared with those in 7 osteoporosis patients without MGUS matched for age, sex, and osteoporosis severity and 7 other age and sex matched patients with MGUS without OS. The MGUS + PS patients were followed for 9 years (4.5 to 20) so slowly progressive myeloma could be excluded. RESULTS: Cytokine levels were the same in the three groups of patients but MGUS + OP patients had higher urinary calcium levels (ca/cr = 0.21 +/- 0.08 vs 0.12 +/- 0.1 (OP) and 0.13 (MGUS); p = 0.04), decreased osteocalcin levels (7 +/- 4.6 ng/ml vs. 12 +/- 4 (OP) and 11.5 +/- 5 (MGUS); p = 0.01) and increased surface resorption (8 +/- 1.4 vs. 3.6 +/- 1.2 (OP) and 5.5 +/- 1.7 (MGUS); p = 0.05). DISCUSSION: It has been demonstrated that MGUS in patients with increased resorption and lower osteocalcin levels frequently progresses to active myeloma. The question is raised as to whether, in certain cases of MGUS, in situ stimulation of bone cells by monoclonal plasma cells could exist without ongoing transformation to active myeloma.     

Comparison of in-phase and opposed-phase GRE and conventional SE MR pulse sequences in T1-weighted imaging of liver lesions

PURPOSE: Our goal was to compare in-phase (IP) and opposed-phase (OP) GRE and conventional SE sequences in T1-weighted (T1-W) imaging of the liver and to evaluate chemical shift GRE imaging in characterizing liver/lesions for fat content. METHOD: IP and OP T1-W GRE with fast low angle shot (FLASH) technique and T1-W SE sequences were compared in 162 patients at 1.0 T. Chemical shift GRE imaging was used to characterize lesions with fat content. Two hundred sixteen lesions were analyzed in three groups of liver: (a) "normal" liver (n = 74 with 110 lesions); (b) cirrhotic liver (n = 76 with 85 lesions); and (c) fatty liver (n = 12 with 21 lesions). Liver/lesion contrast and liver/lesion contrast-to-noise ratio were assessed for lesion detectability. The percentage of signal intensity variation (SIV) between IP and OP images was used to characterize lesions for fat content. RESULTS: The OP GRE sequence had significantly higher contrast for normal and cirrhotic livers (p < 0.001), and the IP GRE sequence had significantly higher contrast and contrast-to-noise ratio for fatty liver (p < 0.001). There were no significant differences between OP, IP, and T1-W SE imaging in cirrhotic cases for contrast-to-noise ratio (p < 0.28). Chemical shift imaging detected fat in 21 lesions (9.7%, mean SIV, 191.1%) (sensitivity and specificity 100% when compared with fine needle aspiration cytology). CONCLUSION: OP GRE sequences could replace conventional SE sequences in T1-W imaging in nonfatty livers, whereas in fatty livers, T1-W SE sequences could be obviated, but both OP and IP sequences are necessary. Chemical shift imaging (OP and IP) can be used to accurately characterize lesions for fat content.     

Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple myeloma

High-dose cyclophosphamide (HD-CY) has been shown to decrease the tumor mass in multiple myeloma (MM) patients and to be effective in the mobilization of PBPC. By administering hematopoietic growth factor the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of CY could be reduced. Thirty-two patients with stage II and stage III MM were treated to mobilize and harvest a sufficient amount of PBPC for autologous transplantation. Sixteen patients received 4 g/m2 CY and 16 patients 7 g/m2 CY in divided doses of 1 g/m2 every 2 h. Both patient groups were comparable for disease stages as well as previous therapies. Twenty-four hours after chemotherapy 300 micrograms GCSF were administered subcutaneously once daily until the last day of leukapheresis. Administration of 7 g/m2 HD-CY resulted in statistically significantly higher peak values for CD34+ progenitor cells (47.86/microliters vs 18.75/microliters, P = 0.0198) in the peripheral blood. PBPC autografts containing > 2.5 x 10(6) CD34+ cells/kg BW could be obtained at the first attempt from 14 of 16 patients treated with 7 g/m2 CY as compared to 10 of 16 patients treated with 4 g/m2 CY (P = 0.11). The analysis of potentially malignant CD19+ B cells showed a highly significant lower mean CD19+ cell content/kg BW per leukapheresis in the 7 g/m2 compared to the 4 g/m2 CY group (0.75 vs 1.81 x 10(6), P = 0.001). WHO grade IV treatment-related non-hematologic toxicity was not observed. We prefer the 7 g/m2 CY dosage followed by cytokine administration for the mobilization of PBPC in advanced state MM patients pretreated with alkylating agents.     

Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 25 tumors

Lipoblastoma/lipoblastomatosis is an uncommon benign adipose tissue tumor of children. Since 1958, 25 of these tumors from 24 patients have been reviewed in the Department of Pathology at The Children's Hospital of Philadelphia. Tumors were resected from 19 boys (79%) and five girls, and 20 patients (84%) were < or =5 years of age at diagnosis. Twenty-three tumors presented as painless superficial soft-tissue masses; one tumor was retroperitoneal and was discovered because of vomiting; one hand tumor was present at birth. Tumors occurred in an extremity (n = 11 patients), the head and neck (n = 5), groin (n = 2), axilla (n = 2), back (n = 1), chest (n = 1), flank (n = 1), labia (n = 1), and retroperitoneum (n = 1). Thirteen tumors occurred on the left side, and five occurred on the right. Lesions measured 1.0-21.0 cm in greatest dimension; 15 of 25 (60%) measured < or =5.0 cm. The largest (retroperitoneal) tumor weighed 450 g. Eleven tumors were discrete lipoblastoma, and 14 had irregular margins (lipoblastomatosis). Microscopically, the tumors displayed adipocytes in different stages of maturation; lobules bordered by septae that were cellular in 11 cases; prominent blood vessels in 19 cases; and myxoid foci in 13 cases. Chart review of 22 patients showed that one tumor recurred 4 years after resection; one tumor recurred after 7 years as fibrolipoma; and one incompletely resected tumor enlarged and at second resection was lipoma. There were no metastases. Three patients also had hemangioma. Juvenile aponeurotic fibroma occurred in one patient near the site of resection of a lipoblastoma 4 years earlier. We conclude that lipoblastoma/lipoblastomatosis behaves benignly, occurs in both superficial and deep sites, occasionally attains large size, may mature, can recur, and may be associated with other benign soft-tissue lesions. Complete surgical excision is the treatment of choice.     

Operative risk and prognostic factors of typical bronchial carcinoid tumors

BACKGROUND: This study estimated operative risk and examined factors determining long-term survival after resection of typical carcinoid tumors. METHODS: From 1976 to 1996, 139 consecutive patients (66 male and 73 female patients with a mean age of 47 +/- 15 years) underwent thoracotomy for typical carcinoid tumor. The tumors were centrally located in 102 patients (73.4%). RESULTS: Radical resection was performed in 106 patients (7 pneumonectomies, 13 bilobectomies, and 86 lobectomies) and conservative resection in 33 (3 segmentectomies, 3 wedge resections, 20 sleeve lobectomies, and 7 sleeve bronchectomies). There were no postoperative deaths. Complications occurred in 19 patients (13.7%). The morbidity rate was not increased after bronchoplastic procedures (chi 2 = 0.033, not significant). Staging was pT1 in 107 patients (77.0%) and pT2 in 32 (23.0%); 13 patients (9.4%) had nodal metastases. Seventeen patients have died (12.2%), during follow-up, but only three deaths were related to the disease. The overall survival rate at 5, 10, and 15 years was estimated to be 92.4%, 88.3%, and 76.4%, respectively; estimated disease-free survival was 100% at 5 years and 91.4% at 10 and 15 years. Estimated survival of patients with lymph node metastasis was 100% at 5, 10, and 15 years. Univariate analysis failed to demonstrate any prognostic significance for sex, tumor size (T1 versus T2), tumor location (central versus peripheral), and type of resection. CONCLUSIONS: These data confirm an excellent prognosis after complete resection of typical carcinoid tumors, including those with lymph node metastases. Parenchyma-saving resections should be preferred.     

Postoperative pain and fatigue after laparoscopic or conventional colorectal resections. A prospective randomized trial

BACKGROUND: Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue. The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue, and may improve postoperative recovery after colorectal resections. METHODS: Sixty patients were included into a prospective randomized trial to determine the influence of laparoscopic (n = 30) or conventional (n = 30) resection of colorectal tumors on postoperative pain and fatigue. Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia (PCA), visual analog scale for pain while coughing (VASC), and visual analogue scale for fatigue (VASF). Efficacy of pain medication was assessed by visual analogue score at rest (VASR). RESULTS: Preoperative age, sex, stage, and localization of tumors were comparable in both groups. The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group (median, 1.37 mg/kg; 5-95 percentile 0.71-2. 46 mg/kg) than the laparoscopic group (0.78 mg/kg; 0.24-2.38 mg/kg, p < 0.01). Postoperative VASR was comparable between both groups, but VASC was higher from the first to the seventh postoperative day (p < 0.01). Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day (p < 0. 05). CONCLUSIONS: This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection. Patients also experience less fatigue after minimal invasive surgery. Because of these differences, the duration of recovery is shortened, and the postoperative quality of life is improved after laparoscopic colorectal resections.     

Cervicothoracic tumors: results of resection by the "hemi-clamshell" approach

OBJECTIVES: Our goal was to describe the "hemi-clamshell" approach for the resection of primary and metastatic tumors of the cervicothoracic junction, evaluate its morbidity and mortality, and present survival data on a series of 42 patients who underwent resection with the use of this technique. METHODS: We conducted a retrospective review of the records of all patients of a single surgeon undergoing resection of tumors of the cervicothoracic junction. Data collected includes tumor type and involvement, type of resection, complications, and survival. RESULTS: Forty-two patients underwent resection of various primary (n = 28) and metastatic (n = 14) tumors of the cervicothoracic junction over 6.5 years by means of the hemi-clamshell approach. En bloc resection of the tumor and invaded structures was successful in all but two patients (5%), who required an additional posterolateral thoracotomy to facilitate removal of tumor invading the posterior chest wall. Invaded structures that were resected included lung (n = 22), vertebral body (n = 7), chest wall (n = 8), central veins (n = 10), thyroid (n = 3), carotid artery (n = 1), and cervical esophagus (n = 1). Four major complications occurred in three patients, and nine minor complications occurred in eight patients. There were no deaths. The overall 5-year actuarial survival was 67.4%. CONCLUSIONS: Tumors of the cervicothoracic junction are represented by a variety of histologic types and can be both primary and metastatic. The hemi-clamshell approach is a successful technique for the exposure and resection of these tumors. This approach has significant advantages over other previously reported techniques. The complication rate is low and the mortality rate is zero in this series, the largest yet reported. Long-term survival is acceptable if complete resection can be performed.     

Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience

PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.     

Type-oriented intraoperative and adjuvant chemotherapy and survival after curative resection of advanced gastric cancer

Recent observations and our experience that histologic types of gastric cancer related significantly to patterns of recurrence prompted us to develop intraoperative and postoperative chemotherapy based on the preoperatively diagnosed histologic types of cancer and to evaluate its effectiveness by a prospective randomized trial. This chemotherapy regimen consisted of the intraoperative administration of mitomycin C (MMC) and postoperative administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT) (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were randomly assigned to one of three treatment groups: no intraoperative chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.     

Extended operations after induction therapy for stage IIIb (T4) non-small cell lung cancer

Twenty-three patients with stage IIIb (T4) non-small cell lung cancer received induction chemotherapy (median, 2 cycles) with (n = 12) or without (n = 11) radiation (median, 45 Gy) before operation. Nine tumors involved the carina (n = 8) or lateral tracheal wall (n = 1), 11 were located centrally and invaded the proximal pulmonary artery (n = 6), veins (n = 3), or both (n = 2), three were apical tumors involving T4 structures, and six were associated with histologically diseased mediastinal nodes. Five complete and 18 partial responses were observed after induction treatment. Resection of all residual tumor at the primary site and involved vestiges was possible in 21 patients (91%); in two apical tumors, tumor was left behind. Nine right tracheal sleeve and 11 intrapericardial pneumonectomies and three resections of apical tumors were performed; 11 patients (48%) had radical mediastinal lymph node dissection. Complete sterilization of the primary tumor was observed in 3 patients (13%). Mean operating time was 209.3 +/- 86.8 minutes, and mean blood loss was 896.9 +/- 1031 mL. Major postoperative complications occurred in 6 patients (26%), including hemothorax requiring drainage (n = 1) or reoperation (n = 1), acute distress syndrome (n = 2), and bronchopleural fistula (n = 2), and their incidence was significantly higher (p = 0.0003) among patients receiving induction chemoradiation than among those receiving chemotherapy alone (42 versus 9%). Early (< 1 month) postoperative mortality was 8.6% (n = 2). With a median follow-up of 25 months (range, 12 to more than 39 months), the projected 3-year overall survival was 54%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primitive cerebral neuroectodermal tumors excluding medulloblastomas: a retrospective study of 30 cases

We present a retrospective study of 30 cases of primitive cerebral neuroectodermal tumors (PNET), excluding medulloblastomas, referred to us postoperatively for additional therapy to evaluate prognostic factors and treatment efficiency. The histologic types were: pinealoblastomas (n = 7); ependymoblastomas (n = 2); medulloepitheliomas (n = 4), and other PNET (n = 17). The tumor was located in the supratentorial area in 24 patients and in the posterior fossa in 6 patients. Among the supratentorial tumors, 8 were metastatic. Maximal surgical resection was performed. Sixteen of 30 patients had no measurable disease after surgery and were considered as standard-risk (SR) cases, and 14 with a local residue or metastasis as high-risk (HR) cases. The objective of postsurgical treatment was to avoid radiotherapy in children below 4 years of age. It consisted of radiotherapy alone in 6 patients, chemotherapy alone in 17, and radiotherapy with chemotherapy in 7. Furthermore, high-dose chemotherapy (busulfan, thiotepa) and autologous bone marrow transplantation, performed in 6 patients, yielded a response rate of 3/6. Event-free survival (EFS) of SR patients was 37% at 3 years (95% confidence interval (CI) 14-60%) and overall survival 44% (95% CI 26-62%). Only 1 of the HR patients achieved a complete remission and all of them died early. The critical prognostic factors appear to be the completeness of initial surgical resection and absence of metastasis. These tumors have a poor prognosis. Novel strategies (high-dose chemotherapy) are needed to improve their outcome because the children concerned are very young and the effects of radiotherapy are particularly deleterious when tumors are situated in the supratentorial area.     

Unraveling the mysteries of environmental medicine

BACKGROUND: In an outbred pig model of total bowel transplantation, we previously showed that simultaneous donor-specific bone marrow infusion (DSBMI), rather than promoting engraftment, sensitizes recipients and causes rejection; it also aggravates the risk of generalized graft-versus-host disease (GVHD) and infection, and tends to reduce recipient and graft survival. Small and large animal models of bone marrow-induced transplant tolerance suggest that some form of recipient preconditioning (RPC) may facilitate engraftment of co-transplanted bone marrow cells and fully expose their tolerogenic potential. METHODS: In a preclinical model, we prospectively studied the effect of RPC on simultaneous DSBMI and total (i.e., small and large) bowel transplantation. RPC consisted of whole body irradiation with 400 R (day 0); some recipients additionally received horse anti-pig antithymocyte globulin (days -2, -1, and 0). We studied six groups of outbred pigs, all of which underwent at least a total bowel transplant: group 1, nonimmunosuppressed control pigs (n=5); group 2, nonimmunosuppressed DSBMI pigs (n=13); group 3, tacrolimus pigs (n=7); group 4, DSBMI+tacrolimus pigs (n=15); group 5, RPC+nonimmunosuppressed DSBMI pigs (n=11); and group 6, RPC+DSBMI+tacrolimus pigs (n=14). RESULTS: RPC did not prolong overall survival at 7, 14, 21, and 28 days after transplant. Survival rates were 100%, 100%, 86%, and 71% in group 3; 71%, 43%, 29%, and 29% in group 6; 55%, 9%, 0%, and 0% in group 5; and 60%, 0%, 0%, and 0% in Group 1. Moreover, RPC (groups 5 and 6) increased the incidence of death from rejection, GVHD, and infection when compared with group 3. Survival was significantly higher for RPC+DSBMI+tacrolimus pigs (group 6), compared with RPC+nonimmunosuppressed DSBMI pigs (group 5). Survival greater than 28 days was noted only in pigs that received tacrolimus after transplant: 71% in group 3 versus 29% in group 6. With both RPC and DSBMI (groups 5 and 6), rejection, GVHD, and infection were not mutually exclusive events. In groups 5 and 6, at autopsy, the incidence of rejection and GVHD was 17%; rejection and infection, 17%; and GVHD and infection, 45%. A combination of all three immunologic events was noted in 14%. CONCLUSIONS: RPC, combined with DSBMI, and with or without posttransplant immunosuppression, does not prolong survival after total bowel transplantation. Rather, it increases the incidence of death from rejection, GVHD, infection, or a combination of these three immunologic events. According to this preclinical study, RPC and unmodified DSBMI do not improve patient and graft outcome after total bowel transplantation and need to be refined before being applied clinically.     

Efficacy of granisetron in the prevention of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation

We conducted this study to compare granisetron, 5-HT3 antagonist, with conventional antiemetics in the prophylaxis of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation in 41 patients. The conditioning chemotherapy regimen included either cytosine arabinoside 2 g/m2 x 4 and cyclophosphamide 60 mg/kg x 2 (CA, CY), or busulfan 4 mg/kg x 4 and cyclophosphamide 60 mg/kg x 2 (BU, CY). In CA and CY regimen, the clinical effective rate with granisetron against emesis was 94.1% on the 1st day, compared with 7.6% in the control group. On day 2 and 3, the effective rate with granisetron was 58.8% and 23.5%, respectively, compared with 0% in the control group. In the BU and CY regimen, control of emesis with granisetron on day 5 and 6 was 66.7%, against 20.0% in the control group. Based on these data, we concluded granisetron is superior to conventional antiemetics in the prophylaxis of emesis induced by conditioning for allogeneic bone marrow transplantation.     

Effects of carbon dioxide pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy on body weight and tumor growth

BACKGROUND: The oncologic consequences of intraperitoneal carbon dioxide (CO2) insufflation during the laparoscopic resection of cancer are under debate. The effect of other insufflating gases or gasless laparoscopy on cancer requires study. OBJECTIVE: To study body weight and tumor growth in rats after CO2 pneumoperitoneum, air pneumoperitoneum, and gasless laparoscopy. METHODS: On day 1, an 8-mg bolus of ROS-1 tumor was placed under the renal capsule of both kidneys in rats. In experiment A, rats had either CO2 insufflation (n=10) or a gasless laparoscopic bowel resection (n=10) on day 3 and were humanely killed after 7 days. In experiment B, rats had either a laparoscopic bowel resection with CO2 insufflation (n=11) or insufflation with air (n=11) on day 3 and were killed after 7 days. In both experiments, postoperative weight loss and tumor growth were measured, and the differences were tested with an analysis of covariance. RESULTS: Renal subcapsular tumor growth in the group having gasless laparoscopy was less than that in the group having CO2 pneumoperitoneum (P=.04). Postoperative weight loss in these groups showed no differences (P=.55). No differences in tumor growth or weight loss were found between rats having insufflation with CO2 and those having insufflation with air (P=.61 and P=.68, respectively). CONCLUSIONS: The restoration of body weight after a laparoscopic surgical procedure was similar with CO2, air, or gasless laparoscopy. Gasless laparoscopy was associated with less renal subcapsular tumor growth than was insufflation with CO2. Therefore, the application of gasless techniques in laparoscopic oncologic surgical treatment demands further study.     

Cryosurgical ablation of hepatic tumors

BACKGROUND: Cryosurgical ablation of hepatic tumors relies on nonspecific tissue necrosis due to freezing as well as microvascular thrombosis. Patients with selected primary and metastatic hepatic malignancies who are not candidates for surgical resection are afforded potentially curative benefit using this technique. METHODS: Forty patients underwent cryosurgery for hepatic malignancy related to colorectal metastasis (n = 27), hepatocellular carcinoma (n = 8), metastatic breast (n = 2), metastatic neuroendocrine (n = 2), and metastatic ovarian carcinoma (n = 1). Intraoperative ultrasound (IOUS) was used in all patients to help locate the tumor and guide the cryosurgical trocar to the lesions. RESULTS: Indications for cryosurgical ablation included bilobar and centrally located disease, poor medical risk, insufficient hepatic reserve, and involved margin after wedge resection. Major complications included hepatic parenchyma cracking requiring transfusion in 5 patients, 1 postoperative biliary stenosis, and 1 inferior vena cava injury. There were 3 postoperative deaths from non-hepatic-related events. Based on Kaplan-Meier analysis the estimated overall survival for patients with hepatocellular carcinoma (60% at 18 months) was compared with patients with colorectal metastases (30% at 18 months). Nine patients (23%) are currently free of disease with an average follow-up of 17.7 months. The pattern of failure was identified at the site of cryosurgical ablation in 2 of 88 lesions. CONCLUSIONS: Cryosurgical ablation of selected hepatic malignancies is a safe and viable treatment for patients not amenable to surgical resection.     

Nitric oxide-induced blood-brain barrier dysfunction is not mediated by inhibition of mitochondrial respiratory chain activity and/or energy depletion

The six reported cases were separated into 2 groups: 1) the tumors of sporadic type, carcinoids (n = 2) and neuro-endocrine carcinomas (n = 2); 2) the gastrin-promoted tumors (n = 2). The purpose of this retrospective study was to review for each group of tumors, the clinicopathologic characteristics, prognosis factors and optimal management. In the first group, patients with a small and well differentiated tumor revealed by digestive bleeding, were treated by wedge excision and are alive and well 24 and 22 years later; the patients with large, invasive and poorly differentiated tumors were treated by subtotal (n = 1) and total (n = 1) gastrectomy, and died 1 year and 3 years later with metastases. In the second group, one patient with a small asymptomatic carcinoid tumor revealing chronic atrophic gastritis, was treated by endoscopic resection, without recurrence 3 years later; another patient with asymptomatic multifocal carcinoid tumors (about 100) associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1, was treated by total gastrectomy and is alive and well 7 years later. No patient had carcinoid syndrome. Synaptophysin was the most sensitive marker and secretion of serotonine was detected in 2 tumors. Conclusion: Sporadic carcinoids serotonin and neuro-endocrine carcinomas are life-threatening tumors and need aggressive surgical therapy: their prognosis depends on tumors size, histological differentiation and mostly on tumor extension. In contrast, gastrin-promoted carcinoids do not result in disseminated disease and death, and a rather conservative approach seems appropriate.