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Biomedical subjects

P Lasser

Publications and source records attributed to P Lasser.

At least 91 records · Page 5Linked to original sources

Preoperative portal vein embolization for extension of hepatectomy indications.

To render hepatectomy feasible in patients with an initially deficient volume of the future remnant liver (FRL), we redistributed portal blood flow rich in hepatotrophic substances toward the FRL. Redistribution was achieved with preoperative portal vein embolization (POPE) feeding the future resected liver. POPE was performed in 31 patients, under fluoroscopic guidance, via a percutaneous access. POPE was well tolerated and surgery was practicable in 24 patients without severe postoperative liver failure. Seven operations were cancelled, but only one due to insufficient hypertrophy of the FRL. FRL volume values were 90 to 560 mL (mean 260 mL) before POPE and 160-783 mL (mean 443 mL) after POPE, which represents a median increase of 79% +/- 50%. Hypertrophy of the FRL was 90% +/- 52% after 30 days with cyanoacrylate, 53% +/- 6% after 43 days with Gelfoam, and 44% +/- 30% after 35 days with coils. Slight shrinkage was obtained in the volume of the embolized liver, for which resection was planned. Overall survival was 2-62 months (mean 26 months), disease-free survival was 0-60 months (mean 19 months), and 7 patients are disease-free and alive 14 to 60 months (mean 43 months) after surgery. Although exclusively applicable in a limited subset of patients, POPE widens the possibilities of curative hepatectomies, because it induces sound hypertrophy of unembolized liver segments. Cyanoacrylate seems to ensure better and faster hypertrophy.

Adolescent↗

Dynamic contrast-enhanced subtraction versus T2-weighted spin-echo MR imaging in the follow-up of colorectal neoplasm: a prospective study of 41 patients.

PURPOSE: To compare dynamic contrast-enhanced subtraction (DCES) and T2-weighted spin-echo (SE) magnetic resonance (MR) imaging in the differentiation of fibrosis from recurrence during the follow-up of treated colorectal neoplasms. MATERIALS AND METHODS: Forty-one patients with 39 malignant and 16 benign lesions confirmed by means of surgery (n = 23), biopsy (n = 24), or 12-month follow-up examination (n = 8) underwent DCES MR imaging and T2-weighted SE MR imaging. Enhancement of an abnormal pelvic structure within the first 90 seconds on DCES images or high signal intensity on T2-weighted SE images was considered indicative of malignancy. RESULTS: Sensitivity, specificity, and positive and negative predictive values were, respectively, 97%, 81%, 93%, and 100% for DCES MR imaging and 77%, 56%, 81%, and 56% for T2-weighted MR imaging. The number of correctly classified lesions was significantly higher with DCES imaging compared with T2-weighted imaging (P < or = .006). CONCLUSION: DCES imaging is more accurate than T2-weighted SE imaging for differentiating fibrosis from recurrence during the follow-up of treated colorectal neoplasms.

Colon↗

Surgery for lung metastases from colorectal cancer: analysis of prognostic factors.

PURPOSE: To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer. PATIENTS AND METHODS: A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify significant prognostic factors. RESULTS: Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level. CONCLUSION: Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.

Adenocarcinoma↗

[Major hepatectomy after intra-arterial chemotherapy for initially unresectable liver tumors. Frequency, technical problems, results and indications].

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resecable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This draw-back is circumvented by using techniques: such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major, hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗

[Primary ano-rectal melanoma. Report of 9 cases].

We report nine cases of anorectal melanoma illustrating the histopathological features of these tumors. In all cases, the diagnosis was made at symptomatic stage. Eight patients were treated by surgical procedure which consisted of abdominal perineal resection or local excision. The tumor was either monomorphous, composed of epithelioid or spindle cells, or polymorphous containing both cell types. One case was characterized by small cells resembling plasma cells. Pigmentation was inconstant. Tumor cells were marked by antibodies directed against the S100 protein (9 cases/9), HMB45 (4 cases/7) and vimentin (5 cases/7). As suggested by these cases, the diagnosis of melanoma should be systematically kept in mind in case of an anorectal tumor with unusual histopathological features.

Aged↗

[Krukenberg tumors. Analysis of a series of 28 cases].

We report a retrospective series of 28 patients with Krukenberg tumors treated at the Gustave Roussy Institute from 1973 to 1990. Mean age of these women was 42 years. The patients were classed into two groups: depending on whether the ovarian metastasis (group 1) or the primary cancer (group 2) was discovered first. The primary tumor was identified in 20 cases (18 cases of linitis, 1 tumor of the cecum, 1 tumor of the appendix). The primary tumor remained unknown in 8 cases. Twenty-seven patients underwent radical total hysterectomy or bilateral adnexectomy. Gastrectomy was possible for 11 of the 18 cases of linitis; hemicolectomy and appendectomy were performed for the cecal and appendicular tumors respectively. Diagnosis of a primary tumor of the appendix was made after systematic appendectomy and of two Krukenberg tumors after systematic bilateral adnexectomy. In the first group of patients, both localizations were treated in 6 cases, one in 12 including 4 because gastrectomy was not initially possible and in 8 because the primary tumor was unknown. In the second group, the two localizations were treated in 7 cases, and one in 2 cases because gastrectomy was not possible. Surgery was not performed in one patient due to diffuse carcinosis. Bilateral ovarian metastases were seen in 26 out of the 28 cases and 26/28 had chemotherapy without any appreciable effect. Bone metastasis predominated (9 cases), followed by pleuropulmonary (5 cases) and liver (3 cases) metastasis. Overall median survival was 20 months; 14 months in the first group and 29 months in the second. Appendectomy and exploration of the colon and the stomach were performed in all cases in which the Krukenberg tumor was discovered intraoperatively. An endosonographic exploration of the stomach is recommended if the primary tumor is not localized. Bilateral adnexectomy should always be performed in patients with linitis whatever the age. Surgical treatment of the two localizations is not always sufficient for cure.

Adult↗

[Treatment of metastatic malignant insulinomas. 2 cases].

Malignant insulinomas are slow growing tumours for which the prognosis is worsened by metastatic disease and sequellae of excess hormone secretion. Management of unresectable tumours includes intravenous chemotherapy and local treatments such as palliative surgery and transcatheter arterial embolization of liver metastases. Long-term survival can also be improved by inhibition of secretory products of the tumour with either octreotide, a somatostatin analogue, or diazoxide. We report two cases of malignant insulinomas with liver metastases for which objective responses were obtained with combination of local treatment and intravenous chemotherapy.

Aged↗

Intermittent vascular exclusion of the liver (without vena cava clamping) during major hepatectomy.

Intermittent vascular exclusion of the liver (IVEL) combines clamping of the hepatic pedicle with clamping of the main hepatic veins without interruption of caval flow. In this retrospective study, eight cases of total IVEL and eight of partial IVEL were analysed (involving only the middle and left hepatic veins) during major hepatectomy for malignant tumours. Liver parenchyma was pathological in nine cases. IVEL was feasible in 16 of the 18 attempts and was efficient in reducing bleeding during hepatectomy in 15 cases. Mean duration of IVEL was 60.2 (range 37-140) min, mean blood loss was 1230 (range 300-2800) ml and there were no postoperative complications related to the procedure. The major advantages of this technique of liver vascular exclusion (good tolerance and possibility of long duration) merit its inclusion in the list of different clamping techniques available for use during hepatectomy.

Adult↗

Prognostic factors in resectable gastric cancer: results of EORTC study no. 40813 on FAM adjuvant chemotherapy.

BACKGROUND: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. METHODS: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. RESULTS: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p = 0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage and "adequacy" of surgery. The multivariate analysis retained preoperative Hb level, T, N, and "adequacy" of surgery for time of survival; and T, N, "adequacy" of surgery and adjuvant chemotherapy for recurrence time. CONCLUSIONS: Disease stage is the most important prognostic factor. "Adequate" surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Adenocarcinoma↗

Is simultaneous hepatectomy and intestinal anastomosis safe?

BACKGROUND: To assess the safety of simultaneous, "one-stage," hepatectomy and intestinal anastomosis, we retrospectively studied 53 patients who underwent such a procedure, with 76 digestive tract sutures. They represented 80% of all the cases eligible for one-stage procedures among 332 liver resections for malignant tumors. METHODS: The medical records of the patients were retrospectively analyzed to assess details of the surgical procedures, postoperative mortality and morbidity, and postoperative liver function, with special attention being paid to the prothrombin time and the bilirubin value on days 1, 2, 3, and 7. RESULTS: No postoperative mortality occurred and the postoperative morbidity rate was 19%. Only 2 cases of digestive tract anastomotic leakage occurred, which led to reoperation. Hepatectomy-related complications were noted in 5 patients (3 biliary fistulas, 1 hemorrhage and 1 transient liver failure), and pulmonary infections occurred 3 times. The technical difficulties of the one-stage procedure are discussed, focusing on the choice of the incision, the risk of sepsis for the liver if there is an intestinal aperture, possible repercussions of liver impairment and hepatic pedicle clamping on bowel suture healing, and the risk of digestive fistula according to the location of the bowel suture. CONCLUSION: It appears that this one-stage procedure is safe if the bowel is systematically cleaned before the operation, if an appropriate Rio-Branco incision is used, and if the risk of postoperative liver failure is low. It seems preferable to use intermittent hepatic pedicle clamping rather than continuous clamping (when feasible), and to temporarily protect a low rectal anastomosis with a colostomy.

Adult↗

Phase I-II randomized study on prehepatectomy recombinant interleukin-2 immunotherapy in patients with metastatic carcinoma of the colon and rectum.

BACKGROUND: This study, which investigates prehepatectomy immunostimulation with recombinant interleukin-2 (rIL-2), had two goals: to evaluate the tolerance of rIL-2 in association with major hepatectomy, and to verify whether preoperative immunostimulation is effective (neoadjuvant immunotherapy). In animal experiments, the conjunction of shed tumor cells into the circulation during surgery and severe surgery-induced immunodepression can promote the dissemination of the disease. Perioperative immunostimulation by rIL-2 reduces the incidence of metastases in animals. STUDY DESIGN: This prospective phase I-II randomized study included 19 patients with potentially resectable hepatic metastases from adenocarcinomas of the colon and rectum. Two-thirds were randomized to the rIL-2-treated group and one-third to the control group. Preoperative rIL-2 was administered by continuous intravenous infusion over five days and stopped two days before major hepatectomy. The dose of rIL-2 was gradually increased, from 3 x 10(6) IU/m2/day to 12 x 10(6) IU/m2/day. At least three patients were studied at each dose level before increasing the rIL-2 dose. Nineteen patients were eligible for the study (12 in the rIL-2 group and seven in the control group). Toxicity during infusion and intraoperative and postoperative complications were evaluated. Immunological monitoring consisted of repeated determination of lymphocyte counts and phenotypic analysis of lymphocyte subpopulations. Non-major histocompatibility complex-restricted cytotoxicity was assayed against K562 and DAUDI tumor cell lines. RESULTS: Toxicity during rIL-2 infusion was acceptable, similar to that of other phase I studies, and surgery was never delayed. Morbidity and mortality rates after major hepatectomy were not different between the two groups and it appeared that prehepatectomy rIL-2 at a dose of 12 x 10(6) IU/m2/day was well tolerated. During the postoperative course, the mean lymphocyte count was higher in the rIL-2 group (p < 0.05), without qualitative modification of the lymphocyte subsets. Immunological modifications were dose related. High cytotoxicity against K562 and DAUDI cells was constant at the 12 x 10(6) dose level. CONCLUSIONS: Preoperative five-day infusion of rIL-2 before major hepatectomy for colorectal metastases is well tolerated and reverses postoperative immunodepression.

Adenocarcinoma↗

Frequency, technical aspects, results, and indications of major hepatectomy after prolonged intra-arterial hepatic chemotherapy for initially unresectable hepatic tumors.

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility, and results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5) or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resectable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44, and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This drawback is circumvented by using techniques, such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗

Efficacy of combined 5-fluorouracil and cisplatinum in advanced gastric carcinomas. A phase II trial with prognostic factor analysis.

Combined chemotherapy has demonstrated a degree of efficacy in gastric carcinoma. As 5-fluorouracil (5FU) and cisplatinum are two of the most active drugs, we have tested the efficacy of combined 5FU and cisplatinum in a prospective phase II trial. Cycles were administered every 4 weeks and consisted of 5FU 1000 mg/m2/day 5 days continuous intravenous (i.v.) infusion and cisplatinum 100 mg/m2 on day 2. Cycles were repeated according to tolerance and efficacy. 87 patients entered the study, 57 with metastatic or recurrent tumour (M) and 30 with locally advanced gastric cancer (LAGC). The response rate for the 83 evaluable patients was 43% [95% confidence interval (CI) 30-56%]. There were four complete responses (5%), 32 partial responses (39%), 34 cases of stable disease and 13 cases of progressive disease. Responses were more frequent in patients with a good performance status (P = 0.02), with their primary located in the cardia (P = 0.003), with a non-linitis plastica tumour form (P = 0.003) or a tumour containing less than 50% of independent cells (P = 0.016). Median survival was 9 months for the total population. It was better in patients with a good performance status (P = 0.01), and those who did not have linitis plastica (P = 0.005). Toxicity was acceptable, although grade 3-4 neutropenia was reported in 22% of the cycles, mucositis in 14% and 3 patients died of septic complications. The combination of 5FU and cisplatinum is effective in terms of tumour response in advanced gastric cancer and warrants testing with the other active regimens.

Adult↗

Neoadjuvant chemotherapy in locally advanced gastric carcinoma--a phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum.

Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates.

Adult↗

Phase I and pharmacological study of intra-arterial hepatic administration of pirarubicin in patients with advanced hepatic metastases.

Intra-arterial hepatic (i.a.h.) administration of the doxorubicin analogue pirarubicin was evaluated in a phase I trial, based on preclinical studies that showed an advantage of pirarubicin over doxorubicin after locoregional hepatic administration. Pirarubicin was given to 9 patients with metastatic liver disease with intrapatient dose escalation. Of the 58 cycles evaluable for tolerance, no hepatobiliary or vascular toxicity was observed. The dose-limiting toxicity was granulocytopenia: the maximum administered doses ranged from 50 to 120 mg/m2, suggesting variable rates of pirarubicin hepatic extraction between patients. Pharmacokinetic data obtained in 7 patients, in which a direct comparison of intravenous (i.v.) and i.a.h. administration was possible, indicated a median i.v./i.a.h. ratio of 7.4 for the maximal plasma concentration, and a median ratio of 4 for the area under the plasma concentrations versus time curves, suggesting a high pirarubicin hepatic extraction. An unexpectedly high response rate was observed: two complete (colorectal carcinoma) and two partial responses. These data demonstrate that i.a.h. pirarubicin not only produced high locoregional concentrations and reduced systemic exposure, but can also achieve responses in metastatic liver disease of colorectal origin.

Agranulocytosis↗