Molecular correlates of bcl-2-enhanced growth following androgen-ablation in prostate carcinoma cells in vivo

BACKGROUND/AIMS: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.     

Enhanced glycosylation and sulfation of secretory proteoglycans is coupled to the expression of a basic secretory protein

BACKGROUND: Because the prognosis of patients with hepatocellular carcinoma is not fully understood, particularly regarding therapy, we have evaluated it in a series of patients with a homogeneous diagnostic and therapeutic work-up. METHODS: From 1985 to 1996, 42 variables were recorded prospectively in 178 constructive patients who had a diagnosis of hepatocellular carcinoma. Treatment consisted of liver transplantation ( n = 22), partial hepatectomy (n = 11), arterial, chemoembolization ( n = 52), systemic or regional chemotherapy (n = 51), and other therapies (n = 5); 37 patients received no specific therapy. Statistical analysis was performed according to a Cox model. RESULTS: There were no differences between the survival of patients receiving chemotherapy, other therapies, or no treatment (control group n = 93). survival rates a 1,3, and 5 years were 81%, 74%, and 74% for liver transplantation, 72%, 58%, and 58% for hepatectomy, 55%, 26%, and 13% for chemoembolization, and 13%, 3%, and 0% for the control group. Cirrhosis, systemic syndrome, bilobar involvement, Child's stage C disease, and treatment were independent predictors of survival. CONCLUSIONS: This series shows that certain easily accessible parameters may help establish individual prognosis and stratify patients in clinical trials and indicates that chemoembolization, partial resection, and liver transplantation can prolong life expectancy of patients with hepatocellular carcinoma.     

Prospective randomized trial of chemoembolization versus intra-arterial injection of 131I-labeled-iodized oil in the treatment of hepatocellular carcinoma

Intra-arterial injection of radioactive Lipiodol has shown promising results in patients with hepatocellular carcinoma (HCC) and portal obstruction. The aim of this prospective, randomized trial was to compare the efficacy and tolerance of 131I-labeled Lipiodol and chemoembolization for the treatment of patients with HCC. From September 1990 to September 1993, 142 patients (135 men, 7 women; age: 65 +/- 6.6 years) were randomly assigned to treatment groups and given either intra-arterial injections of 131I-labeled Lipiodol (60 mCi; 2.2 GBq) (n = 73) or chemoembolization (70 mg cisplatin) (n = 69). Subsequent injections were given at 2, 5, 8, 12, and 18 months. Tumor response was assessed on the basis of tumor size and serum alpha-fetoprotein levels. Patient tolerance was assessed clinically and angiographically. Survival rate was the main end-point. A total of 129 patients (65 in the 131I-labeled Lipiodol group and 64 in the chemoembolization group) were available for analysis; 13 were excluded, mainly because of portal vein thrombosis. The two groups were comparable. Actuarial survival curves were not significantly different between the two groups. Overall survival rates at 6 months, 1, 2, 3, and 4 years were 69%, 38%, 22%, 14%, and 10%, and 66%, 42%, 22%, 3%, and 0% in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Reduction in tumor size was similar for the two groups, with complete response in 1 and 0 patients and partial response in 15 and 16 patients in the 131I-labeled Lipiodol and chemoembolization groups, respectively. Tolerance was significantly better in the 131I-labeled Lipiodol group both clinically (3 severe side effects vs. 29 in the chemoembolization group; P < .001) and angiographically (1 arterial thrombosis vs. 10 in the chemoembolization group; P < .01). In terms of patient survival and tumor response, radioactive 131I-labeled Lipiodol and chemoembolization were equally effective in the treatment of HCC, but tolerance to 131I-labeled Lipiodol was significantly better.     

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.     

The liver transplant program of the Hospital General Universitario Gregorio Mara?ón: an analysis of the first 100 patients

During a 3-year period between 1990 and 1993, 100 patients received orthotopic liver transplantation at the "Gregorio Mara?ón" University General Hospital. The mean age of the patients was relatively high (46.9 +/- 10 years), with an important number of cirrhotic patients (91%). The rate of primary liver failure was relatively low (4.5% of transplantations) although 12 cases with more than 55 years were included in the present series. Eleven retransplantations were performed, 8 for early failure of the graft and 3 for chronic failure. Postoperative complications of the graft were vascular in 9 cases, biliary in 17 cases, and acute rejection (cellular) in 70 patients, although only 50 of these patients required treatment with steroid boluses. Infections were diagnosed in 60 cases with 80% of major infections, 6 of them caused by Aspergillus fumigatus that were lethal in all the cases. Postoperative survival was 82%, 72%, 69% and 69% at 1 month, 6 months, 1 year and 2 years respectively.     

Rectus sheath haematoma in elderly patients: a diagnostic challenge

BACKGROUND: Transarterial oily chemoembolization (TOCE) is frequently employed as a non-operative treatment for hepatocellular carcinoma (HCC). Serious complications of TOCE are well known but ruptured HCC as a fatal complication of TOCE has not been reported previously. METHODS: A retrospective study was performed on all patients who received TOCE for treatment of HCC from January 1989 to October 1996; the complication of ruptured HCC within 2 weeks from the procedure was recorded. RESULTS: During the study period, 391 patients received a total of 1443 sessions of TOCE (mean 3.7 sessions per patient) for the treatment of HCC, with an overall median survival of 10.4 months. Six patients developed ruptured tumour within 2 weeks after TOCE, resulting in an overall incidence of 1.5 per cent per patient or 0.4 per cent per procedure. All except one patient died 1-25 days after tumour rupture. Factors common to these six patients included: (1) male sex; (2) large tumour size (range 8-17 cm in diameter); (3) tumour located in the right lobe of the liver; (4) tumour ruptured after the first session of TOCE; and (5) TOCE performed as primary treatment without previous hepatic resection. CONCLUSION: Ruptured HCC is a serious complication of TOCE although the incidence is low. It occurred predominantly in men after the first session of TOCE for a large irresectable tumour of the right lobe.     

Cardiac transplantation in New Zealand: eight years experience

Between December 1987 and December 1995, 62 patients underwent orthotopic cardiac transplantation at Green Lane Hospital. Their cardiac dysfunction resulted from dilated cardiomyopathy (32), coronary artery disease (21), rheumatic heart disease (7), congenitally corrected transposition of the great arteries (1) and hypertrophic cardiomyopathy (1). Before transplantation all patients were in New York Heart Association (NYHA) functional class III or IV. Eight patients (13%) died in the perioperative period and a further seven (11%) died 1 to 4 years after transplantation. Actuarial 1 and 3 year survival was 87% and 80% respectively. Forty-five of forty-seven surviving patients were in NYHA functional class I at the time of analysis. The results confirm that cardiac transplantation has a limited but valuable role in the treatment of end stage myocardial dysfunction.     

Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power

Tumoral recurrence rate and survival of patients with hepatocellular carcinoma (HCC) treated by orthotopic liver transplantation (OLT) depend on tumor stage. Thereby, from the beginning of our program, we selected only patients with solitary tumors < or = 5 cm without vascular invasion, thus avoiding the use of the tumor-node-metastasis (TNM) staging system as a selection tool. The present study reports the results obtained in 58 consecutive patients (52 +/- 8 years, 47 males) with HCC (7 incidentals) transplanted between 1989 and 1995. Transplantation was indicated because of tumor diagnosis in 40 cases and advanced liver failure in 18. Mean tumor size at staging was 28.2 +/- 12.1 mm. No adjuvant treatment was applied during the waiting period (58.9 +/- 45.1 days). The pathological tumor-node-metastasis (pTNM) classification allocated 15 patients to stage I, 19 to stage II, 11 to stage IIIA, and 13 to stage IVA showing preoperative understaging in 43% of the cases with known tumor. After a median follow up of 31 months, only two patients have shown tumor recurrence and fifteen have died, the 1-, 3-, and 5-year survival being 84%, 74%, and 74%. All HCV+ patients remain infected and 94% showed significant liver disease (6 cirrhosis). Six patients have had a second transplant. In conclusion, the application of restrictive criteria not following the TNM staging system prompts excellent results for liver transplantation in patients with HCC, both in terms of survival and disease recurrence, even without applying adjuvant treatment; however, the survival data should be tempered by the appearance of complications that may worsen the long-term prognosis.     

Development of an MRI-compatible needle insertion manipulator for stereotactic neurosurgery

At the University of California, San Francisco, 17 patients who met the following criteria-hepatic tumor unresectable because of location or inadequate liver reserve, no metastases, HBsAg negative, no tumor larger than 5 cm in diameter, and no more than three tumors--were enrolled prospectively in a protocol employing preoperative chemoembolization to assess whether orthotopic liver transplantation (OLT) could cure a majority of highly selected patients with hepatocellular carcinoma (HCC). Thirteen patients had biopsy-proven HCC, 2 had the fibrolamellar variant, and 2 had radiological findings of HCC but no biopsy confirmation. Fourteen had underlying liver disease. All arteriographically apparent lesions were chemoembolized using a mixture including Gelfoam powder, doxorubicin, mitomycin-c, and cisplatin. Eight patients with poor hepatic reserve were chemoembolized when a donor organ became available, whereas 9 patients were chemoembolized and then placed on the waiting list. The only complication of chemoembolization was a gangrenous gallbladder in 1 patient. Thirteen patients underwent liver transplantation (2 patients without prior histological confirmation of carcinoma had no identifiable tumor at OLT); 3 patients developed metastases between the time of enrollment and donor organ availability and subsequently died; and 1 patient underwent a trisegmentectomy. Ten of the 11 patients with biopsy-proven HCC who underwent transplantation remain free of recurrent cancer at a median of 40 months; 1 patient died at 6 months of lymphoproliferative disease with no cancer found at autopsy. Although the role of chemoembolization is uncertain, these data show that the majority of carefully selected patients with HCC may achieve long-term survival with OLT.     

The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma

Seventy-four patients who had a Ewing sarcoma of bone were managed with preoperative and postoperative chemotherapy and operative resection, with or without postoperative irradiation. The primary objectives of the study were to determine the histological response to preoperative chemotherapy in terms of the percentage of tumor necrosis and to assess the relationship between the histological response and the oncological outcome. The minimum duration of follow-up of the surviving patients who were continuously free of disease was five years. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded semiquantitatively. Grade I indicated necrosis of 50 per cent of the tumor or less; grade II, necrosis of more than 50 per cent but less than 90 per cent; grade III, necrosis of 90 to 99 per cent; and grade IV, necrosis of 100 per cent of the tumor. Of the seventy-four tumors, forty-four (59 per cent) were exquisitely sensitive to chemotherapy and had complete (grade-IV) or nearly complete (grade-III) necrosis. In contrast, fourteen tumors (19 per cent) had little or no response to chemotherapy (grade I) and sixteen (22 per cent) had a moderate degree of necrosis (grade II). The histological response to preoperative chemotherapy (p = 0.0001), followed by the size of the tumor (p = 0.001), were the most important predictors of event-free survival. At five years, the rate of event-free survival was zero of fourteen patients who had had a grade-I response, six of sixteen who had had a grade-II response, and thirty-seven (84 per cent) of forty-four who had had a grade-III or IV response. The risk of local recurrence was most strongly associated with the operative margins; there were only four local recurrences (6 per cent) after sixty-seven resections with negative margins. Local recurrence may also have been influenced by the histological response and the use of local radiation. There were no local recurrences after operative treatment of six tumors that had been associated with pathological fracture. The histological response to preoperative chemotherapy and the size of the primary tumor are the most important clinical predictors of the outcome of operative treatment of non-metastatic Ewing sarcoma. These indicators should be used to identify patients who are at high risk for metastasis as such patients may be candidates for more intensive or novel therapies.     

Temporomandibular joint derangement after air bag deployment: report of two cases

BACKGROUND: The outcome of 60 renal transplantations in 53 patients with end-stage renal disease (ESRD) because of lupus nephritis was studied retrospectively and compared with 106 controls matched for age, sex, maximum panel-reactive antibody (PRA) level, and date of transplantation. METHODS: The patients received their transplants over a 260-month period (21.5 years) between October 1971 and August 1993. The population was predominantly women (90%), and the mean age at the time of the transplantation was 33.2 years (range: 21-54 years). Fifty-six transplants (93%) were from cadaveric donors, and 4 (7%) were from living-related donors; 46 patients (86%) had primary allografts, and 7 (14%) received a second allograft. The duration of disease before transplantation was 93.6+/-6.2 months, and the duration of dialysis before transplantation was 48+/-6 months. RESULTS: No patient had clinically active systemic lupus erythematosus (SLE) at the time of transplantation. The 1-year graft and patient survival rates were 83% and 98%, and the 5-year graft and patient survival rates were 69% and 96%. Actuarial graft and patient survival rates in SLE patients were not significantly different from those of the matched control group. Chronic rejection was the major risk factor for graft loss. Lupus nephritis recurred in the graft of one patient 3 months after transplantation, and there were extrarenal manifestations of SLE in four others. CONCLUSIONS: The present study confirms that patients with SLE can receive transplants with excellent graft and patient survival rates and a low rate of clinical recurrent lupus nephritis.     

In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model

The purpose of this study is to assess the feasibility, clinical tolerance, local control, and survival rates using a combined-modality treatment program of intraoperative radiation, chemotherapy, and external beam radiation for the management of patients with pancreatic cancer. One hundred eighty patients with biopsy-proven adenocarcinoma of the pancreas have been treated by a single surgical practice between 1979 and 1992. Of these, 105 had locally advanced but unresectable primary tumors (stages 2 and 3). All patients were treated with a program of multimodality therapy, including surgery, chemotherapy, and radiation therapy. Three groups were identified. Group I (33 patients) received intraoperative radiation therapy (IORT) as part of their treatment. Group II (43 patients) received intraoperative radiation in the form of iodine-125 (I-125) implantation. Group III (29 patients) received no intraoperative radiation. All three groups were comparably similar with respect to age at presentation, amount of preoperative weight loss, preoperative symptoms, and tumor location. Overall perioperative mortality was 4.8 per cent (five patients), with no difference between groups noted. Perioperative complications occurred in 32 (30.4%) of the 105 patients. Complications occurred in only 18.1 per cent of patients in Group I (IORT), compared with 39.5 per cent of Group II (I-125) patients (P < 0.01). Group III patients (no intraoperative radiation) experienced complications in 31.0 per cent of cases (P = 0.09 vs Group I). Actuarial survival was 18 months for Group I (IORT) versus 15 months for Group II (I-125). One- and 2-year actuarial survival rates were 60 and 17 per cent for patients in Group I (IORT) and 56 and 19 per cent for Group II (I-125). Actuarial local control rates for patients receiving IORT (Group I) was 70 per cent at 2 years. Patients with pancreatic cancer historically have poor survival and local control rates despite aggressive chemotherapy and radiation. The addition of intraoperative radiation to the combined modality management of pancreatic cancer offers markedly improved survival rates and local control with minimal morbidity for patients with unresectable disease. Intraoperative radiation in the form of IORT can be delivered with a significantly fewer complications than I-125 seed implantation.     

Evaluation of intra-arterial infusion chemotherapy for advanced gastric cancer

We evaluated the therapeutic efficacy of intraarterial infusion chemotherapy in advanced gastric cancer, its side effect and patient prognosis, in comparison with systemic infusion. Of 125 cases of advanced gastric cancer, 41 cases received intraarterial chemotherapy (A group) and the rest were given systemic infusion (S group). Protocols of chemotherapy were 5-FU + MTX in 49 cases, 5-FU + cisplatin in 62, and 5-FU + MMC in 14. Location of the disease was the peritoneum in 69 cases, nodes in 59, liver in 38, and other sites, 33. The response rate of A group was significantly higher than that of S group, at 31% and 13% respectively. Although 41% of cases showed side effects (> or = grade 2), there was no significant difference between the 2 groups. The median survival period and 1-year survival rate were 8.4 months and 35%, respectively, and there was no significant difference between the 2 groups. In cases with liver metastasis, the prognosis of A group was better than that of S group. The results suggest that intra-arterial infusion chemotherapy is an effective treatment for liver metastasis from gastric cancer.     

Free revascularized jejunal loop repair following total pharyngolaryngectomy for carcinoma of the hypopharynx: report of 90 patients

Ninety patients with carcinoma of the hypopharynx underwent pharyngolaryngectomy and reconstruction with a jejunal free autograft. Fifty-five patients had primary surgery and 35 salvage surgery for recurrence after radiotherapy. Following primary surgery 28 patients had postoperative radiotherapy and 27 did not. Complications occurred in 51 per cent of patients, the most common being necrosis of the jejunal graft (19 per cent); 12 per cent developed significant stenosis and 4 per cent died in the perioperative period. Eleven per cent of patients developed a fistula. The total number of complications diminished as the experience of the unit increased. Median follow-up was 4.9 years. Of patients treated with primary surgery, 48 per cent developed primary site recurrence (at 3 years) and 53 per cent neck node recurrence (at 5 years). The tumour-specific 5-year survival rate for all patients was 42 per cent. Following primary surgery 28 per cent survived for 5 years and after salvage surgery the rate was 59 per cent. Positive resection margins and extensive neck disease adversely affected survival (P = 0.02 and P = 0.001 respectively). The free revascularized jejunal graft is a safe and predictable method of repair following total pharyngolaryngectomy.     

Prognosis of hepatocellular carcinoma patients with extrahepatic metastases

BACKGROUND/AIMS: There is no effective treatment for hepatocellular carcinoma (HCC) with extrahepatic metastases. This study investigated the survival and causes of death in HCC patients with extrahepatic metastases. MATERIALS AND METHODS: We retrospectively analyzed 34 HCC patients with extrahepatic metastases who received systemic chemotherapy without other anticancer treatment except prior hepatectomy. We classified causes of death as cancer death and death from other causes, and subclassified cancer deaths into hepatic cause, extrahepatic cause and cachectic cause. Each cause of death was analyzed in the two subgroups comprised of 10 patients with bone metastases alone and 22 patients with metastatic lesions in sites other than bone. RESULTS: Thirty-two of the 34 patients had died at the time of analysis. The median survival time and the 1-year survival rate were 4.6 mo and 20.3%, respectively. Incidence of hepatic cause, extrahepatic cause, cachectic cause and death from other causes were 21 (66%), 7 (22%), 2 (6%) and 2 (6%), respectively. In the subgroup of 10 patients with bone metastases alone, nine (90%) died from hepatic causes, but none died from extrahepatic causes. In the group of 22 patients with metastatic lesions in sites other than bone, 7 (32%) patients died from extrahepatic causes. CONCLUSION: The causes of death in HCC patients with extrahepatic metastases depended on metastatic site at the time of diagnosis. The results of this study may be useful in the design and analysis of future clinical trials of the HCC therapy.     

Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter

BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.     

Androgen and oestrogen receptors in hepatocellular carcinoma and surrounding liver parenchyma: impact on intrahepatic recurrence after hepatic resection

Seventy-eight patients in whom androgen or oestrogen receptors, or both, were assayed in hepatocellular carcinoma (HCC) and the surrounding liver were discharged from hospital after curative resection of the tumour. Intrahepatic recurrence was evaluated retrospectively after 28-128 months follow-up to determine the association with receptor status. Androgen and oestrogen receptors in HCC significantly influenced the intrahepatic recurrence rate. The recurrence-free 5-year survival rate was 55 per cent for patients who had androgen receptor-negative tumours, 24 per cent for oestrogen receptor-negative, 10 per cent for oestrogen receptor-positive and 0 for androgen receptor-positive (P = 0.0322). Recurrence-free 5-year survival in 57 patients who had both receptor assays was 75 per cent for patients who had androgen receptor-negative, oestrogen receptor-negative tumours, 50 per cent for androgen receptor-negative, oestrogen receptor-positive, but 0 for androgen receptor-positive, oestrogen receptor-positive and androgen receptor-positive, oestrogen receptor-negative (P = 0.0104). The presence or absence of androgen or oestrogen receptor in the liver, however, was not associated with intrahepatic recurrence (P = 0.7534). Thus, androgen receptors are strongly associated with intrahepatic recurrence of HCC, while oestrogen receptors are weakly associated. Receptor status in the normal liver was not related to intrahepatic recurrence.     

Long-term results of preoperative radiation therapy alone for stage T3 and T4 rectal cancer

BACKGROUND: There has been a resurgence of interest in the use of preoperative radiation therapy, with or without chemotherapy, for locally advanced rectal cancer. The purpose of this study was to analyse the time course and pattern of failure for 74 patients with clinical stage T3 or T4 (cT3-4) rectal cancer treated with preoperative radiation therapy for whom long-term follow-up was available. METHODS: Seventy-four patients with cT3-4 rectal cancer received a median of 45.0 Gy radiation alone followed by surgery 4-8 weeks later. Median follow-up was 90 months; two-thirds of patients were followed for at least 60 months. RESULTS: Following radiation therapy the pathological stage was 4 per cent pT0, 26 per cent pT1-2 and 70 per cent pT3-4. Thirty-two per cent had involved lymph nodes. The actuarial 5-year rates of local control, freedom from distant metastasis and disease-specific survival were 80, 64 and 73 per cent respectively. The corresponding 10-year rates were 73, 51 and 50 per cent. Median times to detection of local and distant recurrence were 34 and 24 months respectively. Eighty per cent of local recurrences were detected within 54 months; 80 per cent of distant recurrences were detected within 57 months. CONCLUSION: In this analysis, the time to detection of both local and distant recurrences following preoperative radiation therapy for advanced rectal cancer was surprisingly long. Almost 5 years (57 months) of follow-up were required to detect 80 per cent of all failures. The 5-year local control rate of 80 per cent compares favourably with that achieved by more aggressive chemoradiation regimens for fixed cancers; however, the high distant failure rate with radiation therapy alone suggests that adjuvant systemic therapy should be investigated.     

Primary nonampullary/periampullary adenocarcinoma of the duodenum

Primary duodenal adenocarcinoma not involving the ampullary region is rare. Our aim was to review the outcome of these patients and determine the factors that affect survival. We performed a retrospective review of all patients with primary, nonampullary duodenal adenocarcinoma at the Cleveland Clinic Foundation from January 1986 through December 1996. Twenty-six patients with primary, nonampullary duodenal malignancies were identified. There were 16 adenocarcinomas, 3 gastrinomas, 3 stromal tumors, 3 leiomyosarcomas, and 1 carcinoid tumor. Patients with adenocarcinoma had symptoms present an average of 6.1 months. Tumors were identified by upper gastrointestinal contrast study and esophagogastroduodenoscopy in 90 per cent and 87 per cent of patients, respectively. Twelve of 13 (93%) cancers found in the third or fourth portion of the duodenum were adenocarcinomas. Seven of the 16 adenocarcinomas were resectable on exploration. Those that were contained within the serosa have not recurred (mean, 6 years); one of the two patients with locally invasive adenocarcinoma remains disease free. The average survival for patients with unresectable disease was 6.7 months. The 5-year survival rates were: all adenocarcinoma, 38 per cent; resectable, 86 per cent; and unresectable, 0 per cent. All patients presenting with weight loss or obstructive symptoms died of disease; those with melena survived long term. Patients with tumors other than adenocarcinoma had a 90 per cent 5-year survival. We conclude that patients typically present with a long history of symptoms. Distal duodenal malignancies are most frequently adenocarcinomas. Upper gastrointestinal contrast study or endoscopy is often diagnostic. Patients with weight loss and/or obstructive symptoms had invasive disease and a morbid prognosis. Aggressive surgery is warranted, and most with resectable disease (86%) had long-term survival.     

Pre-operative chemoembolization of hepatocellular carcinoma in cirrhotic patients

BACKGROUND/AIMS: The aim of the study was to evaluate clinical and pathological effects of transcatheter arterial chemoembolization (TACE) before surgical resection for hepatocellular carcinoma (HCC) in cirrhosis (55 patients); results were compared with a group of 45 patients undergoing surgical resection without TACE. METHODOLOGY: From March 1989 to December 1997, 55 cirrhotic patients, affected by surgically resectable HCC not larger than 5 cm with unifocal or bifocal tumor lesions, underwent TACE pre-operatively. RESULTS: Massive necrosis was observed in 26%, necrosis > 50% in 38% of lesions. Neoplastic cells were found in 47% of cases within the capsule or in the pericapsular tissue. Satellite nodules showed a low rate of necrosis. Mortality and morbidity in the pre-operative TACE group were 1.8% and 29%, respectively, and 4.4% and 33%, respectively, in the control group. One-, 3- and 5-year patient survival rates were 87%, 70% and 39%, respectively, versus 79%, 38% and 19%, respectively (p<0.02), in the control group. Disease-free survival was 40% and 28% at 3 years and 5 years with pre-operative TACE versus 20% and 11% (p<0.05). CONCLUSIONS: Pre-operative TACE can be performed with low morbidity. TACE can necrotize the main lesion and temporarily arrest portal diffusion of neoplastic cells by acting on microvascular infiltration. No evident effect on satellites and pericapsular neoplastic foci was observed. The long-term patients and disease-free survival rates were improved upon.