Abstract: The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naïve patients with metastatic CRC.
Abstract: ABSTRACT: BACKGROUND: Hepatoid adenocarcinoma (HAC) is a peculiar type of extrahepatic adenocarcinoma generally characterized by adenocarcinomatous and hepatocellular carcinoma (HCC)-like foci. Stomach is the most frequent site where hepatoid adenocarcinoma occurs, although it has been described in many other organs. On the other side, liposarcoma is a rare, malignant tumor that develops from fat cells. CASE PRESENTATION: We describe here a case of hepatoid carcinoma in collision with a liposarcoma of the left colon serosa in a 71-year-old man. It presented as an abdominal mass involving several organs, falsely mimicking metastatic colonic adenocarcinoma. Recognition of this entity was evident on microscopic evaluation following surgery. The patient had an objective response following liposomal antracycline chemotherapy, with a 3-year overall survival. CONCLUSION: To our knowledge, this is the first case of a hepatoid tumor colliding with a liposarcoma of the left colon serosa reported to date.
Abstract: BACKGROUND: In gastric cancer, the recurrence rate is high even after curative surgery. A relevant issue is the identification of independent prognostic factors to select high-risk patients; such features can be used as predictive factors for tailored therapies. In this study we have investigated the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for predicting cancer behavior and clinical outcome in gastric cancer patients undergoing potentially curative surgery. METHODS: Epidermal growth factor receptor determination using a commercially available immunohistochemistry (IHC) kit was performed in tissues from 82 gastric cancer patients receiving primary surgical treatment and in 25 normal gastric mucosa specimens from noncancer patients. The EGFR positivity was correlated with disease recurrence and survival in univariate and multivariate analyses. RESULTS: Forty-four percent (36 cases) of gastric cancers were EGFR positive. In 66 curatively treated patients, EGFR expression correlated with disease recurrence and poorer survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, advanced tumor extension (T(3) or T(4)), nodal metastases, and EGFR expression were the only independent covariates. In particular, EGFR expression was shown to be a significant predictor of poor prognosis among gastric cancer patients having the same stage according to the current TNM staging system. CONCLUSIONS: These findings suggest that EGFR expression may be useful in identifying high-risk gastric cancer patients undergoing potentially curative surgery. Multimodal treatments should be considered in the adjuvant treatment of these patients.
Abstract: BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.
Abstract: BACKGROUND AND OBJECTIVES: As a significant number of curatively treated gastric cancer patients will ultimately relapse, there is an urgent need to investigate new prognostic markers for identification of high-risk patients. In this study, we investigated the possible role of molecular markers involved in cell cycle regulation (B1 and D3 cyclins, and p27) and cell protection (metallothionein, MT) in predicting tumor behavior and clinical outcome in gastric cancer patients. METHODS: Analysis of the above indicators was performed by immunohistochemistry on 73 gastric cancer patient samples and 25 normal gastric mucosa specimens. RESULTS: Normal gastric mucosa cells displayed low expressions of B1 and D3 cyclins and MT, and intense p27 staining. Conversely, gastric tumor cells showed higher cyclin D3 and MT, and lower p27 expressions. B1 cyclin expressions were not different between normal and tumor tissue. p27 and MT expressions were altered in almost all cancer samples, and were strongly correlated with tumor progression. Advanced extent of the primary tumor, nodal metastasis, low p27, and high MT expressions were the best combination of variables for prediction of poor clinical outcome. Each marker predicted outcome better than staging based on tumor-node (TNM) system. Survival and recurrence rates decreased as molecular alterations increased. Finally, molecular profile determination correctly predicted the prognosis in patients with same TNM stage. CONCLUSIONS: p27 and MT expressions strongly correlated with clinical outcome allowing to identify an unfavorable group of patients that may benefit from tailored treatments. The role of B1 and D3 cyclins in gastric cancer remains to be elucidated.
Abstract: BACKGROUND: To investigate the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for prediction of cancer behavior and clinical outcomes in colon cancer patients undergoing potentially curative surgery. METHODS: EGFR determination using a commercially available immunohistochemistry kit was performed in tissues from 149 colon cancer patients receiving primary surgical treatment and in 25 normal colon mucosa specimens from noncancer patients. EGFR positivity was correlated in univariate and multivariate analyses with disease recurrence and survival. In addition, p27, p53, and vascular endothelial growth factor expression were assessed by immunohistochemistry in 104 patients and correlated with EGFR tumor expression and clinical outcome. RESULTS: EGFR expression was detected in approximately one third of colon cancer patients (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was correlated with disease recurrence and worse survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, Dukes' staging, p27, and EGFR expression were the only independent covariates. In particular, in Dukes' A and B patients the 5-year survival probability was 96% for EGFR-negative and high p27 expression cases and was 30.7% for EGFR-positive and low p27 expression cases. CONCLUSIONS: EGFR expression was an independent prognostic indicator of disease recurrence and poor survival in colon cancer patients undergoing curative surgery. In the context of novel therapeutic options such as molecularly targeted therapies, these findings suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR-positive colon cancer patients.
Abstract: BACKGROUND: The purpose of this study was to evaluate the feasibility of primary inguinal repair with open tension-free and sutureless technique using a new polypropylene "patch and plug system" (Prolene 3D patch), and the quality of the treatment in terms of reduction of postoperative discomfort. METHODS: Fifty-six consecutive patients, mean age 54.5+/-11.2 years, with primary unilateral uncomplicated inguinal hernia, were treated in a day-surgery setting. Collected data included: pain scores at 24 hours, 72 hours, and 7, 15, and 30 days after operation, analgesic medications, return to work and to heavy house and/or moderate sporting activities, and quality of life as measured by Short Form 36 health survey questionnaire (SF-36) before the operation and at 6 months follow-up. RESULTS: Postoperative pain was low: the mean visual analog scale (VAS) scores were 2.8 at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively. Analgesic drugs were not used by 66.0% (n=37) of the patients. The mean global time to return to work and to heavy activities was 9.9+/-4.6 and 14.6+/-7.0, days, respectively. Patient satisfaction showed a significant improvement in all SF-36 domain scores at 6 months follow-up (P<0.001). There were no major complications, recurrences, or mortality. CONCLUSIONS: The new mesh seems to satisfy all requirements of a feasible, reliable, and effective device for repairing primary inguinal hernia with high patient comfort.
Abstract: BACKGROUND: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy and activity in advanced gastric cancer. We assessed the clinical activity and the toxicity of weekly docetaxel in combination with capecitabine in untreated patients with advanced gastric cancer. PATIENTS AND METHODS: A total of 38 patients were treated with docetaxel 36 mg/m2 on days 1, 8, and 15 i.v., plus capecitabine, 625 mg/m2 bid per os on days 5 to 18 repeated every 4 weeks. RESULTS: All patients were assessable for response to treatment and for toxicity. Major responses were observed in eight patients (21%), with three patients achieving a CR (7.8%) and five showing a PR (13%). The median time to progression was 5.4 months and the overall survival was 7.7 months. The safety profile of this schedule was acceptable with a low rate of myelossuppression, diarrhoea and hand-foot syndrome. CONCLUSIONS: The combination of docetaxel and capecitabine at the doses and schedule investigated in this study is safe, but does not show significant activity in untreated patients with advanced gastric cancer.
Abstract: The role of epidermal growth factor receptor (EGFR)-driven signaling in different stages of colorectal carcinogenesis, as well in the acquisition of therapy resistance, has been established. Multiple strategies have been developed for the therapeutic targeting of EGFR. Cetuximab is a chimeric monoclonal antibody selective for EGFR with efficacy alone or in combination with irinotecan in the treatment of metastatic colorectal cancer patients, who have progressed to using irinotecan-containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Based on this data, the combination of cetuximab with standard chemotherapy regimens such as irinotecan/ 5-FU/folinic acid (FA) or oxaliplatin/5-FU/FA are currently being investigated in Phase III trials for chemotherapy-naive patients with metastatic colorectal cancer.
Abstract: The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.
Abstract: Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an approximately 100-kb region on 18p11.32 that was of particular interest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU. Analysis of TYMS by fluorescence in situ hybridization identified TYMS gene amplification in 23% of 31 5-FU-treated cancers, whereas no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1,021 days, P <0.01). These data suggest that genetic amplification of TYMS is a major mechanism of 5-FU resistance in vivo and have important implications for the management of colorectal cancer patients with recurrent disease.
Abstract: BACKGROUND: To the authors' knowledge, little is known to date regarding the prognostic relevance of measuring serum levels of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, in patients with colon carcinoma who undergo surgery. METHODS: Preoperative and postoperative VEGF serum levels were determined by enzyme-linked immunoadsorbent assay in 81 patients with colon carcinoma who were undergoing surgery. Fifty healthy individuals served to define normal VEGF serum levels. RESULTS: Preoperative VEGF serum levels were significantly higher in the group of patients with colon carcinoma (mean, 504.1 pg/mL +/- 223 pg/mL; range, 285-1390 pg/mL; 95% confidence interval [95%CI], 49 pg/mL) compared with the control group (mean, 78.1 pg/mL +/- 22 pg/mL; range, 40-110 pg/mL; 95%CI, 4.3 pg/mL; P < 0.001). Multiple regression analysis demonstrated a significant correlation (r) between preoperative VEGF serum levels and age (r = - 0.275; P = 0.013), Dukes stage (r = 0.488; P < 0.001), and carcinoembryonic antigen (CEA) levels (r = 0.285; P < 0.018). No significant correlation was found between preoperative VEGF serum levels and disease site, patient gender, tumor size, tumor grade, or performance status. Moreover, preoperative VEGF serum levels were significantly lower in patients who underwent curative surgery compared with patients who underwent noncurative surgery (443 pg/mL +/- 117 pg/mL vs. 821 +/- 353 pg/mL, respectively; P < 0.0001). Logistic regression analysis selected preoperative VEGF and CEA serum levels as the only good prognostic indicators of curative and noncurative surgery (P < 0.001; relative risk, 2.98 and 2.03, respectively). Furthermore, VEGF serum levels dropped significantly after surgery, with a further downward trend until the 30th postoperative day (P < 0.001). Stepwise regression analysis selected preoperative VEGF serum level as the only variable associated significantly with the prediction of both disease-specific survival and disease-free survival (P = 0.001). CONCLUSIONS: Preoperative serum VEGF levels may be useful for predicting outcome in patients with colon carcinoma who undergo surgery.
Abstract: PURPOSE: Conventional staging procedures are often unable to precisely predict prognosis in colorectal cancer (CRC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (p27 and p53), apoptosis (p53 and p27), and tumor neoangiogenesis [p53, vascular endothelial growth factor (VEGF), and microvessel count] in predicting tumor behavior and clinical outcome in CRC patients EXPERIMENTAL DESIGN: Analysis of the above indicators was performed by immunohistochemistry on 104 CRC patient samples and 25 normal colon mucosa specimens. RESULTS: Intense p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining and VEGF cytoplasmic accumulation <10%, and low microvessel count. In contrast, in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed in 52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple regression analysis showed that molecular markers were strongly correlated. In patients treated with curative surgery, a significant relationship was seen between p27 down-regulation and Dukes' stage, nodal status, and the presence of distant metastases. VEGF overexpression correlated significantly with Dukes' stage, tumor (t) and metastasis (m) parameters, and left site. Stepwise regression selected p27, p53, VEGF, and Dukes' stage as the best combination of variables capable of predicting both disease-specific and disease-free survival. CONCLUSIONS: The investigated indicators may be useful for the prediction of outcome and recurrence rate in curatively treated CRC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CRC patients.
Abstract: PURPOSE: Early-stage colon cancer patients (Dukes A or B; pT1-T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis. METHODS: In 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments. RESULTS: No clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate. CONCLUSIONS: Assessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.
Abstract: Ependymomas outside the confines of the cranium and spinal cord are rare. Direct extension into the soft tissues of the sacrococcygeal area may occur from a primary ependymoma of the spinal cord, cauda equina or filum terminale. Alternatively they may occur as a primary pre-sacral, pelvic and abdominal tumour, or as a primary tumour of the skin and subcutaneous tissue of the sacrococcygeal area without any demonstrable connection with the spinal cord. The Authors report a case of myxopapillary ependymoma of the ischioanal fossa, demonstrated by MRI. To our knowledge, our case is the first lesion reported at this site.
Abstract: A giant cystic lesion of the left upper abdomen associated with a smaller ovarian cyst in a young female patient is reported. Laboratory data revealed elevated serum levels of carbohydrate antigen 19-9 (CA 19-9), carcino-embryonic antigen (CEA), cancer antigens 50 and 125, and tissue polypeptide antigen. In contrast, the serum levels of interleukin 10, a cytokine involved in modulating immune responses and produced by many cancer histotypes, were normal. Since ovarian cancer or cystic adenocarcinoma of the tail of the pancreas were not ruled out, the patient underwent laparotomy. After splenectomy and ovariectomy, the tumour marker serum levels normalized. Histology and immunohistochemical analysis revealed a true splenic cyst with the inner epithelium strongly positive for CA 19-9 and CEA and high levels of cancer antigens in the fluid. The ovarian lesion was a serous cystadenoma. The inner epithelium showed no immunoreactivity for tumour markers which were not measurable in the fluid. True cysts of the spleen are rare; in a few cases, high serum levels of CA 19-9 and CEA have been reported. In such instances, cyst resection or splenectomy is indicated to rule out malignant lesions and to remove the cancer antigen producing epithelium. The reported case shows that the epithelium lining true splenic cysts may produce, besides CA 19-9 and CEA, other tumour markers, in particular cancer antigens 50 and 125. In addition, normal serum values of interleukin 10 correctly predicted the benign nature of the lesion.
Abstract: True cysts of the spleen are rare. In a few cases, high serum levels of carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) have been reported. It has been suggested that they are produced by inner epithelium of the cyst. In such instances, cyst resection or splenectomy is indicated to rule out malignant lesions and to remove cancer antigen-producing epithelium. Furthermore, a high serum level of interleukin (IL)-10, an immunosuppressive cytokine, has been described in many neoplastic diseases, suggesting it as a potential new diagnostic method. Giant cystic lesion of the left upper abdomen associated with ovarian tumor was diagnosed in a young patient. Laboratory data revealed elevated serum levels of several tumor markers [CA 19-9, CEA, cancer antigens (CA) 125 and 50, and tissue polypeptide antigen]. In contrast, IL-10 serum level was normal. After splenectomy and ovariectomy, tumor marker serum levels normalized. Histology and immunohistochemical analysis revealed true splenic cyst with inner epithelium strongly positive for CA 19-9, CEA, and high levels of cancer antigens in fluid. Ovarian lesion was a serous cystoadenoma; its inner epithelium showed no immunoreactivity for tumor markers that were not measurable in fluid. The reported case showed that epithelium lining true splenic cysts may produce, in addition to CA 19-9, CEA, and other tumor markers, in particular CA 125 and CA 50. When malignant disease is suspected, IL-10 serum level could be useful to correctly predict the nature of the lesion.
Abstract: BACKGROUND:Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. We used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers. METHODS: We studied 180 patients with no evidence of lymph-node or distant metastases at the time of surgery. DNA from paraffin-embedded tumours was tested for imbalances of chromosome 8p and 18q by digital SNP (single-nucleotide polymorphism)-a technique in which each allele in a sample is directly counted. Surviving patients had median follow-up of 68 months, and disease recurrence was used as the clinical endpoint. FINDINGS: Tumours were divided into three groups: "L" tumours (n=93) had allelic imbalances of chromosomes 8p and 18q, "L/R" tumours (n=60) had allelic imbalances of either chromosome 8p or 18q but not both, and "R" tumours (n=27) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% (95% CI 80-100) for patients with R tumours, 74% (61-87) for patients with L/R tumours, and 58% (47-69) for those with L tumours. These differences were significant (p<0.0001) and were independent of other variables--eg, Duke's stage A tumours of class L were much more likely to recur than Duke's stage B tumours of class R (p=0.002). INTERPRETATION: In patients without metastasis, allelic imbalance is a better predictor of prognosis than histopathological stage.
Abstract: The prognostic significance of IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery was investigated. To this end, 50 candidate patients with colon cancer for surgery were admitted to the study. Of these, 30 could be subjected to a potentially curative surgery. Cytokine serum levels at several time points before and after surgery were measured by ELISA. Circulating levels of IL-10 and IL-6 were found to be elevated in cancer patients with respect to controls. Both IL-10 and IL-6 serum levels were demonstrated to predict the likelihood of curative surgery (predictive accuracy, 83.3%). IL-10 serum levels returned to normal in all but 6 patients who underwent curative surgery. These latter had tumor recurrence (predictive accuracy, 100%). In contrast, IL-6 serum levels significantly decreased in all patients, regardless of whether cure was surgically achieved, but did not normalize. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly predicting the disease-free survival rate. Stepwise regression selected tumor stage, basal IL-10 serum level, and basal CEA serum level as the best combination of variables for prediction of the likelihood of tumor recurrence. In conclusion, preoperative serum levels of IL-10 were shown to be useful markers for predicting both likelihood to perform curative surgery and, in combination with the 16th postoperative day IL-10 serum levels, tumor recurrence (predictive accuracy, 73.6 and 96%, respectively). IL-6 serum levels were found to have a more limited prognostic role.
Abstract: OBJECTIVES: This study evaluated the concurrent treatment of chemoradiation followed by esophagectomy in the management of locoregional esophageal carcinoma. The main end points were to determine the resectability of the tumor and the pathologic tumor response. An accessory aim was to evaluate the survival rate. PATIENTS AND METHODS: Thirty-nine patients were treated as follows: 5-fluoruracil, 1,000 mg/m(2), by 24-h IV infusion for 4 days, and cisplatin, 100 mg/m(2), on day 1. Concurrent radiotherapy was delivered at a total dose of 40 Gy in daily fractions of 2 Gy five times per week. The performance of an esophagectomy was planned 4 weeks after induction treatment and restaging. RESULTS: All patients completed the preoperative treatment. A potentially radical resection was performed in 29 patients, and a complete or partial histologically proven response was observed in 9 patients (23%) and 20 patients (51%), respectively. The 3-year overall survival rate was 40%. The 3-year rates of overall survival and disease-free survival were 88% and 76%, respectively, in patients with complete response (p < 0.0012), and 16% and 17%, respectively, in patients with partial response (p < 0.0013). Age, histology, and response represented the best prognostic model related to survival. CONCLUSIONS: The results of this combined approach appear to be better than those reported with surgery alone. Despite the small number of patients in the series and the inclusion of patients with different histotypes, we concluded that patients with the squamous histotype show a better outcome than those with adenocarcinoma.
Abstract: Elevated interleukin-10 (IL-10) and IL-6 serum levels in advanced gastrointestinal cancer patients have been shown previously. To investigate the behavior and the prognostic role of IL-10 and IL-6 serum levels in gastric and colon cancer patients undergoing surgery, we studied the relationship between these cytokine levels and surgical radicality and outcome. Seventy-eight patients with gastric or colon cancer were admitted to the study, and 50 underwent radical surgery. Cytokine serum levels were measured by ELISA the day before surgery and 16 days after surgery. Circulating levels of IL-10 and IL-6 were found to be higher in cancer patients than in controls. Both IL-10 and IL-6 serum levels were demonstrated to be able to predict likelihood to perform radical surgery. IL-10 serum levels returned to normal in all but 8 radically resected patients. These 8 patients had tumor recurrence. In contrast, IL-6 serum levels were shown to significantly decrease in all patients but not to normalize regardless of the radicality of the operation. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly affecting the disease-free survival rate. Stepwise regression selected tumor stage, number of metastatic resected nodes, and basal IL-10 serum level as the best combination of variables for prediction of likelihood of tumor recurrence. Preoperative IL-10 serum levels may be a useful marker to predict likelihood of performing radical surgery. Abnormally high postoperative IL-10 values negatively affected disease-free survival and tumor recurrence. IL-6 serum levels were found to have a more limited prognostic role.
Abstract: Interleukin-8 (IL-8) is a pleiotropic cytokine that has also been shown to exert effects relevant to cancer growth and progression. Cancer progression is believed to be contributed to by the ability of this cytokine to promote angiogenesis and mitogenic effects. As IL-8 production at the tumor site may determine elevated serum levels of this cytokine because of hematogenous leakage, it is conceivable that patients with high IL-8 serum levels may have tumors actively producing this cytokine. The aim of this study was, therefore, to assess IL-8 serum levels in 60 non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and to correlate them with prognosis. IL-8 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, IL-8 serum levels were shown to be significantly increased in stage IV patients compared with stage III patients. When basal IL-8 serum levels in cancer patients were analyzed according to response to chemotherapy, responders were shown to have significantly lower IL-8 serum levels than nonresponders. On univariate analysis, the IL-8 serum level was included among the variables capable of affecting both overall survival (OS) and time to treatment failure (TTF). However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-8 serum levels. In conclusion, this study showed that IL-8 serum levels were elevated in advanced NSCLC patients and correlated with both OS and TTF, but they were shown not to be an independent prognostic factor.
Abstract: The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.
Abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to regulate immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. A poor prognosis in patients with multiple myeloma, renal cell carcinoma, ovarian cancer, or prostate cancer has been associated consistently with elevated IL-6 serum levels. The aim of this study was, therefore, to assess IL-6 serum levels in 68 advanced gastrointestinal cancer patients and to correlate them with prognosis. IL-6 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, patients with disseminated cancer displayed significantly higher IL-6 serum levels than patients without apparent metastases. On univariate analysis, both overall survival (OS) and time to disease progression (TTP) were shown to be affected by IL-6 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-6 serum levels while confirming the role of previously established variables, such as performance status, carcinoembryonic antigen (CEA) serum levels, and distant metastases. In conclusion, this study showed that IL-6 serum levels were elevated in advanced gastrointestinal cancer patients and correlated with both OS and TTP. However, they were shown not to be an independent prognostic factor.
Abstract: The development of thyroid tissue can occur in any moment of the migration of the thyroid along the thyroglossal duct from the tongue, resulting in lingual (at tongue base), sublingual (below the tongue), prelaryngeal (in front of the larynx), and substernal (in the mediastinum) ectopy. Thyroglossal duct cyst is the most common type of clinical abnormality related to thyroid ectopy. Surgical removal of such ectopic tissue is justified since some Authors describe thyroid cancer arising from aberrant thyroid tissue. The Authors report a case of thyroid ectopy in a patient who underwent 20 years before a left thyroid resection with isthmectomy; during the operation the surgeon described a hypertrophic pyramidal lobe which was left in situ and the patients did not receive any hormone suppressing therapy.
Abstract: BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy. METHODS: In this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed throughout surgery. The following parameters were analyzed: mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH. RESULTS: All the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation. CONCLUSIONS: Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations.
Abstract: Interleukin (IL)-10 is a Th2 type pleiotropic cytokine that has been found to be produced at the tumor site and to be increased in sera of patients suffering from different types of cancer. IL-10 has been shown to hinder a number of immune functions, i.e., T lymphocyte proliferation, Th1 type cytokine production, antigen presentation, and lymphokine-activated killer cell cytotoxicity. To assess its prognostic value, we measured serum levels of IL-10 in 118 patients with advanced solid tumors before treatment, after completion of therapy, and during follow-up. Other prognostic variables, to which IL-10 results were compared, were analyzed as well. IL-10 serum levels were found significantly elevated in cancer patients with respect to healthy controls. Of interest, a significant decrease in IL-10 serum levels was observed in the responder group, whereas a significant increase was recorded in the non-responder group. Using univariate and multivariate analyses, a significant relationship was shown between IL-10 serum levels and both overall survival (OS) and time to treatment failure (TTF). Stepwise regression analysis selected IL-10 serum level, performance status (PS), and stage as the best association of variables with significant impact on OS and TTF. In conclusion, this study shows that IL-10 has an independent prognostic significance in patients with advanced solid tumors and may be useful for monitoring disease progression.
Abstract: STUDY OBJECTIVE: To investigate the prognostic significance of interleukin (IL)-10 serum levels in advanced non-small cell lung cancer (NSCLC) patients. DESIGN: IL-10 serum levels were measured before chemotherapy, on completion of therapy, and at follow-up by means of a commercially available enzyme-linked immunoassay. The results were then analyzed in comparison with other prognostic variables, and a model predicting overall survival (OS) and time to treatment failure (TTF) was finally generated. SETTING: University hospital. PATIENTS: Sixty consecutive patients with TNM stage III or IV NSCLC undergoing conventional platinum-based regimens. RESULTS: Elevated levels of serum IL-10 were found in cancer patients with respect to healthy control subjects (17.7 +/- 4.4 vs 9.2 +/- 1.5 pg/mL, respectively; p < 0.05), with patients with metastatic disease showing significantly higher levels than patients with undisseminated cancer (21.0 +/- 4.2 vs 14.3 +/- 1.2 pg/mL, respectively; p < 0.05). Following completion of treatment, patients were classified as responders if they had achieved either one of the following: complete response, partial response, or stable disease; and nonresponders, in case of progressive disease. Retrospective analysis of basal IL-10 serum levels in these two subgroups showed a significant difference between responders and nonresponders (15.2 +/- 2.2 vs 21.4 +/- 4.2 pg/mL, respectively; p < 0.05). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.4 +/- 4.2 vs 26.0 +/- 4.3 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05), whereas values in responders were found to have significantly decreased (15.2 +/- 2.2 vs 14.8 +/- 2.2 pg/mL, prechemotherapy and postchemotherapy, respectively; p < 0.05). Using univariate and multivariate analyses, both OS and TTF were shown to be affected by the mean pathologic levels of IL-10. Stepwise regression analysis identified IL-10 serum level and stage as the prognostic factors related to OS, and IL-10 serum level and performance status as the prognostic factors related to TTF. CONCLUSIONS: In conclusion, this study shows that the measurement of pretreatment IL-10 serum levels is of independent prognostic utility in patients with NSCLC and may be useful for detection of disease progression.
Abstract: OBJECTIVE: To investigate anorectal manometric findings in patients with haemorrhoids and to evaluate the clinical effects and physiological consequences of adding a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. DESIGN: Randomised prospective study. SETTING: Teaching hospital, Naples. PATIENTS: 48 consecutive patients with prolapsed piles who had anorectal manometry; 10 healthy volunteers served as controls. INTERVENTIONS: Resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. 6 patients were excluded because anal pressures were not raised, so 42 patients were randomised. 22 patients had haemorrhoidectomy plus LIS; and 20 had haemorrhoidectomy alone. MAIN OUTCOME MEASURES: Morbidity, continence, and anorectal manometry. RESULTS: Sphincter anomalies were found in 87.5% (n = 42) of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned to the normal ranges after sphincterotomy. Those who had LIS did better postoperatively than those who had did not. 4 patients who did not have a sphincterotomy developed anal strictures. No patient who had LIS developed incontinence of faeces. CONCLUSIONS: High anal pressures are common in patients with haemorrhoids suggesting that they may have a pathogenetic role; anorectal manometry is useful in the investigation of anal pressure patterns; and when indicated, lateral sphincterotomy avoids pain, urinary retention, and stenosis, and is safe.
Abstract: The aim of this prospective randomized study was to investigate anorectal manometric findings in hemorrhoid patients and to evaluate the clinical benefits and physiological consequences of additioning a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. Anorectal manometry was preoperatively performed in forty-eight consecutive patients with prolapsed piles; resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. Ten healthy volunteers served as controls. Six patients were excluded because no raised and pressures were found. Forty-two patients were randomised: Group 1 (n = 22) patients underwent haemorrhoidectomy plus LIS; Group 2 (n = 20) patients underwent haemorrhoidectomy alone. Postoperative course was carefully evaluated; all patients were questioned about continence and anorectal manometry was repeated twice. Sphincter anomalies were found in 87.5% of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned into the normal ranges after sphincterotomy. Postoperative course was better in LIS group. Anal stricture was seen in four patients without sphincterotomy; no patients with LIS experienced and incontinence. This study shows that high and pressures are very frequent in hemorrhoid patients; they are not due to hypertensive and cushions and might have a pathogenetic role. Anorectal manometry is very useful to identify patients with raised anal pressures; in these cases additioning a lateral internal sphincterotomy to haemorrhoidectomy seems justified; it significantly improves postoperative course and can be safely performed.
Abstract: Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P = 0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed.
Abstract: OBJECTIVE: To evaluate the diagnostic and therapeutic approach to gallstone ileus. MATERIAL AND METHODS: A gallstone ileus report, diagnosed by integrated radiological approach, treated by minilaparotomy plus enterolithotomy and followed up for two years. RESULTS: Traditional radiologic findings, ultrasonography and computed tomography showed both the stone in the bowel lumen and the cholecystoduodenal fistula with air in the biliary tract. The enterolithotomy alone worked out the obstruction and no complication was observed. DISCUSSION: Integrated radiologic examinations are indicated in defining nature, site and seriousness of gallstone ileus. In most cases surgical treatment is mandatory to work out both the bowel occlusion and bilioenteric illness even though it is often wiser to perform an operation of enterolithotomy alone owing to the general and local conditions of the patient. After this surgical approach, bilioenteric fistula disappears in most cases with no residual lithiasis; in the cases in which fistula and/or lithiasis persist, a decisive surgical operation can be performed in a second step.
Abstract: Hereditary colorectal cancer is a clearly identified entity today; it is transmitted as a dominant autosomal heritage, and represents about 25% of large bowel malignancies. The poor prognosis of this tumor, one of the most frequent in Western Countries, despite the improvements in therapeutic field, is due to a delated diagnosis that affects an advanced stage of disease in which the results of treatment are significantly worse, whereas cumulative 5-year survival rate is 35% vs 95% in early stage tumors. Existence of an inherited cancer, even in the absence, at present, of specific biomarkers, allows to identify a high risk population in which early diagnosis of colorectal cancer is possible, on the basis of anamnestic and clinical features. Only in this way, with the extension of the results to general population, prognosis of colorectal cancer will be improved.
Abstract: Laparoscopic cholecystectomy is associated with a significant risk of gallbladder perforations with bile and stone spillage. The retrieval of dropped stones is sometimes impossible, and intraperitoneally retained stones can be the source of serious complications, such as inflammatory masses or abscesses. The authors describe a patient in whom a large retroperitoneal abscess developed as a result of missed stone fragments during cholecystectomy. Although several cases of intraperitoneal abscess have been reported in the literature, retroperitoneal collection is very uncommon. Crushed and infected stones seem to be the essential prerequisite for abscess formation. Therefore, every attempt should be made to avoid stone spillage and intra-abdominally retained stones. Conversion to open surgery has to be considered in the presence of adverse factors, such as primary acute cholecystitis or cholecystitis induced by previous sphincterotomy, or bilirubinate stones believed to be infected. Abdominal abscess treatment requires removal of missed stones by surgical incision or new laparoscopic procedure because simple percutaneous drainage is usually unsuccessful.
Abstract: It is controversial whether cell DNA measurement is a reliable method to predict prognosis in radically resected large bowel carcinomas. A study using strict rules was undertaken on 54 consecutive patients to clarify the usefulness of DNA ploidy by image cytometric analysis as a prognostic indicator. The tumors were 39% diploid and 61% aneuploid. DNA ploidy was not related to more advanced stages and it, with histological grade and Dukes' stage, was an independent covariate and influenced both disease-free and overall survival. Aneuploid tumors showed the worse prognosis in all Dukes' stages. This prospective study shows that DNA ploidy is an important independent prognostic indicator of clinical outcome and recurrence rate, and it should be used to both select high-risk patients and guide postoperative treatments, particularly in early-stage large bowel carcinomas.
Abstract: BACKGROUND: Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. In this study, the authors investigated the prognostic significance of IL-10 levels in the sera of 58 patients with advanced gastric or colorectal carcinoma. METHODS: IL-10 serum levels were measured before chemotherapy, on completion of chemotherapy, and at follow-up by means of a commercially available enzyme-linked immunoadsorbent assay kit. The results then were analyzed in comparison with other prognostic variables and a model predicting overall survival (OS) and time to disease progression (TTP) was generated. RESULTS: Elevated levels of serum IL-10 were found in carcinoma patients compared with healthy controls (19.6 +/- 6.8 pg/mL vs. 9.2 +/- 1.5 pg/mL; P < 0.0001), with those patients with metastatic disease showing significantly higher levels than patients with undisseminated disease (21.9 +/- 6. 7 pg/mL vs. 15.5 +/- 3.6 pg/mL; P = 0.0003). Retrospective analysis of prechemotherapy IL-10 serum levels showed a significant difference between responders and nonresponders (15.8 +/- 2.5 pg/mL vs. 21.6 +/- 7.6 pg/mL; P < 0.0001). Moreover, a further significant increase in IL-10 serum levels was observed in nonresponders at the end of therapy (21.6 +/- 7.6 pg/mL prechemotherapy vs. 31.3 +/- 11.6 pg/mL postchemotherapy; P < 0.0001) whereas no significant differences were observed in responders. Using univariate analysis, both OS and TTP were shown to be affected by the median pathologic levels of IL-10; multivariate analysis related to OS and TTP identified performance status and IL-10 serum level as the relevant prognostic factors, respectively. Finally, stepwise regression analysis identified IL-10 serum level and metastases as the prognostic factors related to both OS and TTP. CONCLUSIONS: The results of the current study show that measurement of pretreatment serum levels of IL-10 is of independent prognostic utility in patients with advanced gastrointestinal carcinoma and may be useful for the detection of disease progression.
Abstract: Serious complications can be carried by intestinal anastomoses, particularly in the distal and proximal part of the gastrointestinal tract. The biofragmentable anastomosis ring (BAR) has been shown to be a safe anastomotic technique, but its clinical applicability in the extraperitoneal rectum has not yet been completely established. This study compared BAR anastomoses and stapled anastomoses in the middle rectum. Thirty-six consecutive patients initially suitable for elective colorectal anastomosis in the middle rectum were enrolled into this study. All patients had intraperitoneal rectum carcinoma, and 31 underwent a colorectal anastomosis in the middle extraperitoneal rectum. They were randomly allocated to a stapled technique or BAR anastomosis. Intraoperative findings and technical drawbacks, tumor behavior, and postoperative course were recorded. All patients were followed up, and late stenosis rate was investigated by endoscopy. The procedure was carried out in each of the 15 patients randomized to receiving a BAR anastomosis. No major difficulties were encountered, and the time needed was even less than that required for a stapled anastomosis. One patient in the stapled group had an early bleeding that required a further laparotomy. No significant differences in postoperative complications were noted between the two groups, although one patient with stapled anastomosis experienced a clinical leakage that needed loop colostomy. Biofragmentability was regular; buttons were eliminated in 3 weeks without any bowel disturbance. BAR ring insertion in the deep pelvis did not produce a shorter colonic resection. The late stenosis rate was similar between the groups. This study shows that in extraperitoneal middle rectum BAR anastomosis is as feasible and safe as the stapled method. The latter is more expensive, and manual suture is more difficult. Therefore the BAR is now the method of choice for this anastomosis in the authors' unit.
Abstract: Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical removal; it may be done by resection or total hepatectomy. Although multicentric carcinogenesis predicts that liver transplantation is likely adequate to treat both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the advanced stages or in absence of end-stage liver disease and therefore liver resection remains the treatment of choice for radical cure of HCC. However, low resectability and high recurrence rate make surgery alone ineffective. Unresectable HCC may be converted to resectable by multimodality radiation/chemotherapy, and embolization of portal branch feeding tumour, improving the function of the nonembolized liver, can extend the surgical indications for HCC. Adjuvant chemoembolization has already shown to reduce recurrence rate after radical resection and it should be widely applied. In unresectable or not converted HCCs as well as in postoperative recurrence, alternative therapies, particularly as multimodality treatment, can improve survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma, waiting for further studies on newer modalities (prevention and gene therapy, especially), represents the best way to improve long-term results.
Abstract: Since the peritoneal cavity is the most common site of initial recurrence in patients after surgery for gastric cancer, an intraperitoneal (IP) adjuvant treatment was tested in patients with resected gastric cancer with serosal involvement. Between March 1986 and September 1991, 44 consecutive patients with resected T3/T4-N0/N+ gastric cancer were given an IP combination, including cisplatin or carboplatin, etoposide, and alpha interferon-2b. The overall survival of these patients was compared with that observed in 47 historical controls (admitted to the same institutions from 1983 to 1986) with similar prognostic characteristics, who had not received adjuvant treatment after surgery. No major complication relating to the IP route was observed. Mild to moderate abdominal pain occurred in nine patients. Grade 3-4 myelotoxicity occurred in 14 patients. Interferon had to be reduced in five patients and suspended in one because of severe fatigue. Emesis occurred in 23/28 patients given cisplatin and 9/16 given carboplatin. At the time of this analysis (September 1992) median follow-up was 42 months (range 12-78) in the group receiving IP treatment, and 97 months (range 74-128) in the historical controls. There had been 20 deaths among treated patients compared with 36 in the control group. The 5-year estimated survival rate was significantly better in the patients who received IP adjuvant treatment (44% +/- 9 versus 23% +/- 6; P = 0.016). Using the Cox proportional hazard model with a backward procedure to correct for the influence of prognostic pretreatment variables, IP treatment again afforded a significant advantage in terms of survival (P = 0.04). Adjuvant IP immunochemotherapy appears to improve prognosis compared with historical controls in patients having operable gastric cancer with serosal infiltration.
Abstract: The caudate lobe is the only real and constant hepatic lobe of mammals and it requires a better delimitation in a modern conception of human liver segmentation. Owing to its dorsal, central and low anatomical situation, this lobe is connected to many segments of the liver and its inflow and outflow vessels are complex and variable. The authors, who studied 242 human livers, describe the typical pattern of these vessels and their anatomical and numerical variants. By its portal branches the lobe seems to depend upon the left lobe of the liver and its arterial and portal inflow as well as its hepatic vein system are better than these of other segments of the liver; moreover this segment can be compared to a quadrangular pyramid which presents an external part, superficial with easy surgical access, and an internal part, deeper and very difficult to resect. It is possible to remove segment I of the liver without any other hepatic resections but, usually, a partial resection of the lobe is performed or a left lateral segmentectomy is required. In liver cancer, the invasion of the lobe generally means widespread tumor dissemination and its resection is not justified; on the contrary, the caudate lobe should be resected for radical operation in hilar cholangiocarcinoma. The tendency of the caudate lobe to overlap with the other 2 liver lobes and its very good inflow and outflow systems explain its ability to avoid postoperative hepatic failure because it can support the hepatic vein drainage and it has a considerable disposition to regenerate.
Abstract: The authors, who studied 605 human livers according to various techniques, present their own anatomo-surgical conception of human liver segmentation, based on the distribution of the whole intrahepatic Glisson's system, and by dividing the liver into two hemi-livers, right and left (the term "lobe" being reserved, according to Tôn-Thât-Tùng, for the classical anatomical lobes): the right hemi-liver is subdivided into two segments: anterior and posterior; the left hemi-liver is subdivided into three segments: medial (IV), lateral-anterior (III) and lateral-posterior (II); the dorsal segment (I) or the classical Spigel's lobe tends to overlap both half livers (more on the left than on the right). The authors then describe, indicating the percentages, the typical patterns and anatomical variants of intersegmental fissures and the portal system. During the discussion, the authors say that, according to their experience, the right hemi-liver segments can be divided into some smaller units: the posterior segment into two subsegments (VI and VII) and the anterior ones into three subsegments (V, VIIIi and VIIIe); and they justify the segmental division of the left hemi-liver. The authors conclude that statistical and analytical study can define a typical anatomical pattern but that, owing to many anatomical variants, it is easier to perform the transparenchymal approach to the vasculo-biliary structures, enveloped in the same Glisson's capsule, rather than to make long and dangerous dissections at the porta hepatis.
Abstract: Androgen receptors (AR) in the cytosol of hepatocellular carcinoma (HCC) were assayed in 45 unselected patients in whom radical hepatic resection was performed. Thirty-one patients had detectable amounts of ARs in tumors, ranging from 2.3 to 82.6 fmol/mg protein with the dissociation constants (Kd) of 4.1 - 30.9 x 10(-10) M. The receptor was not found in the remaining 14 cases. AR negative HCCs were significantly more common among women and nonalcoholic patients. Otherwise, there were no significant difference in the clinicopathologic background between patients with AR positive HCCs and those with AR negative tumors. Three patients died of liver failure in the former group, whereas two died in the latter; one patient died of liver failure and the other died of pneumonia (results were not statistically significant). Excluding those five operative deaths, the recurrence rates were 67.9% in the group of patients with AR positive HCCs and 33.3% in the group of patients with AR negative tumors (0.1 less than p less than 0.05). The 5-year survival rate was significantly better (p less than 0.05) in patients with AR negative HCCs (62.2%) than in those with the positive tumors (17.3%). In light of the current results and previous experimental works by others, it is likely that testosterones enhance the growth and invasiveness of human HCC, which is mediated by AR in the tumor.
Abstract: During the period between January 1980 and December 1987, 229 male and 39 female adult patients with primary hepatocellular carcinoma (HCC) were hospitalized in our unit. Radical hepatic resection was carried out in 90 (39.3%) males and 17 (43.6%) females in whom no specific cancer treatment had been attempted preoperatively. The 1-, 3-, and 5-year survival rates in the male and female patients were 78% and 70%, 45% and 52%, and 19% and 52%, respectively. The difference was significant after 47 months. No substantial differences were found between the two groups with respect to age, preoperative clinical condition and laboratory data, method of liver resection, postoperative morbidity and mortality, postoperative adjuvant chemotherapy, and histopathology of HCC and the liver. Only the incidence of alcohol abuse was significantly different, being higher in male than in female patients. However, the survival analysis demonstrated that alcohol abuse had had no influence on recurrence rate and long-term survival in either male or female patients. As a control, survival was analyzed for the patients with similar clinicopathological background but without HCC who had undergone distal splenorenal shunt for esophageal varices. There was no significant difference between the male and female patients. The current clinical results seems to support our hypothesis based upon sex hormone receptor studies that HCC may be androgen-dependent.
Abstract: During the past 8 years we have treated 268 patients with primary hepatocellular carcinoma (HCC); total extirpation of the tumor was carried out in 138. Thirty-one of the patients with resectable HCCs had already been treated with transcatheter arterial embolization (TAE) of the liver before they were referred to us. The clinical values of preoperative TAE were retrospectively evaluated for those 31 patients and for the remaining 107 patients without TAE. There were no substantial differences between the two study groups in the clinical and histopathologic backgrounds. No differences were observed in the extent of liver resection, estimated blood loss during surgery, and operation time. During surgery, however, troublesome intra-abdominal complications relevant to TAE were encountered in 15 patients, and detection of tumors was impossible, even with intraoperative ultrasonography, in five patients in the group with TAE. Such findings were not present in any of the patients without TAE. Postoperative morbidity and mortality rates were similar in the two groups. There was no significant difference in the rate of recurrence of tumor in the liver, but the recurrence time was significantly shorter in the group with TAE. TAE did not improve the long-term survival rates in patients either with or without cirrhosis. Results of our study seem to indicate that preoperative TAE is meaningless in the treatment of resectable HCCs and therefore should be avoided, particularly in patients with advanced cirrhosis of the liver.
Abstract: Preoperative detectability rates of hepatocellular carcinoma smaller than 5 cm in 113 cirrhotic patients were 91 percent by ultrasonography, 93 percent by computed tomography, and 92 percent by selective angiography. The combination of two methods produced detectability rates of 97 to 99 percent. One hundred three patients underwent various types of hepatic resection with the aid of intraoperative ultrasonography. Forty-four tumors (43 percent) were embedded in the liver, and these tumors were not detected by conventional surgical exploration. The detectability rates were 38 percent for hepatocellular carcinomas smaller than 2 cm, 57 percent for 2 to 3.5 cm tumors, and 71 percent for 3.5 to 5 cm tumors. All undetectable hepatocellular carcinomas were identified by intraoperative echography. The overall detection rate by this method was 98 percent, which was substantially higher than the preoperative rate. Intraoperative ultrasonography is a useful and indispensable method for performing atypical minor hepatectomy for the treatment of small hepatocellular carcinomas associated with liver cirrhosis.
