Hepatic arterial chemotherapy for liver cancer over a period of 8 years

Hepatic arterial chemotherapy was performed for 27 patients with primary (3), metastatic liver cancer (21), and 3 other cases, over a period of 8 years. Chemotherapy was performed by intermittent hepatic arterial infusion of 5-FU or FAM (in case of metastatic tumor from colorectal cancer), FAM (from gastric cancer), and CDDP or Farmorubicin (HCC). Hepatic resection was performed in 10 cases of metastatic tumor from colorectal cancer, and 8 cases of 10 were curative operation. The 5-year survival rates of curative liver resection group, and non-curative liver resection or non-resection group were 57.1% and 12.5%, respectively. As is the case with metastatic cancer from gastric cancer, pancreatic cancer, and hepatocellular carcinoma (HCC), the prognosis was poor except for one CR case of HCC. We concluded that hepatic arterial chemotherapy may be recommended for a curative resected case of liver metastasis from colorectal cancer.     

Comparison in survival between hepatic metastases of gastric and colorectal cancers

BACKGROUND/AIM: The outcome after hepatectomy and non-surgical treatment of liver metastases from gastric and colorectal malignancies are reported. METHODOLOGY: Between April 1988 and March 1994, 176 patients with metastatic liver cancer were treated at the First Department of Surgery, Kyoto Prefectural University of Medicine Hospital. RESULTS: All patients received multi-disciplinary treatment, and 51 underwent hepatectomy. The survival after hepatectomy for metastatic liver cancer from a colorectal primary was better than that for gastric cancer. The survival after hepatic arterial infusion (HAI) therapy for metastases from gastric cancer was better than that for colorectal cancer. CONCLUSION: Surgical resection may be the best treatment for liver metastases from colorectal cancer. HAI may be a better option for liver metastases from gastric cancer.     

Resection of hepatic metastases from colorectal cancer

BACKGROUND/AIMS: Long term results of hepatic resection for metastases from colorectal cancer depend upon several factors which are related to both features of primary cancer and of metastases. The aim of this study was to evaluate prognostic factors that best correlate with long-term results. MATERIALS AND METHODS: Fifty-eight hepatic resections were performed for colorectal cancer metastases. Long-term results were evaluated in relation to age of patients, features of primary tumor, features of metastases, section margin, number of intra-operative blood transfusions and execution of adjuvant chemotherapy. RESULTS: Overall 5-year survival rate was 17%. 5-year survival rate in patients with stage B primary tumor was 63%, in patients with late metachronous metastases it was 28%, in patients with section margin > 1 cm it was 33% and in patients who did not receive intra-operative transfusions it was 45%. Patients with a solitary metastasis or with metastases sized less than 4 cm and those who received adjuvant chemotherapy also showed a better survival than the others. CONCLUSIONS: Better results were observed in patients without nodal involvement of the primary tumor. Patients with a small solitary metachronous metastasis that appeared more than one year after the colorectal resection and resected with a section margin of more than 1 cm, also showed good results.     

Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors

BACKGROUND: Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. METHODS: Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. RESULTS: All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89% decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. CONCLUSION: To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival.     

血浆D-二聚体水平与转移性胃癌患者生存期的关系

Objective: The principal purpose of this study was to determine the relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients. Methods: We retrospectively collected the data of plasma D-dimer in metastatic gastric cancer patients admitted in our Department (Department of Oncology, The Affiliated Changzheng Hospital, The Second Military Medical University, Shanghai, China) from October 2006 to October 2008 and analyzed the relationship between level of plasma D-dimer and survival time along with other clinicopathologic parameters. Results: A total of 82 patients were studied in our research, 52 were males and 30 females, and the mean age was 57 years. The 48 cases had a normal plasma D-dimer level (< 300 μg/L) and 34 had a high plasma D-dimer level (≥ 300 μg/L). In the normal and high plasma D-dimer level groups, the mean survival times were 10.9 (95% CI: 9.8-12.2) months and 6.8 (95% CI: 4.4-7.6) months respectively, and the difference was statistically significant. Conclusion: Metastatic gastric cancer patients with high plasma D-dimer level had significantly shorter survival time than those with normal plasma D-dimer level. Level of plasma D-dimer can be referred as a potential predictor in metastatic gastric cancer patients.     

Metastatic adenocarcinoma to the uterine cervix from gastric cancer. A clinicopathologic analysis of 16 cases

BACKGROUND: Metastatic adenocarcinoma to the uterine cervix from gastric cancer is rare, and the clinicopathologic features of this metastasis are unclear. METHODS: A clinicopathologic review of 16 patients with metastatic adenocarcinoma to the uterine cervix from gastric cancer was performed. RESULTS: The ages of the patients ranged from 29 to 57 years, and 81.3% of the patients were premenopausal. Nine of the patients had undergone gastrectomy previously. In 11 patients the histologic type of the gastric cancer was poorly differentiated adenocarcinoma and, in 5 patients, signet ring cell carcinoma. The cervical metastasis was diagnosed 11-121 months (mean, 57.5 months) after the diagnosis of the gastric cancer in 10 of the patients. In six patients, the cervical metastasis was discovered synchronously or before the diagnosis of the gastric cancer. The colposcopic findings were normal in 57.1%, but 56.3% had abnormal cervical smears. In all patients, tumor cells were present in the dilated lymphatics of the cervix. Metastases to the uterine body and bilateral ovaries were common, and half of the patients had metastases to the paraaortic lymph nodes. Extirpation of the cervix was performed in six patients. The prognosis was poor, regardless of the treatment method. CONCLUSIONS: The route of metastasis to the cervix is surmised to be retrograde lymphatic, and this extension is often slow. Periodic gynecologic examinations should be performed indefinitely for premenopausal female patients with advanced gastric cancer.     

Characteristics and clinical outcome of proximal-third gastric cancer

BACKGROUND: It is generally accepted that the prognosis of patients with proximal gastric cancer (PGC) is worse than that of patients with more distal gastric cancer. STUDY DESIGN: The aim of this study was to compare the clinical features and outcomes of PGC with those of middle- and distal-third gastric cancers. A total of 646 primary gastric cancers was analyzed as a retrospective study. RESULTS: Proximal gastric cancer occurred in 21.8% of the 646 cancers analyzed, and approximately 21% of PGCs had esophageal invasion. The 5-year survival rate for patients with PGC was significantly lower than that of patients with more distal tumors. When the PGC group was divided into patients with esophageal invasion and without esophageal invasion, patients with esophageal invasion had significantly worse outcomes. When corrected for depth of invasion, lesions with esophageal invasion had significantly worse outcomes than those of other sites in T2 curative cancers. Proximal gastric cancer with esophageal invasion was characterized by a larger tumor, deeper penetration, and a higher incidence of lymph node metastasis compared with tumors in other sites, and in multivariate analysis of all curative cases, these variables were independent prognostic factors for survival. The frequency of positive proximal margins of PGC was higher than those of other sites. CONCLUSIONS: The relatively poor prognosis associated with PGC is mainly from advanced tumor stages of esophageal invasion. Early detection is the most important strategy to improve the survival of patients with PGC. In addition, aggressive lymph node dissection and chemotherapy for esophageal invasion should be considered even if the tumor invasion is moderate (T2 tumor), and a tumor-free margin is important.     

Determinants of survival following hepatic resection for metastatic colorectal cancer

Hepatic resection remains the only potentially curative treatment for metastatic colorectal cancer. This retrospective review study was undertaken in an attempt to identify factors that influence patient survival following hepatic resection for metastatic colorectal cancer. From January 1978 to December 1993, a total of 301 patients underwent a total of 345 planned hepatic resections for metastatic colorectal cancer. Of those, 245 patients had one resection, 44 had two resections, and 12 had three resections. For all patients the overall median survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was 17.2%. Average hospital stay was 9 days. Statistical analysis included univariate analysis using log rank comparisons, Kaplan-Meier survival curves, and multivariate analysis using Cox proportional hazards regression. The statistically significant factors that influenced survival were distribution of liver metastases, unilobar versus bilobar (p = 0.0001), resected versus nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins (p = 0.001). Surprisingly, the disease-free interval and the original stage of the primary tumor did not predict survival (p = not significant). Other factors that had no influence on survival were type of resection, size and number of liver metastases, ABO blood group, and the number of perioperative blood transfusions. For those patients who underwent resection of unilobar metastases with tumor-free margins, the 5-year survival rate was 29% with a median survival of 35 months and eight survivors > 7 years. In addition, one patient with bilobar disease had survival > 7 years and five patients who had resection of hepatic metastases and extrahepatic cancer simultaneously had survival > 3 years. Our data support the concept that patients with unilobar metastatic disease who undergo surgical resection with tumor-free surgical margins can be afforded a significant opportunity at long-term survival with acceptable morbidity, mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic disease (or both) who undergo complete resection can enjoy a long-term survival. In these subgroups of patients resection should be considered on an individual basis.     

Lumbar disc degeneration in relation to occupation

Angiogenic growth factors are essential for cancer metastasis, and the growth of metastatic foci also depends on these angiogenic growth factors as well as autocrine or paracrine growth factors. We therefore investigated whether vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase) are localized more often in primary tumors with hepatic metastasis than in those without such metastasis and whether transforming growth factor (TGF-alpha) and epidermal growth factor receptor (EGF-R) are coexisted more often in hepatic metastases than in primary tumors of gastric cancer. Resected specimens from 82 patients with gastric cancer were examined immunohistochemically. The primary antibodies used were anti-VEGF, anti-dThdPase, anti-TGF-alpha and anti-EGF-R. VEGF expression was found to be higher in primary cancers with than in those without hepatic metastasis (p < 0.001), while VEGF was frequently observed in both hepatic metastases and in the primary tumors. Localization of dThdPase was also higher in advanced than in early gastric cancers (p = 0.021). High co-presence of TGF-alpha and EGF-R was detected more frequently in cancers with deep gastric wall invasion than in those without such invasion (p = 0.050), and also more often in cancers with venous invasion (p = 0.007) and those in the advanced stage (p = 0.020). Co-presence of TGF-alpha and EGF-R was found to be higher, though not significantly, in hepatic metastases (58.8%) than in primary tumors (29.4%). These findings suggest that localization of VEGF may play an important role in hepatic metastasis, and that the expression of VEGF, dThdPase and the TGF-alpha/EGF-R pathway may be responsible for the growth of hepatic metastasis.     

Usefulness of percutaneous low output microwave tissue coagulation therapy for solitary liver cancer

The possible use of percutaneous transhepatic low output microwave tissue coagulation therapy (PMCT) using ultra-sonography under local anesthesia for solitary liver cancer was studied. The subjects were 13 patients having primary or metastatic liver cancer with solitary liver tumor less than 3 cm in diameter, including 7 hepatocellular carcinomas and 6 metastatic liver cancers. PMCT was performed continuously 3 times at an output of 30 watts for 30 seconds at a time. Tumors less than 3 cm in diameter were completely coagulated by irradiation from 2 to 6 times, judging by enhanced CT. No tumor recurrence was recognized in the coagulation area. However, in two cases of metastasis from pancreatic carcinoma, multiple metastases were found at another site in the liver by 2 months after PMCT. Thus, the results suggest that PMCT is a useful therapy for small liver tumor as a local control.     

Immunohistochemical study of MT-MMP tissue status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis

Matrix metalloproteinase (MMP) expression is associated with advanced-stage cancer and contributes to tumor progression, invasion, and metastasis. Membrane type matrix metalloproteinase (MT-MMP) has a potential transmembrane domain at the C terminus and activates pro-MMP-2, which is mainly produced from interstitial fibroblasts. Its expression on the membrane of invasive tumor cells results in the pericellular space degradation at cell-matrix contact sites and renders cancer cells more invasive at the migration front. To elucidate the relationship between MT-MMP expression and metastasis and prognosis in gastric cancer patients, MT-MMP expression was analyzed immunohistochemically in 127 primary tumors and results were correlated with several prognostic parameters and patient's survival. MT-MMP immunoreactivity was stained on the cell membrane of cancer cells and fibroblasts in the invasion front. MT-MMP was detected in 72 tumors (57%) (MT-MMP-positive). MT-MMP expression was closely associated with macroscopically invasive type, nodal involvement, lymphatic invasion, vessel invasion, and peritoneal dissemination. Patients with MT-MMP-positive tumor had a significantly worse prognosis than those with MT-MMP-negative tumor (p<0.001). Multivariate analysis showed MT-MMP overexpression as an independent prognostic factor in gastric cancer patients. Immunohistochemical analysis for MT-MMP may be an indicator of metastatic potential or the prognosis of gastric cancer patients.     

Alpha and omega: studying resuscitation at the beginning and end stages of life

BACKGROUND: To clarify whether or not multiple pulmonary metastases from colorectal cancer are contraindicated for a surgical resection, we retrospectively evaluated the influence of the number of pulmonary metastases on both the postthoracotomy survival and the pattern of the first failure. METHODS: From 1981 to 1993, 36 patients underwent a complete resection for pulmonary metastases from colorectal cancer. RESULTS: Of the various factors investigated including gender, primary site, disease-free interval, tumor size, the number of metastases, type of resection, and the history of hepatic metastases, only the number of pulmonary metastases was found to be significantly related to postthoracotomy survival. The rate of disease-free survival at 5 years was 62% for solitary metastasis (n = 17), 35% for two metastases (n = 8), and 0% for four or more metastases (n = 11). The pattern of failure also differed according to the number of pulmonary metastases. In particular, the incidence of local recurrence at the primary site increased with the number of pulmonary metastases (ie, 1 of 17 patients with a solitary metastasis, 3 of 8 with two metastases, and 6 of 11 with four or more metastases). CONCLUSIONS: These results suggest that multiple metastases might indicate the presence of local recurrence at the primary site; therefore, in cases of multiple pulmonary metastases, the primary site should be thoroughly explored.     

Current data of the science and medical practice: evaluation of the discrepancies

Eleven patients with hepatic metastases from colorectal cancer survived more than 5 years after the resection were reviewed. There were 3 (27.3%) disease-free survivors, the longest survival period was 7 years and 2 months. Compared with 41 survivors of less than 5-year duration after resection, it was shown that close follow-up after resection of the primary cancer, detecting early subclinical hepatic metastases, preoperative lower level of CEA, tumor less or equal to 5 cm in size, single metastatic nodule and radical resection were important factors influening long-term survival (P < 0.05). It is of the opinion that early diagnosis, early resection and re-resection after detecting subclinical local recurrence and metastases play important role in improving long-term response.     

Methods in the evaluation of medical students]

BACKGROUND: Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. METHODS: From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). RESULTS: The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984-89, but had risen to 60.9% by 1990-95. CONCLUSIONS: Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.     

Pulmonary neoplasm with solitary cerebral metastasis. Results of combined excision

Twenty-two patients underwent excision of a primary pulmonary neoplasm and solitary cerebral metastasis. Six patients had metastatic tumor removed on two occasions and there was one operative death in 28 craniotomies. Seven of 22 patients (32 per cent) survived one year following craniotomy and were free of significant symptoms for one year. Survival for at least 9 months and freedom from significant symptoms was achieved in a total of 12 patients (55 per cent). Relief of severe neurologic symptoms for a minimum of 3 months was achieved in 17 patients (77 per cent). The over-all one-year survival rate was 45 per cent and the average survival period is 14 months with 3 patients still living. The following factors had a favorable bearing on the outcome: Stage 1 lung cancer at pulmonary resection, whole-brain radiation therapy, and a longer interval between pulmonary resection and cerebral metastasis. The experience encourages us to pursue an aggressive surgical approach to pulmonary neoplasm and solitary cerebral metastasis.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.     

The incidence of solitary pulmonary metastasis from carcinoma of the large intestine

Two hundred and two consecutive patients who underwent resection of an adenocarcinoma of the colon or rectum from January 1958 to December 1972 were evaluated for the development of a metastatic tumor in the lungs. In the 185 patients who survived the 30 day postoperative period, 30 malignant pulmonary lesions were subsequently recognized. Six of these were a solitary lesion and 24 were multiple lesions. Three of these malignant lesions were proved to be other than metastatic disease. Metastatic adenocarcinoma from the colon or rectum was proved to be present in 27 patients, an incidence of 14.5 per cent. Only four of these lesions were solitary, 14.8 per cent of the metastatic pulmonary lesions. The solitary metastatic tumors represented an incidence of 2.1 per cent in this patient population, but long term tumor-free survival was possible with appropriate pulmonary resection of the metastatic disease. It is suggested that periodic roentgenographic examination of the chest, every four to six months, be an integral part of the postoperative follow-up study carried out on these patients.     

SEM examination of secondary dentine under and opposite cervical carious lesions

CASE REPORT: We report a typical complication of hepatic artery infusion therapy (HAI) in a patient with colon cancer metastatic to the liver. One year after the last HAI-therapy the patient presented with upper gastrointestinal bleeding. Endoscopy showed a large duodenic ulcer penetrating into an adjacent hepatic colon cancer metastasis. The hepatic artery catheter was visible at the ground of the duodenic ulcer. CONCLUSION: Thirty-five percent of patients under HAI-therapy develop gastric/duodenic ulcers. The severity of the HAI complication presented here, however, is quite uncommon.     

Surgical intervention for patients with stage IV-A hepatocellular carcinoma without lymph node metastasis: proposal as a standard therapy

OBJECTIVE: The aim of this study was to evaluate the effects of surgical treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly advanced HCC patients has yielded poor long-term survival. Surgical intervention has been initiated in an effort to improve survival. METHODS: The outcome of 150 patients who underwent hepatic resection was studied. Survival analysis was made by stratifying stage IV-A HCC patients into two groups-those with and those without involvement of a major branch of the portal or hepatic veins. Those with involvement were further divided into subgroups according to major vascular invasions. RESULTS: Patients who had multiple tumors in more than one lobe without vascular invasion had a significantly better 5-year survival rate (20%) than those with vascular invasion (8%) (p < 0.01). The survival rate of patients with hepatic vein tumor thrombi (10%) was better than the rate for those with tumor thrombi in the inferior vena cava (0%), in whom no patients survived more than 2 years, although the survival rate for those with portal vein tumor thrombi in the first branch (11%) was no different from the rate for that in the portal trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to 1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A HCC patients brought longer survival rates for some patients. We recommend surgical intervention as an effective therapeutic modality for patients with advanced HCC.