Clinical outcome of deep-seated atypical lipomatous tumor of the extremities with median-term follow-up study.

AIMS: There is no consensus on the best surgical treatment for deep-seated atypical lipomatous tumor (ALT) of the extremities; furthermore, the appropriate duration for follow-up observation remains unclear. We investigated clinical and functional median-term outcomes in the primary operations for ALT of the extremities in order to find its best treatment methods and observation periods. METHODS: From 1996 to 2009, we diagnosed 41 patients with deep-seated ALT of the extremities. Wide resection was performed on 11 patients and marginal resection was performed on 30 patients. The minimum follow-up was 5 years (median, 8.5; range, 5-17.4). Patients were evaluated for their local recurrence, dedifferentiation, and post-operative function using the ISOLS/MSTS scoring system. RESULTS: Recurrence and dedifferentiation rates were both 0% for the wide resection group, while the rates were 23% (7/30) and 3% (1/30) for the marginal resection group, respectively. Median duration before recurrence was 7.2 years (range, 4.0-14.2). Local recurrence-free survival rate was significantly higher in the wide resection group (P = 0.013). In the marginal resection group, 10% (3/30) of the cases showed residual tumor. The localization of these tumors was all intermuscular. The ISOLS/MSTS scores were 98% (range, 90-100) for wide resection and 99% (range, 93-100) for marginal resection, with no statistical difference (P = 0.694). No ALT-related deaths occurred during the observation period. CONCLUSIONS: In addition to long-term (at least 8 years) of continuous observation, a wide resection is necessary in order to prevent recurrence, dedifferentiation, and residual tumor.

Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The safety of laparoscopic surgery for rectal cancer following chemoradiotherapy (CRT) has not been fully established. The aim of our retrospective study was to examine the outcomes and the factors contributing to the difficulty of laparoscopic surgery after CRT. METHODS: Eighty-seven consecutive rectal cancer patients treated with CRT were analyzed. Clinicopathological factors were compared between laparoscopic surgery (n = 57) and open surgery (n = 30) groups, and factors that correlated with operation time and blood loss were analyzed in low anterior resection (LAR) cases in the laparoscopic surgery group (n = 46). RESULTS: There was less blood loss in the laparoscopic surgery group than in the open surgery group (191 vs. 1,043 ml, p = 0.0001), and the operation time in the two groups was similar (329 vs. 322 min, p = 0.8). The rate of conversion from laparoscopic surgery to open surgery was 1.8 %. There was no significant difference in the morbidity rate (laparoscopic surgery 22.8 % vs. open surgery 33.3 %, p = 0.3). All circumferential resection margins were clear. Three-year cumulative rates of local recurrence were as follows: laparoscopic surgery: 1.9 % vs. open surgery: 8.4 % (p = 0.4), and distant recurrence was 28.5 % in laparoscopic surgery vs. 22.7 % in open surgery (p = 0.8) and these rates were not significantly different. In laparoscopic LAR cases, a shorter distance of the tumor from the anal verge was associated with a longer operation time. A high computed tomography Hounsfield units value of the mesorectum (CTV) was associated with increased blood loss in the first 23 cases, but not in the other 23 cases. CONCLUSIONS: Laparoscopic surgery following CRT was safe and feasible. A shorter anal verge was associated with a longer operation time. Blood loss increased in cases with high CTV, but this can likely be mitigated by experience.

Two cases of diverticulitis in patients with Williams syndrome.

Williams syndrome is rare and associated with physical anomalies and mental retardation. It is a disease resulting from a gene deletion of chromosome 7. The main concurrent medical conditions typically associated with Williams syndrome are heart defects such as supravalvular aortic stenosis, mental retardation, and unusual physical characteristics. It is also associated with colon diverticulosis and diverticulitis. In the present article, we report on 2 cases of diverticulitis in patients with Williams syndrome, in whom surgery was performed. In many cases of diverticulitis in patients with Williams syndrome, surgical treatment is indicated. It is important to take diverticulitis into consideration when examining a patient with Williams syndrome presenting with abdominal pain and consider surgical treatment if necessary.

A case of fulminant amebic colitis with multiple large intestinal perforations.

Amebic colitis normally causes mucous and bloody diarrhea stool as predominant symptoms, thus leading to a course of chronic colitis. However, though rare, there exists a fulminating type that causes intestinal perforations due to wide necrosis of the large intestine. We encountered a case of fulminant amebic colitis that lead to death due to multiple large intestinal perforations. The patient was a 72-year-old female. The patient was admitted to our hospital with symptoms of fever, abdominal pain, and diarrhea. She continued to have a fever of over 38 degrees C and increased left abdominal pain. An abdominal computed tomography scan revealed free gas on the abdominal side of the kidney. Therefore, gastrointestinal perforations were diagnosed and surgery was performed. In surgery, many perforated parts were observed from the appendix to the descending colon, and subtotal colectomy was performed. However, sepsis and disseminated intravascular coagulation occurred, and the patient died on the eighth postoperative day.

Pancreatic pleural effusion with a pancreaticopleural fistula diagnosed by magnetic resonance cholangiopancreatography and cured by somatostatin analogue treatment.

A 69-year-old man with chronic alcoholic pancreatitis developed a left-sided massive pleural effusion. Magnetic resonance cholangiopancreatography clearly demonstrated the pancreatic cyst and the fistula connecting the cyst with the left pleural cavity, resulting in the diagnosis of pancreatic pleural effusion with a pancreaticopleural fistula. Conservative somatostatin analogue treatment completely eradicated the pancreatic pleural effusion and closed the pancreaticopleural fistula.

Amelioration of retrovirus-mediated gene transfer into hepatocellular carcinoma cells.

Recombinant retroviruses are by far the most frequently used vehicle in clinical gene therapy. No serious side-effects have been reported so far in clinical gene therapy trials using recombinant retroviral systems. Low titers of recombinant retroviruses, however, have limited the usefulness of recombinant retroviruses. To improve the efficiency of retrovirus-mediated gene transfer, we previously introduced the polyomavirus early region into amphotropic PA317 cells and established a modified retroviral packaging cell line, PAMP51. We demonstrate here that recombinant retroviruses produced by PAMP51-derived retroviral producing cells have approximately 10-fold higher titers compared with those produced by conventional PA317-derived retroviral producing cells. Importantly, recombinant retroviruses produced by PAMP-derived retroviral producing cells could infect hepatocellular carcinoma cells much more efficiently and could induce much stronger expression of a lacZ reporter gene in HCC cells compared with those produced by PA317-derived ones. These results indicate that recombinant retroviruses prepared from PAMP51-derived retroviral producing cells are much more useful than those prepared from PA317-derived ones and that the use of PAMP51 retroviral packaging cells may open up new avenues for the treatment of various types of cancer including hepatocellular carcinoma.

Intravenous readministration of an adenoviral vector performed long after the initial administration failed to induce re-expression of the original transgene in rats.

Although most humans have been exposed to wild-type adenoviruses in their childhood, titers of neutralizing antibodies against viruses decrease with the passage of time. In the present study, we infused adenoviruses carrying the lacZ gene into the tail vein of rats, and re-infused the same adenoviruses long after the initial administration. However, development of neutralizing antibodies against adenovirus and proliferation of adenovirus-specific T cells were elicited profoundly by adenoviral readministration, and transgene expression was not induced in rats. Our results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings for the treatment of cancer.

Comparison of gene therapy with the herpes simplex virus thymidine kinase gene and the bacterial cytosine deaminase gene for the treatment of hepatocellular carcinoma.

BACKGROUND: Bystander effects induced by suicide gene/prodrug systems play an essential role in achieving successful antitumor effects. Although it has been shown in several in vitro studies that the bacterial cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) system is superior to the herpes simplex virus thymidine kinase (HSV-TK) gene/ganciclovir (GCV) system, we examined here which suicide gene system was more promising in vivo for the treatment of hepatocellular carcinoma (HCC). METHODS: BNL1ME A.7R.1 murine HCC cells were retrovirally transduced with the HSV-TK or CD gene, and bystander effects caused by the appropriate prodrug treatment were examined not only in vitro but also in vivo. RESULTS: The CD/5-FC system was superior to the HSV-TK/GCV system in HCC cell elimination in vitro. The bystander effect of the HSV-TK/GCV was shown to be substantially dependent on cell-to-cell contact, whereas that of the CD/5-FC was not. However, antitumor effects on HCC and tumor immunity to parental HCC induced by the HSV-TK/GCV system were not inferior and even superior to those induced by the CD/5-FC system. Bystander effects induced by the suicide gene/prodrug systems in immunocompetent syngeneic mice were much more profound than those induced in vitro. However, significant bystander effects were not observed in athymic nude mice. CONCLUSIONS: These results suggest that both HSV-TK/GCV and CD/5-FC systems are useful for the treatment of HCC. The results also suggest that T-cell-mediated immune responses elicited by the suicide gene/prodrug systems play a substantial role in antitumor effects in vivo.

Cancer gene therapy with HSV-tk/GCV system depends on T-cell-mediated immune responses and causes apoptotic death of tumor cells in vivo.

To examine the immunological mechanisms involved in cancer gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene and ganciclovir (GCV), murine hepatocellular carcinoma (HCC) cells, BNL1ME A.7R.1, were transduced retrovirally with the HSV-tk gene. HSV-tk-transduced cells exhibited a more than 2,000-fold higher sensitivity to GCV compared with untransduced parental cells. When HSV-tk-transduced HCC cells were mixed with parental cells at a 50% ratio and implanted subcutaneously into immunocompetent syngeneic mice, complete inhibition of tumor formation was achieved by GCV treatment. Conversely, no significant inhibitory effects on tumor formation were observed in athymic nude mice. When established solid tumors in immunocompetent mice containing HSV-tk-transduced cells at an only 5% ratio were treated with GCV, marked infiltration by lymphocytes including CD4(+) and CD8(+) ones, and apoptotic death of tumor cells were induced, and significant reduction or even complete regression of tumors was achieved. Furthermore, such cured mice rejected rechallenge with parental HCC cells into the contraflank regions. Our results indicate that cancer gene therapy with the HSV-tk/GCV system can indeed induce efficient antitumor effects and protective immunity in immunocompetent mice but not in nude mice, indicating that T-cell-mediated immune responses may be a critical factor for achieving successful gene therapy against cancer using the HSV-tk/GCV system.

Stromal expression of urokinase-type plasminogen activator receptor (uPAR) is associated with invasive growth in primary liver cancer.

AIMS/BACKGROUND: Expression of urokinase-type plasminogen activator receptor (uPAR) was studied in 25 hepatocellular carcinomas (HCCs) and seven cholangiocellular carcinomas (CCCs) by immunohistochemistry. METHODS AND RESULTS: uPAR was expressed mostly by host cells distributed along the tumour-host interface in all cases of HCC and CCC, and its expression was higher in CCC. These uPAR-positive cells were identified as macrophages by observation of serial sections stained for CD68, a marker for macrophages. Cancer cells were positive for uPAR in only one case of poorly differentiated HCC with sarcomatous changes and in three cases of CCC. Hepatocellular carcinomas were classified into two types: those with a fibrous capsule (expansive type) and those without a fibrous capsule (invasive type). Invasive-type HCCs showed more prominent expression of uPAR by macrophages than expansive HCCs (p<0.001), to approximately the same degree as that of CCC. Extrahepatic metastasis was observed in two of 16 expansive HCCs, five of nine invasive HCCs and six of seven CCCs. CONCLUSIONS: Our findings suggest that uPAR expression mainly by macrophages is associated with invasive growth of cancer cells into the surrounding tissue in primary carcinoma of the liver.

Effects of Nd:YAG laser irradiation on morphometry and lung function in elastase-induced emphysema in rats.

BACKGROUND & OBJECTIVE: Although thoracoscopic laser ablation therapy has been hailed as an effective surgical treatment for diffuse emphysema, no one has as yet made an in-depth study of the efficacy of this treatment. This investigation was undertaken to research the effects of laser pneumoplasty on an animal model of emphysema. STUDY DESIGN/MATERIALS AND METHODS: Eight weeks after elastase treatment, the rats' left lungs were irradiated using contact Nd:YAG laser. Pulmonary function tests were performed 4 weeks after irradiation and the lungs were prepared for histologic examination. RESULTS: Dense fibrous scars beneath the pleura were observed at 4 weeks after irradiation. Although mean linear intercept values of irradiated lungs were not much lower than those in the non-irradiated elastase-treated group, laser irradiation caused a significant decrease in lung volume. While there was no significant difference in quasistatic compliance, elastic recoil pressure of the lung increased to control levels at total lung capacity volume. CONCLUSION: We conclude that laser therapy does not cause normalization of compliance, or improvement in the deeper part of the emphysematous lung, but rather a peripheral volume reduction and "encasement effect" on the lungs as a result of fibrotic scars.

Experimental ablation of emphysematous rat lung with Nd: YAG laser: lung changes studied by histopathology and SEM.

Laser ablation has been employed as a therapeutic measure for chronic pulmonary emphysema. As yet, however, its effect is not understood on firm pathological basis. We aimed to study, both histopathologically and using Scanning Electric Microscopy (SEM), the changes produced by irradiation with contact Neodymium-yttrium aluminum garnet laser (Nd: YAG laser) in rat lungs with experimentally induced emphysema. Emphysema was produced in 34 rats by instilling elastase via airways. Eight weeks after the instillation, the emphysematous left lung was irradiated under thoracotomy with contact Nd: YAG laser at a power of 5 watts. The animals were sacrificed in acute as well as chronic phase for histopathological observation of lung and scanning electron microscopy. Laser caused necrotic and inflammatory changes in the subpleural zone of lung. Immediately after irradiation, the alveolar septa were destroyed as visualized by SEM, only leaving the elastic skeleton. In a chronic phase, the necrotic zone was collapsed and replaced with a thick fibrous scar which seemed to serve more or less to keep the organ from being excessively inflated. In this model, irradiation induces subpleural dense scarring, which, by "encasing" an emphysematous lung, is expected to more or less normalize the excessive compliance.

Hepatocellular carcinomas supplied by inferior phrenic arteries.

PURPOSE: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). MATERIAL AND METHODS: A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. RESULTS: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4. CONCLUSION: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

[A case of systemic artery to pulmonary vessel fistula].

A case of systemic artery to pulmonary vessel fistula was reported in this paper. A 44-year-old male who complained recurrent hemoptysis was admitted to our hospital. The angiography revealed an abnormal vascular network in the peripheral part of the 3rd intercostal artery. In this study, two isolated small aneurysms were also recognized in the right bronchial artery. For the purpose of surgical resection for them, video assisted right upper lobectomy was performed. Pathological study on resected specimen showed an artery came from extrapleural space penetrated the pleura and go deeper into the lung parenchyma the artery joined the arteriovenenous plexus which was located just beneath the thinned wall of the bronchiole. It is supposed that recurrent bleeding from the plexus perforated the thinned bronchial wall and caused intrabronchial hemorrhage.

Injection of ethanolamine oleate into a segmental portal branch for pharmacologic hepatic segmentectomy in dogs.

RATIONALE AND OBJECTIVES: Currently available treatments for hepatocellular carcinoma are not satisfactory in terms of recurrence rates. In this study, we injected ethanolamine oleate (EO) into a portal branch in an attempt to cause necrosis of a liver segment in which hepatocellular carcinoma might be located. METHODS: Nine dogs received EO injections via a balloon catheter into a segmental portal branch of the liver. RESULTS: Immediately after injection, 80-100% of the liver cells in the EO-injected segment underwent coagulative necrosis. After 1 week, the EO-injected segment had become completely necrotic in two dogs. Only a few viable hepatocytes were still observed around the arteries and beneath the liver capsule in another dog. No pathologic changes were observed in the lungs, kidneys, or heart of any dog. There was a correlation between the EO dosages and the volume of the EO-injected liver tissue. CONCLUSION: EO injection into a portal branch results in the pharmacologic destruction of the corresponding liver segment. This procedure may be beneficial in the treatment of hepatic malignancies.