Transit endoscopic ultrasound of colorectal cancer using a 12 MHz catheter probe.

The objective of this study was to examine the accuracy of a 12 MHz ultrasound catheter probe in the pre-operative staging of colorectal cancer by assessing the depth of tumour infiltration and involvement of pericolonic lymph nodes. 159 patients with colorectal cancer who underwent ultrasound examination with a 12 MHz catheter probe were studied prospectively. The results of this imaging procedure were compared with the histological findings of the resected specimens. The accuracy of the 12 MHz ultrasound catheter probe for depth of invasion (T category) was 85% (131/154) for all tumours, 87% (46/53) for pT1 tumours, 60% (9/15) for pT2 tumours, 89% (74/83) for pT3 tumours and 67% (2/3) for pT4 tumours. The accuracy for tumours of the rectum and colon was 81% and 89%, respectively. The accuracy of the probe for nodal staging (N category) was 67% (76/114) overall. The sensitivity was 70% (33/47), the specificity 64% (43/67), the positive predictive value 58% (33/57) and the negative predictive value 75% (43/57). Endoscopic ultrasound using a 12 MHz catheter probe accurately assessed tumour stage, although nodal staging remained suboptimal. This method may aid in the selection of treatment for patients with colorectal cancer.

E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivo.

E7070 (N-(3-Chloro-7-indolyl)-1,4-benzenedisulphonamide) was selected from our sulphonamide compound collections via antitumour screening and flow cytometric analysis. Following treatment with E7070, the cell cycle progression of P388 murine leukaemia cells was disturbed in the G1 phase. The cell-killing effect on human colon cancer HCT116 cells was found to be time-dependent. In the panel of 42 human tumour cell lines, E7070 showed an antitumour spectrum that was distinct from those of other anticancer drugs used in clinic. Animal tests using human tumour xenograft models demonstrated that E7070 could cause not only tumour growth suppression, but also tumour regression in three of five colorectal and two of two lung cancers. In the HCT116 xenograft model, E7070 was shown to be superior to 5-FU, MMC and CPT-11 (irinotecan). Furthermore, complete regression of advanced LX-1 tumours was observed in 80% of E7070-treated mice. All of these observations have promoted this drug to clinical evaluation.

A comparison of an open and laparoscopic appendectomy for patients with liver cirrhosis.

Liver cirrhosis is a critical factor contributing to morbidity and mortality in abdominal surgery, because patients with cirrhosis have a particularly high risk of developing bleeding, infection, and ascites. Laparoscopic appendectomy (LA) recently has gained a lot of attention around the world; however, comparisons between the benefits of LA and those of conventional open appendectomy (OA) for patients with liver cirrhosis have yet to be sufficiently compiled. In the present retrospective study, 40 patients with liver cirrhosis who were diagnosed with acute appendicitis before surgery underwent an appendectomy (OA in 25 patients and LA in 15 patients). This study focused on the operative time, amount of postoperative pain, use of analgesics, the restart of a normal diet, number of complications, length of hospital stay, and cost-effectiveness of the procedure in such patients. The amount of postoperative pain and the length of hospital stay were significantly smaller in the LA group. The mean values of the serum C-reactive protein on postoperative days 1, 3, and 7 were significantly less in the LA group. The number of wound infections and wound bleeding was also less in the LA group. The difference in the total cost of hospitalization was not significant. The cost of the operation was greater in the LA group than in the OA group, whereas the hospitalization cost in the LA group was less than that in the OA group. The results of this study suggest that LA may be superior to OA for the treatment of postoperative pain and postoperative complications for patients with liver cirrhosis. Long-term follow-up studies are still necessary, however, to determine any possible decrease in the number of late complications.

[A case of wide-spread emphysema following the extraction of mandibular third molar under intravenous sedation].

A 45 year-old male underwent lower left third molar extraction under intravenous sedation. During the surgical extraction of the mandibular left impacted third molar using a high-speed air-turbine drill, the patient complained of compression at the level of the right breast without any abnormal vital signs. Radiological investigation and CT scan showed a picture of bilateral, subcutaneous and mediastinal emphysema involving the bilateral face, neck and pectoral area. Following the antibiotic therapy, the drainage was performed through bilateral pectoral incisions by thoracic surgery. The patient recovered within two days and underwent the completion of this surgery under general anesthesia one month later.

The therapeutic strategies in performing emergency surgery for gastroduodenal ulcer perforation in 130 patients over 70 years of age.

BACKGROUND/AIMS: Gastroduodenal ulcer is a very common illness in Japan. As the number of elderly persons in Japan increases the same as in Europe and America, the number of such patients requiring a gastroduodenal emergency operation has also increased. Regarding the complications of peptic ulcer, a perforation remains the most important fatal complication. The aim of this study is to investigate the operative risk factors and the long-term recurrence rates and to define the optimal surgical procedures in emergency situations in elderly patients. METHODOLOGY: From April 1988 through March 1997, 130 patients over 70 years of age with a perforated gastroduodenal ulcer (a duodenal ulcer perforation in 50 patients and a gastric ulcer perforation in 80 patients) were operated on in an emergency situation in our clinic. We investigated the following items; medical illness, preoperative risk factor, optimal surgical procedure, postoperative organ failure and the cumulative recurrence-free rates after surgical treatment. RESULTS: A significant correlation with mortality was observed in patients with established comorbidity in the following organs: lung (P = 0.03), heart (P = 0.02), kidney (P = 0.04), and diabetes (P = 0.03). The highest postoperative mortality rate was recorded in patients who underwent a simple closure of a duodenal ulcer perforation (4 patients; 26.7%), while the lowest postoperative mortality rate was recorded in patients who underwent a simple closure and vagotomy of a duodenal ulcer perforation (3 patients; 12.5%). In gastric ulcers, the mortality rate in patients with a gastrectomy was significantly higher than in patients with a simple closure. The practical application of the three risk factors (preoperative shock, delay to surgery over 24 hours, and medical illness) was shown by the progressive rise in the mortality rate with the increasing number of risk factors. Based on the 5 postoperative years after treating a perforated duodenal ulcer, the cumulative recurrence rate after a simple closure (63.6%) was significantly higher than that after a simple closure and vagotomy (38.1%) (n = 0.02) or after gastrectomy (0%) (P < 0.001). At 5 years postoperatively, the cumulative recurrence rate after a simple closure (41.2%) was significantly higher than that after a gastrectomy (15.9%) (P < 0.01). CONCLUSIONS: In conclusion, in an emergency situation, elderly patients are in a highly unfavorable prognostic condition due to their advanced age, and comorbidity, which thus leads to poorer results, not only worldwide, but also in Japan. Based on our findings, in duodenal ulcer cases, a simple closure and vagotomy is recommended because of its low mortality and minimal stress, except for cases with a giant perforation measuring over 20 mm in diameter at the perforation hole or with severe duodenal stenosis. In stomach ulcer cases, a gastrectomy may be recommended because of its low recurrence rate.

Effect of E7010 on liver metastasis and life span of syngeneic C57BL/6 mice bearing orthotopically transplanted murine Colon 38 tumor.

PURPOSE: E7010 is an orally active sulfonamide antitumor agent showing good activity against various subcutaneously inoculated rodent tumors and human tumor xenografts. The purpose of this study was to evaluate the effect of E7010 on liver metastasis and life span of mice bearing orthotopically transplanted murine Colon 38 tumor. METHODS: Orthotopic transplantation of murine Colon 38 tumor as intact tissue yielded hepatic metastasis with a high incidence in about 1 month in C57BL/6 mice, and the mice died in about 2 months with cachexia. In this model, the maximum tolerated dose of E7010 (100 mg/kg per day) was administered orally on various schedules, including for 14 days or daily until death, starting at 14 days after transplantation, or for 8 days from 21 days after transplantation. RESULTS: E7010 showed tumor growth inhibition (T/C=40%) at the orthotopic site similar to that at the subcutaneous site (T/C = 32%) when administered from 14 days after transplantation. When E7010 was started from 21 days after transplantation, it significantly decreased the number of hepatic metastases (control 17.1+/-20.8, E7010 2.6+/-5.3), although inhibition of tumor growth at the orthotopic site was only moderate (T/ C=60%). The administration of E7010 until death produced a significant increase in life span (control 49.8+/-8.9 days, E7010 62.5+/-6.1 days). Although the tumor weight of the E7010-treated group on the day of death was similar to that of the untreated group (control 1.166+/-0.507 g, E7010 1.211+/-0.632 g), there were significantly fewer liver metastases in the E7010-treated group (control 41.3+/-31.1, E7010 2.0+/-2.0). CONCLUSION: E7010 suppressed tumor growth at both primary and metastatic sites and increased life span in an orthotopic transplantation model of murine Colon 38 tumor in syngeneic C57BL/6 mice. Hepatic metastasis was inhibited more effectively than the growth of the primary tumor.

[A remarkably improved multimetastatic gastric cancer with the use of TS-1 and CDDP].

A 62-year-old male presented to our hospital with jaundice. On the abdominal ultrasound and abdominal CT, there was evidence of multiple, massive liver metastases with dilatation of intrahepatic bile ducts, thickened wall of the stomach from the body to the antrum, direct invasion to the pancreas, multiple lymph node metastases, and ascites. We believed it was Stage IV and too far advanced for surgery. Therefore, ST-1 60 mg bid was started, and CDDP 50 mg was infused in the seventh week. On the follow-up CT and ultrasound three months later, the thickening of the gastric wall and the lymph node metastasis had improved and the border between the stomach and the pancreas had become clearer. The liver metastases seen on both lobes had decreased significantly both in size and number. The dilatation of the intrahepatic bile ducts disappeared, and the liver function normalized. No side effects were evident during the treatment with the medications.

Preoperative staging of rectal cancer using a 7.5 MHz front-loading US probe.

BACKGROUND: Conventional echoendoscopes have disadvantages when used for staging colorectal cancer including the inability to pass the instrument through tight stenosis and limited maneuverability. This study evaluated the preoperative use of a newly developed 7.5 MHz front-loading ultrasound probe (FLUP) for local staging of rectal cancer. METHODS: A 7.5 MHz FLUP, diameter 7.3 mm, was used in this study. The mechanical shaft portion of the probe can be passed in retrograde fashion through the accessory channel of a standard colonoscope. Thirty-nine patients with rectal cancer underwent ultrasonography with this probe. The tumors were staged using the TNM system, and the results were compared with the histologic findings of the resected specimens. RESULTS: The FLUP proved to be satisfactory, with respect to maneuverability, for traversing stenosis and accurate recognition of small tumors under direct endoscopic control. The accuracy of the FLUP for T staging was 82% (32 of 39) for all tumors, 90% in pT1, and 79% in pT2 to pT4 tumors. The accuracy of the FLUP for N staging was 72% (23 of 32) overall. The sensitivity was 83%, the specificity was 65%, the positive predictive value was 59%, and the negative predictive value was 87%. CONCLUSIONS: The 7.5 MHz FLUP appears to be useful for preoperative local staging of rectal cancer. This system makes it technically easier to image small cancers as well as advanced rectal cancers.

A focused compound library of novel N-(7-indolyl)benzenesulfonamides for the discovery of potent cell cycle inhibitors.

A series of compounds containing an N-(7-indolyl)benzenesulfonamide pharmacophore was synthesized and evaluated as a potential antitumor agent. Cell cycle analysis with P388 murine leukemia cells revealed that there were two different classes of potent cell cycle inhibitors; one disrupted mitosis and the other caused G1 accumulation. Herein described is the SAR summary of the substituent patterns on this pharmacophore template.

Leiomyosarcoma of the thyroid gland with rapid growth and tracheal obstruction: A partial thyroidectomy and tracheostomy using an ultrasonically activated scalpel can be safely performed with less bleeding.

Primary leiomyosarcoma of the thyroid gland is rare, and to the best of our knowledge only nine well-documented cases have been previously reported in the world literature. We herein report a 90-year-old female patient with primary leiomyosarcoma of the thyroid gland who showed a rapid tumor growth and tracheal obstruction. The patient was successfully treated by a partial resection of the thyroid gland using an ultrasonically activated scalpel and emergency tracheostomy. Immunohistochemically, the tumor cells showed positive reactivity to smooth muscle actin and negative reactivity to thyroglobin. Palliative surgery successfully allowed the patient to recover from the symptoms of dyspnea related to this rare disease. The use of an ultrasonically activated scalpel and tracheostomy thus allowed us to safely perform a thyroidectomy with substantially less bleeding than normal.

Discovery of novel antitumor sulfonamides targeting G1 phase of the cell cycle.

Described herein is the discovery of a novel series of antitumor sulfonamides targeting G1 phase of the cell cycle. Cell cycle control in G1 phase has attracted considerable attention in recent cancer research, because many of the important proteins involved in G1 progression or G1/S transition have been found to play a crucial role in proliferation, differentiation, transformation, and programmed cell death (apoptosis). We previously reported our first antitumor sulfonamide E7010 as a novel tubulin polymerization inhibitor. Interestingly enough, continuous research on structurally related compounds led us to the finding of another class of antitumor sulfonamides that block cell cycle progression of P388 murine leukemia cells in G1 phase, but not in M phase. Of the compounds examined, N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide (E7070) showed significant antitumor activity against HCT116 human colon carcinoma both in vitro (IC(50) 0.11 microg/mL in cell proliferation assay) and in vivo (not only growth suppression but also a marked reduction of tumor size in nude mice). Because of its promising efficacy against human tumor xenografts and its unique mode of action, E7070 is currently undergoing phase I clinical trials in European countries.

Rapid development of hepatic metastasis with high incidence following orthotopic transplantation of murine colon 38 carcinoma as intact tissue in syngeneic C57BL/6 mice.

BACKGROUND AND OBJECTIVES: Orthotopic transplantation of human colon tumors was a useful method for producing hepatic metastasis in mice. In many cases, however, it took about 3 months for evaluation. We examined an in vivo model of hepatic metastasis for only 4 weeks by conducting orthotopic transplantation of murine Colon 38 tumor using intact tissue in syngeneic mice and determined the efficacy of chemotherapeutic agents against hepatic metastasis. METHODS: Twenty milligrams of tumor tissues were prepared from subcutaneously (s.c.) growing Colon 38 tumor and orthotopically transplanted on the cecum in C57BL/6 mice. Mice were autopsied about 4 weeks after transplantation. Metastases to various organs were detected macroscopically or histochemically and tumor invasion into the cecum was observed histochemically. In experimental chemotherapy, mice bearing orthotopically transplanted Colon 38 tumor were separated into three equal groups and were either treated with fluorouracil or cisplatin (CDDP), or untreated. Four weeks after transplantation, activities of both agents against local tumor growth and hepatic metastasis were evaluated. RESULTS: Macroscopic metastases to various organs including the liver, the lung, and the peritoneum were developed during days 28 to 32 after inoculation. The frequency of hepatic metastasis was 96% (N = 23). Histological examination indicated that the local tumor invaded various layers of the cecum and metastasized to the liver and lung hematogenously. In experimental chemotherapy with fluorouracil and CDDP, only fluorouracil decreased the incidence of mice with hepatic metastasis (2/8 cases), compared with vehicle treatment (7/8 cases) and the number of metastatic nodules in the liver (P = 0.016), although the inhibition against local growth of CDDP in T/C [45%; mean tumor weight of the test group (T) compared with that of the control group (C)] was similar to that of fluorouracil (53%). CONCLUSIONS: This model, with its rapid development of hepatic metastasis in high frequency, should be useful as a screening assay to find anti-metastatic agents for colorectal carcinoma.

[Case of varicella-zoster pneumonia with bronchioalveolar lavage confirmed by the detection of VZV DNA in the bronchial washing by the polymerase chain reaction].

A 32-year old male was admitted to our hospital complaining of cough, fever, and skin eruptions. He was coctacted with a child who had chickenpox 3 weeks before the onset. He showed the elevating of antibody to varicella-zoster virus. Despite of the administration of Acyclovir for four days, cough was not relieved and a chest X-ray film showed infiltrative shadow in right middle lobe of the lung. Bronchoscopic examination revealed vasicle and edema, and the varicella-zoster virus (VZV) DNA was detected in the bronchoalveolar lavage by the polymerase chain reaction. The patient in first case confirmed by the virus DNA in the bronchial washing by the PCR.

Transanal endoscopic microsurgery for T1 rectal cancer in patients with synchronous colorectal cancer.

We treated T1 rectal cancer in three patients with synchronous colorectal cancer by transanal endoscopic microsurgery (TEM) before performing a radical operation for the second lesion. On pathological examination, all rectal specimens resected by TEM showed cancer invasion within the submucosal layer, while the margins of the specimen were completely free of cancerous tissue. Few complications were encountered with either the TEM for the rectal lesions or the succeeding radical operation for the second lesions. When patients present with synchronous colorectal cancer, including T1 rectal cancer, local excision of the rectal lesion via TEM can help to improve the patient's quality of life without affecting the curability of the disease.

Tumor stage in the proximal colon under conditions of a proximal shift of colorectal cancer with age.

BACKGROUND/AIMS: Although the incidence of proximal colon cancer is known to increase with age, the prognosis of proximal colon cancer remains unclear. METHODOLOGY: One thousand two hundred and five patients with colorectal cancer were analyzed with regard to tumor location, age and Duke's stage. RESULTS: When Duke's stage was compared with tumor location, an advanced Duke's stage was found more frequently in the proximal colon than in the distal colorectum (p<0.01). In Duke's A colorectal cancer, the incidence of tumors limited to within the submucosal layer decreased from 73.1% in patients under 65 years of age to 60.9% in patients over 65 years of age. CONCLUSIONS: Since advanced stage cancer was more frequently found in the proximal colon than in the distal colorectum, careful examination for the early detection of proximal colon cancer, particularly in the elderly, is called for.

Possibility of different cancer development between the proximal and distal colon: comparison of the distribution between adenomatous polyps and cancer.

BACKGROUND/AIM: The aim of this study was to compare the distribution of adenomatous polyps with that of cancer in the colon by using adenomatous polyps removed by colonoscopy. METHODOLOGY: 1223 adenomatous polyps removed by an endoscopic polypectomy were compared with 226 colon cancers with regard to their distribution, size and age. RESULTS: With patients over 65 years of age, the incidence of adenomatous polyps was lower in the proximal colon than in the distal colon, however, the incidence of cancer was higher in the proximal colon than in the distal colon (p<0.05). The distribution of adenomatous polyps according to size was also significantly different between the proximal and distal colon (p<0.05). CONCLUSION: These results thus suggest that some difference may exist in cancer development between the proximal and distal colon.

Natural history of hepatectomy regarding liver function: a study of both normal livers and livers with chronic hepatitis and cirrhosis.

BACKGROUND/AIMS: The cirrhotic liver has been shown to regenerate after hepatectomy based on the findings of various imaging techniques. However, little has been reported so far regarding the restorative process using the liver function test in a long series after hepatectomy of both normal and injured livers. METHODOLOGY: A retrospective review was performed of 48 patients who underwent hepatic resection due to either primary or secondary liver cancers. They were histologically divided into three groups of 6 normal, 23 chronic hepatitis and 19 cirrhotic liver patients. In addition, the hepatitis group was divided into two groups according to the resected volume, which were 16 of a small resected volume and 7 of a large volume. For these patients, both a complete blood count and normal liver function test were performed before operation, and 7 and 14 days, 1, 3, and 6 months, and 1, 2, and 3 years, postoperatively. RESULTS: In the normal patient group, almost all test results recovered to their preoperative levels by 14 days to 1 month postoperatively. In the cirrhotic group, however, the red blood cell count and hematocrit levels did not recover to preoperative levels until 3 months postoperatively, while the GPT levels, the total bilirubin and albumin all recovered by one month postoperatively. However, the total cholesterol level needed 6 months to recover. In the large resection hepatitis group, the GPT level needed 7 days to recover, while the albumin and total cholesterol level needed three months to do so. In addition, the platelet level decreased significantly at 3 months postoperatively and thereafter it seemed to remain at a lower level. CONCLUSIONS: We demonstrated that a hepatic resection in patients with chronic liver disease requires a longer period of time to recover to preoperative levels based on the type of underlying liver parenchymal disease and the extent of resection.

Appraisal of a manual blunt dissection for an intraoperative diagnosis of extrahepatic cancer invasion.

BACKGROUND/AIMS: Liver cancer extension to the adjacent organs does not necessarily indicate tumor invasion. It is very hard to diagnose extrahepatic cancer invasion to the adjacent organs using preoperative imaging. This study was undertaken, therefore, to determine the real cancer invasion using a manual dissection. METHODOLOGY: Of the 51 consecutive patients with liver cancer, 6 cases with extrahepatically growing tumors were suspected to have cancer invasion both preoperatively and intraoperatively. Thus, we diagnosed whether or not any real extrahepatic cancer invasion was present by either removing the tumour by hand or by performing a blunt gauze dissection. RESULTS: Three hepatocellular carcinomas and one metastatic cancer were stripped off from the adjacent organ using a manual blunt dissection. However, the other two tumors could not be removed in the same manner and therefore a combined resection of the invaded portion had to be performed along with the hepatectomy. A postoperative detailed pathological examination revealed no cancer cells on the surface of the adjacent organ in the former 4 tumors. Cancer invasion was recognized, however, on the outside of the liver in the latter 2 combined resected tumors. CONCLUSIONS: An accurate intraoperative diagnosis of extrahepatic cancer invasion can be made using manual blunt dissection.

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

A new technique for repairing a blunt injured duodenum.

Repairing a blunt injured duodenum remains a problem for surgeons because of the difficulty in early diagnosis, associated organ injuries, and frequent anastomotic site leakage. We have devised a simpler and safer procedure for transecting the ligament of Treitz and performing a debridement of the duodenum The duodenum is freed and exposed by transecting the ligament of Treitz. The injured site is then resected with appropriate debridement. The remnant stumps of the duodenum and the jejunum are anastomosed. The advantages of our method are less invasion, a more physiologic state, and no retention of food in the repaired duodenum. This technique reduces tension in the repaired wound and also reduces mortality and morbidity.