The influence of axillary reverse mapping related factors on lymphedema in breast cancer patients.

PURPOSE: Upper extremity lymphedema (LE) is a harmful breast cancer complication. It has been reported that patient- or treatment-related risk factors of LE. Axillary reverse mapping (ARM) has been performed to prevent LE during axillary lymph node dissection (ALND) by visualizing the upper extremity lymphatics. We investigated whether ARM related factors included novel predictive risk factors of LE. METHODS: ARM revealed fluorescent axillary nodes (ARM nodes) in 76 patients by fluorescence imaging. Only ARM nodes within the ALND field were removed. Twenty-four (32%) patients developed LE (LE+) and 52 did not (LE-) during a median 24-month post-surgical follow-up period. We retrospectively evaluated the clinical features and ARM factors of LE+ and LE-. RESULTS: The positive ARM node rate among LE+ was 42%, significantly greater frequency than that among LE- (13%: p ≤ 0.05). Cranial collectors (lymphatic ducts along or above the axillary vein) were significantly more frequent in LE- (44%) than in LE+ (21%: p ≤ 0.05). Multivariate analysis revealed postoperative radiation and positive ARM nodes to be positive risk factors and cranial collectors to be a negative risk factor of LE. CONCLUSIONS: ARM factors could predict the incidence of LE post-axillary surgeries in breast cancer patients.

A novel laparoscopic technique for stapled colon and rectal anastomosis.

BACKGROUND: We present new techniques of stapling anastomosis at laparoscopic colorectal surgery with retrospective review of data. METHODS: A triangulating stapling technique (T method) was performed in 101 laparoscopic colectomies. Adouble stapling technique (DST) with rectal division by a conventional linear stapler (Abd method) was used in 5 cases of upper/middle rectal cancers and subsequent eversion of the distal rectum from the anus (Ev method) was used for 4 low rectal cancers. Four hundred ninety-six colectomies and 280 rectal surgeries were reviewed. RESULTS: Leakage was lower in the T group (0.5%, n=196) than in the hand-sewn group (3.0%, n=233). Leakage of the DST using a laparoscopic linear stapler (12.1%, n=91) was significantly higher than with conventional DST (2.1%, n=189). There was no leakage with either Abd method or Ev method. The T-method is acceptable after laparoscopic colectomy. CONCLUSION: New methods of rectal division using conventional devices are expected to yield reliable anastomosis at laparoscopic rectal surgery.

Expression of thrombospondin-1 inversely correlated with tumor vascularity and hematogenous metastasis in colon cancer.

Solid tumors require neovascularization for growth and metastasis. Angiogenesis depends on the local balance between various molecules that induce and inhibit neovascularization. Thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the correlation between expression of TSP-1 and tumor vascularity, and determined its prognostic significance in colon cancer. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were TSP-1-negative. TSP-1 expression was inversely correlated with prognosis. Patients with TSP-1-negative tumors had a significantly worse prognosis than did those with TSP-1-positive tumors. Frequency of hepatic recurrence was significantly higher in patients with tumors that were TSP-1-negative. In conclusion, TSP-1 is an important negative-regulator of tumor angiogenesis, and TSP-1 may be useful for predicting recurrence in patients with colon cancer.

[Day surgery for adult inguinal hernia].

The mesh plug technique for adult inguinal hernia repair is easy to perform and results in a good postoperative quality of life. It allows inguinal hernia surgery to be performed as day surgery, but some problems may occur. We performed day surgeries tp repair 110 adult inguinal hernias, and the results are reported here. The procedures are as follows. Under local anesthesia, the inguinal canal and hernial sac are freed. Then the internal ring and the weakness of the posterior wall are estimated. The plug is inserted and then the mesh is on layed. As a result, all of our cases were successful under local anesthesia. After surgery, 5 subcutaneous hematomas occurred. Six patients required subsequent hospitalization: one because of subcutaneous hematoma; and 5 for pain control. In summary, the mesh plug technique under local anesthesia for adult inguinal hernia repair is a useful method for day surgery, but some an on-call system after surgery is necessary and hospitalization for postoperative complications may be required.

[Expandable metallic stent for the treatment of left-sided colonic obstruction with malignant disease].

Recently, it was reported that an EMS (expandable metallic stent) was useful for treatment of colorectal obstruction. In our department, EMSs were used for seven patients with left-sided colonic obstruction with unresectable malignant disease. After these treatments with EMS, their symptoms were improved and they were able to intake food. Stomal formation was avoided except in one patient with severe soiling. In conclusion, EMS is thought to be useful for the improvement of quality of life in the patients with unresectable malignant colonic obstruction.

Laparoscopic adrenalectomy for benign adrenal tumors.

Laparoscopic adrenalectomy has been rapidly accepted for treatment of benign adrenal tumors. To evaluate the advantages of laparoscopic adrenalectomy, we examined 55 patients who underwent laparoscopic adrenalectomy. In all patients, adrenal tumors were successfully removed. The mean operating time was 143 minutes, and the estimated mean blood loss was 49 mL in all patients. The postoperative course was uneventful in all cases. The mean frequency of administration of analgesics was only 2.9 times, and the time elapsed to first walking after surgery was 17 hours. The peak white blood cell count and C-reactive protein values after surgery were 8,266 +/- 1,963/mm3 and 2.5 +/- 1.2 mg/dL, respectively. Of the 55 patients, 44 underwent total adrenalectomy and another 11 underwent partial adrenalectomy, which was introduced in the expectation of preserving normal adrenal cortex; it is therefore indicated in solitary and peripherally located benign tumors. The mean operating time was 154 minutes for the total adrenalectomy, which was longer than that of partial adrenalectomy (92 minutes). The estimated blood loss was 50 mL for the total and 46 mL for the partial adrenalectomy. The postoperative course was uneventful and surgical outcome was excellent in each group. In conclusion, our results are encouraging enough to suggest that laparoscopic adrenalectomy should be a preferential therapeutic option for benign adrenal tumors; also, partial adrenalectomy could be a safe, effective, and less invasive procedure in selected cases.

Expression of vascular endothelial growth factor and thrombospondin-1 in colorectal carcinoma.

Solid tumors require neovascularization for growth and metastasis. Vascular endothelial growth factor (VEGF) is a well-characterized inducer of angiogenesis, while, thrombospondin-1 (TSP-1) is thought to be an antiangiogenic factor. In this study, we examined the expressions of these antigens and their relationship with microvessel density, and determined their prognostic significance. One hundred specimens resected from patients with colorectal adenocarcinoma were examined using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumors that were VEGF-positive and TSP-1-negative than in other tumors. Patients with VEGF-positive tumors had a significantly worse prognosis than did those with VEGF-negative tumors, and TSP-1 expression was inversely correlated with prognosis. The frequency of hepatic recurrence was significantly higher in patients with tumors that were VEGF-positive and TSP-1-negative than in all other patients. In conclusion, VEGF and TSP-1 are important regulators of tumor angiogenesis, and combined analysis of VEGF and TSP-1 may be useful for predicting recurrence in patients with colorectal adenocarcinoma.

[A late phase II study of raltitrexed (ZD 1694) in chemotherapy-naive patients with advanced colorectal cancer].

A multicenter co-operative late phase II study of raltitrexed (ZD1694), a specific thymidylate synthase (TS) inhibitor, was conducted in chemotherapy-naive patients with advanced colorectal cancer. Raltitrexed was infused intravenously over 15 minutes once every three weeks. Between April 1996 and September 1998, 61 patients were enrolled and 58 were eligible. Fourteen patients experienced a partial response (PR), 22 no change (NC), 20 progressive disease (PD) and 2 no evaluable (NE). The overall response rate was 24.1% (95% CI: 13.9-37.2%). Responses were seen in lung (22.7%), liver (22.9%) and deep lymph nodes (10.0%). Median survival was 11.6 months. Grade 3 or 4 toxicities were: leukopenia (13.8%), neutropenia (24.1%), hemoglobin decrease (15.5%), FBC decrease (6.9%), hematocrit decrease (6.9%), thrombocytopenia (6.9%), transient SGPT increase (6.9%), nausea/vomiting (20.7%), anorexia (15.5%), and asthenia (6.9%). These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.

The thoracoscopic approach for internal mammary nodes in breast cancer.

BACKGROUND: This pilot study was conducted to estimate the use of the thoracoscopic surgery as a new approach for the internal mammary nodes (IMN) in breast cancer. PATIENTS AND METHODS: For this study, 21 women with breast cancer who underwent the approach for nodes IMN were enrolled. All the women had suspicious IMN metastasis and no distant metastasis. RESULTS: Thoracoscopic IMN dissection was performed safely for 20 of the women, with an average operative time of 44 min. One woman was excluded from the procedure because of pleural adhesion. The patients were restricted from walking for 1.3 days because of chest drainage, but no patients had severe complication or chest wall deformity after the operation. Six patients had positive IMN outcomes. After surgery, 10 of the 20 patients had a lower tumor node metastases (TNM) staging. Two patients who tested positive for IMN and three who tested negative experienced a relapse, but none had pleural dissemination in a median follow-up period of 24 months. CONCLUSION: Thoracoscopic surgery may be useful in managing patients with IMN.

External pancreatic juice drainage through a percutaneous endoscopic drainage tube for the patient with a postoperative pancreatic juice leakage.

Percutaneous endoscopic gastrostomy (PEG) has been widely accepted for patients who have no swallowing ability but have an intact gut. Its clinical application is mainly for nutritional support and decompression of the intestine in patients with bowel obstruction. In this paper, we report external pancreatic juice drainage through a percutaneous endoscopic drainage tube in a patient with postoperative pancreatic juice leakage. Soon after this procedure, pancreatic juice leakage subsided. This procedure was minimally invasive for the patient and may be a new application of PEG to maintain the good quality of life (QOL) in a patient with pancreatic juice leakage.

Expression of the mismatch repair gene hMSH2 in sporadic colorectal cancer.

At least four genes involved in DNA mismatch repair (MMR), hMSH2, hMLH1, hPMS1 and hPMS2, have been cloned and characterized. These genes have been demonstrated to be altered in the germline of patients with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is an autosomal dominant disease characterized by a preponderance of proximal colon, young age of onset, increased multiplicity, and improved stage-specific survival. In this study, we examined the expression of hMSH2 protein in sporadic colorectal cancer (CRC). As a result, the frequency of right-sided CRC and multiple CRCs were significantly higher in the patients with hMSH2-negative CRC than in those with hMSH2-positive CRC. The rate of p53 positivity was significantly lower in the hMSH2-negative tumours than that in the hMSH2-positive tumours. The disease-free survival rate tended to be higher in the patients with hMSH2-negative CRC than in the patients with hMSH2-positive CRC. Our findings suggest that both the clinicopathological and biological features of hMSH2-negative sporadic CRC seemed to be similar to those of HNPCC. To clarify the mechanism of carcinogenesis in HNPCC and sporadic CRC, further investigations of genetic alterations caused by MMR genes will be needed.

Cyclin D1 overexpression and prognosis in colorectal adenocarcinoma.

Recently, it has been reported that cyclin D1 plays a major role in oncogenesis in various cancers; however, there have been few studies on the association of cyclin D1 overexpression and prognosis of patients with malignant tumors. We evaluated the prognostic significance of cyclin D1 overexpression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal adenocarcinomas were investigated by staining with a monoclonal antibody against cyclin D1. As a result, both overall survival and disease-free survival were significantly poorer in the patients with tumors strongly positive for cyclin D1 than in those with cyclin-D1-negative or weakly positive tumors. The 5-year survival rate of the patients with tumors strongly positive for cyclin D1 was 53.3%, while the 5-year survival rates of patients with cyclin-D1-negative and weakly positive tumors were 96.2 and 78.8%, respectively. Moreover, multivariate analysis indicated that cyclin D1 overexpression is an independent predictor of disease recurrence in our patients. In conclusion, cyclin D1 overexpression may be useful as a predictor of disease recurrence in colorectal adenocarcinoma.

Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis.

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.

Laparoscopic adrenalectomy: comparison with the conventional approach.

Laparoscopic adrenalectomy (LA) was performed on 14 patients with adrenal tumors. Herein we describe the laparoscopic procedure and the patients' clinical course compared with those of patients who underwent the conventional posterior or transabdominal approach (PA, TA). The 14 patients included four men and 10 women aged 28 to 69 years. Clinical diagnoses in this series were primary aldosteronism in seven patients, Cushing's adenoma in four patients, and nonfunctioning tumor in three patients. Maximum diameters of the adrenal tumors ranged from 10 to 48 mm. In all patients, the adrenal tumors were removed successfully. The mean operating time was longer for LA- than for PA- or TA-treated patients (185 versus 99 and 143 min), whereas the mean blood loss was smaller for LA- or PA-treated (92 and 126 ml) than for TA-treated patients (407 ml). The patients' postoperative condition, as assessed in terms of the number of febrile days, leucocytosis, and elevation of C-reactive protein value, was significantly better with LA. In addition, the frequency of administration of analgesics was lower and the time required until the patient could walk were shorter after LA than after PA and TA. In conclusion, laparoscopic adrenalectomy appears to be a minimally invasive and safe therapeutic option that may become a standard procedure for adrenal surgery.

[Malignancy of colorectal cancer analyzed by expression of cyclin D1].

We evaluated the clinical significance of cyclin D1 expression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal cancers were investigated by staining with a monoclonal antibody against cyclin D1. The possible correlations among cyclin D1 expression, clinicopathologic factors and prognosis were studied. There was no significant association between cyclin D1 expression and various clinicopathological factors. However, disease-free survival was significantly worse in the patients with cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors. Cyclin D1 overexpression may be useful as a predictor of disease recurrence in patients with colorectal adenocarcinoma.

Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma.

[Single-dose toxicity studies of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in mice, rats and dogs].

Comparative single-dose toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a new drug for the treatment of urinary frequency and incontinence, were conducted in ddY mice and Sprague-Dawley rats after oral(p.o.),intraperitoneal(i.p.) and subcutaneous(s.c.) administration, and in Beagle dogs after p.o. administration. The p.o. LD50 values of NS-21 were 852 and 1167 mg/kg for male and female mice, 2839 and 1739 mg/kg for male and female rats, respectively. The i.p. LD50 values were 324 and 390 mg/kg for male and female mice, and 423 and 359 mg/kg for male and female rats, respectively. No death occurred in mice and rats at doses up to s.c. 5000 mg/kg. Minimum lethal dose for dogs could not be determined because of vomiting. Mydriasis was noted in all three species tested without regard to administration route. In addition, decreased spontaneous locomotor activity, prone or lateral position, hypopnea, hypothemia, ataxic gait, twitch and clonic convulsion were observed in mice and rats after p.o. and i.p. administration. In rats, salivation was observed after p.o. administration and lacrimation was observed after p.o. and i.p. administration. After s.c. administration, scab formation at the site of injection was observed in mice and rats. In dogs, vomiting, hyperemia of both conjunctiva and oral mucosa, prone position, tremor and clonic convulsion were observed after p.o. administration. Body weight was decreased or its gain was suppressed in mice and rats without regard to administration route. Body weight and food consumption were decreased in dogs after p.o. administration. Pathological examination showed congestion of lung in dead mice and rats after p.o. and i.p. administration. Distention of small intestine was observed in dead mice and rats after p.o. administration and in sacrificed rats after p.o. administration. Adhesion between the abdominal organs was observed in sacrificed mice and rats after i.p. administration. Thymic atrophy associated with a decrease in its organ weight was observed in dogs after p.o. administration.

[Intraperitoneal single-dose toxicity studies of active metabolite, optical isomers, hydrolysis products and bi-product of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in mice].

NS-21, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, is a new drug for the treatment of urinary frequency and incontinence. To evaluate acute toxicities of its related compounds including the optical isomers of NS-21 ((S)NS-21 and (R)NS-21), the active metabolite of NS-21 ((R/S)RCC-36), the optical isomers of (R/S)RCC-36 ((S)RCC-36 and (R)RCC-36), the hydrolysis products of NS-21 (RCC-32 and RCC-38) and the bi-product of NS-21 (RCC-66), single-dose intraperitoneal toxicity studies were conducted in ddY mice. The LD50 values of these compounds in male and female mice were as follows: 199 and 184 mg/kg for (S)NS-21, 261 and 240 mg/kg for (R)NS-21, 74 and 100-150 mg/kg for (R/S)RCC-36, 93 mg/kg for (S)RCC-36 in both sexes, 83 and 104 mg/kg for (R)RCC-36, higher than 510 mg/kg for RCC-32 in both sexes, 340-510 mg/kg for RCC-38 in both sexes, and 1000-2000 mg/kg for RCC-66 in both sexes, respectively. The clinical signs included decreased spontaneous locomotor activity, prone or lateral position, ataxic gait, clonic convulsion, hypopnea, hypothermia, pale skin, mydriasis, abdominal distention and unkempt fur for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36 and (R)RCC-36, decreased spontaneous locomotor activity, prone position, ataxic gait, clonic convulsion, tail elevation and hypopnea for RCC-32 and RCC-38, and decreased spontaneous locomotor activity and unkempt fur for RCC-66. Body weight was decreased or its gain was suppressed for every compound examined. Pathological examination of the dead mice showed atrophy of the thymus and spleen, intestinal distention with the retention of dark red contents, white spots or white materials in the abdominal fatty tissue for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36, (R)RCC-36 and RCC-66, but no treatment related change for RCC-32 and RCC-38. Adhesion between the abdominal organs was observed in survivors treated with (S)NS-21, (R)NS-21, (S)RCC-36, (R)RCC-36, RCC-32 and RCC-66.