Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma.

BACKGROUND: Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. METHODS: Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. RESULTS: In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. CONCLUSION: PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection.

Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists.

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30-40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (kappa) statistics for multiple raters. The kappa-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The kappa-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275-0.315, with a standard error of 0.083-0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis.

[Castleman lymphoma originated from the posterior mediastinum resected thoracoscopically: report of a case].

We report thoracoscopic resection of Castleman lymphoma originated from the posterior mediastinum. The patient was a 19-year-old woman, who was pointed out to show an abnormal shadow in the left upper lung in the chest X-ray photograph. It was diagnosed as a blood-rich posterior mediastinal tumor by dynamic MRI, and thoracoscopic surgery was performed. The tumor was adjacent to the vertebral body of the fourth thoracic vertebra. Although operation involved 2 hours and 40 minutes and 670 ml of bleeding due to a strong adhesion between the tumor and the intercostal muscle and considerable bleeding from the tumor itself, it was successfully removed under thoracoscopy. The tumor was elastic and hard, and 50 x 45 x 25 mm in size. The histopathological diagnosis was a Castleman lymphoma, hyaline vascular type. The postoperative course was satisfactory, and the patient was discharged from the hospital on the 7th postoperative day. Castleman lymphoma originated from the posterior mediastinum tends to bleed considerably during its resection. If a blood-rich posterior mediastinal tumor was found preoperatively, thoracoscopic operation must be advanced carefully keeping this disease in mind.

[Cases of death after surgery for pathologic stage I non-small cell lung cancer].

We clinically examined cases of death from pathologic stage I non-small cell lung cancer with the aim of improving the 5-year survival rate after surgery for this condition. The subjects were 70 patients with p-stage IA (20 cases of death) and 59 patients with p-stage IB (26 cases of death) from among those who underwent surgery for p-stage I non-small cell lung cancer between 1986 and 2000. 1) Of 30 patients who died from p-stage I lung cancer, 20 had distant metastases and 10 had recurrence in the thoracic cavity. Of 16 patients who died from other diseases, 5 had respiratory organ disease, 5 had cancers of other organs and 6 had circulatory organ disease. 2) Of 30 patients who died from p-stage I lung cancer, 20 (66.7%) had distant metastases, with lung metastasis occurring most frequently, in 10 of them (33.3%). The most common cause of death of patients with p-stage IB lung cancer was recurrence in the thoracic cavity. 3) The mean durations of survival (mean +/- standard deviation) after surgery for lung cancer of the patients who died from p-stage I lung cancer (30 patients) were 36.3 +/- 22.2 months for the 20 patients with distant metastases and 26.2 +/- 14.3 months for the 10 patients with recurrence in the thoracic cavity, the difference between groups was 10 months, but was not significant. 4) The 5-year survival rate in 45 patients who underwent p-stage IA mediastinal lymph node dissection was 83.1% whereas that in 25 patients without p-stage IB mediastinal lymph node dissection was 50.9% showing a significant difference of 32.2% (p < 0.01). 5) The patients in p-stage IA who died from other diseases were all men (10 patients). The mean durations of survival after surgery for lung cancer in the patients who died from other diseases were 35.2 +/- 19.0 months in the patients with respiratory organ disease, 37.0 +/- 23.9 months in those with cancers of other organs and 60 +/- 19.1 months in those with circulatory organ disease. 6) The 5-year survival rate after surgery in all cases of death was 76% in the patients in p-stage IA and 61.4% in those in p-stage IB. The 5-year survival rates in the patients excluding those who died from other diseases were 85% in the patients in p-stage IA (60 patients) and 60.3% in those in p-stage IB (53 patients) (p < 0.01). 7) To improve the 5-year survival rate in the patients with p-stage IA lung cancer, it is necessary to prevent death from other diseases in men. It is still possible to improve the 5-year survival rate in the patients with p-stage IB lung cancer by raising the accuracy of mediastinal lymph node dissection during surgery.

Expression profiling of sulfotransferases in human cell lines derived from extra-hepatic tissues.

To explore the physiological roles of sulfotransferases (SULTs) in extra-hepatic tissues, we examined the expression of eight SULT genes by reverse transcription (RT)-PCR in human cell lines that were established from various tissues. Expression levels of SULTs were low in neural cell lines such as NB-1 and GI-1, and high in epithelial cell lines, such as Caco-2 and BeWo. SULT1C2 expression was abundant in all cell types, whereas that of SULT1E1, SULTIBI or SULT2B1 was restricted to a specific cell type. SULT1C1, which can catalyze the sulfation of N-hydroxy-2-acetylaminofluorene, was expressed in Caco-2, BeWo and KB562. Induction of differentiation did not generally affect SULT expression, although that of SULT1C2 was reduced after differentiation of the neuroblastoma cell line, NB-1, was induced. The profile of SULT expression in the culture cells obtained here gives clues to understanding the physiological roles of SULT enzymes in extra-hepatic tissues or organs.

The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in nonsmall cell lung carcinoma patients.

BACKGROUND: Angiogenesis has important effects on tumor growth and metastasis. It is regulated by a variety of angiogenic and angiostatic factors. METHODS: To evaluate the effects of tumor cell-derived angiogenic factors, we performed an immunohistochemic study to evaluate the intratumoral expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in relation to intratumoral microvessel density (IMD) in tumors from 104 nonsmall cell lung carcinoma (NSCLC)patients. RESULTS: Fifty-four carcinomas were VEGF-positive, 47 carcinomas were IL-8-positive, and 53 carcinomas were hypervascular tumors. There was no significant correlation between the percentages of positive VEGF-staining and positive IL-8-staining in NSCLCs (rho = 0.174, P = 0.080). The IMD of VEGF-positive carcinomas was significantly greater than that of VEGF-negative carcinomas (P = 0.023). In addition, the IMD of IL-8-positive carcinomas was significantly greater than that of IL-8-negative carcinomas (P =0.013). The overall survival rate of patients with hypervascular tumors was significantly lower than that of patients with hypovascular tumors (41.0% versus 67.0%, P = 0.004). Cox proportional-hazards regression model also demonstrated that angiogenesis was one of the significant factors in predicting the survival of NSCLC patients (relative risk = 1.944, P = 0.041). CONCLUSIONS: Intratumoral expression of VEGF and IL-8 was associated with angiogenesis in NSCLCs. Tumor angiogenesis significantly affected the prognosis of NSCLC patients.

Comparative trial of stent-like balloon angioplasty versus coronary stenting for acute myocardial infarction.

Primary PTCA has been shown to be superior to any thrombolytic regimen and offers higher reperfusion rates and better coronary flow grades. Its limitations include recurrent ischemia (10%-15%), infarct-related artery reocclusion (5%-10%), angiographic restenosis (35%-50%), and need to perform repeat PTCA or CABG at 6-month follow-up (20%). Thus, the current role of coronary stenting for acute myocardial infarction (AMI) is very promising. From December 1995 through January 1997, 335 patients underwent primary angioplasty during the first 12 hr from symptom onset at our institution. We performed a retrospective study comparing the in-hospital and 6-month follow-up outcome of 61 patients who underwent coronary stenting (stent group) against 61 patients with optimal (residual lesion stenosis < 30%) balloon-only primary angioplasty (stent-like group). Patients were routinely treated with aspirin, and ticlopidine was given only to the stent group. In-hospital major adverse cardiac events (MACE) rate was 11.5% without statistical differences between the groups. Cardiac death rate was similar in both groups (4.9 vs. 6.6%; P = 1.0) and only two (3.3%) patients from the stent group and none from the PTCA group had nonfatal myocardial reinfarction. At 6-month follow-up, the rate of recurrent angina was higher in the stent-like group (30.9 vs. 7.1%; P < 0.001). Multivariate analysis showed that only stenting of the infarct-related artery was a borderline independent predictor for MACE (OR = 0; 95% CI = 0-1; P = 0.057). Primary stenting for AMI reduces the rate of recurrent angina or symptoms and MACE at 6-month follow-up.

[A case with lung metastasis of osteosarcoma occurred 21 years after the operation of osteosarcoma on left tibia].

The patient was a 38-years-old woman. A chest X-ray film demonstrated the presence of an abnormal lesion. Her past history included osteosarcoma on the left tibia for which she received amputation of the left inferior limb at 17 years of age without any relapse thereafter. Considering that the patient might have lung metastasis of osteosarcoma on the basis of lung biopsy performed under CT guide, and then a tumor was removed under the thoracoscope. The tumor, 2.8 x 2.2 x 2.1 cm in size, was located right under the pleura at left S10 with its inside being filled up with fragile necrotic tissues. When compared pathohistologically with the primary lesion of osteosarcoma which had occurred 21 years before, the lung tumor was almost identical in terms of the tumor cell morphology but had a higher cell density without evidence of osteoid formation. The diagnosis of lung metastasis of osteosarcoma was established on the basis of the clinical course and the immunohistochemical staining. It is extremely rare case that osteosarcoma recurs in the form of lung metastasis 21 years after the operation of primary lesion. We report this case as a valuable one to identify the prognosis of osteosarcoma and the development mechanism of lung metastasis.

Establishment and characterization of chondrocyte cell lines from the costal cartilage of SV40 large T antigen transgenic mice.

Complete understanding of the physiology and pathology of the cartilage is essential to establish treatments for a variety of cartilage disorders and defects such as rheumatoid arthritis, congenital malformations, and tumors of cartilage. Although synthetic materials have been used in many cases, they possess inherent problems including wear of the materials and low mechanical strength. Autograft has been considered very effective to overcome these problems. However, the limitation of the transplant volume is a major problem in autograft to be overcome. The costal cartilage is the most serious candidate for donor site transplantation, since it is the largest permanent hyaline cartilage in the body. To investigate the possibility using the costal cartilage as a transplant source, we have established and characterized three mouse chondrocyte cell lines (MCC-2, MCC-5, and MCC-35) derived from the costal cartilage of 8-week-old male SV40 large T-antigen transgenic mice. At confluence, all the cell lines formed nodules that could be positively stained with alcian blue (pH 2.5). The size of nodules gradually increased during culturing time. After 2 and 6 weeks of culture, RT-PCR analysis demonstrated that all three cell lines expressed mRNA from the cartilage-specific genes for type II collagen, type XI collagen, aggrecan, and link protein. Furthermore, type X collagen expression was detected in MCC-5 and MCC-35 but not in MCC-2. Any phenotypic changes were not observed over 31 cell divisions. Immunocytochemistry showed further that MCC-2, MCC-5, and MCC-35 produced cartilage-specific proteins type II collagen and type XI collagen, while in addition MCC-5 and MCC-35 produced type X collagen. Treatment with 1alpha, 25-dihydroxyvitamin D(3) inhibited cell proliferation and differentiation of the three cell lines in a dose-dependent manner. These phenotypic characteristics have been found consistent with chondrocyte cell lines established from cartilage tissues other than costal cartilage. In conclusion, costal cartilage shows phenotypic similarities to other cartilages, i.e., articular cartilage and embryonic limbs, suggesting that costal cartilage may be very useful as the donor transplantation site for the treatment of cartilage disorders. Furthermore, the cell lines established in this study are also beneficial in basic research of cartilage physiology and pathology.

E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer.

BACKGROUND: E-Cadherin plays a major role in maintaining the intercellular junctions in epithelial tissues. The reduction of E-cadherin expression in cancer cells may be associated with tumor differentiation, metastasis, and a poor prognosis. METHODS: Immunohistochemistry for E-cadherin expression was performed on 109 tumors from patients with non-small cell lung cancer who underwent operations. RESULTS: With respect to membranous immunostaining, 57 carcinomas were E-cadherin-positive, 39 carcinomas E-cadherin-reduced, and 13 carcinomas E-cadherin-negative. The percentage of poorly differentiated tumors in the impaired E-cadherin expression group was significantly higher than that in the E-cadherin-positive group (p = 0.005). Furthermore, the frequency of lymph node metastases in tumors with impaired E-cadherin expression was significantly higher than that in the E-cadherin-positive tumors (p = 0.011). A Cox regression analysis revealed that E-cadherin expression was a significant factor in the prediction of survival for patients with non-small cell lung cancer (p = 0.002). CONCLUSIONS: E-Cadherin expression was associated with tumor differentiation, lymph node metastasis, and prognosis in patients with non-small cell lung cancer.

[Lobectomy of two or more lobes in patients with lung cancer].

We clinically examined patients who had undergone resection of two or more lobes for lung cancer. The subjects were 50 patients (25 who underwent pneumonectomy and 25 bilobectomy) who underwent lobectomy of two or more lobes from among those with primary non-small cell lung cancers in our hospital between 1975 and 1999; these individuals were assigned to Group A, and compared with 166 patients with lobectomy in Group B. The five-year survival rate was 27.7% in Group A, which differed significantly from the rate of 55.6% in Group B (p < 0.01, Kaplan-Meier method with log-rank test). The percentage of Stage I patients was 34% (17 patients) in Group A and 60.2% (100 patients) in Group B: this difference was significant (chi 2 test, p < 0.01). There were more patients with advanced cancer in Group A than in Group B. However, the five-year survival rates of Stage I patients were 52.4% in Group A and 77.6% in Group B, and significantly different (p < 0.05). In a comparison with respect to histological type, the five-year survival rates also differed significantly between Group A and B (p < 0.01 for adenocarcinoma, p < 0.05 for squamous cell carcinoma, with higher values in Group B for both). Resection of two or more lobes was indicated based on infiltration of the main tumor into adjacent lobes in 19 patients (38%), infiltration of lymph node metastasis into a bronchus or pulmonary artery in 14 (28%), direct infiltration of the main tumor into a bronchus in 10 (20%), and for other reasons in 7 (14%). The five-year survival rates for these groups were 15.8, 22.1, 54 and 42.9%, respectively. There was a significant difference between the patients with infiltration of cancer into adjacent lobes and those with direct infiltration into a bronchus (p < 0.05). The prognosis of patients with resection of two or more lobes was poorer than that of patients with lobectomy even in Stage I. In particular, infiltration of cancer into adjacent lobes accompanied lymph node metastasis in more than 50% in cases, and appeared to suggest a poor prognosis.

Expression of telomerase components in oral keratinocytes and squamous cell carcinomas.

Telomerase activity was measured using a telomeric repeat amplification protocol (TRAP), and expressions of the telomerase components, telomerase associated protein 1 (hTEP1), human telomerase RNA component (hTR), and human telomerase reverse transcriptase (hTERT) were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) in cultured normal oral keratinocytes and oral squamous cell carcinoma (SCC) cells. Telomerase localization was analyzed by in situ hybridization (ISH) in normal, precancerous and cancerous oral tissues. There was a strong correlation of telomerase activity with the expression levels of hTERT but not with hTEP1 or hTR mRNA in the cultured cells. Not only hTEP1 and hTR but also hTERT expression were detected in the basal cells of normal oral mucosa, and the cells expressing these mRNAs were also seen in the upper layer of leukoplakia of gingiva, and a heterogeneous pattern of expression was observed in the oral SCC tissues. These results indicate that there are at least two steps in the increase of telomerase activity during carcinogenesis in oral squamous cells; a change in distribution of cells expressing these telomerase components and the over-expression of hTERT gene in individual cells.

Reverse correlation of E-cadherin and snail expression in oral squamous cell carcinoma cells in vitro.

The loss of E-cadherin expression has been shown to correlate to the invasion and metastasis of many types of carcinomas. We established E-cadherin positive (HOC719-PE) and negative (HOC719-NE) clones from an oral squamous cell carcinoma (SCC). HOC719-PE cells showed epithelial morphology with E-cadherin expression in the cell membrane, whereas HOC719-NE cells demonstrated fibroblastic morphology without E-cadherin expression. In invasion assay and three dimensional culture, HOC719-NE showed much higher invasive ability than HOC719-PE cells. These cells expressed similar levels of mRNAs for alpha- and beta-catenin. However, HOC719-NE cells, but not HOC719-PE cells, showed strong expression of snail, a transcription factor implicated in the differentiation of epithelial cells into mesenchymal phenotype. This reverse expression of snail and E-cadherin was further observed in other SCC cells including HOC313, and TSU cells that we previously reported to show no expression of E-cadherin protein. These results indicated that the expression of snail has a key role for the acquisition of more invasive and metastatic phenotypes of SCC and the clones we reported here will be useful tools for understanding the mechanism of the transition from epithelial to mesenchymal SCC cells.

[A case of sarcoidosis with simultaneous involvement of the lower brainstem and the whole cervical cord and the extraocular muscles].

We report a 63-year-old woman with sarcoidosis which involved the spinal cord, lower brainstem and extraocular muscules simultaneously. In this patient, uveitis developed in 1991 and the skin lesion in 1992. A biopsy of the skin lesion showed changes consistent with sarcoidosis. The ocular and dermal symptoms improved with oral corticosteroid. In October 1997, she noted the left blepharoptosis and numbness of the hands. The MRI showed diffuse swelling of the lower brainstem and the cervical and upper thoracic cord. These lesions showed high intensity signal on T2WI and low intensity signal on T1WI. T1WI with contrast enhancement revealed localized enhancement within the spinal lesion at the C4/5 level. The ocular MRI showed swelling of the left superior rectus muscle and upper levator palpebral muscle. The steroid pulse therapy and subsequent oral administration of prednisolone markedly improved the clinical symptoms. MRI after treatment showed marked improvement of both the spinal cord and ocular muscle lesions. To our knowledge, the simultaneous occurrence of myelopathy and symptomatic extraocular musculopathy in the condition has not been reported previously.

A case of primary squamous cell carcinoma of the breast with rapid progression.

Primary squamous cell carcinoma of the breast is a rare disease for which no definite treatment or prognosis has been established. This report describes our experience with one case of primary squamous cell carcinoma of the breast that ended in death after rapid progression. The patient was a 58 year old woman who visited our hospital complaining of a growing tumor and pain in the right breast. Ultrasonographically the tumor consisted of solid tumor and a large cyst. Squamous cell carcinoma was diagnosed by fine-needle aspiration cytology. Neoadjuvant CEF was given, but the tumor continued to grow, so CEF was discontinued after one course and modified radical mastectomy was performed subsequently. There was no evidence of metastasis to lymph nodes. About 5 months post operatively CT of the head and chest X-ray demonstrated metastatic lesions in the brain and lungs. Resection of the cerebral tumor was performed. About 1 month after the operation, however, a new metastatic brain tumor was found and the patient later died.

[A case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis].

We report a rare surgically-treated case of G-CSF-producing large cell carcinoma of the lung with gastric metastasis. A 65-year-old male was admitted to our hospital because of fever, anemia and epigastralgia. Chest X-ray examination and CT scanning revealed a round mass shadow (8 cm) in contact with the chest wall in the right upper lung field and metastasis to the mediastinal lymph nodes. Laboratory examination showed a WBC of 16,800/mm3, CRP of 11.6 mg/dl, and a serum G-CSF of 90 pg/ml. Upper gastrointestinal series and gastroscopy showed an ulcerating submucosal tumorous lesion in the pyloric antrum. The lung carcinoma was treated by right upper lobectomy with chest wall resection. After 1 month, gastrectomy was performed. After the operation, the WBC normalized, and the CRP and serum G-CSF levels decreased. Histopathological examination demonstrated a poorly differentiated large cell carcinoma in the lung and a metastatic lesion in the stomach. Immunohistochemical staining with anti-G-CSF mono-clonal antibody showed negative results in the lung but positive results in the stomach. He was discharged 3 weeks after gastrectomy but died of aggravation of the general condition associated with local recurrence in the chest wall 2 months after discharge.

Transglutaminase-mediated dual and site-specific incorporation of poly(ethylene glycol) derivatives into a chimeric interleukin-2.

To expand the applications of poly(ethylene glycol) (PEG)-protein conjugates for clinical use, we have developed a novel method for dual and site-specific incorporations of PEG derivatives into proteins using a substrate peptide (AQQIVM, named TG2) and transglutaminase (TGase). In our previous studies, TG2 was shown to be a special peptide with two adjacent Gln substrates for guinea pig liver transglutaminase (G-TGase). We have now constructed a chimeric protein (named rTG2-IL-2) of human interleukin-2 (IL-2), in which TG2 was fused to the N-terminus of IL-2. For the G-TGase-catalyzed reaction, rTG2-IL-2 was dually and site-specifically modified with alkylamine derivatives of PEG (PEG10, average M(r) 10 kDa) at both the Gln2 and Gln3 residues in the appended tag. To demonstrate the effectiveness of the G-TGase-catalyzed PEG-incorporation, we have compared the characteristics and the biological properties of PEG10-rTG2-IL-2 species with two PEG10 molecules attached to rTG2-IL-2 [(PEG10)(2)-rTG2-IL-2] with that of (PEG10)(2)-rhIL-2(R), in which PEG10 was randomly incorporated into rhIL-2 by a general procedure using a N-hydroxysuccinimidyl ester of PEG (PEG10-COOSu) (M(r) 10 kDa). (PEG10)(2)-rTG2-IL-2 was found to be superior in its in vitro bioactivities and equivalent in its pharmacokinetic profiles to (PEG10)(2)-rhIL-2(R). Unlike most previous methods, this approach can place dual PEG chains at designed sites on chimeric proteins without decreasing their bioactivities. Thus, TGase-catalyzed PEG-incorporation would improve the therapeutic utility of PEG-protein conjugates.

Comparative study of Tc-99m MIBI and TI-201 SPECT in predicting chemotherapeutic response in non-small-cell lung cancer.

PURPOSE: Tc-99m MIBI can be excluded from cytosol against its concentration gradient as a suitable transport substrate by P-glycoprotein. Tc-99m MIBI has also been shown to be more effective than TI-201 chloride for evaluating the response to chemotherapy in patients with small-cell lung cancer. The relation between Tc-99m MIBI accumulation by the tumor and its response to chemotherapy were evaluated in patients with non-small-cell lung cancer (NSCLC) and compared with the same parameters achieved using TI-201 chloride. METHODS: Thirty-eight patients with NSCLC were examined before chemotherapy was begun. They were classified according to the results of a follow-up computed tomogram into two groups: responders were patients in whom there was a > or =50% decrease and nonresponders were patients in whom there was a <50% decrease in the sum of the product of the maximum perpendicular diameters of all measurable lesions. All patients underwent dual-isotope imaging with TI-201 chloride and Tc-99m MIBI just before chemotherapy. Regions of interest were placed over the tumor uptake (T) and contralateral normal lung tissue (N) areas on one coronal view with a clearly defined lesion, and the T:N ratio and retention index were calculated. RESULTS: The delayed T:N ratio and retention index for Tc-99m MIBI in the responder group were significantly greater (P<0.05) than those in the nonresponder group. There was no significant correlation between the T:N ratio and retention index and tumor response using TI-201 chloride. CONCLUSION: Tc-99m MIBI SPECT may be more effective than TI-201 chloride SPECT for evaluating the response to chemotherapy in patients with NSCLC.