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Biomedical subjects

Masaki Kitajima

Publications and source records attributed to Masaki Kitajima.

At least 109 records · Page 6Linked to original sources

Significance of metastasis detected by molecular techniques in sentinel nodes of patients with gastrointestinal cancer.

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Esophageal Neoplasms↗

The evolution of primary chemotherapy in breast cancer treatment.

Primary chemotherapy may be thought of as having evolved over three generations. First-generation primary chemotherapy followed trials which proved that the prognosis of breast cancer patients receiving primary chemotherapy was the same as that of patients receiving post-operative chemotherapy. Second-generation primary chemotherapy followed trials which demonstrated that regimens containing anthracyclines and taxanes yielded complete pathological response rates (pCR)of over 20%. Third-generation primary chemotherapy followed trials which demonstrated that inclusion of newer agents, such as trastuzumab and capetitabine, in combination with taxanes could yield pathological CR rates of over 30%. In third-generation primary chemotherapy, predictive factors, especially those analyzed by DNA array analysis, play a key role. Other issues, including the relevance of sentinel node biopsy after primary chemotherapy and the importance of marking the site of the primary tumor before primary chemotherapy in cases showing cCR, are highlighted. This article deals with the history of the evolution of primary chemotherapy, along with a discussion of some relevant issues.

Antineoplastic Combined Chemotherapy Protocols↗

Lymphoscintigraphy for the visualization of sentinel lymph nodes and body contour.

BACKGROUND: It is important to create clear lymphoscintigraphic images when assessing the sentinel lymph nodes. This clarity needs to reach a level where the sentinel lymph nodes (SLNs) and the body contour are clearly visible. We have developed a simple image processing method using the division of primary and scattered photon counts. METHODS: Twenty patients with breast cancer were enrolled in this study. Manual injection of 150 MBq of Tc-99m tin colloid with small particle size into the peritumoral and subdermal regions was performed. Lymphoscintigraphy using a conventional gamma camera was performed three hours after the injection. Dual energy windows were set from 130 to 150 keV for the primary photons and 70 to 110 keV for the scattered photons. An anterior view of the chest and a lateral view from the affected side were obtained. Primary photon image counts were divided by the scattered photon image counts for each pixel after the addition of some constant counts to each pixel of the acquired image to improve the contrast of the scintigrams. We evaluated the ability to accurately visualize the body contour and the SLNs on the processed image. RESULTS: Image processing time was 20 to 40 seconds for each patient. In every case, the processed image clearly identified the body contour. The processed images allowed the identification of the same number of SLNs as the original images. CONCLUSIONS: This proposed method for image processing is a simple and useful means to clearly visualize both SLNs and body contours.

Adult↗

Inhibition of bone metastasis from breast cancer with pamidronate resulting in reduction of urinary pyridinoline and deoxypyridinoline in a rat model.

BACKGROUND: Breast cancers frequently metastasize to bone, in a process in which osteoclasts play a major role. Bisphosphonate pamidronate, a specific inhibitor of osteoclasts, has been widely used in the treatment of bone metastasis (BM). In this study, using an animal model of BM, we examined the prophylactic and treatment effects of pamidronate against BM and clarified the relationships between BM, pamidronate and bone resorption markers such as urinary pyridinoline and deoxypyridinoline. METHODS: Bone metastases were established by inoculating c-SST-2 (spontaneously developed rat mammary adenocarcinoma) cells into the thoracic aorta of 27 rats, which were then divided into three groups of rats: the untreated control group, the pre-treatment group, consisting of rats treated with pamidronate (10 mg/kg) injected subcutaneously a day before tumor inoculation, and the post-treatment group, in which rats were injected with pamidronate a week after tumor inoculation. Three weeks after tumor inoculation, blood and urine samples were collected. The subjects were then sacrificed to harvest the thoracic and lumbar vertebrae for histological examination, consisting of staining with hematoxylin and eosin and tartrate resistant acid phosphatase (TRACP). RESULTS: The incidence of BM was 70.0%, 44.4% and 37.5% in the control, pre-treatment and post-treatment groups, respectively. Although there was no significant difference among the groups, the rate of BM in the treated groups was lower than that of the control group and no bone destruction was observed in treated rats. The TRACP-stained specimens revealed that there were numerous osteoclasts contributing to the control group tumor burden. The urinary levels of pyridinoline and deoxypyridinoline were reduced by pamidronate. CONCLUSION: Our results suggest that pamidronate prevents the development of BM and the destruction of bone associated with BM. Maintaining the values of Pyr and Dpyr at low levels with pamidronate might lead to inhibition of the incidence and development of BM.

Amino Acids↗

Sentinel nodes of malignancies originating in the alimentary tract.

The feasibility of the sentinel node concept for malignancies originating in the alimentary tract is attracting much interest among researchers in the field of gastrointestinal oncology. We have tested more than 350 such cases and obtained favorable and promising initial results. The detectability of sentinel nodes using endoscopically injected Tc-99m tin colloid for these tumors exceeded 90%. Although the false negative ratio was not so low (approximately 10%), most of these cases had an inaccurate preoperative evaluation of mural invasion and/or a technically unfavorable injection. When the indication is restricted to patients with early-stage disease, and when the radioactive colloid is properly administered, sentinel node navigation therapy would be applicable for gastrointestinal malignancies. To achieve successful sentinel node navigation surgery it is essential to accurately identify sentinel nodes, and lymphoscintigraphy is a very useful test to confirm the location of sentinel nodes preoperatively. However, image processing is required for lymphoscintigrams because the original image depicts only high activity at the injection site and faint radioactivity in the sentinel nodes. We have clearly imaged the silhouette of the body using Compton scattered photons, and have also proposed several methods to improve the contrast between the injection sites and sentinel nodes. Many sentinel nodes can be clearly visualized by subtraction of the background activity with heterogeneous distribution. The development of the portable gamma camera, enabling intraoperative imaging, also contributes to less invasive biopsy of sentinel nodes. We have obtained promising initial results using a portable imaging device with semiconductor detectors. These promising results suggest that sentinel node navigation therapy including radiotherapy will be a new therapy for early-stage gastrointestinal malignancies in the near future, with nuclear medicine contributing to the establishment of new, less invasive therapies for gastrointestinal cancer.

Colorectal Neoplasms↗

Effects of preinjury administration of corticosteroids on pseudointimal hyperplasia and cytokine response in a rat model of balloon aortic injury.

Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.

Angioplasty, Balloon↗

Hepatic artery pseudoaneurysm associated with cholecystitis that ruptured into the gallbladder.

Pseudoaneurysm of the hepatic artery due to cholecystitis may be very rare, and in our survey of the literature, the present case report is the first case of such a pseudoaneurysm. A 64-year-old woman presented with upper gastrointestinal bleeding and severe epigastric pain. Upper gastrointestinal tract endoscopy revealed blood coming out of the papilla of Vater. Color-Doppler ultrasound imaging showed a pulsatile wave pattern in an echogenic lesion inside the gallbladder. Contrast-enhanced computed tomography demonstrated a 3-cm pseudoaneurysm in the distended gallbladder. Angiography disclosed extravasation originating from the right hepatic artery. Emergency selective transcatheter arterial embolization was performed, with intravascular stainless steel microcoils, and complete occlusion of the pseudoaneurysm was achieved. The patient underwent cholecystectomy with resection of the extrahepatic bile duct and biliary reconstruction in a Roux-en-Y fashion. Macroscopically, the resected gallbladder contained clotted blood and multiple cholesterol stones. Microscopically, the mucosa of the gallbladder showed extensive necrosis and many inflammatory cells. The final diagnosis was pseudoaneurysm of the hepatic artery associated with calculous gangrenous cholecystitis. Although the mechanism of the pseudoaneurysm remains speculative, severe inflammatory reaction in the gallbladder may have infiltrated the liver parenchyma and may have eroded the wall of the hepatic artery, thus forming a pseudoaneurysm. Hemobilia is one of the important differential diagnoses when unexplained gastrointestinal bleeding is observed, especially in patients with hepatobiliary diseases.

Aneurysm, False↗

Intraductal growth of a nonfunctioning endocrine tumor of the pancreas.

Intraductal growth of nonfunctioning endocrine tumors of the pancreas may be very rare, and our survey of literature shows only two cases have been described. We report a case of a 43-year-old man with a nonfunctioning endocrine tumor of the pancreas that uniquely grew within the lumen of the main pancreatic duct (MPD) without ductal involvement and completely obstructed the MPD. Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) were very helpful to delineate the intraductal growth of the tumor and to determine the resection line of the pancreas. A nonfunctioning pancreatic endocrine tumor is important to consider on differential diagnoses when complete obstruction of the MPD is demonstrated on ERCP. It is speculated that the tumor originated from precursor cells of the pancreatic duct or islet cells adjacent to the MPD and slowly proliferated within the lumen of the MPD.

Adult↗

Surgery for advanced gastric cancer after coronary artery bypass grafting using the right gastroepiploic artery: report of a case.

Ischemic heart disorders are often treated by coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA). We report the case of a 57-year-old man with a history of CABG using the RGEA, who underwent D2 radical total gastrectomy followed by Roux-en-Y anastomosis, with successful dissection of the #6 lymph nodes, while preserving the RGEA. The patient had a 9-month history of gastric cancer, during which time the Maruyama Vaccine (Specific Substance Maruyama, or SSM) was given as alternative therapy. This case report serves to demonstrate that radical gastrectomy can be safely performed after CABG using the RGEA, and that gastric cancer will progress in spite of SSM therapy.

Adenocarcinoma↗

Diagnosis and treatment of a gastric hamartomatous inverted polyp: report of a case.

Gastric hamartomatous polyps are rare and difficult to diagnose. We report the case of a 43-year-old woman admitted to our hospital after an upper gastrointestinal series revealed a submucosal tumor. Upper gastrointestinal endoscopy showed a submucosal tumor (SMT), which was eroded with a depression on its surface, in the upper corpus. Endoscopic ultrasonography showed a heterogeneous tumor in the third layer. A laparoscopic wedge resection of the stomach allowed us to perform complete resection of the tumor, which measured 2.8 cm in diameter. The pathological diagnosis was a gastric hamartomatous inverted polyp. The postoperative course was uneventful. Only 27 cases of gastric hamartomatous polyps have been reported in Japan. Hamartomatous inverted polyps without a stalk are classified as the "SMT type" because the tumor is inverted into the submucosal layer, whereas polyps with a stalk are classified as the "polyp type." All of the polyps in past reports were resected endoscopically; however, laparoscopic wedge resection may be indicated for SMT-type hamartomatous inverted polyps larger than 2.0 cm in diameter.

Adult↗

Granular cell tumor of the breast preoperatively diagnosed by fine-needle aspiration cytology: report of a case.

Granular cell tumors (GCTs) have a characteristic cytological appearance, and fine-needle aspiration cytology (FNAC) has been suggested to be the diagnostic modality of choice. However, the differential diagnosis has not yet been well described. We herein describe a rare case of GCT of the breast and discuss the differential diagnosis. A 53-year-old woman presented to our hospital with a left breast mass. In clinical and radiological examinations, the mass was suspected to be malignant. Cytologically, the tumor was composed of cohesive groups of cells with a syncytial appearance, and the cells contained abundant, finely eosinophilic cytoplasmic granules and small round-to-slightly-oval nuclei, thus suggesting the presence of benign GCT. The results of immunohistochemical staining supported the proposed deviation from Schwann cells. This case emphasizes the fact that GCTs are a rare but important possibility in the differential diagnosis of breast tumors, and that FNAC may provide clinically useful information on the management of such lesions.

Biopsy, Needle↗

Advanced gastric endocrine cell carcinoma with distant lymph node metastasis: a case report and clinicopathological characteristics of the disease.

Gastric pure endocrine cell carcinoma (ECC) is extremely rare. ECC occasionally shows multidirectional differentiation; that is, adenocarcinomatous and/or squamous proliferation. Because gastric ECC has aggressive biological behavior and shows frequent metastasis to liver and lymph nodes even in the early stage, the prognosis of patients having this disease is extremely poor. We treated a 75-year-old woman with advanced gastric pure ECC with total gastrectomy and lymph node dissection, and reviewed all the previously reported cases of this disease. We compared the clinicopathological findings of ECC with those of gastric carcinoma (GC) and found that ECC had significantly more frequent invasion to lymphatic and vascular lumens ( P < 0.01) and more frequent metastasis to lymph nodes ( P < 0.01) and liver ( P < 0.05) compared to GC. Gastric ECC smaller than 5 cm in the greatest dimension showed a higher percentage of advanced lesions (>T2) than GC ( P < 0.05), which could result in the difficulty of finding early ECC. The findings of the analyses we made in this report may account for the poor prognosis of this disease.

Aged↗

Clinical and pathological disappearance of peritoneal dissemination in a patient with advanced gastric cancer receiving chemotherapy with S-1 and low-dose cisplatin.

A 54-year-old woman with severe abdominal distention suffered from massive ascites. Cytological examination revealed adenocarcinoma cells, leading to a diagnosis of peritonitis carcinomatosa. Gastrointestinal fiberscopy (GIF) resulted in a histological diagnosis of type 4 advanced gastric cancer with signet-ring cell carcinoma. The clinical diagnosis was confirmed to be cT3(SE)cN1cM0cH0cP1, cStage IV gastric cancer, type 4, according to the Japanese classification of gastric carcinoma. The patient was treated with S-1 and low-dose cisplatin (CDDP) in order to alleviate the critical state of the disease. After the third cycle of the regimen, the clinical response of P1 was classified as a partial response (PR) according to the World Health Organization (WHO) criteria. The patient's appetite loss and abdominal discomfort were markedly alleviated. The patient experienced grade 2 leukocytopenia throughout the regimen. Surgery was performed. Ascites and peritoneal disseminated lesions were not observed, and cytological examination of the peritoneal washes was negative. Total gastrectomy with D1 lymph node dissection was performed, and the surgical diagnosis was sT3(SE)sN0sM0sH0sP0; sStage II. Microscopically, viable cancer cells were found to be scattered throughout the subserosal-serosal layers in the resected stomach. All of the samples from lesions that were potentially cancers involving peritoneal dissemination were diagnosed as fibrous scar tissues without any viable cancer cells. The patient is alive without recurrence at 10 months after surgery and 14 months after the initial chemotherapy. Thus, systemic chemotherapy with S-1/low-dose CDDP achieved desirable control of peritoneal disseminated cells, as assessed microscopically, suggesting that the regimen may be an effective strategy for the treatment of advanced gastric cancer with peritonitis carcinomatosa.

Ascites↗

Metachronous gastric carcinoma from a gastric tube after radical surgery for esophageal carcinoma.

BACKGROUND: Cases of metachronous gastric carcinoma arising from a gastric tube used for reconstruction have been increasing in long-term survivors of esophageal cancer in recent years. We investigated the characteristics of gastric tube carcinoma to determine the most appropriate approach to managing it. METHODS: Between 1980 and 1997, 508 patients underwent radical esophagectomy for esophageal carcinoma at Keio University Hospital. Reconstruction was performed with a gastric tube in 414 (81.5%) of them, and 8 of them developed a metachronous carcinoma in the gastric tube. The clinical and pathologic characteristics of the gastric tube carcinomas were evaluated in this study. RESULTS: Gastric cancer was detected during follow-up endoscopic examinations or in an upper gastrointestinal series in seven patients. All of the cancers were diagnosed as adenocarcinoma histopathologically. Endoscopic mucosal resection was performed in two patients, partial resection of the residual stomach was performed in three patients. One patient was treated by endoscopic mucosal resection as palliative therapy, since he had severe pulmonary emphysema. Total resection of the gastric tube was attempted in 2 advanced cases but was unsuccessful because of direct invasion of other organ by the cancer. The 5 patients who underwent curative resection are alive with no subsequent recurrence. CONCLUSIONS: Since early diagnosis permits less invasive treatment and curative treatment is difficult in advanced cases, strict postoperative examinations are important after radical esophagectomy to ensure early detection of metachronous gastric carcinoma arising from gastric tubes used for reconstruction.

Adenocarcinoma↗

Recent development of sentinel lymph node biopsy for breast cancer in Japan.

The number of breast cancer cases undergoing sentinel lymph node biopsy (SLNB) has been increasing with the number of articles published in Japan. SLNB using the dye method alone is performed in about one-third of patients. Analysis of questionnaire responses from 40 institutions in Japan revealed an identification rate by the dye method alone of 87%, compared with 96% using the combined method; the combined method is now recognized in Japan as superior to the dye method alone. No dyes have been specifically approved by the government for use in SLNB, and physicians have been using several inappropriate dyes as tracers for SLNB, such as indocyanine green, patent blue, indigo carmine, and isosulfan blue. The colloidal radiotracers used in Japan include tin colloid, stannous phytate, rhenium sulfate and human serum albumin. Albumin colloid and sulfur colloid are not commercially available in Japan. Small-size tin colloids, stannous phytate and rhenium sulfate all yield good results in terms of detection and false-negative rates. Provided that the surgeon has adequate experience in SLNB, a negative sentinel node can serve as a substitute for negative results from axillary lymph node dissection. Although many institutions have introduced SLNB, few reports have focused on the results of SLNB without axillary dissection because of short follow-up times and small number of patients. The final decision as to whether SLNB is an adequate substitute for axillary dissection awaits the results of prospective randomized trials.

Axilla↗