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Biomedical subjects

T Nagakawa

Publications and source records attributed to T Nagakawa.

At least 19 recordsLinked to original sources

Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?

BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined. METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease. CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.

Adult

Role of nodal involvement and the periductal soft-tissue margin in middle and distal bile duct cancer.

OBJECTIVE: To determine the pattern of middle (Bm) and distal (Bi) bile duct cancers in an attempt to optimize surgical treatment. SUMMARY BACKGROUND DATA: Lymph node involvement and neural plexus invasion are the prognostic factors most amenable to surgery in Bm and Bi disease. However, a detailed analysis of these factors has not been conducted. METHODS: Fifty patients with Bm and Bi disease (Bm 14 patients, Bi 36 patients) were examined histopathologically. A precise determination was made of lymph node involvement and neural plexus invasion. Important prognostic factors were examined by clinicopathologic study to apply these findings to surgical management. RESULTS: Frequencies of nodal involvement for Bm and Bi disease were 57% and 71%, respectively. The inferior periductal and superior pancreaticoduodenal lymph nodes were most commonly involved. Neural plexus invasion occurred in 20% of patients, particularly involving the plexus in the hepatoduodenal ligament and pancreatic head. Tumor was present at the surgical margin in 50% and 14% of patients with Bm and Bi disease, respectively. Five-year survival rates were 65% in the absence of nodal metastasis and 21% with nodal metastasis. A significant correlation existed between absence of tumor at the surgical margin and survival. A Cox proportional hazard model projected absence of tumor at the surgical margin, followed by nodal involvement, as the strongest prognostic variables. CONCLUSIONS: Absence of tumor at the surgical margin and nodal involvement are important independent prognostic factors in Bm and Bi disease. Skeletonization of the hepatoduodenal ligament, including portal vein resection, is necessary for patients with Bm disease, and a wide nodal dissection is essential in all patients.

Adult

Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan-1.

Bafilomycin A1, a specific inhibitor of vacuolar type H(+)-ATPase, can inhibit the growth of a variety of cultured cells in a dose-dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitro and in vivo was examined using an MTT assay and an in vivo tumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan-1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan-1 cell line tumour received 4 weeks of bafilomycin A1 (1.0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P < 0.05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan-1 human pancreatic cancer cells through apoptosis.

Adenocarcinoma

Cationic trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

We examined whether human pancreatic ductal cancer cells express and secrete pancreatic cationic trypsinogen in vitro which can be spontaneously converted into active trypsin at acidic pH (pH 4.5-5. 5), in contrast to anionic trypsinogen. Cationic trypsinogen expression at the mRNA level was observed in differentiated Capan-1 and BxPC-3 cell lines. However, expression was not detected in either poorly-differentiated Panc-1 or undifferentiated MIAPaCa-2 cell line. The gelatinolytic activity of the activated form of trypsinogen in each conditioned medium in the presence of enterokinase (1.0 microg/ml) (a band with a molecular weight of approximately 23 kDa) corresponded well to the level of cationic trypsinogen mRNA. The spontaneous activation of trypsinogen also was observed by gelatin zymography of the acid-loaded conditioned medium (pH 5.5). These findings suggest that trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton.

Culture Media, Conditioned

[Clinical assessment of contrast-enhanced ultrasonography for the diagnosis of gall bladder diseases].

We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) with intra-arterial injection of CO2 microbubbles in 37 cases of gall bladder diseases. CEUS clearly visualized arterial flow and vascularity in every lesions without debris and gave us the precise information of vascular structure for the differential diagnosis of gall bladder tumors. For example, highly bifurcated tumor vessels and strong enhancement was observed in gall bladder cancer and we could detect relatively strong enhancement along the lumen with lack of enhancement of Rokitansky-Aschoff sinus in localized-type adenomyomatosis. Though CEUS is now an invasive modality, it will enable us to understand the non-invasive modality such as color doppler imaging with intra-venous administration of microbubbles in the future.

Carbon Dioxide

[The evaluation of the pre-operative interviews using information sheets].

This investigation deals with patients of more than 15 years of age and family members of children younger than 12 years of age to evaluate the pre-operative interviews using information sheets. The information sheets describe the anesthetic management and complications in a simple style. Sixty% of the patients and 75% of the children's family felt anxiety about the anesthesia and/or the operation (P < 0.05). More than a half of the patients did not want to receive informations about the anesthetic management and the risk of anesthesia. On the other hand, 9% of children's family did not want to know informations about the risk (P < 0.05). More than 80% of patients read the information sheets after the pre-operative interviews and about a half of patients answered that their anxiety before the surgery decreased. In this investigation, the children's family wanted to have information about the anesthesia or the operation more than patients themselves. The pre-anesthetic interviews using information sheets is useful to give information about anesthesia and to relieve anxiety of the patients and the children's family.

Adolescent

Neurotrophin-3 expression in human pancreatic cancers.

Some neurotrophic factors stimulate process outgrowth in peripheral and/or central nerve fibres. There is no published report that has focused on the expression of neurotrophic factors in human pancreatic cancer except basic fibroblast growth factor. This study was therefore designed to examine the mRNA and protein levels of neurotrophin-3 (NT-3), which is one of the representative neurotrophic factors. The mRNA level for NT-3 was first investigated in eight pancreatic cancers and two samples of normal pancreas, using reverse transcription-polymerase chain reaction (RT-PCR). NT-3 protein expression was then studied in 47 human pancreatic cancers, using a monoclonal antibody against human NT-3 protein. There was a notable difference in the level of NT-3 mRNA between normal and pancreatic carcinoma tissues, with no evident difference in the expression of the beta-actin gene. Immunohistochemically, 34 of 47 pancreatic cancers (72 per cent) were mildly to markedly immunoreactive for NT-3 in the cytoplasma. Immunoreactivity was usually more pronounced at the infiltrative margins of the tumours. These observations suggest that pancreatic carcinoma overexpresses NT-3.

Adult

Total resection of the head of the pancreas preserving the duodenum, bile duct, and papilla with end-to-end anastomosis of the pancreatic duct.

Many surgeons have recently attempted operative procedures for limited resection of the head of the pancreas. This site-specific approach has emerged as a result of precise diagnostic radiologic studies that have become available. The author performed a new operative procedure in 2 patients with mucin-producing pancreatic cysts that included total resection of the head of the pancreas with careful regard to its vasculature. The procedure provided a way of resecting the head of the pancreas while preserving the duodenum, bile duct, and papilla. The pancreatic duct was cut 5 mm before the point of confluence with the bile duct, and an end-to-end anastomosis was performed on the pancreatic duct. Both patients were discharged within 1 to 1.5 months after surgery, without complication. The operative procedure requires no processing of the jejunum, only a simple anastomosis of the pancreatic duct.

Anastomosis, Surgical

Solitary cystic tumor of the pancreas: EUS-pathologic correlation.

BACKGROUND: It is clinically important to distinguish neoplastic from non-neoplastic pancreatic cysts. METHODS: Retrospective correlations were made between pathologic and EUS data from 52 pancreatic solitary cystic tumors: mucinous cystadenoma (10), mucinous cystadenocarcinoma (7), serous cystadenoma (5), ductectatic mucinous cystic tumor (10), solid and papillary epithelial neoplasm (5), and non-neoplastic cyst (15). The mean tumor size was 3.5 cm (range, 1.2 cm to 6.0 cm). RESULTS: Six classifications of the internal structures of these cysts were developed: thick wall type, tumor protruding type, thick septal type, microcystic type, thin septal type, and simple type. Although all neoplastic cysts belonged to the first four types, all non-neoplastic cysts belonged to the last two types. The accuracy of EUS for differentiating tumors was estimated at 96% and 92%, respectively, by two observers. CONCLUSIONS: EUS may become a mandatory modality for differentiating pancreatic solitary cystic tumors and choosing an optimal treatment.

Adenocarcinoma

Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic spread and mode of recurrence.

BACKGROUND: Nodal status is one of the most important prognostic factors for carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of recurrence were analyzed by determining the frequency of nodal involvement and antemortem and postmortem examination of patients with recurrent disease. METHODS: From 1974 to 1994, 36 patients with carcinoma of papilla of Vater underwent pancreatectomy at the Kanazawa University Hospital. A precise evaluation of the nodal involvement was determined by means of careful pathologic review of the extended lymphadenectomy specimen. The mode of recurrence was determined by use of autopsy and radiographic examinations. RESULTS: Fifteen (42%) of 36 patients had nodal involvement. The lymph nodes with the highest metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b) and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There were no metastases in the perigastric lymph nodes. A significant relationship existed between the gross appearance of the primary tumor and nodal involvement (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The 5-year survival rates for patients with protruding, mixed type, and ulcerative tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were significantly correlated to gross appearance and nodal involvement. Retroperitoneal recurrence and liver metastasis were main modes of recurrence. CONCLUSIONS: Lymph node 13b is important in lymphatic metastasis to the superior mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around the superior mesenteric artery is needed to improve the prognosis of carcinoma of papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving pancreatoduodenectomy may be indicated in patients with carcinoma of the papilla of Vater.

Adult

Inflammatory pancreatic masses: differentiation from ductal carcinomas with contrast-enhanced sonography using carbon dioxide microbubbles.

OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of contrast-enhanced sonography using carbon dioxide microbubbles to differentiate inflammatory pancreatic masses from ductal carcinomas of the pancreas. SUBJECTS AND METHODS: Fifty-five patients, including 35 patients with ductal carcinomas and 20 with inflammatory pancreatic masses, underwent contrast-enhanced sonography, CT, and digital subtraction angiography (DSA). Carbon dioxide microbubbles were prepared by mixing 10 ml of carbon dioxide and the same amount of 25% soybean oil vigorously. Carbon dioxide microbubbles were injected through an angiographic catheter that was placed in the celiac axis. Vascularity of the tumors as determined by those three techniques was interpreted by three physicians who had no knowledge of the pathologic results. RESULTS: Contrast-enhanced sonography was best at revealing tumor vascularity among the three techniques. On contrast-enhanced sonography, 19 (95%) of the 20 inflammatory pancreatic masses were isovascular and 32 (91%) of the 35 ductal carcinomas were hypovascular. In contrast, the isovascularity of inflammatory masses was five (25%) on CT, and two (10%) on DSA, respectively. The sensitivity and accuracy rate of differentiating both diseases on contrast-enhanced sonography were 98% and 95%, respectively; on CT, they were both 73%; and on DSA they were both 67%. From our results, an isovascular mass is probably an inflammatory mass, whereas a hypovascular mass is most likely a ductal carcinoma on contrast-enhanced sonography. CONCLUSION: Contrast-enhanced sonography can help differentiate an inflammatory pancreatic mass from a ductal carcinoma.

Adenocarcinoma

Diagnostic features on images in primary small cell carcinoma of the pancreas.

Small cell carcinoma of the pancreas is a rare tumor with very poor prognosis, but the tumor is successfully treated by chemotherapy. Therefore, small cell carcinoma must be differentiated from other pancreatic tumors on images. A 71-year-old man presented with digestive symptoms. Multiple hypoechoic masses were detected on transabdominal ultrasonography and lateral shadow and posterior echo enhancement on endoscopic ultrasonography. The dynamic computed tomography scan revealed that the tumor walls were hypervascular at an early phase, and that the central portions were gradually stained at a late phase with differences among the tumors; tumor stains were also found on angiography. The distal site of the main pancreatic duct was completely interrupted, as seen on endoscopic retrograde pancreatography. The resected specimens were composed of circumferential hard walls and internally necrotic, hemorrhagic contents of different degrees and were microscopically diagnosed as small cell carcinoma. The tumor has to be differentiated from hypervascular pancreatic tumors, especially islet cell tumors.

Aged

[Changes in lymph node dissection for pancreatic cancer].

Two step pancreatoduodenectomy for periampullary carcinoma was first reported in 1912 by Kausch. Pancreatoduodenectomy performed for carcinoma of the head of the pancreas was first reported in 1937 by Brunschwig. Before this report, all previous pancreatoduodenectomy had been performed for other periampullary tumors. By the 1960's, pancreatoduodenectomy was performed for pancreatic cancer without lymph node dissection. However, Fortner advocated regional pancreatectomy for pancreatic cancer in 1973. In our institute, also, extended radical pancreatectomy by translateral retroperitoneal approach has been performed during the past 2 decades. Many Japanese surgeons also adopted extend pancreatectomy. In the 1980's, extended radical pancreatectomy consisted of paraaortic lymph node dissection, total pancreatectomy, and complete resection of extrapancreatic nerve plexus. However, based on the many clinicopathologic studies, pancreatoduodenectomy was better operative procedure than total pancreatectomy. Although extended radical pancreatectomy has the advantage of long-time survival, disadvantage of nutritional status and quality of life was produced by this operative procedure. Tarverso and Longmire reported new operative procedure of pylorus preserving pancreatoduodenectomy (PPPD) in 1978. Recently, this operative procedure was indicated for pancreatic cancer. However, there is a question whether PPPD is the best operative procedure for pancreatic cancer or not.

Humans

The role of skin blood flow in pressure ulcer development during surgery.

Laser Doppler flowmetry was used to examine the relationships between skin blood flow and pressure ulcer development. Blood flow in the skin over the iliac and sacral bony prominences was measured intraoperatively in 24 consecutive patients undergoing lengthy surgical procedures. Patients who did not develop pressure ulcers postoperatively had a 500% mean increase in blood flow during the procedure as compared with the preoperative levels. Blood flow levels decreased during surgery in patients who developed pressure ulcers postoperatively. There was no statistical difference in the lengths of surgery between the two groups. These results suggest that the body's failure to increase blood flow in response to extended pressure during surgery may contribute to pressure ulcer development.

Blood Flow Velocity

Lymphatic flow and neural plexus invasion associated with carcinoma of the body and tail of the pancreas.

BACKGROUND: Lymph node status and neural plexus invasion are the most important prognostic factors that may be amenable to surgery for carcinoma of the body and tail of the pancreas. The pattern of lymphatic spread and neural plexus invasion were evaluated by analysis of various clinicopathologic factors. METHODS: Twenty patients with carcinoma of the body and tail of the pancreas underwent pancreatectomy with systemic regional lymph node dissection at Kanazawa University Hospital. A precise evaluation of their lymph node involvement and neural plexus invasion was determined. RESULTS: Sixteen of 20 patients (80%) had lymph node involvement. The lymph nodes with a high metastatic rate were those along the splenic artery (50%), the inferior body lymph nodes (35%), the lymph nodes around the common hepatic artery (25%), and the paraaortic lymph nodes (20%). There was no relationship between tumor size, histologic type, and lymph node involvement. Plexus invasion was observed in 14 patients (70%). The most frequent site was the splenic plexus, but between 15% and 20% of the patients had celiac or superior mesenteric plexus invasion. There was no relationship between tumor size, histologic type, and neural plexus invasion. CONCLUSIONS: Based on these results, extended lymphadenectomy including the paraaortic lymph nodes, celiac lymph nodes, and superior mesenteric lymph nodes may improve the prognosis for patients with carcinoma of the body and tail of the pancreas. Extrapancreatic neural plexus dissection, especially of the celiac plexus and superior mesenteric plexus, also is necessary.

Adenocarcinoma

Results of extensive surgery for pancreatic carcinoma.

BACKGROUND: Since 1973, 210 patients with pancreatic carcinoma have undergone surgery in our clinic, including 144 with carcinoma of the head of the pancreas. Of these 144 patients, macroscopic curative resections were performed on 53 (36.8%). Five patients (9.4%) died within 30 postoperative days, and an additional 3 (5.7%) died within 60 days. The overall median survival was 13 months. Eight of the patients who underwent macroscopic curative resection survived 5 years, giving a 5-year survival rate of 27.4% using the Kaplan-Meier method. The 5-year survival rate was 39.7% after a microscopically curative resection and 0% after a microscopically noncurative resection. METHODS: Outcome was compared based on the extent of pancreatic cancer by constructing survival curves according to the general rules published by the Japan Pancreas Society. RESULTS: There was no statistically significant difference in survival based on tumor size or stage. However, there was a significant difference in the survival of patients with the absence (so) or presence (se) of invasion to the anterior capsule of the pancreas, the absence (rpo) or presence (rpe) of invasion of the retroperitoneal tissue, the absence (ew0) or presence (ew2) of invasion at the surgical margin of resection, and the extent (n0 to n2) of lymph node metastasis. CONCLUSIONS: The results of this study suggest that extended radical pancreatectomy may be indicated for patients with pancreatic carcinoma because standard dissection may fail when the tumor has spread to the retroperitoneum or extrapancreatic nerve plexus.

Adult

Four cases of selenium deficiency in postoperative long-term enteral nutrition.

Because selenium is seldom added to formulations for enteral nutrition (EN), postoperative patients who are supported with EN are at risk for selenium deficiency. This report describes four cases of suspected selenium deficiency in long-term EN. Two patients underwent pancreaticoduodenectomy, one underwent total gastro-pancreatectomy, and one underwent esophageal resection and reconstruction with jejunal autotransplantation. They all developed malabsorption syndrome within 2 yr after operation. Enteral nutritional support with an elemental diet was provided continuously for 7-11 yr. Over the past 1-2 yr they experienced increasing bilateral muscular pain and weakness in the legs, gait disturbance, palpitation, and shortness of breath. Investigation for possible trace element deficiency revealed very low levels of selenium in the blood. After 10-20 d of supplementation with daily intravenous administration of selenious acid 0.16 mg/d (100 micrograms/d of selenium), their blood levels of selenium rose and their symptoms resolved. They were then continued on a maintenance regimen of oral sodium selenite 0.13 mg/d (60 micrograms/d of selenium).

Aged