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Background/aims: Invasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show poor prognosis similar to ductal adenocarcinomas. The aim of this study was to evaluate the molecular indicators of invasion and risk factors of recurrence of IPMNs., Methodology: For 46 curative resections of IPMNs, we analyzed the expression of apomucin antigens (MUC1, MUC2 and MUC5AC), p53 and Ki67 using resected specimens., Results: All 46 IPMNs were classified into 4 groups; MUC1+/p53+, MUC1+/p53-, MUC2+ and MUC1-/MUC2-. The incidence of MUC1 expression increased according to the grade of dysplasia and all of 5 invasive carcinomas expressed MUC1. None of the invasive carcinoma, but almost half of IPMNs of non-invasive carcinoma and sever dysplasia expressed MUC2. Additionally, p53 expression was limited to invasive IPMNs and a non-invasive IPMN which recurred after the operation. The Ki67 labeling index was increased according to the grade of dysplasia and was highest in the MUC1+/p53+ group. In the MUC2+ cases, Ki67 labeling index was significantly higher than that in the MUC1-/MUC2- cases. MUC5AC was expressed in all IPMNs., Conclusions: The expression of MUC1, MUC2 and p53 might be indicators of malignancy and the expressions of MUC1 and p53 were the predictors of tumor invasion and recurrence.

Background/aims: Intraductal papillary mucinous neoplasms have a better prognosis than ductal adenocarcinomas of the pancreas. The aim of this study was to evaluate the malignant potential of IPMNs by their preoperative images., Methodology: Forty-three intraductal papillary mucinous neoplasms were divided into 3 duct ectatic types using preoperative images (the main duct type, the branch duct type, and the mixed type), and into 2 groups using resected specimens (the malignant group including severe dysplasia based on the WHO classification and the benign group). The diameters of the tumor, main pancreatic duct and mural nodule were measured on the images., Results: Two thirds of main duct type cases were in the malignant group. For the branch duct and mixed types, the diameters of the tumor and detectable mural nodules were larger in the malignant group than in the benign group. A tumor diameter larger than 3.5cm and a mural nodule diameter larger than 6mm were risk factors for malignancy (p < 0.05)., Conclusions: The main duct type, a tumor larger than 3.5cm of the branch duct or mixed type, and a mural nodule larger than 6mm were all indicators of malignancy risk.

Purpose: Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up., Methods: Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio., Results: The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P<0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate., Conclusion: Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Purpose: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer., Patients and Methods: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions., Results: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients., Conclusion: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.

The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.

Pancreatic intraepithelial neoplasia (PanIN) is a recently proposed nomenclature for putative precursor lesions of pancreatic cancer, which are designated as PanIN-1 through -3 according to their increasing grade of dysplasia. A stepwise progression model of PanINs has been proposed, and multistep genetic alterations in PanINs are being investigated. PanIN-1A and PanIN-1B may remain unchanged for a long period. PanIN-3 potentially progresses toward invasive ductal carcinoma (IDC), and there are several case reports suggesting such progression. In these reported patients, PanIN-3 was found in specimens from partial pancreatectomies, and IDC manifested in the pancreatic remnant 17 months to 29 years after the surgery. We describe herein a patient with PanIN-3, in whom IDC manifested in the distal remnant pancreas 69 months after segmental pancreatectomy. Of the reported cases, including the present one, four of the patients were male and three were female, and the age at the first operation ranged from 46 to 70 years. Intraductal papillary-mucinous tumor (IPMT) is an entity that is distinct from PanIN. However, IPMTs of small size resemble PanINs morphologically. Loss of Dpc4 expression has been reported in the invasive component of IPMT, as well as in PanIN-3 and IDC. Analysis of mucin expression patterns has been reported, suggesting that, in practice, MUC1-positive MUC2-negative IPMTs may not be distinguishable from PanINs. There may be overlapping lesions between PanINs and IPMTs. Should the paradigm of the ductal origin of IDC be accepted, PanINs and a fraction of IPMTs would represent precursors of IDC.

A 39-year-old woman came to us complaining of severe anemia (hemoglobin: 2.3 g/dl) and a painful right breast that was entirely occupied by an ulcerative, foul-smelling tumor approximately 20 cm in maximum dimension. The tumor, which was determined to be mucinous adenocarcinoma at biopsy, had invaded the chest wall with multiple lung metastases (T4cN2M1 stage IV). After a blood transfusion, the patient received the following multimodal treatment: concurrent chemoradiotherapy (50 Gy), intraarterial infusion chemotherapy consisting of doxorubicin 50 mg, mitomycin-C 10 mg, and cisplatin 50 mg, and skin graft surgery. After intraarterial infusion chemotherapy, the fungating tumor disappeared. The patient experienced a relapse of right pleural effusion 2 years later and received multimodal treatment. Now, March 30, 2000, the patient is doing well without local recurrence, 8 years after her first admission. The combination of intraarterial infusion chemotherapy and radiotherapy plays a role in successful treatment of extensive local disease of the breast.

A 35-year-old woman with locally advanced stage IIIB breast cancer (medullary carcinoma) 12 cm in diameter underwent neoadjuvant chemotherapy consisting of three courses of intraarterial infusion [adriamycin (ADR), mitomycin (MMC), cisplatin (CDDP), 5-fluorouracil (5FU)] and four cycles of systemic chemotherapy (ADR, epirubicin, cyclophosphamide, MMC, CDDP) for three months. The tumor markedly diminished after the first course of intraarterial infusion chemotherapy, with a 3-cm tumor remaining after the completion of preoperative administration. Pathologically complete response was noted in specimens resected following breast conservation surgery. Postoperative radiotherapy was added and adjuvant chemohormonal therapy was continued for two years. The patient is alive without recurrence and has been able to conserve the breast for the past eight years, neoadjuvant chemotherapy including intraarterial infusion enabled breast conservation treatment even for huge-sized locally advanced breast cancer.

We analyzed response, side effects, and local control rates of a multimodal treatment consisting of intraarterial infusion chemotherapy (IAIC) and radiotherapy with or without surgery for patients with locally advanced or recurred breast cancer. Thirty-three patients, clinically diagnosed as stage IIB in 1, IIIA in 2, IIIB in 12, IV in 18, were treated from 1991 to 1998. Twenty-five were primary and eight were recurrent cases after surgery. IAIC started as initial treatment up to three times maximum. In most cases, doxorubicin 50 mg, cisplatin 50 mg, and mitomycin 10 mg were infused in the subclavian and/or internal mammary artery. After IAIC, patients in primary cases underwent radical mastectomy or breast conservation surgery, after radiotherapy at a total dose of 50 Gy/25 fractions/5 weeks with a boost of 10 Gy. In recurrent cases, a full dose of radiotherapy was delivered. Clinical objective and complete response rates were 78% and 9% after IAIC. Despite a high rate of residual positive margin (67%) or clinically residual carcinoma, local recurrence developed only in 2 patients (6%) and local control rates at 5 years were calculated as 89%. Bone marrow suppression was frequent, and skin vesiculation (15%) and ulceration (9%) were experienced after IAIC. Skin ulcer (6%), brachial plexus neuropathy (3%), and radiation pneumonitis (3%) occurred as late toxicity. IAIC was effective as an induction treatment and radiotherapy played a role of local control for patients with locally advanced or recurrent breast cancer.

Background/aims: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma., Methodology: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients., Results: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01)., Conclusions: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.

We have been treating patients with operable thoracic esophageal cancer according to our own protocol. It includes the initial concurrent chemoradiotherapy (CRT) followed by continuous CRT or surgery. Patients with good response to initial chemoradiotherapy were allowed to continue chemoradiotherapy, whereas the others were treated with surgery. However, there were two cases which showed discrepancies in the clinicopathological response. Both patients received initial chemoradiotherapy, including two courses of cisplatin (100-120 mg), 5-fluorouracil (750-1000 mg for 4 days) and radiation (44-50 Gy). On completion of the initial chemoradiotherapy, all diagnostic imaging modalities including barium swallow, esophagoscopy, endoscopic ultrasonography and thoracic computed tomography strongly implicated residual tumor with a reduction rate of 40-50%. The patients underwent radical esophagectomy 15-20 days after initial chemoradiotherapy. Pathological specimens only revealed thickening of the esophageal wall due to inflammatory change without residual carcinoma. These facts suggest the current limitations of diagnostic images in evaluating the response to chemoradiotherapy.

A 51-year-old man with increasing dysphasia was admitted to our hospital on March 18, 1985. Several examinations revealed thoracic esophageal squamous cell carcinoma 11 cm in length staged T3N0M0 (stage IIA) by UICC 1987. As he rejected our proposal of surgery, definitive radiotherapy (60 Gy) was delivered, and complete response was obtained. The patient had been doing well for 5 years after radiotherapy until superficial local recurrence was discovered at a periodic endoscopic examination. High-dose-rate intraluminal brachytherapy (10 Gy/2 Fr) was administered. After a 3-year disease-free interval, superficial recurrence developed in the same location, and early gastric cancer was detected as a secondary cancer. Radical salvage surgery was performed. The patient was alive and disease free 5 years and 5 months after surgery. We present this rare case of a patient who survived 14 years after the initial radiotherapy. The present case demonstrated the importance of long-term follow-up after radiotherapy, long-term local controllability of relatively low doses of intraluminal brachytherapy after superficial recurrence, and the feasibility of salvage surgery as long as local recurrence is limited to within the mucosal layer.

Mucinous carcinoma of the male breast is a rare histological type of cancer. We describe a 35-year-old male with mucinous carcinoma of the right breast. His breast mass enlarged subacutely, and became painful over a period of 2 months. Ultrasonography demonstrated echoes of a large multilocular cystic lesion with partially heterogenic internal echoes suggesting a phyllodes tumor. A modified radical mastectomy was performed, and histopathologic examination revealed mucin-producing solid or cribriform atypical cells with fibrous granulation tissue and hemosiderin deposition. The patient recovered uneventfully, and is still free of recurrence 30 months after his operation. The prognosis for male breast cancer can be improved by early diagnosis and appropriate multidisciplinary therapy.

Anomalies of the biliary ductal system are not uncommon, and their clinical significance is variable. We present herein the case of a 70-year-old Japanese woman found to have an anomalous duplicated cystic duct, which is an extremely rare congenital anomaly. Intraoperative delineation of the anomaly by real-time cholangiograms assisted us in being able to subsequently perform a safe cholecystectomy. This case serves to demonstrate the importance of being aware of the possibility of potential biliary variations in order to avoid ductal injuries during biliary surgery.

Extrathoracic invasions or metastases from thymomas are extremely rare. We describe herein the case of a patient with malignant thymoma which recurred three times during an 8-year period and invaded directly into the peritoneal cavity, involving the gastrointestinal tract. The huge thymoma was completely resected, along with the fornix of the stomach, the transverse colon, and the 8th, 9th, and 10th ribs. Careful observation and multidisciplinary treatment against recurrent thymoma will be requisite for this patient, even though the tumor has been completely resected.

The factors influencing the healing process of pancreaticojejunostomy (P-J) following pancreaticoduodenectomy (PD) are still ill defined, allowing the recommendation of various anastomotic methods. We conducted a prospective study to determine the risk factors influencing the protracted healing of P-J, examining 100 consecutive patients who underwent PD followed by P-J, performed as an end-to-side "mucosa-to-mucosa" anastomosis using vertical mattress sutures (VMS method). Protracted healing of P-J was classified as either peripancreatic sepsis (PPS), defined as prolonged suppurative discharge of less than 50 ml a day from the drain beneath the P-J for more than 1 week; or a pancreatic fistula (PF), defined as prolonged discharge of more than 50 ml a day with a high amylase content (> 1000 IU) for more than 1 week. There were 80 patients with a malignant neoplasm, and 20 with benign disease. The overall incidence of healing problems following P-J was 9%, which included 6 patients (6%) with PPS and 3 (3%) with PF. Apart from an advanced age of more than 70 years, none of the patients' characteristics or postoperative complications influenced the healing of P-J. The type of reconstruction, an anastomotic stent, the duct size, and a "soft" pancreas were not risk factors either. In conclusion, no factors, apart from the age or any special problem of an individual patient, influenced the dehiscence of P-J when the VMS method was used after PD.

This study was undertaken to determine whether short-term continuous epidural analgesia using morphine would relieve pain after laparoscopic cholecystectomy. The authors retrospectively reviewed the clinical data of 182 cases who had undergone a laparoscopic cholecystectomy. These cases were divided into four groups according to their anesthetic modes as follows: a control group with general anesthesia only (n = 37); group I, general anesthesia combined with one shot of epidural morphine (n = 78); and group II, general anesthesia combined with continuous epidural analgesia using morphine (IIa for 12 h (n = 33); IIb for 8 h (n = 34)). The pain score on a four-category verbal scale and the frequency of analgesic use were investigated. There were no differences in the background characteristics of the patients among the groups, except for the duration of surgery (I vs IIa; P = 0.006). The pain scores were significantly different between the control group and the other groups. The frequency of analgesic use in the control group was also significantly higher than in the other groups. A tendency toward a higher frequency of analgesic use in group I, compared with that in groups IIa and IIb, was observed. These findings thus suggest that short-term continuous epidural analgesia using morphine can effectively relieve postoperative pain after a laparoscopic cholecystectomy.

Laparoscopic splenectomy has been accepted as a feasible extension of minimally invasive surgery, which has undergone dramatic improvements in both technology and instrumentation. We performed a laparoscopic splenectomy in a 7-year-old girl with hereditary spherocytosis. The patient recovered rapidly and returned to unrestricted activities quickly. The appropriate positioning of each laparoscopic port is essential for a good operative view and smooth access. It is also important to dissect the hilum of the spleen meticulously. Laparoscopic splenectomy in the pediatric age group appears to be another promising extension of laparoscopic surgery.

We report herein the case of a women receiving tamoxifen therapy for breast cancer who developed vaginal bleeding, subsequently found to be caused by unusual endometrial polyps. Upon presentation, ultrasonography and magnetic resonance imaging (MRI) demonstrated a tumor within the uterus. A hysterectomy was performed, and macroscopic examination showed polyp-like lesions of the uterus. Histologically, these polyps demonstrated cystically dilated glands and stromal proliferation, and were diagnosed as endometrial polyps. Although tamoxifen has few side effects, any signs or symptoms of gynecological abnormalities should be carefully evaluated in patients on long-term tamoxifen therapy.

Vascular lesions of the duodenum, including hemangioma, are rare causes of gastrointestinal bleeding. We herein describe a 52-year-old woman with a solitary cavernous hemangioma of the duodenum that caused chronic gastrointestinal bleeding. Repeated upper gastrointestinal endoscopy and a barium meal study revealed a solitary vascular tumor in the fourth portion of the duodenum, although the initial investigations including selective angiography were unsuccessful. A wedge resection of the duodenum was performed and microscopical examination showed a cavernous hemangioma. Vascular lesions should therefore also be considered in the differential diagnosis of patients with gastrointestinal bleeding of unknown origin.

A prospective, randomized study was conducted to determine whether simultaneous infusion of lipid emulsion with an amino acid-dextrose-electrolyte solution would reduce the incidence of thrombophlebitis (TP) during postoperative peripheral parenteral nutrition (PPN). Thirty patients who had undergone gastric resection for adenocarcinoma were randomly divided into two groups according to whether they were infused with 10% lipid emulsion (group A) or 5% glucose solution (group B) simultaneously with the amino acid-glucose solutions. The total osmolarity of the infusion solutions in each group was 853 mOsm/l. The incidence of complications due to TP, namely, redness and/or edema beneath the cannula insertion site and/or pain, was investigated. There were no differences in the background characteristics of the patients in groups A and B, except regarding concurrent resection of other organs (P = 0.03). The incidence of edema in group A was significantly lower than in group B on postoperative days 2 and 4, although there was no difference in the incidence of redness and pain between the two groups. These findings suggest that the simultaneous infusion of lipid emulsion has a preventive effect against TP during postoperative PPN, and may be a practical means of providing PPN after gastrointestinal surgery.

Sepsis was induced in rats by cecal ligation and puncture. A nutrient mixture was infused that also contained either (A) sodium 2-ketoisocaproate (NaKIC) or (B) NaHCO3, at 18.75 mmol kg/day. In group A, 34 of 43 rats (79%) survived, while only 24 of 44 rats (55%) in group B survived (P < 0.02). In a second experiment, cecal ligation and puncture were performed 1 week after bilateral adrenalectomy or sham adrenalectomy. All adrenalectomized rats died within 2 days of CLP, whether corticosterone replacement level was low, normal, or high. Four of eight sham-adrenalectomized rats receiving NaHCO3 died, but none of seven receiving NaKIC died. Combining both experiments by ANOVA, the effect of KIC on survival in adrenal-intact animals is highly significant (P = 0.002). In NaKIC-infused rats, blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as blood levels of oxidized glutathione and ratio of oxidized/reduced glutathione were significantly lower. We conclude that KIC infusion improves survival of septic rats by an antioxidant mechanism, probably involving reaction with hydrogen peroxide.

Congenital biliary atresia (CBA) is a disorder of early infancy that needs early and accurate diagnosis because the curability may be increased if surgical therapy (hepatic porto-enterostomy) is performed early in the disease course of this condition. But immediate differentiation of CBA from neonatal hepatitis (NH) is very difficult, and even special tests for differential diagnosis are of limited value because of some hazards, including the length of time required, technical difficulties, and so on. The data on 14 patients with CBA and 20 with NH admitted to Tenri Hospital were analyzed by two statistical methods (discriminant analysis and probit analysis) and then scores combining several simple variables were calculated. We tried to differentiate these two conditions by the scoring systems mentioned above, and checked the results of these methods against cases in other hospitals (CBA 6 cases and NH 15 cases). Our scoring systems presented here showed higher discriminant power than any single variable test, including the 131I-BSP excretion test, and can be used where there is no time for differential diagnosis.

Three cases of obstruction of the afferent loop following a Billroth II type gastrectomy were preoperatively detected by ultrasonography. The obstructions in the 3 patients were caused by volvulus, internal herniation and recurrence of gastric cancer, respectively. The important US findings which helped diagnose this condition were a dilated intestinal loop without gas echo in the upper abdominal cavity and echo lucent swelling of the pancreas. Ultrasonography is very useful for the early and easy detection of this life-threatening condition which requires immediate surgery.

A 28 year-old Japanese male with Crohn's disease maintained on total parenteral nutrition for 5 consecutive years showed congestive cardiomyopathy. His symptoms (palpitation and precordial pain), arrhythmia on ECG and cardiomegaly on chest X-ray film were progressive. By intravenous selenium supplementation of 100 micrograms/day (selenite) his symptoms disappeared dramatically and plasma selenium level, erythrocyte selenium level and glutathione peroxidase activity improved to normal ranges. It is suggested that this myocardial damage was caused by selenium deficiency.