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Choledochal cyst (CC)-a congenital anomaly of the bile duct-is rare. We report a 28-year-old woman complaining of epigastralgia who was transferred to our hospital. Physical examination revealed severe tenderness to abdominal palpation without symptoms of diffuse peritonitis. Urgent contrast-enhanced abdominal computed tomography indicated the dilated common bile duct (CBD) was perforated, with a presumed diagnosis of perforated CC. Endoscopic external biliary drainage was performed immediately as a bridging procedure to the definitive surgery. Additional evaluations confirmed a type IVa CC, according to Todani's classification, but no signs of malignancy. Twenty-two days after biliary drainage, laparotomy was performed. A large cystic mass was found in the CBD with a perforated scar on the right-side wall. Because inflammation around the pancreas head was too severe to perform cyst excision safely, the patient underwent subtotal stomach-preserving pancreatoduodenectomy. The postoperative course was uneventful, and the patient was discharged on the 29th postoperative day. Pathologic examination of a specimen showed no malignancy, and the patient has remained well during the 3-year follow-up. Our experience with this case suggests that definitive single-stage surgery for perforated CC in an adult can be performed safely owing to external biliary drainage as a bridging procedure, if manifestation of diffuse peritonitis is not evident.

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We have previously classified wall invasion patterns of gallbladder carcinoma (GBC) cases into two groups, i.e., the infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor differentiation, aggressive infiltration and decreased postoperative survival in terms of its histological differentiation, lymphatic invasion, venous invasion, lymph node status, neural invasion and mode of subserosal infiltration. In the present study, we analyzed 42 surgically-resected subserosal invasive gallbladder adenocarcinomas, invading the perimuscular connective tissue (pT2). The cumulative 5-year survival rate in the series was 48.7%. Lymphatic invasion (p=0.021), venous invasion (p=0.020), mode of subserosal infiltration (p<0.001), histological differentiation (p=0.030) and biliary infiltration (p=0.007) were noted, respectively, at a significantly higher incidence in more aggressive infiltration or poor differentiation in the DG type. The cumulative 5-year survival rate of curative resection cases was lower in patients with the DG type than in those with the IG type (68.9 versus 20.2%, respectively, p=0.006, log-rank test). On Cox's proportional hazard regression modeling, the low degree of venous/perineural invasion and IG type of wall invasion pattern were associated with a significant improvement in overall survival. Our data suggest that the wall invasion pattern is an independent predictor of survival in subserosal invasive GBC. Regarding the clinical application of our concept, on the classification of patients with subserosal invasive GBC based on a combination of the wall invasion pattern and lymph node status, the overall survival rate in patients with the DG type and/or N2 metastasis (n=21) was lower than in patients with the IG type and N0, 1 metastasis (n=21) (p=0.0023, log-rank test). The wall invasion pattern could contribute to decision-making concerning curative resection for subserosal invasive GBC.

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Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in the literature. We encountered a rare case of leiomyosarcoma of the pancreas, treated successfully by surgery. A 41-year-old woman was referred to our hospital for further examinations of a pancreatic tumor. Imaging studies demonstrated a solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This mass had a nonuniform content and was encapsulated. We performed distal pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal carcinoma. Macroscopically, a sagittal section of the operative specimen showed a well-circumscribed yellowish-white mass without any cystic changes. Immunohistological examination revealed that α-smooth muscle actin, desmin, and vimentin were positive, and the labeling index of MIB-1 was 50% or more. Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating from the pancreas. During 14 months of follow-up to date, there has not been any evidence of local recurrence or distant metastasis.

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Pancreatic endocrine tumors (PETs) rarely involve the main pancreatic duct. We report a case of malignant nonfunctioning pancreatic endocrine tumor (NFPET) with prevalent intraductal growth. A 47-year-old woman was referred to us after ultrasonography at a routine health check showed diffuse swelling of the pancreas. Preoperative imaging showed a solid mass in the tail of the pancreas and a bulging intraductal mass in the main pancreatic duct. We performed total pancreatectomy because the tumor occupied almost the entire lumen of the main pancreatic duct. Histological examination confirmed well-differentiated endocrine carcinoma. We review reported cases of the intraductal growth of NFPETs and discuss the pathogenesis of these unusual tumors.

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A 35-year-old woman who had visited an other hospital because of epigastralgia and anorexia was found to have a giant abdominal tumor, and was referred to our hospital. On admission, the abdomen was markedly distended. Abdominal CT scan and MRI showed the presence of a retroperitoneal tumor which occupied almost the entire abdominal cavity. She was operated a under a diagnosis of retroperitoneal liposarcoma. The tumor was located between the subphrenic space and the pelvic cavity, and was compressing the stomach, duodenum, pancreas and colon. Removal of the retroperitoneal tumor, including the right kidney, was performed. The resected tumor was 34 × 28 × 20 cm, weighed 5.5 kg and showed a variety of finding. The pathological diagnosis was a mixed type of retroperitoneal liposarcoma, consisting of well-differentiated type and myxoid type. We reported a case of giant retroperitoneal liposarcoma, with a review of the literature.

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BACKGROUND: The surgical decision regarding where to resect the pancreas is an important judgement that is directly linked to the surgical procedure. An appropriate surgical margin to resect intraductal papillary-mucinous neoplasm (IPMN) of the pancreas based on the distance of tumor spread (DTS) in the main pancreatic duct has not been adequately documented. We analyzed the appropriate surgical margin based on the DTS in the main pancreatic duct of IPMN and the positive rate at the pancreatic cut end margin. METHODS: Forty patients with main duct- or mixed-type IPMN diagnosed histopathologically who underwent surgery at Tokai University Hospital between 1991 and 2008 were retrospectively analyzed. The resection line was determined to achieve a 2-cm surgical margin in patients with main duct- or mixed-type IPMN and as limited a resection as possible to remove the dilated branch duct in patients with branch duct-type IPMN according to macroscopic type. The dysplastic state of the epithelium was judged as positive for carcinoma in situ (high-grade dysplasia) or adenoma (very low to moderate dysplasia) and judged as negative for hyperplasia or normal. RESULTS: The mean DTS in the main pancreatic duct was 41.6 +/- 30.0 mm, and that of the distance of tumor absence was 13.6 +/- 12.4 mm. The positive rate at the pancreatic cut end margin in frozen sections was 29.7%. The final positive rate at the pancreatic cut end margin was 26.2%. There has been no evidence of local recurrence in the remnant pancreas. DTS in the main pancreatic duct of IPMN was correlated with the maximum diameter of the duct (R = 0.678). CONCLUSION: Distance of tumor spread offered important insights about the appropriate site to resect the pancreas and the positive rate at the cut end margin in IPMN.

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The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.

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A perivascular epithelioid tumor (PEComa) is a rare tumor probably arising from the perivascular epithelioid cells. Only three cases of pancreatic PEComa have been reported in the English-language literature. The present report describes an extremely rare case of pancreatic PEComa. A 47-year-old Japanese woman complained of lower abdominal pain and a well-demarcated solid tumor was found in the pancreatic head. There was no history of tuberous sclerosis complexes. Pylorus-preserving pancreaticoduodenectomy was thus performed. There was a well-demarcated, solid tumor measuring 17 mm in the pancreatic head. The tumor was composed of a diffuse proliferation of epithelioid tumor cells with many blood vessels but no adipose tissue. The tumor cells expressed HMB45 and alpha-smooth muscle actin. Ultrastructurally, the tumor cells possessed many membrane-bound granules that were positive for HMB45 on immunoelectron microscopy. The results of immunoelectron microscopy show that some PEComas possess not only typical melanosomes or premelanosomes but also aberrant melanosomes.

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We report two cases of isolated spontaneous dissection of the superior mesenteric artery (SMA). Both patients complained of abdominal pain with sudden onset and were given diagnoses of dissection of the SMA based on abdominal CT scanning. CT showed dissention of the SMA with thrombosis of the false lumen and narrowing of the true lumen. Therefore there were no symptoms of bowel ischemia, and after hospitalization both cases received conservative therapy with anticoagulation and antiplatelet therapy. Spontaneous dissection of the SMA without aortic dissection is very rare, and only 53 cases have been recorded in Japan.

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Gallbladder carcinomas (GBC) frequently show vascular invasion and metastasis when the carcinoma cells invade the perimuscular connective tissue (pT2 according to the TNM classification) through the muscular layer. In this study, two intramural invasion patterns were defined as (i) infiltrative growth (IG) type, infiltrative growth in the muscle layer without destruction and (ii) destructive growth (DG) type, massive growth with destruction of the muscle layer. Sixty-six surgically resected gallbladder adenocarcinomas invading the perimuscular connective tissue (pT2) and beyond the gallbladder wall, including the visceral serosa, (pT3/pT4) were examined. The overall survival rate of the patients with the DG type was significantly lower than that of the patients with the IG type (p = 0.018). Lymphatic invasion (37.5% of IG and 62.5% of DG, p = 0.014), venous invasion (41.9%, 58.1%, p = 0.089), nodal status (30.4%, 69.6%, p = 0.015) and scirrhous growth (INFgamma) (31.0%, 69.0%, p = 0.0035) were more frequently detected in DG cases than in IG cases. In addition, median survival and survival rates were statistically analyzed. The patients with a high grade of lymphatic and venous invasion had lower survival rates (p < 0.0001 and p < 0.05, respectively). The patients with the DG type and scirrhous growth (INFgamma) also had lower survival rates (p < 0.05 and p < 0.0001, respectively) than did patients with the IG type and expansive/intermediate growth (INFalpha,beta). On multivariate analysis, neural invasion (odds ratio, 0.157; 95% confidence interval, 0.039-0.629) was an independent predictor of mortality. In conclusion, the DG invasion pattern is an indicator of high malignant potential and indirectly worsens the prognosis of patients with gallbladder adenocarcinoma.

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Our previous study demonstrated that the pT2 and pT3-4 gallbladder carcinomas can be classified into two groups, i.e. infiltrative growth type (IG type) and destructive growth type (DG type) and that the DG type is associated with poor differentiation, aggressive infiltration, and decreased postoperative survival. The present study focused on the clinicopathologic significance of laminin-5gamma2 chain expression as an indicator of local aggressiveness and Ki-67 labeling index (Ki-67 LI) as an indicator of the cell proliferation activity of gallbladder carcinoma. Ki-67 LI was higher in the DG type (26.3%) than in the IG type (21.4%), and the rate of high-grade cell proliferation cases (Ki-67 LI > or = 30%) was high in the DG type (P = 0.012). Gallbladder carcinoma cases with high Ki-67 LI were significantly associated with poorly differentiation (P = 0.089) and distant lymph node metastasis (P = 0.079). Laminin-5gamma2 expression patterns of gallbladder carcinoma were divided into two distinct types, extracellular staining and cytoplasmic staining. The extracellular staining was subclassified into two groups, basement membrane staining and stromal staining. In the basement membrane staining, laminin-5gamma2 was present in the basement membranes surrounding neoplastic glandular structures. The basement membrane staining of laminin-5gamma2 was more frequent in the IG type (40%) than in the DG type (12.9%) (P = 0.025). The stromal staining was more frequent in the DG type. Furthermore, the stroma-positive group was more closely associated with decreased overall survival than the stroma-negative group (P = 0.028). The cytoplasmic staining was not significantly correlated with invasion pattern in gallbladder carcinoma (P = 0.545). Univariate analysis demonstrated that laminin-5gamma2 stromal staining is a predictor of lymphatic invasion, venous invasion, neural invasion, the mode of subserosal infiltration, and lymph nodal status. Multivariate analysis revealed the mode of subserosal infiltration is the strongest predictor of stromal invasion (P = 0.068). In conclusion, high-grade cell proliferation and stromal laminin-5gamma2 staining were significantly correlated with a wall-invasion pattern of aggressive gallbladder carcinoma indicating destructive growth (DG type).

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Pancreatic cancer is considered resectable only when there are no distant metastases or infiltration of surrounding organs or arteries. We describe a patient with primarily inoperable locally advanced pancreatic adenocarcinoma who underwent curative surgical treatment after preoperative chemotherapy. A 61-year-old woman was admitted for further evaluation of a pancreatic head mass discovered fortuitously on a health screening. Examination revealed locally advanced pancreatic cancer with infiltration of the superior mesenteric artery. After a partial response was obtained by chemotherapy with gemcitabine (GEM) and S-1, we performed pancreaticoduodenectomy. Microscopically, the main tumor was replaced with fibrotic tissue, and there were only a few residual adenocarcinoma cells in the pancreatic head. The radicality of the surgery was R0, according to the TNM classification. Our results suggest that neoadjuvant treatment with GEM/S-1 on a sustainable regimen offers the possibility of a multimodal treatment concept for all patients and a higher radical-resection rate in patients with otherwise unresectable pancreatic cancers.

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Reconstruction by pancreaticoenterostomy has generally been employed after medial pancreatectomy for tumor. As a less invasive procedure, here we report three patients who successfully underwent pancreatic end-to-end anastomosis after medial pancreatectomy. The subjects consisted of 2 patients with serous cystadenomas and 1 patient with an intraductal papillary mucinous tumor. These tumors were detected in the pancreatic neck or body, and the maximal tumor diameters ranged from 10 to 33mm. The pancreatic duct diameters were 2 mm in 2 patients and 4 mm in 1 patient. The procedure was carried out by ductal anastomosis and parenchymal anastomosis with interrupted sutures. A pancreatic tube was inserted for decompression at the anastomotic site in all patients. The mean operative time was 3 hours and 31 minutes, and the intraoperative blood loss was 428 mL. Although pancreatic fistula was observed in 2 patients with the normal pancreas, conservative therapy relieved this complication. Neither tumor relapse nor stenosis of the pancreatic duct at the anastomotic site was detected in any patient, with a follow-up of 4 to 27 months. Our experience confirmed that in selected cases, this reconstructive procedure was feasible and safe for physiological reconstruction without involvement of the digestive tract.

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Hepatocellular carcinoma rarely metastasizes to the orbit. We report on a 72-year-old man with a past history of resection for hepatocellular carcinoma and recurrent HCC, who presented with diplopia and left painful proptosis. Head scans revealed a large and irregular mass in the left orbit that caused destruction of the orbital bone superiorly and posterolaterally. A biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. The tumor was surgically excised and histological findings revealed moderately differentiated hepatocellular carcinoma, resembling hepatocytes with a tendency to form trabeculae. Immunohistochemically, the tumor cells showed positive reaction against low-molecular-weight keratin and α-fetoprotein. There have been only 12 previous cases of hepatocellular carcinoma metastatic to the orbit cited in the literature. We presented here a rare case of hepatocellular carcinoma metastatic to the orbit.

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Hepatocellular carcinoma (HCC) is rarely metastasized to the pharyngeal region. We report the case of a 59-year-old man admitted to our hospital with a complaint of hematemesis. An endoscopic examination revealed a tumor located in the left piriform sinus. Histological examination showed metastasis from HCC. Subsequent abdominal examinations demonstrated mild liver cirrhosis due to chronic HCV infection and primary nodules in the lateral segment of the liver. The pharyngeal tumor was completely removed by endoscopic polypectomy after radical hepatectomy for HCC. The patient died of recurrence of HCC 8 months after the first admission. With the presentation of this case, we review the literature reported so far.

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Sialyl Lex antigen, a member of a family of high molecular weight glycoproteins, is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Lex have not yet been established in human gallbladder carcinomas. In this study, we analyzed the clinicopathological significance of sialyl Lex expression and patients' prognosis in cases of human gallbladder adenocarcinoma. Sialyl Lex immunoreactivity was detected not only in cancer cells (cytoplasmic type; 51.9%, 28/54) but also in cancer stroma (stromal type; 38.9%, 21/54). Stromal sialyl Lex expression was detected in 50.0% (20/40) and 7.1% (1/14) of T2-4 and T1 cancers, respectively (p<0.05). Stromal sialyl Lex-positive gallbladder cancers frequently showed lymphatic invasion, venous invasion and lymph node metastasis (54.3, 50.0 and 60.0%, respectively) (p<0.05), and the expression was associated with a poor outcome. Sialyl Lex expression plays important roles in the vascular invasion and metastasis of human gallbladder adenocarcinoma.

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Pancreatic cancer is a malignant tumor with an extremely poor prognosis. The mechanisms of the aggressive growth and metastasis are not yet extensively understood. Over-expression of epidermal growth factor receptor (EGFR) was suggested to be associated with malignant transformation of pancreatic cancer. We examined EGFR expression in 77 cases of invasive ductal adenocarcinoma of the pancreas, and analyzed the relation between the EGFR expression pattern and clinicopathological factors. EGFR immunoreactivity was detected in 41.6% (32/77) of human pancreatic cancers; i.e. diffuse expression in 32.5% (25/77) and focal expression in 9.1% (7/77). The EGFR expression was associated with gender (p<0.05), histological differentiation (p<0.05) and metastatic status of TNM classification (p<0.01). The observations suggested that EGFR expression plays important roles in metastasis, especially liver metastasis and recurrence of human pancreatic cancer.

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Undifferentiated spindle and giant cell carcinoma of the common bile duct has not been reported previously. We present here a case of 71-year-old man with the undifferentiated spindle and giant cell carcinoma of the common bile duct, including immunohistochemical findings. A nodular infiltrating tumor was located at the lower portion of the extrahepatic bile duct, and measured 1.2 x 0.6 cm in size. Histologically, the tumor was composed of proliferated sarcomatoid spindle tumor cells. Numerous multinucleated giant cells were intermingled with the sarcomatoid spindle tumor cells. Immunohistochemically, the tumor cells were positive for both cytokeratin and vimentin. We speculated that the tumor originated from epithelial cells, and showed sarcomatoid neplastic changes.

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Pancreatic cancer is a malignant tumor with an extremely poor prognosis. Thrombospondin-1 (TSP-1) was suggested to be a potential regulator of tumor growth and metastasis. We examined TSP-1 expression in 77 cases of invasive ductal adenocarcinoma of the pancreas, and analyzed the correlation between the TSP-1 expression pattern and clinicopathological features in pancreatic cancer. TSP-1 immunoreactivity was detected in the cancer stroma. The diffusely positive and focally positive patterns of TSP-1 were found in 33 (42.9%) and 40 (51.9%) of 77 cases, respectively. The TSP-1 diffuse expression was significantly correlated with lymph node metastasis (p<0.01), neural invasion (p<0.05) and TNM stage (p<0.01). The prognostic significance of clinicopathological parameters were analyzed by univariate and multivariate analysis using the log-rank test and the Cox proportional hazards model. Based on the univariate analysis, histological differentiation (p<0.01), lymphatic invasion (p<0.01), venous invasion (p<0.05), neural invasion (p<0.01), TNM stage (p<0.01) and TSP-1 expression (p<0.01) were significant parameters. These observations suggested that TSP-1 plays important roles in cancer cell growth and metastasis of human pancreatic cancer, and that stromal TSP-1 immunoreactivity is a good prognostic predictor of patients with pancreatic cancer.

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