Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases.

BACKGROUND: Intrahepatic lymphatic invasion is an adverse prognostic factor after hepatectomy for colorectal liver metastases (CLMs). However, most patients in previous reports had liver resection before the era of FOLFOX/FIRI-based chemotherapy. METHODS: Forty-six patients who underwent hepatectomy for CLMs from 2004 to 2020 were evaluated. We histologically evaluated portal invasion, intrahepatic lymphatic invasion, and biliary invasion on hematoxylin-eosin slides. We also collected the following clinicopathologic factors: gender, age, timing, the number and maximum size of CLMs, preoperative tumor markers, neutrophil/lymphocyte ratio, location, and lymph node metastases of primary cancer, and chemotherapy after hepatectomy. A multivariate Cox proportional hazard model was used to define the relationship between overall (OS) or disease-free survival (DFS) and clinicopathologic factors. RESULTS: Histological invasions were portal invasion in 8 (17.4 %), intrahepatic lymphatic invasion in 6 (13.0 %), and biliary invasion in 5 (10.9 %). Chemotherapy for recurrence after hepatectomy (n = 29) was performed in 22 and 14 of those who received FOLFOX/FIRI-based chemotherapy. By multivariate analysis, the number of CLMs (p < 0. 01) and presence of intrahepatic lymphatic invasion (p = 0.02) were independent predictors of recurrence. The number of CLMs (p = 0.02) and prehepatectomy carcinoembryonic antigen level (p = 0.02), but not intrahepatic lymphatic invasion (p = 0.18), were independent predictors of survival using multivariate analysis. CONCLUSIONS: The presence of intrahepatic lymphatic invasion adversely affected patient's DFS, but not OS in patients with CLMs in the era of FOLFOX/FIRI chemotherapy. FOLFOX/FIRI-based chemotherapy might improve OS, even in patients with positive intrahepatic lymphatic invasion.

Ectopic pancreatic adenocarcinoma in Meckel's diverticulum: a case report.

BACKGROUND: Malignant neoplasms arising from Meckel's diverticulum are rare and an adenocarcinoma in Meckel's diverticulum originating from ectopic pancreatic tissue is even rarer. Herein, we report a patient with an ectopic pancreatic adenocarcinoma in Meckel's diverticulum who was successfully treated with surgery and chemotherapy. CASE PRESENTATION: A woman in her sixties presented to another hospital with abdominal pain. Plain computed tomography suggested an abdominal tumor and she was referred to our hospital. Enhanced computed tomography revealed a 23-mm low-density tumor in the abdominal cavity. Surgery was performed with a tentative diagnosis of a mesenteric tumor, such as a gastrointestinal stromal tumor, schwannoma, or lymphoma. First, we inspected the peritoneal cavity with a laparoscope. This revealed numerous nodules in the small bowel mesentery, suggesting peritoneal dissemination. A 20-mm-diameter white tumor was found in the small intestine and diagnosed as a small intestinal cancer. The small intestine was partially resected laparoscopically through a small skin incision. The patient's postoperative course was uneventful, and she was discharged on postoperative day 9. Pathological examination revealed well-differentiated adenocarcinoma in the small intestine. The tumor had developed from a sac-like portion protruding toward the serosal side and had a glandular structure lined with flattened atypical cells. Neither pancreatic acinar cells nor islets of Langerhans were evident, suggesting a Heinrich type 3 ectopic pancreas. The final diagnosis was an adenocarcinoma originating from an ectopic pancreas in Meckel's diverticulum. After a smooth recovery, the patient commenced chemotherapy for pancreatic cancer. CONCLUSIONS: We present a very rare case of ectopic pancreatic carcinoma in Meckel's diverticulum.

DUPAN-2 as a Risk Factor of Early Recurrence After Curative Pancreatectomy for Patients With Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Several patients with pancreatic ductal adenocarcinoma (PDAC) experience postoperative early recurrence (ER). We evaluated PDAC patients to identify the risk factors for postoperative ER (≤6 months), including preoperative serum DUPAN-2 level. METHODS: We retrospectively evaluated 74 PDAC patients who underwent pancreatectomy with curative intent. Clinicopathological factors including age, sex, body mass index, postoperative complications, pathological factors, preoperative C-reactive protein/albumin ratio, neutrophil/lymphocyte ratio, modified Glasgow prognostic score, preoperative tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, SPAN-1, and DUPAN-2), and history of adjuvant chemotherapy were investigated. Early recurrence risk factors were determined using multivariate logistic regression analysis. RESULTS: Recurrence and ER occurred in 52 (70.3%) and 23 (31.1%) patients, respectively. Univariate analysis revealed that postoperative complications, C-reactive protein/albumin ratio ≥0.02, neutrophil/lymphocyte ratio ≥3.01, carbohydrate antigen 19-9 ≥ 92.3 U/mL, SPAN-1 ≥ 69 U/mL, DUPAN-2 ≥ 200 U/mL, and absence of adjuvant chemotherapy were significant risk factors for ER. In multivariate analysis, DUPAN-2 ≥ 200 U/mL (P = 0.04) and absence of adjuvant chemotherapy (P = 0.02) were identified as independent risk factors for ER. CONCLUSIONS: A higher level of preoperative DUPAN-2 was an independent risk factor for ER. For patients with high DUPAN-2 level, neoadjuvant therapies might be required to avoid ER.

Elevated Preoperative DUPAN-2 Level Predicts Locoregional Recurrence After Pancreatectomy in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: The diagnostic value of serum DUPAN-2 level has been reported; however, the relationship between preoperative DUPAN-2 level and recurrence pattern has not been fully investigated in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 50 patients with PDAC who underwent pancreatectomy. The relationships between clinicopathologic factors and site-specific disease-free survival (DFS) were analyzed using Cox proportional hazard and receiver operating characteristic (ROC) curve analyses. RESULTS: The tumor location was the pancreatic head in 31 patients and the body/tail in 19 patients. Of the 50 patients, 34 had recurrence (median DFS, 11 months). Fifteen patients had hematogenous recurrence, and 16 had locoregional recurrence. In multivariate analysis, adjuvant chemotherapy [p=0.01; odds ratio (OR)=8.10; 95% confidence interval (CI)=1.58-41.6] and venous invasion (p=0.01; OR=8.33; 95%CI=1.53-45.4) were significant factors for hematogenous recurrence-free survival, whereas the neutrophil-to-lymphocyte ratio (p=0.03; OR=2.57; 95%CI=1.10-5.98) and DUPAN-2 level (p<0.01; OR=1.00; 95%CI=1.000-1.002) were significant factors for locoregional recurrence-free survival. In ROC curve analysis, the area under the curve of DUPAN-2 level was 0.613 for hematogenous recurrence and 0.682 for locoregional recurrence. In the log-rank test, the hematogenous and locoregional recurrence-free survival rates of patients with higher DUPAN-2 levels were significantly worse than those with lower DUPAN-2 level. CONCLUSION: Elevation of preoperative DUPAN-2 level independently predicts locoregional recurrence after surgery. Patients with elevated preoperative DUPAN-2 level may benefit from neoadjuvant chemoradiation therapy to avoid postoperative locoregional recurrence.

Maximum Diameter of the Gallbladder Determined Presurgically Using Computed Tomography as a Risk Factor for Difficult Emergency Laparoscopic Cholecystectomy in Patients With Mild to Moderate Acute Cholecystitis.

BACKGROUND: Early or emergency laparoscopic cholecystectomy (LC) was recommended in the 2018 Tokyo Guidelines for patients with mild to moderate acute cholecystitis (AC). Although surgical difficulty is frequently encountered during these surgeries, risk factors for predicting surgical difficulties have not been fully investigated, especially based on computed tomography (CT) findings. MATERIALS AND METHODS: We investigated 72 patients who underwent emergency LC with mild (n=45) to moderate (n=27) AC. Patients who previously underwent presurgical percutaneous or endoscopic biliary drainage were excluded from this study. Difficult LC was defined using any of the following surgical factors: surgical duration ≥180 minutes, blood loss ≥300 g, or a conversion to open cholecystectomy. Subsequently, several presurgical clinical factors were analyzed, including sex, age at surgery, experience of the surgeon, interval between symptom onset and surgery, body mass index, diabetes history, presurgical white blood cell count, and C-reactive protein level. Moreover, stones in the cystic duct or perigallblader fluid and the maximum thickness and diameter of the gallbladders were evaluated via presurgical CT. Finally, logistic regression analysis was performed to compare the relationship between surgical difficulty and each clinical factor. RESULTS: The average age at surgery of the included patients was 60.3 (range: 25 to 88 y), surgical duration was 112.2 (range: 29 to 296 min), and surgical blood loss was 55.2 (range: 0 to 530 g). Furthermore, 4 (5.6%) had to undergo open cholecystectomy, whereas postsurgical complications occurred in 5 (6.9%) patients. In addition, the mean postsurgical admission duration was 7 (range: 3 to 63 d). Thus, 12 patients experienced difficult LC, whereas 60 experienced nondifficult LC. Of the evaluated clinical factors, patients who experienced difficult LC showed higher presurgical C-reactive protein levels (10.78 vs. 6.76 mg/dL, P =0.01) and wider gallbladder diameters (48.4 vs. 41.8 mm, P <0.01) than those who experienced nondifficult LC. By univariate logistic regression analysis, results also showed that patients with a maximum gallbladder diameter had a higher risk of experiencing difficulty during emergency LC ( P =0.02). Moreover, the gallbladder diameter's cutoff value was 43 mm after the receiver operating characteristic curve analysis. CONCLUSIONS: In patients with mild to moderate AC, emergency LC can safely be performed. However, performing LC might be technically difficult in patients with AC after the identification of severe gallbladder swelling during presurgical CT.

A comprehensive analysis of immunohistochemical studies in intrahepatic cholangiocarcinoma using the survival tree model.

OBJECTIVE: Various immunohistochemical studies have been performed regarding intrahepatic cholangiocarcinoma (ICC), including the cell cycle-related proteins (p27, cyclin D1, 14-3-3sigma, p53, cyclin B1 and Ki-67), the proto-oncogenes (c-erbB-2 and c-Met), the extracellular matrix proteins (tenascin and laminin) and others (beta-catenin, epidermal growth factor receptor, osteopontin, aquaporin 1, MUC5AC and fascin). Nevertheless, none of these have been proven to be a predictive power of the prognosis with high specificity and sensitivity for ICC. METHODS: Sixty-one patients with ICC were selected and ICC specimens were immunohistochemically stained with the above 16 markers, as previously reported. RESULTS: The immunoreactivity of osteopontin, tenascin and Ki-67 divided the patients with ICC into 4 subgroups by the survival tree model. There was a significant relationship between the location of the tumor, TNM classification, histological differentiation, tumor size, lymphatic permeation, perineural invasion, lymph node metastasis, intrahepatic metastasis and viral infection among the 4 subgroups. In addition, there was a significant difference in survival among the 4 subgroups. CONCLUSION: In this study, the subgrouping by the survival tree model might be helpful for predicting the patients' prognosis in ICC.

Coexistence of mucinous cystic neoplasm occurring in the head of the pancreas with annular pancreas: report of a case.

Mucinous cystic neoplasms (MCN) of the pancreas are rare tumors that are almost exclusively located in the body or the tail of the pancreas. A 60-year-old woman with no history of pancreatic disease was referred to our hospital with a chief complaint of dull pain in the upper abdomen. Abdominal computed tomography showed a multilocular cystic mass of 7.0 cm in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed no communication between the cystic mass and the main pancreatic duct. A pancreatoduodenectomy was performed for the complete resection of the tumor, and an annular pancreas was discovered by accident. The pathological examination of the tumor led to a definitive diagnosis of MCN with ovarian-type stroma. To our knowledge this is the first documented case of MCN occurring in the head of the pancreas and associated with annular pancreas.

Pancreatogastrostomy with an elastic purse-string suture around the gastric orifice after pancreatoduodenectomy.

Postoperative pancreatic fistula (POPF) is a potentially fatal complication of pancreatoduodenectomy (PD). Fixation of the remnant pancreas to the gastric wall is considered essential to prevent anastomotic leakage in patients undergoing pancreatogastrostomy (PG) after PD. PG was performed with invagination of the pancreatic stump. To limit the number of sutures in the pancreas parenchyma to three or four, we placed an elastic purse string suture around the orifice of the posterior gastric wall in an attempt to fix the gastric wall to the remnant pancreas. We performed PG using this technique in 30 patients. According to the international POPF criteria, POPF developed in three (10%) patients; as grade A in one, and grade B in two. These results demonstrate the potential advantage of performing PG after PD, by using this invaginated technique with an elastic suture.

Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Liver transplantation is an accepted treatment option for patients with otherwise untreatable hepatocellular carcinoma (HCC). The present study assessed the outcome of living donor liver transplantation (LDLT) under extended selection criteria based on a single-center experience. METHODS: A total of 60 patients who underwent LDLT for HCC were included. Our indication for LDLT included HCC without extrahepatic spread or macroscopic vascular invasion. The size and number of HCC nodules were not limited. Recurrence-free survival rates according to various factors were compared to identify risk factors for recurrence. RESULTS: Forty patients (67%) preoperatively exceeded the Milan criteria. The median follow-up was 437 days (range: 23-1,385 days). The overall 1- and 3-year actuarial survival rates were 88.4 and 68.6%, respectively. HCC recurred in eight patients (14.3%) within a mean follow-up of 288 days; all were patients who exceeded the Milan criteria. The 1-, 2- and 3-year recurrence-free survival rates of patients who fulfilled the Milan criteria were 100%, 100%, and 100%, respectively, whereas those of patients who exceeded the criteria were 83.0%, 74.0%, and 74.0%, respectively. Tumor diameter >5 cm was significantly associated with worse prognosis, but the number of tumors was not. A preoperative des-gamma-carboxy prothrombin value >300 mAU/ml was strongly associated with the high recurrence rate. These two variables were significant in multivariate analysis. CONCLUSIONS: LDLT was shown to offer acceptable results in patients who exceeded the Milan criteria. The indication for LDLT can therefore be expanded beyond the Milan criteria, especially for patients with small multiple tumors <5 cm.

Successful pylorus-preserving pancreaticoduodenectomy for a patient with carcinoma of the papilla Vater two years after living donor liver transplantation.

Liver transplantation has been recognized as the treatment for various kinds of end-stage liver diseases. Standardized surgical technique, potent immunosuppressive agents and diligent postoperative care have made it possible for patients to survive for a longer period. For this reason, recurrent primary disease and/or de novo malignancy regarded as chronic immunosuppressant have been paid a great deal of attention. Even pancreas cancer after liver transplantation is extremely rare and has never been successfully treated. Furthermore, cancer of the papilla Vater, which is less frequent than pancreas cancer after liver transplantation has not been reported as yet. In this paper we discuss the first case of cancer of the papilla Vater, which was successfully treated by pylorus-preserving pancreaticoduodenectomy two years after a living related liver transplantation using a left lobe. In addition, we discuss the type of malignancy after liver transplantation.

Surgical Resection for Pulmonary Metastasis from Pancreatic and Biliary Tract Cancer.

AIM: To determine the efficacy of pulmonary metastasectomy for pancreatic and biliary tract cancer. PATIENTS AND METHODS: Ten patients who underwent therapeutic pulmonary metastasectomy after resection for pancreatic and biliary tract cancer at our Institution from 2006 to 2016 were retrospectively evaluated. RESULTS: The primary site was the pancreas in four patients and biliary tract in six. Nine patients had single metastasis, and one patient had bilateral multiple metastases. The median time from surgery for the primary tumor to pulmonary resection was 23.3 months (range= 0-47.1 months). One patient underwent lobectomy, while nine patients underwent partial resection. One patient had incomplete resection due to pleural dissemination. There were no postoperative mortalities or major morbidities. The mean follow-up period was 26.0 months. The median survival time was 38.5 months, and the estimated 5-year overall survival was 38.9% after pulmonary resection. Five patients had recurrent disease after pulmonary resection, with a median recurrence-free interval of 6.0 months. One patient underwent second pulmonary resection for a solitary lung recurrence. CONCLUSION: Despite the poor prognoses of these cancer types, pulmonary metastasectomy can significantly prolong survival in selected patients with pancreatic and biliary tract cancer.

Surgical Outcomes of Non-small Cell Lung Cancer in Patients with a History of Pancreaticobiliary Cancer.

AIM: To determine the efficacy of surgery for non-small cell lung cancer in patients who had previously undergone surgery for pancreaticobiliary cancer. PATIENTS AND METHODS: Seven patients who underwent pulmonary resection for primary lung cancer after curative surgery for pancreaticobiliary cancer at our Institution from 2006 to 2016 were retrospectively evaluated. RESULTS: Five patients had metachronous and two patients had synchronous cancer of pancreaticobiliary and lung origin. The median time between surgeries for the two cancers was 35 months. All patients underwent complete resection of both cancers. The 5-year survival was 68.6% after pulmonary resection. Two patients had recurrence after lung surgery, with a mean recurrence-free interval of 6.5 months. CONCLUSION: Surgery should be considered for lung cancer in patients who have undergone curative surgery for pancreaticobiliary cancer.

Sustained spatial disturbance of bile canalicular networks during regeneration of the steatotic rat liver.

BACKGROUND: Although it is generally considered that livers with moderate steatosis can be safely used in the setting of living-donor liver transplantation, the effect of the regenerative process of such a graft on postoperative liver function is incompletely understood. We assessed the morphologic and functional alterations during the regeneration of fatty liver, with special reference to the biliary system. METHODS: Wistar rats with normal or fatty livers induced by a choline-deficient diet were subjected to 70% partial hepatectomy (PH). The regenerated liver weight and serum parameters were compared. Furthermore, to assess the spatial alterations of bile canalicular networks, the distribution of AGp110, a fibronectin receptor that localizes on the apical (bile canalicular) membrane of the hepatocytes, was analyzed immunohistochemically. RESULTS: The serum albumin levels of the fatty-liver rats decreased significantly after 24 hours, and this continued until day 7. The increase in the total bile acid levels of the fatty-liver group was higher and more prolonged compared with that of the normal-liver group. At 24 hours after PH, discontinuity of the AGp110-positive canalicular network was evident in both groups. At 7 days after PH, the typical AGp110-positive canalicular network was almost restored in the normal-liver group. In contrast, the fatty-liver group showed sustained discontinuity of canalicular networks at the same time point. CONCLUSIONS: The livers with moderate steatosis are associated with prolonged cholestasis after 70% PH, and this was caused, in part, by sustained spatial disturbance of bile canalicular networks during the regenerative process.

Use of steatotic graft in living-donor liver transplantation.

BACKGROUND: The degree of fatty infiltration in hepatic grafts is known to be an important risk factor for primary graft nonfunction in cadaveric liver transplantation. However, the effect of hepatic steatosis in living-donor liver transplantation (LDLT) has not yet been well defined. In this study, we evaluated the impact that the degree of hepatic graft steatosis has on the outcome of LDLT. METHODS: Sixty consecutive donors and recipients who underwent LDLT between October 1996 and August 2001 at Kyushu University Hospital were the subjects of this study. The pathologic findings of the prereperfusion biopsy of the graft were classified into the following three groups according to the degree of macrovesicular steatosis: None (n=23), 0% steatosis; Mild (n=23), 0% to 20% steatosis; and Moderate (n=6), 20% to 50% steatosis. Liver function tests including total bilirubin (at postoperative day [POD] 7), the peak alanine aminotransferase (ALT) and prothrombin time (at POD 3), and both patient and graft survival were compared among the groups. Furthermore, we also compared the donor parameters including the peak ALT and total bilirubin (at POD 3) and the operative time, blood loss, and length of hospital stay after surgery. RESULTS: The 1-year patient and graft survival were comparable among the groups. The peak ALT was significantly higher in the Moderate group (606+/-641 IU/L) than in the None (290+/-190 IU/L) and Mild (376+/-296 IU/L) groups. Total bilirubin (POD 7) and prothrombin time (POD 3) were comparable among the groups. The donor parameters were comparable among the groups except for the fact that the donor body weight of the Mild and Moderate groups were significantly heavier (P<0.0001) than that of the None group. CONCLUSIONS: In conclusion, the use of a fatty liver graft up to the moderate level can be justified in LDLT, even though ischemia-reperfusion injury tends to be severe in such grafts.

Liver transplantation for hepatocellular carcinoma.

The surgical management for hepatocellular carcinoma (HCC) is multiplicity. In Japan, liver resection has generally been considered to be the only curative treatment for HCC. The resectability of a tumor in cirrhotic patients, however, is limited by the diminished functional reserve of the cirrhotic liver and the attendant risk for intraoperative bleeding and postoperative liver failure. In cirrhotic patients, liver transplantation has been considered as the indication for HCC in many countries except Japan. Although the survival rate of patients with HCC who received liver transplants was poor in the early period, it later moved to the same level as for patients with other liver diseases. In 1993, living donor adult liver transplantation was started in Japan and it became an additional option for the treatment of HCC. A shortage of liver donors means that new methods of liver procurement must be explored. Domino liver transplantation using the livers of patients with familial amyloid polyneuropathy was also another option for advanced HCC. For the prevention of a recurrence of HCC, pre-, intra-, and postoperative chemotherapy have been performed after both liver resection and liver transplantation. We should also try to minimize intraoperative dissemination by surgical manipulation. Recently, potential gene therapies for HCC have been studied. Electroporation-mediated IL-12 gene therapy for HCC was found to be effective for both mIL-12-transferred HCC and for distant HCC. For patients with HCC accompanied by liver cirrhosis, liver transplantation remains the ultimate curative therapy. Immunologic and oncologic approaches to HCC can help prevent tumor recurrence and also help us to obtain better results after liver transplantation.

The mechanisms of angiogenesis in hepatocellular carcinoma: angiogenic switch during tumor progression.

Solid tumors constantly require a vascular supply for their progression and metastasis. Hepatocellular carcinoma (HCC) is known to gain its hypervascularity during the process of dedifferentiation and progression. Various angiogenic growth factors and inhibitors regulate this angiogenic switch of HCC. The known endothelial cell-specific growth factors and their receptors can be classified into the vascular endothelial growth factor and angiopoietin families. Both vascular endothelial growth factors and angiopoietins have been found to work cooperatively, and both are essential for HCC angiogenesis. Because small and ill-vascularized HCCs slowly progress and only rarely metastasize, antiangiogenic therapy could therefore be a promising anticancer strategy for HCC.

Characteristics of liver grafts in living-donor adult liver transplantation: comparison between right- and left-lobe grafts.

HYPOTHESIS: Few studies have investigated the results of research focused on living-donor adult liver transplantation. Different characteristics between right- and left-lobe grafts have not yet been clarified in living-donor adult liver transplantation. Left-lobe graft remains an important option, even in adult recipients. SETTING: A single liver transplantation center with a long history of hepatic resection. PATIENTS: Forty-five donors received left-lobe (n = 39) and right-lobe (n = 6) grafts. The clinicopathological data for the donor, graft, and recipient were compared. All left-lobe grafts were extended grafts that included the middle hepatic vein, and 24 of the 39 left-lobe grafts included the left caudate lobe. No right-lobe graft included a middle hepatic vein. RESULTS: The postoperative aspartate aminotransferase and total bilirubin values of the donor in the right-lobe graft group were higher, and the postoperative hospital stay was longer than in the left-lobe graft group. Graft weight in the left-lobe graft group was lighter than in the right-lobe graft group (median weight, 450 vs 675 g). The median graft weight divided by the standard liver volume in the left-lobe graft group was 41% (range, 21%-66%), compared with 52% (range, 47%-75%) in the right-lobe graft group. We found no difference in terms of the incidence of postoperative complications between groups. No difference in induced complications of small-for-size grafts such as intractable ascites and persistent hyperbilirubinemia was evident between groups. The survival rate for grafts at 18 months was 75.0% in the right-lobe graft group compared with 85.6% in the left-lobe group. In the right-lobe graft group, we found a few cases in which a marked poor-perfusion area in the anterior segment caused liver dysfunction. CONCLUSIONS: Left-lobe grafts are a feasible option for living-donor adult liver transplantation, and in the case of right-lobe grafts, hepatic venous drainage is one of the most critical problems.

Prognostic factors in the so-called malignant mesenchymoma: a clinicopathological and immunohistochemical analysis.

The term "malignant mesenchymoma" (MM) has traditionally been applied to a group of malignant soft tissue tumors that are characterized by the presence of two or more different mesenchymal tissue components in the same neoplasm. Currently, sarcomas with multilineage differentiation fulfilling the criteria of MM tend to be diagnosed as specific sarcomas with heterologous differentiation (e.g., de-differentiated liposarcoma) rather than MM; however, some cases of these tumors are difficult to classify. The purpose of this study was to analyze the clinicopathological and immunohistochemical features of these unclassifiable tumors, the so-called MM, and to determine whether some parameters are a useful adjunct for the classification of these tumors from the viewpoint of clinical outcome. Twelve cases of so-called MM were investigated retrospectively. The patients (six male, six female) ranged in age from 6 to 71 years (mean 48 years). Tumor size ranged from 3 to 20 cm (mean 13 cm). Tumor locations included the retroperitoneum (five cases), abdominal wall (two), thigh (two), forearm (one), lung (one), and parotid gland (one). The differentiated mesenchymal components were rhabdomyosarcomatous (RMS) (six cases), liposarcomatous (five), chondrosarcomatous (five), osteosarcomatous (five), or leiomyosarcomatous (four). Follow-up in all cases (range 4-129 months; mean 36 months) showed a 67% local recurrence rate, a 33% metastatic rate, and a 50% disease-related mortality. The patients who were under 40 years of age or who had an RMS component showed significantly worse survival than did patients in the other groups. The other mesenchymal components showed no significant correlation with survival. The immunophenotypes of p53 and mdm2 were almost identical between the two mesenchymal components in each case; however, there was no significant correlation between either of these immunophenotypes and the clinical outcome. None of the other factors (gender, tumor site, tumor size, or MIB-1-labeling index) was found to be a statistically significant prognostic indicator. In conclusion, a patient age under 40 years and the presence of an RMS component appear to be poor prognostic indicators of survival in patients with so-called MM, and to be a useful adjunct for the classification of these tumors.

Morphologic approach to hepatocellular carcinoma development in man: de novo or the so-called 'dysplastic nodule-carcinoma' sequence?

The so-called dysplastic nodule-carcinoma sequence in the liver is generally accepted because hepatocellular carcinoma is not an uncommon finding in precancerous lesions. In order to evaluate the existence and frequency of de novo hepatocarcinogenesis we studied 112 surgically resected early well-differentiated hepatocellular carcinomas showing replacing growth without less differentiated component in themselves. They were divided into two groups: carcinoma in dysplastic area (type A) and carcinoma without dysplastic area (type B) and were analyzed clinicopathologically. We encountered 77 cases of type A (68.8%) and 35 of type B (31.2%). The frequency of type A in cirrhotic group (74.7%) is statistically higher than that of non-cirrhotic group (54.5%) (p=0.0453). Using multivariate analysis, the occurrence of type A was related with higher age, the presence of cirrhosis and hepatitis B surface antigen positive. The tumor size and the presence of fatty change in the tumor tended to relate with type A. We propose two pathways morphologically in early hepatocarcinogenesis, one of which has a close relation to hepatitis B virus and/or cirrhosis.

The impact of splenectomy or splenic artery ligation on the outcome of a living donor adult liver transplantation using a left lobe graft.

BACKGROUND/AIMS: The aim of this study was to clarify the impact of splenectomy or splenic artery ligation on the outcome in living donor adult liver transplantation (LDALT) using a left lobe graft. METHODOLOGY: Forty-eight LDALT cases using a left lobe graft were enrolled in this study. The patients were classified into two groups: Group A (n=40), in which neither a splenectomy nor a splenic artery ligation was performed, and Group B (n=8), in which a splenectomy (n=6) or a splenic artery ligation (n=2) was performed. Indications for splenectomy were as follows: 1) demonstrating a hypersplenism and/or 2) having splenic aneurysms. RESULTS: None of the patients receiving a splenectomy or a splenic artery ligation experienced any septic complication in this series. The graft-recipient weight ratio in group B tended to be smaller than in group A. In group B, all patients were classified into Child's class C or B. The incidence of esophageal varices in group B was significantly higher than in group A. Moreover, the platelet count and the white blood cell count in group B were significantly lower than in group A. No statistical difference was found in postoperative functional cholestasis and intractable ascites. None of the participants in group B experienced both postoperative hyperbilirubinemia and intractable ascites, which were characterized as a small-for-size graft after LDALT. The patient survival rate in group B seems to be better than in group A. In a majority of the cases the portal pressure as well as the portal vein flow after a splenectomy decreased in comparison to that before the splenectomy. CONCLUSIONS: Splenectomy or splenic artery ligation is considered to be beneficial for improving the outcome in LDALT using a left lobe graft.