Short- and long-term outcomes of the Frey procedure for chronic pancreatitis: a single-center experience and summary of outcomes in Japan.

PURPOSE: To evaluate the short- and long-term outcomes of the Frey procedure for chronic pancreatitis (CP). METHODS: The subjects of this study were 12 patients who underwent the Frey procedure for CP between January, 2000 and December, 2016. We assessed pain relief, weight gain, and exocrine/endocrine insufficiency during follow-up. RESULTS: The study population comprised 11 men and 1 woman (91.7% vs. 8.3%; mean age, 50.3 ± 6.8 years; range 39-61 years). Pancreatitis was caused by alcohol in 9 (75%) patients and was idiopathic in 3 (25%) patients. The mean follow-up period was 82.5 ± 46.5 months (range 16.9-152.1 months). There was no operative mortality, but three patients (25%) suffered postoperative morbidity. All patients were pain-free at the time of discharge. There was no case of new-onset diabetes mellitus after surgery, although one patient (8.3%) suffered exocrine insufficiency. The body weight and body mass index of all patients improved during follow-up. Only one patient continued to suffer pain in the long term. CONCLUSION: The findings of this long-term follow-up of patients who underwent the Frey procedure suggest that it offers effective pain relief and is a safe technique for the management of CP.

Multifocal Mass Lesions in Autoimmune Pancreatitis.

A 59-year-old male patient with jaundice was referred to our hospital because of mass lesions in the pancreatic head and tail. An immunological examination revealed an elevated serum IgG4 level. Computed tomography showed two clear boundary mass lesions in the pancreatic head and tail. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images and iso-intensity on T2-weighted images. Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and tail. The possibility of malignant tumors could not be ruled out; therefore, we performed total pancreatectomy. A histopathological examination of the nodular lesions revealed severe lymphoplasmacytic infiltration and inflammatory change around the pancreatic ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the nodules. According to these pathological findings, we diagnosed the patient with IgG4-related multifocal mass lesions of autoimmune pancreatitis (AIP). It is difficult to distinguish between focal type AIP and pancreatic cancer. We herein report a rare case of multifocal mass lesions in AIP and include bibliographical comments.

Hepatectomy for Hilar Cholangiocarcinoma with Right-Sided Ligamentum Teres Using a Hepatectomy Simulation System.

Right-sided ligamentum teres (RSLT) is a rare congenital anomaly often accompanied by variation of the hepatic vasculature. We herein report a surgical case of a hilar cholangiocarcinoma with RSLT in whom preoperative hepatectomy simulation proved useful for understanding the anatomical structure of the liver. A 78-year-old male with obstructive jaundice was referred to our department for further examination. The patient was suspected of having a hilar cholangiocarcinoma originating from the left hepatic bile duct by contrast-enhanced computed tomography (CT), and CT also showed right umbilical portion (RUP). Three-dimensional images of the hepatic vasculature and biliary system reconstructed using a hepatectomy simulation system suggested that all portal branches ramified from RUP were right paramedian branches, and three leftward portal branches from these ran parallel to the peripheral bile ducts confluent with the left hepatic bile duct, where the tumor was present. Hepatic resection of part of the ventral area of the right paramedian sector and left hemiliver was performed along the demarcation line drawn after clamping the portal branches; the ratio of estimated liver resection volume was 28.9%. After the operation, bile leakage occurred. However, the leakage was treated with percutaneous drainage alone, and the patient was discharged 77 days after the operation. The patient is doing well without any signs of recurrence 21 months after the operation. The vascular and biliary anatomy in patients with RSLT is complicated and should be evaluated in detail preoperatively using a hepatectomy simulation system.

Laparoscopic Resection of an Epithelial Cyst in an Intrapancreatic Accessory Spleen.

An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is rare. We herein report a case of a patient with ECIAS who underwent laparoscopic surgery. A 57-year-old woman was referred to our hospital because of a pancreatic tail tumor. She was asymptomatic, and a physical examination revealed no remarkable abnormalities. The levels of the tumor marker carbohydrate antigen 19-9 (CA19-9) and s-pancreas-1 antigen (SPan-1) were elevated. Ultrasonography showed a well-defined homogeneous cystic tumor. Computed tomography showed a well-demarcated cystic tumor in the pancreatic tail. Magnetic resonance imaging showed that the cystic tumor exhibited low intensity on T1-weighted images and high intensity on T2-weighted images. The cystic tumor was diagnosed as mucinous cystic neoplasm preoperatively. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. A histopathological examination revealed the cyst wall to be lined by stratified squamous epithelium within splenic parenchyma, and the ultimate diagnosis was ECIAS. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. ECIAS is very difficult to diagnose preoperatively. Laparoscopic surgery is a safe and minimally invasive procedure for patients with difficult-to-diagnose pancreatic tail tumor suspected of having low-grade malignancy.

Synchronous double cancers of primary hepatocellular carcinoma and cholangiolocellular carcinoma: a case report.

Synchronous double cancers consisting of hepatocellular carcinoma (HCC) and cholangiolocellular carcinoma (CoCC) are extremely rare. We herein report a surgical case of synchronous double cancers in a patient with primary HCC and CoCC. A 45-year-old man with hepatitis B was admitted to our hospital with hepatic tumors. The level of protein induced by vitamin K antagonist (PIVKA-II) was found to be elevated. Computed tomography (CT) revealed a 23-mm tumor with early-phase enhancement and late-phase washout in the 6th segment of the liver, and a 10-mm tumor with slight early-phase enhancement and late-phase washout in the 7th segment of the liver. Magnetic resonance imaging (MRI) revealed that the two tumors in the 6th and 7th segments showed low intensity on T1-weighted images and high intensity on T2-weighted images. Based on those preoperative examinations, the liver tumors were diagnosed as multiple primary hepatocellular carcinomas. The patient underwent a posterior segmentectomy. A histopathological examination revealed that the tumor of the 6th segment of the liver was moderately differentiated HCC, and that the tumor of the 7th segment of the liver was CoCC. The postoperative course was uneventful. However, lymph node recurrence was observed 6 months later and the patient died 20 months after surgery. There are only six reported surgical cases of synchronous double primary liver cancers consisting of HCC and CoCC. We are of the opinion that curative resection may be an effective treatment for double cancer consisting of HCC and CoCC, and that it may provide long-term survival.

Parenchyma-preserving hepatectomy based on portal ramification and perfusion of the right anterior section: preserving the ventral or dorsal area.

BACKGROUND: Anatomical hepatectomy aims to eliminate the spread of malignant tumor cells via portal vein systemically. An anatomical concept of the right anterior section (RAS) and preservation of the liver parenchyma within the RAS has been proposed. METHODS: We focused on the anatomical concept of the RAS based on portal perfusion and described surgical procedures to preserve the ventral or dorsal RAS using preoperative simulation. RESULTS: In 370 patients undergoing a preoperative simulation, the ramification of the tertiary portal branches of the RAS could be divided into three types including the cranio-caudal type; Couinaud's classification in 50% of patients, ventro-dorsal type in 26% of patients, and multiple type in 24% of patients. Then in 32 patients of the ventro-dorsal type, curative parenchyma-sparing hepatectomy of the RAS was performed, preserving the ventral and dorsal RAS in 14 and 18 patients, respectively. There were no differences in the postoperative complications and long-term survival compared with the results obtained after segment 5 or 8 resection (n = 33). CONCLUSION: Three-dimensional simulation revealed three types of portal vein ramification of the RAS. Parenchyma-preserving hepatectomy based on the precise portal ramification may contribute to safe and curative hepatectomy in selected cases with liver neoplasm involving the RAS.

Hepatic Pseudolymphoma with Fluorodeoxyglucose Uptake on Positron Emission Tomography.

A 69-year-old woman with chronic hepatitis B was admitted to our hospital with a hepatic tumor. The levels of 2 tumor markers, carcinoembryonic antigen and carbohydrate antigen 19-9, were slightly elevated; however, the α-fetoprotein and protein levels induced by vitamin K antagonist II were within the normal limits. Abdominal ultrasonography showed a well-defined peripheral hypoechoic mass that was isoechoic and homogeneous on the inside. Computed tomography showed a poorly enhanced tumor of 13 mm in diameter in the 5th segment of the liver. Fluorodeoxyglucose positron emission tomography showed a slight uptake (maximum standard uptake value 3.4) by the hepatic tumor. These findings suggested cholangiocellular carcinoma, and we performed anterior segmentectomy of the liver. A histopathological examination showed a hepatic pseudolymphoma. The patient's postoperative course was uneventful, and she remains alive without recurrence 5 months after undergoing surgery. In most cases, hepatic pseudolymphoma is preoperatively diagnosed as a malignant tumor and a definite diagnosis is made after resection. It is therefore necessary to consider hepatic pseudolymphoma as a differential diagnosis in patients with hepatic tumors.

Granulocyte colony-stimulating factor-producing cholangiocellular carcinoma.

A 61-year-old female was admitted to our hospital with epigastric pain and fever. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, the patient was diagnosed with a granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL). We performed left trisegmentectomy of the liver, bile duct resection, and lymph node dissection. Histologically, the tumor was a poorly differentiated adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G-CSF-producing cholangiocellular carcinoma. The inflammatory reactions and serum G-CSF level transiently improved immediately after surgery. However, 1 month later, the leukocyte count and serum G-CSF level increased again, and recurrence was observed in the remnant liver. The patient died 3 months after the operation. G-CSF-producing cholangiocellular carcinoma is rare. This tumor progresses rapidly, and surgical treatment for advanced condition should be carefully selected.

Primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis: report of a case.

A 70-year-old male was treated for gastric ulcers. Follow-up upper gastrointestinal endoscopy revealed an irregular, elevated tumor in the second portion of the duodenum. Upon pathological inspection of a biopsy specimen, a diagnosis of adenocarcinoma was made, and the patient was admitted to our hospital. Computed tomography showed an irregular mass in the pancreatic head and dilatation of the main pancreatic duct and bile duct. Pancreatic head carcinoma with infiltration of the duodenum was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. A histopathological examination of the resected specimen showed moderately differentiated adenocarcinoma in the minor duodenal papilla and chronic pancreatitis in the pancreatic head. Therefore, primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis was diagnosed. Currently, the patient is alive without recurrence 17 months after the surgery. Primary adenocarcinoma of the minor duodenal papilla is extremely rare. We herein report this case, and also provide a review of the literature.

Granulocyte-colony stimulating factor-producing gallbladder carcinoma.

Abstract A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)-producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF-producing gallbladder carcinoma. Aggressive curative resection for G-CSF-producing gallbladder carcinoma may improve patients' general condition and prognosis.

Multivariate logistic regression analysis for prediction of clinically relevant pancreatic fistula in the early phase after pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (PF) remains a major complication after pancreaticoduodenectomy (PD). We aimed to investigate the predictors of clinically relevant PF after PD. METHODS: We retrospectively analyzed the predictive factors of relevant grade B/C PF using logistic regression analysis of 100 consecutive patients who underwent PD. PF was defined in accordance with the International Study Group on PF (ISGPF). RESULTS: White blood cell count (WBC) of 73.6 × 10(2) /µl, C-reactive protein (CRP) of 9.3 mg/dl and amylase value in drains (d-amylase) of 647 U/I on postoperative day (POD) 4 were proposed as the cut-off values for predicting grade B/C PF with high accuracy by the receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis revealed that the three factors as significant predictive factors and the predicted probability of detecting grade B/C PF was calculated by the following formula; P = 1/[1 + exp{-(2.033 × WBC+3.269 × CRP+2.698 × d-amylase-4.122)}]. P > 0.5 indicates the prospective incidence of the PF. When the cut-off values of the three significant predictors were substituted into the formula, P always showed above 0.5 if more than two predictors were above their cut-off values, indicating a high probability of grade B/C PF. CONCLUSIONS: White blood cell count, CRP and d-amylase on POD4 were predictive factors for clinically relevant PF after PD. These findings indicate that our formula is useful for management of drain after PD.

Regional hepatic regeneration after liver resection correlates well with preceding changes in the regional portal circulation in humans.

BACKGROUND AND AIMS: While portal hemodynamics largely affects the liver regeneration after partial hepatectomy, whether the remnant liver homogeneously regenerates is unclear, especially in humans. We hypothesized that change in flow distribution varies in each remnant portal branch after liver resection in humans and the liver consequently regenerates heterogeneously. METHODS: Twenty-two patients who underwent anatomical hepatic resection preserving intact drainage veins were analyzed. Based on perioperative contrast-enhanced computed tomography, the regional hepatic regeneration in each segment was analyzed using a region growing software. The perioperative change in the distribution of blood flow in each portal branch was assessed using the computational flow dynamics technique. The correlation between the change in the portal flow distribution and the later regional hepatic regeneration was investigated. RESULTS: The distribution of portal blood flow in each remnant branch largely changed at 2 weeks (71-389 %). Each remnant segment also heterogeneously regenerated at 3 months (85-204 %). Meanwhile, a good correlation between the regional regeneration rate at 3 months and the relative change in the flow distribution in each circulating portal branch at 2 weeks was detected in each patient (r = 0.74-0.99). CONCLUSIONS: After partial hepatectomy, the change in blood flow varies in each remnant portal branch and the liver heterogeneously regenerates in humans. The good correlation between the earlier change in the portal flow distribution and the later regional hepatic regeneration strongly suggests that the portal venous flow most likely regulates the non-uniform liver regeneration after hepatic resection in humans.

Rare form of extraovarian primary peritoneal papillary serous carcinoma with solitary cystic lesion mimicking a liver tumor; report of a case.

Extraovarian primary peritoneal serous papillary carcinoma (EOPPC) has a similar clinical presentation to that of ovarian cancer in advanced stages, such as peritoneal dissemination and a large amount of ascites, while EOPPC with a solitary tumor is very rare. We report here a 47-year-old Japanese woman with solitary form of EOPPC mimicking a liver tumor. Ovaries of both sides had no malignant lesion, which was histologically confirmed. Histological examination revealed that the tumor was located at the right diaphragm and partially invaded into the liver, and papillary or ductal proliferation of the tumor cells with an occasional appearance of psammoma bodies was detected. Immunohistologically, the tumor cells were positive for CA 125 and Ber-EP4 and negative for D2-40 or calretinin, ruling out the possibility of mesothelioma, and the diagnosis of the tumor was EOPPC. After the operation, the patient received chemotherapy with carboplatin and paclitaxel, but died 10 months later due the progression of recurrence. The present case is very rare form of EOPPC without any ascites or peritoneal dissemination.

Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case.

We herein report the case of a 48-year-old Japanese female with retroperitoneal epithelioid hemangioendothelioma (EHE), a rare malignant vascular tumor of intermediate grade. She was referred to our hospital because a retroperitoneal tumor was found during a medical checkup, in which strong accumulation of (18)F-fluorodeoxyglucose (FDG) was observed by (18)F-FDG-positron emission tomography (PET). A histological examination of the resected tumor revealed that it consisted of large epithelioid cells with vesicular nuclei, and clear cells with vacuolated cytoplasm and intracytoplasmic lumina. These cells expressed CD31 and vimentin, and the final pathological diagnosis was EHE. Postoperative surveillance with FDG-PET revealed distant metastasis in Virchow's lymph node 7 months after the operation. After dissection of the metastatic lymph node, the patient has been free from recurrence for 13 months. Close follow-up with FDG-PET seemed to be useful for surveillance of the recurrence of this tumor with unpredictable behavior, making an early treatment for the recurrent lesions possible.

Primary squamous cell carcinoma of the liver: an uncommon finding in contrast-enhanced ultrasonography imaging.

Primary squamous cell carcinoma (SCC) of the liver is rare tumor with an unfavorable prognosis. We report a case of advanced primary SCC of the liver arising adjacent to a nonparasitic liver cyst, invading into the right diaphragm and the right lung tissue. Contrast-enhanced ultrasonography (CE-US) demonstrated unique enhancement in the late vascular phase, which was incompatible with those observed in hepatocellular carcinoma, cholangiocellular carcinoma, or metastatic adenocarcinoma. The patient underwent surgical resection of the tumor followed by systemic chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP), while radiation chemotherapy was not applied because of relatively poor performance status. Although postoperative image analysis revealed no recurrence 4 months later, the patient died 13 months after the operation from recurrence. Immunohistological analysis of the resected specimen revealed that this SCC contained many capillary endothelial vessels expressing CD31 or CD34, possibly reflecting the unique imaging pattern in the late vascular phase of CE-US, which has been reported in choangiolocellular carcinoma. In addition, we reviewed which kind of treatment would be suitable for advanced hepatic primary SCC in the literature. From the review, it could be proposed that a combination of radiation therapy, systemic chemotherapy (5-FU and CDDP) and surgical resection, if possible, is appropriate for advanced primary SCC of the liver.

Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters.

BACKGROUND: Accurate preoperative estimation of remnant liver function is critically important for hepatic surgery, and the expression of asialoglycoprotein receptors (ASGPR) is associated with hepatic function. METHODS: Thirty-two patients with hepatocellular carcinoma who underwent surgical resection were studied. To estimate the expression of ASGPR in the remnant liver, simulated surgery was performed on fusion images that combined data from (99m)technetium-galactosyl human serum albumin ((99m)Tc-GSA)/single photon emission computed tomography (SPECT) and computed tomography (CT) scanning. The liver uptake ratio (LUR) of (99m)Tc-GSA and the functional liver volume (FLV) in the remnant liver were predicted and were compared with postoperative liver function parameters. RESULTS: The LUR of (99m)Tc-GSA was strongly correlated with the extent of hepatic ASGPR expression (r = 0.944, p = 5.01 x 10(-16)), being confirmed to be a reliable parameter for the evaluation of liver function. The estimated remnant LUR, but not the estimated remnant FLV, was significantly correlated with postoperative liver function parameters, such as serum total bilirubin (r = -0.430, p < 0.05), prothrombin activity (r = 0.515, p < 0.01), and serum cholinesterase activity (r = 0.546, p < 0.01) at 1 week. CONCLUSION: Preoperative estimation of the extent of ASGPR expression in the remnant liver on CT/GSA-SPECT fusion images correlated well with postoperative liver function parameters, suggesting its usefulness for surgical decisions.

Hepatocyte growth factor gene transfer with naked plasmid DNA ameliorates dimethylnitrosamine-induced liver fibrosis in rats.

AIM: Hepatocyte growth factor (HGF) has various biological properties, including antifibrogenic activity. In the present study, we tested the efficacy of HGF gene therapy using naked plasmid DNA in dimethylnitrosamine (DMN)-induced liver fibrosis in a rat model. METHODS: Naked plasmid DNA encoding human HGF was injected once, together with a hypertonic solution, into the hepatic artery after DMN treatment on three consecutive days per week for 3 weeks. Naked plasmid DNA encoding beta-galactosidase was injected similarly in the DMN-treated control rats. DMN treatment was continued once weekly after gene transfer for additional 3 weeks. RESULTS: The human HGF protein expression was detected in livers transfected with human HGF naked plasmid DNA, gradually decreasing by day 21. The expression of the endogenous rat HGF protein was also upregulated after human HGF gene transfer. Phosphorylation of c-Met, a HGF receptor, was detected only in livers transfected with human HGF plasmid DNA. Fibrosis was attenuated significantly in livers transfected with the human HGF plasmid. Attenuation wasaccompanied by decreased expression of alpha-smooth muscle actin. Increased portal vein pressure after treatment with DMN was suppressed significantly by HGF gene transfer. The upregulated hepatic protein expression of transforming growth factor-beta (TGF-beta) in response to DMN was markedly attenuated by HGF gene transfer accompanied by the increased protein expression for matrix metalloproteinases (MMP)-3 and -13. CONCLUSION: The hepatic arterial injection of human naked plasmid HGF DNA was effective in suppressing liver fibrosis induced in rats by DMN. The mechanisms by which HGF expression attenuated liver fibrosis may include the suppression of hepatic TGF-beta expression and the induction of MMP expression.

Hepatocyte growth factor promotes remodeling of murine liver fibrosis, accelerating recruitment of bone marrow-derived cells into the liver.

AIM: Hepatocyte growth factor (HGF) ameliorates liver fibrosis/cirrhosis in animal models, while the participation of bone marrow-derived cells (BMC) in the repair process of injured organs has recently been reported. In this study we investigated the roles of HGF and BMC in a remodeling process of liver fibrosis. METHODS: C57BL/6 J mice were treated with carbon tetrachloride (CCl(4)) for 10 weeks. At week six, the mice underwent whole body irradiation and transplantation with bone marrow cells from syngenic LacZ-transgenic mice. After the transplantation, gene transfer of HGF into skeletal muscles was performed once a week for four weeks. In the control group, sterile saline was injected. RESULTS: HGF gene transfer ameliorated the CCl(4)-induced liver fibrosis, accelerating recruitment of LacZ-expressing cells into the liver. This phenomenon was accompanied byincreased gelatinase activity in the liver. A large number of the LacZ-positive cells expressed markers of vascular endothelial cells, while some of them had a marker of macrophages. Expression of stromal cell-derived factor (SDF)-1 in the liver was upregulated around the central veins, especially in the HGF gene-transferred animals, recruiting chemokine (C-X-C motif) receptor (CXCR) 4-positive cells in this area. CONCLUSION: Transplanted BMC participate in the HGF-induced remodeling process of liver fibrosis. The roles of HGF in this process include the recruitment of BMC, possibly through increased expression of SDF-1 in part, as well as anti-apoptotic, mitogenic and antifibrotic activities on liver cells.