Proposal for Endoscopic Ultrasonography Classification for Small Pancreatic Cancer.

BACKGROUNDS: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. MATERIALS AND METHODS: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type-no findings around the stricture; A2: Hypoecho stricture type-localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type-tumor on the stricture; B: Dilation type-the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type-tumor located apart from the MPD. RESULTS: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. CONCLUSIONS: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.

Fatal fulminant herpes simplex hepatitis following surgery in an adult.

We present a case of a healthy 72-year-old man with herpes simplex hepatitis (HSVH) development soon after ordinary surgery for biliary stones. A sudden onset of hepatitis associated with high fever and leukopenia emerged on postoperative day 5, followed by a rapid and lethal course (died on day 9), despite an acyclovir therapy on day 8. Postmortem liver biopsy revealed positive immunostaining for herpes simplex virus (HSV) type-1. The serum tests (available after the death) were negative for anti-HSV immunogloblulins, but positive for HSV DNA. A review of 15 cases of postsurgical HSVH along with 42 cases of non-surgical HSH showed that (1): A wide spectrum of surgical procedures was involved; and (2): High mortality (87%) associated with lower rates of ante-mortem diagnosis (20%) and acyclovir treatment (20%). Due to the difficulty in diagnosis and lethal nature, an early clinical suspension and prompt empirical anti-viral intervention are imperative for postsurgical hepatitis with undetermined etiology, characterized by fever and leucopenia.

A series of seton techniques involving "top-down therapy" for patients with Crohn's disease who initially presented with perianal fistulas.

OBJECTIVES: We determined the outcomes of seton treatment through a series of techniques using biological agents (BIOs) in 18 patients with Crohn's disease (CD) who initially presented with perianal fistulas. METHODS: The patients underwent seton drainage using three seton types: a Penrose tube for fistulas with massive purulent discharge, a vessel loop for a small amount of discharge, and a rubber band for unproductive fistulas. If the distal end of the fistula extended more than 4 cm from the anal orifice, the skin and subcutaneous tissue were dissected along the outer edge of the anal sphincter to divide the fistulous tract into two portions. One seton encircled the sphincter from the primary opening throughout the anal canal (medial seton), and the other was inserted through the distal tract outside the sphincter (lateral seton). A BIO was then introduced immediately. When discharge ceased, the Penrose tube or vessel loop was replaced sequentially with a rubber band, which was tied fittingly and subsequently removed in medial to lateral order. RESULTS: The mean interval between fistula onset and CD diagnosis was 2.1 years, and that between CD diagnosis and introduction of BIOs was 0.5 years. The mean follow-up duration was 4 years. The BIOs currently used were infliximab in 10 patients, adalimumab in 7, and ustekinumab in 1. The overall success rate was 94.4%, including unproductive fistulas in 10 (55.6%) patients and fistula disappearance in 7 (38.9%). CONCLUSIONS: Our seton drainage techniques via the "top-down" approach represent a promising avenue for treating perianal fistulas in patients with CD.

Dual drainage using a percutaneous pancreatic duct technique contributed to resolution of severe acute pancreatitis.

A 66-year-old man was admitted for severe acute alcoholic pancreatitis with infected pancreatic necrosis (IPN). Abdominal computed tomography revealed an inflamed pancreatic head, a dilated main pancreatic duct (MPD), and a large cavity with heterogeneous fluid containing gas adjacent to the pancreatic head, and extending to the pelvis. The cavity was drained percutaneously near the pancreatic head on admission; another tube was inserted into the pelvic cavity on hospital day 3. The drained fluid contained pus with high amylase concentration. Nasopancreatic drainage tube placement was unsuccessfully attempted on hospital day 9. On hospital day 23, percutaneous puncture of the MPD and placement of a pancreatic duct drainage tube was performed. Pancreatography revealed major extravasation from the pancreatic head. The IPN cavity receded; the percutaneous IPN drainage tube was removed on hospital day 58. On hospital day 83, the pancreatic drainage was changed to a transpapillary pancreatic stent, and the patient was discharged. Measuring the amylase concentration of peripancreatic fluid collections can aid in the diagnosis of pancreatic duct disruption; moreover, dual percutaneous necrotic cavity drainage plus pancreatic duct drainage may be essential for treating IPN. If transpapillary drainage tube placement is difficult, percutaneous pancreatic duct drainage may be feasible.

Early dual drainage combining transpapillary endotherapy and percutaneous catheter drainage in patients with pancreatic fistula associated with severe acute pancreatitis.

BACKGROUND: The development of pancreatic fistula (PF) associated with pancreatic necrosis is of great concern in the management of severe acute pancreatitis (SAP). We expected that early recognition and intervention of PF combined with percutaneous catheter drainage (PCD) for pancreatic infection may improve SAP outcomes. METHODS: Fifteen consecutive patients with SAP were enrolled. Whenever feasible, fine-needle aspiration for fluid collection was performed to determine infection and amylase concentration. For infection and PF with amylase-rich fluid, PCD and transpapillary endotherapy (preferably naso-pancreatic drainage) were carried out as soon as possible. PCD was intensively managed by irrigating the sized-up and multiple large bore catheters. RESULTS: Infected fluid collection and PF were both detected in 13 (86.7%) patients. Pancreatic duct (PD) disruption (n = 6) and organ failure (n = 5) occurred exclusively in patients with amylase-rich collection ≥10,000 U/L. The median timing of PCD and endotherapy was 15.5 and 16.5 days, respectively. No serious complications or mortality resulted from intervention procedures other than stent occlusion in one (6.7%) patient. Surgical intervention due to uncontrollable infection and visceral organ injury was avoided. Fistula closure was achieved in 12 (92.3%) of 13 PF patients with a median duration of 45 days. Disease-related mortality occurred in one (6.7%) patient. CONCLUSION: Amylase-rich fluid collection ≥10,000 U/L may be an indication for further endoscopic investigation of PD disruption. Early dual drainage combining pancreatic endotherapy and PCD is feasible and safe, and may improve treatment outcome.

Pancreatic mass as an initial manifestation of polyarteritis nodosa: a case report and review of the literature.

Classic polyarteritis nodosa (PAN) that targets medium-sized muscular arteries and microscopic polyangiitis (MPA), characterized by inflammation of small-caliber vessels and the presence of circulating myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA), are distinct clinicopathological entities of systemic vasculitis. A 66-year-old woman presented with fever, cholestasis and positive MPO-ANCA. Radiological examination showed a pancreatic mass compressing the bile duct. Therefore, we performed pancreatoduodenectomy. Histopathological examination revealed that necrotizing vasculitis predominantly affecting the medium-sized vessels, spared arterioles or capillaries in the pancreas, a finding consistent with PAN. Unexpectedly, renal biopsy revealed small-caliber vasculitis and glomerulonephritis, supporting MPA. The initial manifestation of a pancreatic mass associated with vasculitis has only been reported in 7 articles. Its diagnosis is challenging because no reliable clinico-radiological findings have been observed. Clinicians should be aware of such cases and early diagnosis followed by immunosuppression is mandatory. Our findings may reflect a polyangiitis overlap syndrome coexisting between pancreatic PAN and renal MPA.

[Gastric emphysema, a critical condition accompanied by eating disorders: a case report].

Gastric emphysema encompasses a broad spectrum of diseases. A 31-year-old woman presented with severe vomiting and epigastric pain. She had lost body weight for several months, and was later diagnosed as having anorexia nervosa. A radiological study demonstrated intramural gas with huge gastric dilatation and portal venous gas. She underwent total gastrectomy and was rescued from extensive gastric necrosis. Her clinical findings suggest that extraordinary dilation of the stomach increased the intraluminal pressure, thereby resulting in perfusion disturbance and extensive gastric necrosis. There are five other case reports of gastric emphysema associated with eating disorders in the literature. All but one were young women, and one of 4 patients with massive gastric necrosis died due to septic shock. Eating disorders cause gastric emphysema through several unique mechanisms, including gastric muscular atrophy, occlusion of the gastroesophageal junction, and delayed gastric emptying. Gastric emphysema in relation to eating disorders carries a risk of life-threatening complications and requires urgent diagnosis and treatment.

Implication of B lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats.

BACKGROUND: Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear. METHODS: We used lymphopenic (L(-)) rats by single administration of anti-rat lymphocyte serum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) micro-chain from birth, and their vehicle controls. These animals were subjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5 mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatic tissue deposition of IgM or C3 was assessed with immunohistochemistry. RESULTS: The 24-h survival rate in control animals was 20%, whereas those in L(-), T(-), and B (-) animals were 80, 0, and 100%, respectively. Lymphocyte-sufficient control (L(+)) and B cell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-alpha levels 1 h after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 h after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 h after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM, and CH50 levels, showing less histological liver damage. CONCLUSION: B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy.

Clinicopathological features of hepatocellular carcinomas (HCCs) arising in patients without chronic viral infection or alcohol abuse: a retrospective study of patients undergoing hepatic resection.

BACKGROUND: This study was carried out to clarify the etiology and clinicopathological features of hepatocellular carcinomas (HCCs) arising in patients without chronic viral infection or alcohol abuse. METHODS: HCC patients who underwent resection were divided into three groups: a non-B non-C (NBNC) group (n = 13), who were seronegative for hepatitis B surface antigen (HBs Ag) and anti-hepatitis C antibody (HCV Ab), excluding a history of alcohol abuse; a B group (n = 25), who were seropositive for HBs Ag only; and a C group (n = 116), who were seropositive for HCV Ab only. We analyzed the features of tumor- and host-related factors and the outcome of the NBNC group. RESULTS: Hepatic inflammation and fibrosis were less severe in the NBNC group than in the other groups. There were no significant differences in tumor-related factors, except for higher serum levels of alpha-fetoprotein in the NBNC group. Recurrence rates and disease-free survivals were comparable among the three groups. The NBNC group comprised a greater population with one or two recurrent hepatic lesions (P < 0.05), and indocyanine green retention rates and fibrosis scores were preserved after the initial hepatectomy. The NBNC group had higher resection rates for intrahepatic recurrences (75.0%) than the other groups (21.1% and 22.2% in groups B and C, respectively; P < 0.05 and P < 0.05). The survival rate after the initial hepatectomy or detection of the recurrent lesions was significantly better in the NBNC group (both 100% at 5 years) than those in groups B and C (P < 0.05). CONCLUSIONS: NBNC patients maintained good liver function following the initial hepatectomy, and tended to have one or two recurrent lesions. These biological advantages provided NBNC patients more opportunities for repeat resection of intrahepatic recurrences, which may lead to a favorable outcome.

Appraisal of surgical treatment for pT2 gallbladder carcinomas.

This retrospective study was designed to appraise the surgical procedures for pT2 gallbladder (GB) carcinomas. Twenty patients with pT2 GB carcinomas underwent surgical resection. Hepatectomy of segments 4b and 5 was performed in 19 patients, and an extended right hepatic lobectomy was performed in 1. The extrahepatic bile duct was preserved in 8 patients in whom the disease was limited to the GB fundus and/or body. Regional lymphadenectomy was performed in 18 patients. A separate radical second operation was performed in 8 patients after cholecystectomy. Final pathological staging was stage IB in 15 patients, IIB in 4, and IV in 1. Overall 5-year survival rate in those 20 patients was 77% without operative deaths. The 5-year survival rate in 5 patients with nodal metastasis and in 8 patients without extrahepatic biliary resection was 80% and 100%, respectively. A separate radical second operation in 8 patients yielded 75% survival after 5 years. Perineural invasion as a prognostic determinant was closely associated with tumor extending to the neck or the cystic duct. Partial hepatectomy, usually with extrahepatic biliary resection and regional lymphadenectomy, was appropriate as a standard radical operation for pT2 GB carcinoma, but preservation of extrahepatic bile duct is advocated for disease limited to the GB fundus and/or body. Radical second operation enhanced the chance for cure in patients with pT2 GB carcinoma.

Hepatic inflammatory pseudotumor mimicking intrahepatic cholangiocarcinoma: report of a case.

Hepatic inflammatory pseudotumor (IPT) is a relatively rare lesion comprised of proliferating fibrovascular tissue infiltrated by inflammatory cells. IPT has a potential for recurrence and persistent local growth. We present a case of hepatic IPT mimicking a periductal-infiltrating type of intrahepatic cholangiocarcinoma (ICC) in a patient whose serum carbohydrate antigen 19-9 was slightly elevated. We performed a left hepatic lobectomy with resection of the extrahepatic bile duct and regional lymph node dissection under a preoperative diagnosis of ICC. However, histological examination of the resected tumor revealed granuloma tissue with lymphocyte infiltration, mainly by plasma cells, and proliferation into the surrounding connective tissue, and the lesion was ultimately diagnosed as hepatic IPT. This case points out the difficulties in differentiating between hepatic IPT extending along Glisson's sheath and ICC, based on imaging findings alone.

Aggressive hepatectomy for complete remission of metastatic germ cell tumor following chemotherapy: report of a case.

A 12-year-old girl presented with hemoperitoneum caused by disseminated liver tumors accompanying a retroperitoneal germ cell tumor and was rescued by transcatheter hepatic arterial embolization. Following systemic chemotherapy, the liver tumors decreased in size and number, although the retroperitoneal tumor was resistant to therapy. We simultaneously resected the retroperitoneal tumor, and the liver lesions by extended left lobectomy combined with resection of the three major (right, middle, and left) hepatic veins, while preserving the inferior right hepatic vein. The postoperative course was uneventful, and liver regeneration evaluated by serial computed tomography was almost completed by three months following surgery. Pathological examination of the resected tumors revealed benign (mature) teratomas. Since complete removal of tumors critically influences the outcome in patients with mature teratoma, aggressive surgery is advocated for extensive tumors. The present case clearly demonstrated that extended hepatectomy with resection of three major hepatic veins is feasible and provides an opportunity for achieving complete remission in patients with metastatic germ cell tumor of the liver.

Kupffer cells modulate splenic interleukin-10 production in endotoxin-induced liver injury after partial hepatectomy.

BACKGROUND/AIMS: This study was conducted to investigate the implication of Kupffer cells and the spleen in interleukin (IL)-10 production in endotoxin-induced liver injury after hepatectomy. METHODS: Rats were divided into five groups: the S group, sham-operation; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl(3): 7 mg/kg) administration to inhibit Kupffer cell function; the H group, two-thirds hepatectomy; the HG group, hepatectomy and subsequent GdCl(3) administration; the HGS group, hepatectomy and splenectomy with GdCl(3) administration. Lipopolysaccharide (1.5 mg/kg) was intravenously administered for each group 48 h after surgery. RESULTS: GdCl(3) treatment significantly suppressed the elevation of plasma tumor necrosis factor (TNF)-alpha levels by lipopolysaccharide administration with completely inhibited induction of hepatic TNF-alpha and IL-10 mRNAs. In the HG group, marked increase in plasma IL-10 levels associated with enhanced splenic IL-10 mRNA was observed 1 h after lipopolysaccharide administration when compared to those in the H and HGS groups. Plasma TNF-alpha/IL-10 ratio 1 h after lipopolysaccharide administration was higher in the order of H, HGS and HG groups. Hepatic parenchymal damage and the 24-h mortality were lowest in group HG, followed by groups HGS and H. CONCLUSIONS: Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.

Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.

PURPOSE: Disorder of mucosal immunity based on an imbalance between proinflammatory and anti-inflammatory cytokines is believed to be a major factor in the pathogenesis of ulcerative colitis. Platelet-activating factor potentially stimulates the production of proinflammatory cytokines and recruits inflammatory cells. The aim of this study was to determine whether and to what extent platelet-activating factor plays a role in the pathogenesis of ulcerative colitis. METHODS: Using dextran sulfate sodium-induced colitis in rats as a model of ulcerative colitis, we analyzed the composition of cellular infiltrates and the local tissue expression of messenger ribonucleic acid for cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. To directly assess the impact of platelet-activating factor on the development of colitis, we also determined the efficacy of a specific platelet-activating factor receptor antagonist for preventing dextran sulfate sodium-induced colitis. RESULTS: The activity of colitis was well correlated with the upregulation of cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha messenger ribonucleic acid in local tissues and infiltration of cytokine-induced neutrophil chemoattractant-positive neutrophils and ED1-positive macrophages. The platelet-activating factor receptor antagonist effectively ameliorated colitis, along with causing a decrease in the tissue cytokine-induced neutrophil chemoattractant messenger ribonucleic acid level and a decline in neutrophil and macrophage infiltration. However, the antagonist did not alter tissue levels of tumor necrosis factor-alpha messenger ribonucleic acid. CONCLUSION: Platelet-activating factor plays a critical role in the pathogenesis of dextran sulfate sodium-induced colitis through recruitment of cytokine-induced neutrophil chemoattractant-positive neutrophils and macrophages and/or stimulation of cytokine-induced neutrophil chemoattractant release from activated neutrophils. The tissue level of tumor necrosis factor-alpha messenger ribonucleic acid does not closely reflect the activity of colitis.

Beneficial effect of deletion variant of hepatocyte growth factor for impaired hepatic regeneration in the ischemically damaged liver.

This study was conducted to determine the influence of hepatic ischemia and reperfusion (HIR) injury on liver regeneration and the effect of the deletion variant of hepatocyte growth factor (dHGF) under these conditions. Male Sprague-Dawley rats were subjected to 60 minutes of total hepatic ischemia, and two-thirds hepatectomy was performed just before reperfusion. Animals received intravenous administration of either vehicle buffer (vehicle control group) or dHGF (1 mg/kg) (HGF group) at the end of the period of hepatic ischemia and again 6 hours after reperfusion. At 8 hours after hepatectomy, plasma HGF levels in the vehicle control group were significantly lower than those in the nonischemic controls. Plasma aspartate transaminase levels in the vehicle control group reached 3,462 +/- 1,039 IU/L, but levels in the HGF group were significantly inhibited to 1,849 +/- 605 IU/L. The relative liver weight in the vehicle control group was significantly greater than in the HGF group, a finding that was implicated in focal liver necrosis with sinusoidal congestion. Less histological damage was observed in the HGF group. Twenty-four hours after hepatectomy, an increase in the relative liver weight in nonischemic controls and in the HGF group was higher than that in vehicle control group, and the 5-bromo-2?deoxyuridine (BrdU) labeling index in the HGF group was 23% versus 18% in the nonischemic controls. Administration of dHGF significantly improved the 7-day survival to 82% versus 40% in the vehicle control group. dHGF has potential benefit as a pharmacological agent to ameliorate impairment of the hepatic microcirculation and to potentiate a regeneration response in the ischemically damaged liver after hepatectomy and/or liver transplantation.

A 5-year survivor after resection of peritoneal metastases from pedunculated-type hepatocellular carcinoma.

We report herein a 5-year survivor after the resection of peritoneal metastases from pedunculated hepatocellular carcinoma (HCC). A 42-year-old man underwent lateral segmentectomy of the liver, with a diagnosis of pedunculated HCC, on October 10, 1994. The lesion was associated with intratumoral hemorrhage and was covered by the greater omentum, but there were no peritoneal metastases. The patient was readmitted to our hospital 4 months later with right upper quadrant pain. His serum alpha-fetoprotein level was 3ng/dl. Hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCV-Ab) were both negative. Abdominal computed tomography (CT) revealed two nodular lesions in the right upper abdominal cavity. He was diagnosed with peritoneal metastases from HCC. Because there were no other distant metastases, laparotomy was performed to resect these tumors. We found two other tumors, located in the mesentery of the appendix and ileum. All four tumors were resected by partial transverse colectomy and appendectomy. The histopathology of the tumors showed poorly differentiated HCC (Edmondson-Steiner's grade III). The patient has been doing well without recurrent disease for more than 5 years after the second operation. The prognosis of patients with pedunculated HCC is poor. Furthermore, resection for peritoneal metastases from HCC is rare because of the presence of multiple seeding in the abdominal cavity and distant organ metastases. To our knowledge, our patient is the longest survivor after resection of peritoneal metastases from pedunculated HCC.

[The impact of hepatic resection on metastatic colorectal cancer].

Although liver resection is the accepted treatment for patients with metastatic colorectal cancer to the liver, there remains some controversy as to the criteria for patient selection and its impact on the recurrent disease following the operation. One hundred and sixteen patients underwent liver resection for metastaic colorectal carcinoma over the last 23 years at our institution. The actual survival was 50.5% at 5 years, and 38.6% at 10 years, excluding the 30-day operative mortality rate of 1.7%. Positive hepatic lymph nodes, extrahepatic disease, number of tumors (4 or more), and bilobar distribution of the diseases were strongly associated with poor outcome. These prognostic factors were also documented as the major prognostic determinants by 21 consecutive articles we reviewed. Among 52 (45.6%) patients with hepatic recurrence, patients who were acceptable surgical risks and had no extrahepatic diseases or a limited number (one or two) of lung metastasis were candidates for the repeat resection. Consequently, 31 patients underwent repeated hepatic resection. Their survival rate was 53.9% at 3 years and 32.3% at 5 years, with no mortality. This outcome is markedly better than that of untreated patients with an estimated survival of 3 to 24 months. Thus, an aggressive approach to surgical treatment is feasible with low risk and the potentially curative strategy even for recurrent hepatic metastases, providing the opportunity to achieve 5 year survival.