The influence of histological differentiation grade on the outcome of liver resection for hepatocellular carcinomas 2 cm or smaller in size.

BACKGROUND: Small hepatocellular carcinomas (HCC) with poorly differentiated components (PDC) are reportedly at risk of dissemination and needle tract seeding after percutaneous radiofrequency ablation, although it is the preferred treatment for HCC ≤ 2 cm because of the low rate of vascular invasion. On the other hand, the clinical outcomes after hepatectomy for these tumors are still unclear because of their rarity. METHODS: A total of 233 cases of solitary HCC ≤ 2 cm were retrospectively reviewed and divided into two groups according to the presence of PDC: 199 without PDC (NP-HCCs) and 34 with PDC (P-HCCs). The clinicopathological characteristics and prognosis were compared. RESULTS: A comparison of clinicopathological characteristics showed that the elevation of the tumor markers alpha-fetoprotein (AFP) (>20 ng/mL) and des-gamma-carboxyprothrombin (DCP) (>40 AU/L) was significantly frequent in P-HCCs. The 3- and 5-year recurrence-free survival rates for P-HCCS were 39 and 29 %, respectively, which were significantly worse than those for NP-HCCs (64 and 50 %, respectively) (p < 0.01). Initial recurrence of P-HCCs was significantly more frequent, as well as extrahepatic recurrence and advanced recurrence in the early period after the operation. Recurrences with tumor dissemination were observed in 15 % of P-HCCs and 4 % of NP-HCCs (p = 0.03). CONCLUSION: PDC is present in 15 % of HCC < 2 cm and should be suspected when the both tumor markers are elevated. Moreover, significantly worse post-hepatectomy outcomes such as early advanced recurrence or recurrence with dissemination should be taken into account if PDC is present even in HCCs ≤ 2 cm.

Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth.

BACKGROUND: Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. CASE PRESENTATION: A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think that the slight pancreatic duct dilation was the only finding suggestive of pancreatic cancer. CONCLUSIONS: It is difficult to diagnose pancreatic cancer with pseudocyst preoperatively. If a pancreatic cyst is found in patients who had normal tumor marker levels or no history of pancreatitis, we should always consider the possibility of pancreatic cancer. In such cases, slight pancreatic duct dilation may be a diagnostic clue.

Long-term prognosis after resection of cryptogenic hepatocellular carcinoma.

BACKGROUND: We investigated the patterns and predictors of recurrence and survival in cryptogenic non-B, non-C, non-alcoholic hepatocellular carcinoma (CR-HCC). We compared the findings with those hepatitis virus B (B) and hepatitis virus C (C)-HCC. CR-HCC does not include HCC developed on NASH. METHODS: From 1990 to 2011, of 676 patients who underwent primary curative liver resection as initial therapy for HCC at our institution, 167 had B-HCC, 401 had C-HCC, and 62 had CR-HCC. Differences between three groups were analyzed using the Chi-squared test. Cumulative overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method, prognostic factors involved in OS/DFS were evaluated by univariate analysis using the log-rank test, and stepwise Cox regression analysis. RESULTS: Liver function was better in CR-HCC than in B/C-HCC, and mean tumor size was larger in CR-HCC than in B/C-HCC. In CR-HCC, OS was equivalent to that of B/C-HCC, and DFS was equivalent to that of B-HCC. Both tumor-related factors and background liver function appeared to be prognostic factors for three groups. CONCLUSION: Our findings indicate that the probability of survival of advanced CR-HCC was not longer than that of B/C-HCC. Given our findings, a postoperative follow-up protocol for CR-HCC should be established alongside that for B/C-HCC.

Pancreaticogastrostomy in pure laparoscopic pancreaticoduodenectomy--A novel pancreatic-gastric anastomosis technique.

BACKGROUND: Although many surgical procedures are now routinely performed laparoscopically, pure laparoscopic pancreaticoduodenectomy (LPD) is not commonly performed because of the technical difficulty of pancreatic resection and the associated reconstruction procedures. Several pancreatic-enteric anastomosis techniques for LPD have been reported, but most are adaptations of open procedures. To accomplish pure LPD, we consider it necessary to establish new pancreatic-enteric anastomosis techniques that are specifically developed for LPD and are safe and feasible to perform. RESULTS: One patient developed a postoperative pancreatic fistula (International Study Group of Pancreatic Fistula criteria, grade B) and subsequent postoperative delayed gastric emptying (International Study Group of Pancreatic Surgery criteria, grade C). No other major complications occurred. We developed a novel pancreatic-gastric anastomosis technique that enabled us to safely perform pure LPD. The main pancreatic duct was stented with a 4-Fr polyvinyl catheter during pancreatic resection. A small hole was created in the posterior wall of the stomach and was bluntly dilated. A 5-cm incision was made in the anterior stomach, and the pancreatic drainage tube was passed into the stomach through the hole in the posterior wall. The remnant pancreas was pulled into the stomach, and was easily positioned and secured in place with only four to six sutures between the pancreatic capsule and the gastric mucosa. We used this technique to perform pure LPD in five patients between December 2012 and July 2013. CONCLUSIONS: Our new technique is technically easy and provides secure fixation between the gastric wall and the pancreas. This technique does not require main pancreatic duct dilatation, and the risk of intra-abdominal abscess formation due to postoperative pancreatic fistula may be minimized. Although this technique requires further investigation as it may increase the risk of delayed gastric emptying, it may be a useful method of performing pancreaticogastrostomy in pure LPD. TRIAL REGISTRATION: ISRCTN16761283 . Registered 16 January 2015.

Clinical significance of hepatectomy for primary biliary cirrhosis patients with hepatocellular carcinoma: Report of a single center case series and review of the published work.

AIM: Hepatectomy for hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) has seldom been reported, and the clinical significance of this procedure remains unclear, although HCC has often been observed in end-stage PBC patients. METHODS: To understand the characteristics of hepatectomy on HCC in PBC patients, we examined seven cases at our institute, as well as 22 reported hepatectomy cases in the English-language and Japanese published work. Furthermore, to assess the treatment efficacy of hepatectomy for HCC in PBC patients, we compared these patients with viral hepatitis patients who underwent hepatectomies at our institute during the same period. RESULTS: In the review of 29 cases, more than 70% of the patients were aged over 65 years, and the mean Mayo risk score was low at 5.17. The resected tumors were mainly solitary (79%), and the median maximum tumor size was 37 mm. Approximately two-thirds of the patients met the Milan criteria. In the comparison between the PBC and viral hepatitis cases, there were no differences in the postoperative prognoses, although the tumor size was greater in the PBC cases. CONCLUSION: Hepatectomy for HCC in selected PBC cases is a feasible and potentially curative treatment option, similar to hepatectomy for HCC in viral hepatitis patients. This procedure is particularly useful for patients with preserved liver function who are not ideal candidates for liver transplantation.

In hepatocellular carcinomas, any proportion of poorly differentiated components is associated with poor prognosis after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) often consists of various differentiation components in a single tumor. However, the categorization of histologic grade in hepatectomy for those tumors has not been standardized. Some studies have determined the differentiation grade of the tumor according to its worst component, whereas others have determined it according to its predominant component. The present study aimed to resolve the controversy about whether the worst component or the dominant component determines the nature of the tumor, especially focusing on the presence of a poorly differentiated component (PDC). METHODS: In total, 427 hepatectomized patients with solitary HCC were divided into three groups, tumors without a PDC (NP), tumors with a PDC but dominantly consisting of non-PDC as poorly contained (PC), and tumors predominantly consisted of a PDC as poorly dominant (PD). PC was compared with PD and NP. RESULTS: Statistical analysis revealed that large tumors and high alpha-fetoprotein level were significantly more frequent in PC than in NP (P < 0.01 and P = 0.04, respectively), although no remarkable difference was observed between PC and PD. Both recurrence-free and overall survival rates were significantly worse in the PC and PD groups than in the NP group (PC vs. NP: P = 0.01 and P < 0.01, PD vs. NP: P < 0.01 and P < 0.01, respectively), but there was no significant difference in these parameters between PC and PD. CONCLUSIONS: All HCC, including PDC, should be categorized as poorly differentiated HCC regardless of the predominant differentiation component.

Minimum resection margin should be based on tumor size in hepatectomy for hepatocellular carcinoma in hepatoviral infection patients.

AIM: In patients with hepatoviral infection, although a wide resection margin can eradicate the microsatellite lesions around hepatocellular carcinoma (HCC), a large-volume hepatectomy may diminish remaining liver function and become an obstacle for treating recurrent HCC. The optimal width of the resection margin for these patients is still controversial. This study was conducted to investigate the optimal resection margin in hepatectomy for hepatoviral infection patients. METHODS: We retrospectively investigated the influences of the resection margin status on recurrence patterns and long-term prognosis in a group of 311 HCC patients with hepatoviral infection who had a solitary HCC without perioperative anti-HCC treatment. RESULTS: The resection margin status did not statistically influence the postoperative recurrence-free and overall survival rates (3-year recurrence-free survival of 61.0% vs 55.1%, P = 0.33; 5-year overall survival of 74.9% vs 81.5%, P = 0.77 in without a margin vs with a margin, respectively), although resection without a margin increased the local recurrence with marginal significance (P = 0.055). Regarding the width of the resection margin, in 30-mm or smaller HCC, resection margin did not significantly improve the prognosis among hepatoviral infection patients. However, for tumors larger than 30 mm, a resection margin wider than 3 mm showed significant impacts on the prevention of recurrence in spite of the influence of multicentric carcinogenesis. CONCLUSION: The resection margin used for eradication of microsatellite lesions showed differences that were dependent on tumor size in hepatoviral infection patients. Resection margin should be based on not only background liver function but also tumor characteristics.

Elevation of pancreatic enzymes in gallbladder bile associated with heterotopic pancreas. A case report and review of the literature.

CONTEXT: This is the first report associating heterotopic pancreas in the gallbladder and elevated pancreatic enzymes in bile. CASE REPORT: A 60-year-old woman underwent abdominal ultrasonography at a medical check-up, revealing a nodular protrusion at the neck of the gallbladder. It seemed likely to be a lymph node, but we could not exclude the possibility of gallbladder cancer. In order to make a correct diagnosis, laparoscopic cholecystectomy was successfully performed. Pathological examination revealed heterotopic pancreatic tissue in the gallbladder wall. In addition, we detected elevated levels of amylase and lipase in gallbladder bile. CONCLUSIONS: Preoperative diagnosis of heterotopic pancreas in the gallbladder is difficult. However, an increase of pancreatic enzymes in gallbladder bile may potentially play an important role in the occurrence of acalculous cholecystitis and biliary cancer. We need more accumulation of cases to know the true significance of this anomaly.

Superior mesenteric vein resection without reconstruction in pylorus-preserving pancreatoduodenectomy for pancreatic head cancer.

The prognosis of pancreatic cancer is poor, even in resectable patients. The reason for this poor prognosis is partly due to local invasion of the tumor into the tissues around the pancreas. Pancreatic head cancer usually invades the mesentericoportal veins, so the combined venous resection is usually performed during pancreatoduodenectomy for the purpose of obtaining a negative surgical margin. We performed pancreatoduodenectomy for lower pancreatic head cancer together with superior mesenteric vein resection without reconstruction in two patients, after confirming adequate portal venous flow and small intestinal congestion, This is the first report of pancreatoduodenectomy combined with superior mesenteric vein resection without reconstruction for the purpose of obtaining a wide surgical margin.

Intraoperative ultrasonography for reducing bile duct injury during laparoscopic cholecystectomy.

BACKGROUND/AIMS: Laparoscopic cholecystectomy has become a standard procedure for gallstone disease. Bile duct injury during laparoscopic cholecystectomy is one of the most serious complications. The cause of such injury is usually the erroneous interpretation of bile duct anatomy, especially mistaking common bile duct for the cystic duct. A method for the prevention of this injury has not been established. The objective of this study was to test the usefulness of intraoperative ultrasonography for preventing bile duct injury. METHODOLOGY: We performed intraoperative ultrasonography to visualize the junction of the cystic duct and common bile duct before cannulation for intraoperative cholangiography. A total of 200 patients were enrolled in this study from May 2004 to November 2005. RESULTS: In 188 out of 200 cases (94%), the junction was identified by intraoperative ultrasonography before the cholangiography. CONCLUSION: Identification of the junction of the cystic duct and common bile duct before intraoperative cholangiography may reduce bile duct injury in laparoscopic cholecystectomy.

[Feasibility study of adjuvant chemotherapy with S-1 for pancreatic adenocarcinoma].

BACKGROUND: The aim of this study was to assess the feasibility of using S-1 as adjuvant chemotherapy after the resection of pancreatic cancer. METHODS: S-1 was initially administered or ally at a dose of 50 mg twice daily for 14 days, followed by a rest period of seven days to complete one course. Administration was repeated with dose escalation in each cycle until the recommended dose (RD; 80 mg/m2, maximum 120 mg/day), unless grade 3 adverse events were observed. Administration was planned to continue at least 6 months (eight courses). RESULTS: Eighteen patients who had undergone resection of pancreatic adenocarcinoma were enrolled in this study. The RD could be administered to 12 patients(67%), and 80% of the RD was given to five patients(28%). Although grade 3 anemia occurred in one patient, grade 4 hematologic adverse events were not observed. Grade 3 cutaneous toxicity (hand-foot syndrome)was observed in two patients. The cumulative relative total administered dose rate of S-1 was 0. 86. The 3-year relapse-free survival rate was 31. 4%, and the median overall survival time was 25. 3 months. CONCLUSIONS: Long-term postoperative administration of S-1 at the RD is safe and appears to be a promising method of adjuvant chemotherapy.

[A case report of advanced gallbladder cancer with multiple liver metastases effectively treated by concentrated therapy with S-1].

A 65 -year-old male was admitted to our hospital because of epigastregia. Computed tomography (CT) and abdominal ultrasonography (AUS) revealed advanced gallbladder cancer and two S5 liver metastases. Selective gallbladder angiogram revealed his cystic vein was draining into the portal vein (P5), so cholecystectomy and S4a+S5-subsegmentectomy were performed. Pathological study of the resected specimens showed three liver metastases. After surgical resection lumbar metastasis was suspected, so radiotherapy and UFT at 300mg/day were started. Next, we started oral administration of S-1 alone (100mg/body) for 4 weeks followed by a 2-week rest period as one course. 100mg/day was changed to 80mg/body after 3 courses because of grade 2 neutropenia. A total of 31 courses of S-1 80mg/day were administered postoperatively for five years. The patient is alive and free of disease five years and ten months after the operation.

Metachronous resection of metastatic lymph nodes in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Lymph node metastases are common at autopsy; being found in 28% of autopsy cases of hepatocellular carcinoma have lymph nodes metastases. However, effective treatment for metastatic lymph nodes has not yet been established. METHODOLOGY: We resected lymph node metastases in 8 out of 10 hepatocellular carcinoma patients. We assessed the clinical course and the prognosis of these patients to determine the effectiveness of resecting metastatic lymph nodes and the factors related to survival. RESULTS: Eight out of 10 patients underwent lymph node resection nine times, while removal of metastatic lymph nodes proved impossible in two patients. The 1-year survival rate was 89% in resected cases. Two patients survived for more than 2 years without recurrence or with controlled recurrence of their cancer. The two unresectable patients had a poor prognosis, with the largest survival time being 11 months. CONCLUSIONS: Surgical resection is an option for selected patients with lymph node metastases of hepatocellular carcinoma and the complete removal of metastatic lymph nodes may achieve a survival benefit in selected patients. Metachronous lymph node metastases should be resected in patients with a controlled primary liver tumor, because no other treatment option for lymph nodes metastases has yet been established.

Simple method of laparoscopic splenectomy.

BACKGROUND: Although laparoscopic splenectomy was introduced in 1991, it has not become a standard procedure for splenectomy like laparoscopic cholecystectomy for gallstone disease. The reasons for this may include difficulty in grasping the spleen and difficulty with controlling hemorrhage. Here we present a simple method of laparoscopic splenectomy. METHODS: We performed laparoscopic splenectomy in 46 patients from 1994 to 2006. Our procedure had four main features: (1) adoption of a lateral position so that gravity assists with the spleen, (2) exposure of the operative field using two cherry dissectors, (3) only dividing the upper part of the gastrosplenic ligament, and (4) stapling the splenic hilus together with the lower part of the gastrosplenic ligament. RESULTS: Among 46 patients undergoing laparoscopic splenectomy, none of them were converted to open splenectomy. Three patients had postoperative intraperitoneal bleeding from the stapled stump of the splenic artery. In 28 patients during the most recent 3 years, the mean operating time was 71 min and only one patient had postoperative bleeding (hemostasis was achieved laparoscopically). CONCLUSION: Exposure of the operating field using cherry dissector and stapling of the splenic hilus together with the lower part of the gastrosplenic ligament are key points of our method of laparoscopic splenectomy.

Massive mucinous cystadenoma of the appendix with intussusception in an adult: usefulness of reconstructed computed tomography images.

We present an adult patient with a massive mucinous cystadenoma of the appendix that induced intussusception. Multiplanar reconstruction images and maximum intensity projection images enabled us to assess the tumor accurately and characterize the intussusception. Thus, reconstructed computed tomographic images proved highly useful for diagnosis.

[A case of salvage chemotherapy with gemcitabine hydrochloride and nedaplatin for gemcitabine-refractory pancreatic cancer].

A 73-year-old woman with carcinoma of the pancreatic head underwent Whipple?s operation and intraoperative radiation therapy(20 Gy). After surgery, adjuvant chemotherapy with gemcitabine hydrochloride(GEM 1,000 mg every two weeks)was conducted. After 15 courses, the tumor marker CA19-9 gradually increased to 3,770 U/mL, and a supraclavicular lymph node metastasis(Virchow?s node)was detected. We selected the combination of GEM and nedaplatin(1,000 mg and 50 mg every two weeks, respectively)as salvage chemotherapy. After six courses of this nedaplatin/GEM combination, her CA19-9 level was markedly reduced to 657 U/mL and the lymph node metastasis disappeared. There were no adverse reactions. Combined nedaplatin/GEM therapy was continued for nine months(18 courses)until lung metastases occurred. This combination can be effective in some patients with GEM-refractory pancreatic cancer.

[Fatal liver failure associated with gemcitabine hydrochloride therapy].

We report a case of fatal liver failure associated with gemcitabine hydrochloride(GEM)therapy. In February 2005, a 79-year-old man with a history of diabetes mellitus and chronic hepatitis C was admitted for the treatment of carcinoma of the head of the pancreas. Abdominal CT revealed no distant metastases, but the tumor had invaded the portal vein. Surgery was too risky because of his age and condition, so radiation therapy(60 Gy)was combined with GEM(800 mg on days 1 and 8 of a 3-week cycle). The treatment was well tolerated. During the sixth cycle of GEM, total bilirubin gradually increased to 4.0 mg/dL. Abdominal CT revealed neither dilatation of the bile ducts nor liver metastases, and serology showed no reactivation of hepatitis C. Despite administration of prednisolone(50 mg/day), his liver failure rapidly worsened and he died in October 2005. Autopsy revealed extensive centrilobular necrosis of the liver and confirmed a diagnosis of drug-induced liver failure. The hepatotoxicity of GEM is known, but has usually been described as mild, transient, and rapidly reversible. In patients with chronic liver disease, however, GEM has the potential to cause fatal liver failure. Careful monitoring is necessary during GEM therapy, especially in patients with liver dysfunction.

[Modified FOLFOX6 in a patient on hemodialysis with metastatic colorectal cancer].

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.