Efficacy and safety of gemcitabine monotherapy for patients with advanced biliary tract cancer.

OBJECTIVE: The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC). METHODS: Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800-1,000 mg/m²) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic/magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated. RESULTS: In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3/4 hematologic toxicity nor grade 3/4 nonhematologic toxicity was observed. No treatment-related deaths were observed. CONCLUSION: Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC.

Surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma with biliary and portal venous tumor thrombi.

We describe the surgical treatment of a patient with diaphragmatic invasion by a ruptured hepatocellular carcinoma (HCC) associated with biliary and portal venous tumor thrombi. A 67-year-old man was admitted because of jaundice (total serum bilirubin, 6.6 mg/dL). The serum concentration of alpha-fetoprotein was 236.1 ng/mL. The anti-hepatitis C virus antibodies were present in the serum. Computed tomography showed a large hypervascular mass in the right subphrenic region, surrounded by local effusion. Endoscopic retrograde cholangiography revealed dilatation of the left intrahepatic bile duct caused by biliary tumor thrombi extending from the right hepatic duct to the common bile duct. Endoscopic nasobiliary drainage was performed, and the total serum bilirubin level returned to the normal range. Angiography revealed a hypervascular tumor without extravasation of contrast medium in the right lobe and obstruction of the right anterior branch of the portal vein. Right hepatectomy was attempted 15 days after drainage. Severe invasion of the diaphragm by the ruptured HCC was detected. Bleeding of the ruptured HCC stopped spontaneously. Partial resection of the diaphragm was performed, followed by primary suture, without an artificial patch. Tumor thrombectomy was performed from the common bile duct. Macroscopic examination revealed that the ruptured HCC had invaded the diaphragm. Biliary and portal venous tumor thrombi were present. Histopathological examination showed a moderately differentiated HCC with biliary and portal venous tumor thrombi. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Five months after the operation, local and intrahepatic recurrences of HCC were detected. Six months after operation, the patient died of liver failure. In conclusion, the outcome of a patient with diaphragmatic invasion by a ruptured HCC with biliary tumor thrombi was poor, even after curative hepatic resection.

[A successful resected case of advanced esophageal cancer with early gastric cancer responding to neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU].

A 72-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopic examination showed double cancers with thoracic esophageal cancer in the middle esophagus and gastric cancer in the antrum. Pathological examinations of the double cancer revealed the first one to be moderately-differentiated squamous cell carcinoma and the second to be well-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed no distant or lymph node metastases. Clinical stagings of the double cancer were stage II (T2N0M0)in esophageal cancer and stage I A (T1N0M0) in gastric cancer. The patient received neoadjuvant chemotherapy using docetaxel, CDDP and 5-FU. After 2 courses of chemotherapy, the adverse event was grade 2 in leucopenia and grade 2 in alopecia. Repeated macroscopic and histological examinations after chemotherapy revealed that the esophageal cancer had significant reductions in the size of tumors, leading to a partial response, and the gastric cancer had disappeared, leading to a complete response. He underwent thoracoscopy-assisted esophagectomy in the prone position, and laparoscopy-assisted gastric tube reconstruction. This neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU might be effective and tolerable as with patients with double cancer of esophageal and gastric cancers.

[A successful resected case of far-advanced CA19-9-producing gastric cancer by neoadjuvant chemotherapy with S-1 and Cisplatin].

A 66-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor on the gastric upper body, and pathological examinations of the biopsy specimens revealed a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed significant wall thickness of the stomach, and regional and para-aortic lymph node metastases. The CA19-9 level was high: 978 U/mL on admission. He received neoadjuvant chemotherapy using S-1 (120 mg/body, days 1-21) and cisplatin (108 mg/body, days 8) for faradvanced gastric cancer. After neoadjuvant chemotherapy, upper gastrointestinal endoscopy revealed that the gastric carcinoma had significant reductions in the size of its tumors, and CT showed that the lymph node metastases had disappeared, leading to a partial response. He underwent total gastrectomy, distal pancreatectomy, splenectomy and Roux-en Y reconstruction. Pathological examination of the resected specimens showed a small number of cancer cells in the submucosal layer, suggesting a Grade 2 pathological response, and gave a positive reaction to CA19-9 staining. The postoperative CA19-9 level decreased to a normal level. This case is diagnosed as CA19-9-producing gastric cancer. He was treated on an outpatient basis with adjuvant therapy.

Effects of pioglitazone on survival and omental adipocyte function in mice with sepsis induced by cecal ligation and puncture.

BACKGROUND: To examine the effects of pioglitazone, peroxisome proliferator-activated receptor-gamma (PPAR-γ), on mortality and omental adipocyte function in mice with cecal ligation and puncture (CLP). METHODS: Male mice were assigned to receive (1) vehicle/sham-operation, (2) pioglitazone/CLP, or (3) vehicle/CLP. Pioglitazone was injected intraperitoneally for 7 d before operation. Serum and omental tissue were collected before, 24, and 48 h after CLP. Serum levels of adiponectin, cytokine, and chemokine were measured with ELISA. mRNA expressions in omental tissues were determined by RT-PCR. Survival was monitored for 7 d after CLP. RESULTS: Survival after CLP was significantly better in the pioglitazone/CLP than in the vehicle/CLP. Serum adiponectin levels before CLP were higher in the pioglitazone/CLP than in the vehicle/CLP. Treatment with pioglitazone significantly inhibited the increases in the serum interleukin-6 and monocyte chemoattractant protein-1 (MCP-1) levels after CLP and lowered the mRNA expressions of proinflammatory cytokines, interleukin-6, and MCP-1 in omental tissue after CLP. CONCLUSION: The anti-inflammatory effects of pioglitazone on omental adipocyte function appear to be mediated in part by PPAR-γ activation, which down-regulates the production of inflammatory mediators.

Migration of a fish bone into the right renal vein.

We describe a patient in whom a fish bone penetrated the duodenum and migrated into the right renal vein. The bone was successfully removed with surgery. The 75-year-old man was admitted to Nippon Medical School Tama Nagayama Hospital because of right upper abdominal pain persisting for 7 days. The patient's medical history was not relevant to the current disorder. Plain radiography showed no abnormalities. Computed tomography revealed a linear object of high intensity that had penetrated the duodenum and migrated into the right renal vein with thrombus. The object was surrounded by a low-density area, suggesting severe inflammation. The patient had eaten fish 1 day before the onset of abdominal pain. We diagnosed duodenal penetration caused by an ingested fish bone. Endoscopic examination showed erosion, but no fish bone or ulceration was detected in the duodenum. The patient was treated conservatively with fasting, peripheral parental nutrition, and intravenous antibiotics. Three days after admission, non-contrast-enhanced computed tomography showed no movement of the foreign body. The patient continued to have pain, and the decision was made to surgically explore the abdomen. Intraoperative ultrasonography showed that the foreign body had migrated completely into the right renal vein with thrombus. Severe inflammation of the right renal vein was observed. Because we could not remove the foreign body without seriously injuring the right renal vein, right nephrectomy was performed. Macroscopic examination of the surgical specimen confirmed the presence of a fish bone with thrombus in the right renal vein. The patient was discharged 9 days after operation, with no complications.

Biliary obstruction due to a huge simple hepatic cyst treated with laparoscopic resection.

Most hepatic cysts are asymptomatic, but complications occasionally occur. We describe a patient with biliary obstruction due to a huge simple hepatic cyst treated with laparoscopic resection. A 60-year-old Japanese woman was admitted to our hospital because of a nontender mass in the right upper quadrant of the abdomen. Laboratory tests revealed the following: serum total bilirubin, 0.6 mg/dL; serum aspartate aminotransferase, 100 IU/L; serum alanine aminotransferase, 78 IU/L; serum alkaline phosphatase, 521 IU/L; and serum gamma glutamic transpeptidase, 298 IU/L. Abdominal computed tomography, ultrasonography, and magnetic resonance cholangiopancreatography revealed a huge hepatic cyst, 13 cm in diameter, at the hepatic hilum, accompanied by dilatation of the intrahepatic bile duct and obstruction of the common bile duct. We diagnosed biliary obstruction due to a huge hepatic cyst at the hepatic hilum, and laparoscopic surgery was performed. A huge hepatic cyst was seen at the hepatic hilum. After needle puncture of the huge cyst, the anterior wall of the cyst was unroofed, and cholecystectomy was done. Intraoperative cholangiography through a cystic duct revealed stenosis of the duct. Subsequent decapsulation of the cyst was performed in front of the common bile duct. After this procedure, cholangiography revealed that the stenosis of the common bile duct had resolved. Histopathological examination of the surgical specimen confirmed the hepatic cyst was benign. The postoperative course was uneventful, and the results of liver function tests normalized. The patient was discharged 7 days after operation. Computed tomography 3 months after operation revealed disappearance of the hepatic cyst and no dilatation of the intrahepatic bile duct.

A symptomatic giant hepatic hemangioma treated with hepatectomy.

We describe a patient with symptomatic giant hepatic hemangioma treated with hepatectomy. A 53-year-old woman presented with upper abdominal distension and appetite loss. The medical history included multiple hepatic hemangiomas that had been detected 2 years earlier but were left untreated. Initial laboratory tests revealed pancytopenia and mild coagulopathy. Computed tomography and magnetic resonance imaging demonstrated a giant hemangioma, 27 cm in diameter, in the enlarged right lobe of the liver. The inferior vena cava was compressed by tumor without thrombus in the infrahepatic vena cava. The portal venous phase of supramesenteric arteriography revealed compression of the portal vein. There were several hemangiomas in the left lobe. Gastric outlet obstruction due to giant hepatic hemangioma in the right lobe was diagnosed. Laparotomy was performed, and a markedly enlarged liver was detected. Right hepatectomy was performed with an anterior approach. The liver-hanging maneuver could not be performed because of tumor compression of the inferior vena cava. Right hepatectomy was performed with intermittent clamping (Pringle maneuver). Hepatic hemangiomas of the left lobe were not resected because the remnant liver would be reduced. The weight of the resected specimen was 2,100 g. Pathologic examination of the surgical specimen confirmed the presence of benign hepatic hemangiomas. The postoperative course was uneventful, and the patient's appetite improved. The patient was discharged 8 days after the operation. Abdominal distension decreased and laboratory data improved after the operation. Computed tomography revealed hypertrophy of the left lobe of the liver after the operation.

[A case of advanced esophageal carcinoma with nephrotic syndrome completely responding to chemotherapy of docetaxel, nedaplatin and 5-fluorouracil].

A 78-year-old male was admitted to our hospital because of dysphagia. He had been diagnosed as nephritic syndrome at 30 years of age and had been treated with prednisolone 10 mg/day. Blood examination revealed renal dysfunction; BUN 25 mg/dL, Cr 1. 9 mg/dL, and glomerular filtration rate(GFR)47. 4 mL/min. Endoscopy showed a type 2 tumor at the middle thoracic esophagus, and the biopsy specimen revealed moderately differentiated squamous cell carcinoma pathologically. Computed tomography (CT) of the chest and abdomen showed no metastases at distant regions and lymph nodes. Clinical staging was Stage II (cT2cN0cM0). Because of old age and renal function, we chose chemotherapy using docetaxel, nedaplatin and 5-fluorouracil. The adverse event was grade 2 in leucopenia and grade 1 in inappetence, but the renal function did not progress. Repeated endoscopic examinations after chemotherapy revealed that the esophageal cancer was significantly reduced in size, and no cancer cells were pathologically detected by endoscopic biopsy, resulting in a complete response(CR). This chemotherapy of docetaxel, nedaplatin and 5-fluorouracil might be effective and tolerable for patients with renal dys- function due to nephritic syndrome.

[Three cases of squamous cell carcinoma of the esophagus who underwent argon plasma coagulation as salvage treatment for locoregional failure or remnant tumor after chemoradiotherapy].

We report 3 cases of locoregional failure or remnant esophageal squamous cell carcinoma after chemoradiotherapy that were successfully treated by argon plasma coagulation (APC) as a salvage treatment. Ablation was performed using argon plasma coagulation APC300 (ERBE). A power setting of 60W and an argon gas flow of 1.8L/min was used. APC is able to be repeated multiply without adverse reaction, and is an effective treatment to control the tumor growth.

[A successful resected case of far-advanced cancer at the esophagogastric junction by chemoradiotherapy with docetaxel, nedaplatin and 5-fluorouracil].

The patient, a 73-year-old male, was admitted to our hospital because of dysphagia. A far-advanced cancer was diagnosed at the esophagogastric junction by upper gastrointestinal endoscopic examination. Pathological biopsy examinations revealed poorly-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed invasion to the diaphragm. Clinical Stage was IV in an unresectable far-advanced tumor. He received radiation therapy (40 Gy/total, 2 Gy/day×20 times) in combination with chemotherapy using docetaxel (40 mg/m², day 1), nedaplatin (10mg/body, days 1-5) and 5-fluorouracil (500 mg/body, days 1-5). After this combination chemoradiation therapy (CRT), macroscopic examinations showed significant reductions in the size of tumor, leading a partial response according to the RECIST guidelines. He underwent total gastrectomy, partial resection of the lower esophagus via left thoracotomy, and Roux-en Y reconstruction with jejunostomy. Pathological examination of the resected specimens revealed Stage IV (T3N2P1CY0). The postoperative course was uneventful. He was treated on an outpatient basis without adjuvant therapy, and died 6 months after the operation by liver, spleen and lymph node metastases.

Malignant granular cell tumor in the gluteal region with unusual pathologic features.

Malignant granular cell tumors (MGCTs) are very rare soft tissue sarcomas. Definite criteria for pathologic diagnosis and the optimal treatment strategy have not been fully established. Here, we describe a 76-year-old woman with a huge MGCT in the right gluteal region, who developed a local recurrence and died from that tumor 14 months after undergoing an operation for the primary tumor. Although microscopic examination revealed that round and granular tumor cells staining for S-100 protein were dominant, components of the spindle cell sarcoma reacting with alpha smooth muscle actin were partially observed. MGCT is believed to originate from Schwann cells; however, pathologic findings in our case showed both Schwannian and non-Schwannian features. This is the first report on MGCT with these 2 features appearing simultaneously.

Laparoscopic unroofing of a large pseudocyst of the spleen: report of a case.

The treatment of splenic cysts remains controversial. A 25-year-old Japanese woman with a 10-cm-long abdominal mass in the left upper quadrant of the abdomen complained of mild, dull pain. A huge splenic cyst was confirmed on computed tomography and magnetic resonance imaging. The cyst wall was adherent to the splenic parenchyma to approximately 30% of its maximum diameter, calculated with magnetic resonance imaging. Laparoscopic unroofing of the cyst was performed. After the great omentum adhering to the cystic wall of the spleen was dissected, branches from the splenic hilar vessels were clipped. Histological examination of the cyst revealed pseudocyst of the spleen. The postoperative course was uneventful. Laparoscopic unroofing is a safe surgical procedure for patients with symptomatic pseudocyst of the spleen.

Increases in soluble tumor necrosis factor receptors coincide with increases in interleukin-6 and proteinases after major surgery.

BACKGROUND/AIMS: To determine whether increases in soluble tumor necrosis factor receptors (sTNFRs) are associated with the levels of cytokines and proteinases in patients undergoing major surgery. METHODOLOGY: Eleven patients who underwent esophagectomy for squamous cell carcinoma of the thoracic esophagus were studied. The circulating blood concentrations of interleukin-6 (IL-6), IL-8, sTNF-R55, sTNF-R75, elastase/al-proteinase inhibitor complex (elastase) and matrix metalloproteinase-9 (MMP-9) were measured by ELISA or EIA before surgery, just after surgery, and on postoperative days (POD) 1 and 3. RESULTS: The levels of serum IL-6, plasma IL-8, plasma elastase and plasma MMP-9 increased significantly after surgery, peaking just after surgery or on POD 1 and then declining. In contrast, the serum levels of sTNFRs increased approximately 2-fold just after surgery compared with the preoperative values and then remained elevated. The IL-6 level correlated with the levels of sTNF-R55 and sTNF-R75 after surgery. CONCLUSIONS: These results suggest that increases of IL-6, serine proteinases and MMPs may be involved in the upregulation of sTNFRs in patients undergoing major surgery.

A case of unresectable gallbladder cancer responding to gemcitabine after metallic biliary stent implantation.

A 69-year-old woman with a chief complaint of jaundice was referred to our hospital. She underwent exploratory laparotomy under a diagnosis of advanced biliary tract cancer. Histological examination of a biopsy specimen of the gallbladder revealed adenocarcinoma. The tumor was unresectable because of invasion into a wide area of the hepatoduodenal ligament and liver bed. Retrograde transhepatic bile drainage tubes were inserted through the common bile duct into the right and left branches of the intrahepatic bile ducts. After metallic biliary stent implantation, gemcitabine (1,000 mg) was administered intravenously once a week for 2 weeks, followed by 1 week of rest. After 2 courses of chemotherapy, computed tomography showed significant reductions in the size of target tumors and serum CA19-9 levels had normalized. Tumor size was stable for more than 6 months. The patient has been able to maintain a good quality of life without any severe adverse effects of chemotherapy. Gemcitabine therapy after metallic biliary stent implantation might be safe and effective in patients with unresectable gallbladder cancer.

Aggressive undifferentiated colon carcinoma producing granulocyte-colony stimulating factor: report of a case.

We report a rare case of granulocyte-colony stimulating factor (G-CSF)-producing undifferentiated carcinoma of the ascending colon. A 52-year-old Japanese man presented with a rapidly growing, aggressive abdominal tumor, and severe leukocytosis (63 000/mm(3)). The serum level of G-CSF was remarkably elevated to 640 pg/ml (normal, <18.1 pg/ml). The patient underwent palliative cytoreductive surgery for ascending colon carcinoma with lymph node and liver metastases. Histological examination revealed an undifferentiated carcinoma of the ascending colon. The tumor cells were positive for G-CSF on immunohistochemical staining. The leukocyte counts and G-CSF level decreased after surgery. Thus, we diagnosed G-CSF-producing colon carcinoma. His general condition deteriorated rapidly and he died of residual tumor growth on postoperative day 24.

Laparoscopic treatment for torsion of the gallbladder in a 7-year-old female.

A 7-year-old girl was diagnosed with viral enteritis and was admitted to our hospital. Sudden right upper quadrant tenderness appeared 2 days after admission. Ultrasonography revealed a large thick-walled cystic gallbladder and an inflammation-induced hyperechoic cystic duct. The long axis of the gallbladder was in a horizontal rather than a vertical alignment. Computed tomography demonstrated a markedly enlarged gallbladder with a slightly thickened wall and an enhanced twisted cystic pedicle. The diagnosis of gallbladder torsion led to laparoscopic detorsion and cholecystectomy. The gallbladder was gangrenous and was rotated counterclockwise with the attachment of the mesentery to the inferior surface of the liver. Although it occurs more rarely in children than in adults, torsion of the gallbladder must be considered in the differential diagnosis of an acute abdomen. Early diagnosis and immediate laparoscopic intervention can help to achieve an excellent patient outcome.

[A case of the oldest old patient with advanced esophageal cancer responding completely to the combination chemotherapy of docetaxel/5-fluorouracil/nedaplatin with radiation].

An 86-year-old man was admitted with dysphagia. Endoscopic examination revealed an advanced esophageal cancer located in the lower thoracic esophagus. Histological analysis revealed moderately differentiated squamous cell carcinoma. The clinical stage was diagnosed as T2N0M0, stage II. He received radiation therapy in combination with chemotherapy using docetaxel, 5-fluorouracil and nedaplatin. After chemoradiotherapy (CRT), the carcinoma could not be detected by CT or endoscopy, and endoscopic biopsy revealed no cancer cells in categorization as resulting complete response. Adverse event consisted of grade 2 in leukopenia. We could not detect relapse, metastases or late side effect of CRT at present, 24 months after CRT.

[A case of double advanced cancer with esophageal and hypopharyngeal carcinoma responding completely to combination chemotherapy of docetaxel/5-fluorouracil and nedaplatin with radiation].

A 69-year-old male was admitted to our hospital because of dysphagia. The diagnosis was double cancer with hypopharyngeal and esophageal carcinoma from upper gastrointestinal endoscopic examination. Pathological examinations of the double cancer revealed moderately-differentiated squamous cell carcinoma. Computed tomography(CT)of the neck and abdomen showed metastases of the right neck and cardiac lymph nodes. Clinical stagings of the double cancer were Stage III (T1, N1, M0)in hypopharyngeal carcinoma and Stage III (T3, N1, M0)in esophageal carcinoma, respectively. He received radiation therapy in combination with chemotherapy using docetaxel(DOC), 5-fluorouracil (5-FU)and nedaplatin(CDGP). After this combination chemoradiation therapy(CRT), the adverse event was grade 2 in leucopenia and grade 2 in gastrointestinal toxicity. Repeated macroscopic and histological examinations after CRT revealed disappearance of the hypopharyngeal and advanced esophageal carcinoma with lymph node metastasis, leading to a complete response(CR). He had maintained CR for the 20 months since undergoing CRT. This combination chemotherapy of DOC, 5-FU and CDGP with radiation may well be effective and tolerable for patients with double cancer of hypopharyngeal and esophageal carcinoma.