Histological diversity in basaloid squamous cell carcinoma of the esophagus.

Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a distinct variant of esophageal cancer. This study investigated histopathological variations of BSCCE. Thirty-eight surgical and two endoscopically resected specimens of BSCCE were examined. Histological features were classified into five components: solid nest (SN), microcyst and/or trabecular nest (MT), ductal differentiation (DD), cribriform pattern (CP), and an invasive squamous cell carcinoma (SCC) component. The immunohistochemical phenotypes of each component were examined using antibodies against cytokeratin (CK) 7, CK14, and alpha smooth muscle actin (SMA). SN, MT, DD, CP, and SCC were present in 95.0, 97.5, 27.5, 32.5, and 82.5% of the cases, respectively, and combinations of SN & MT, SN & DD, SN, MT & DD, SN, MT & CP, and SN, MT, DD & CP were found in 50.0, 2.5, 10.0, 17.5, and 15.0%, respectively. All the intraepithelial lesions observed in 18 (45.0%) cases were SCC. Immunoreactivity for CK7, CK14, and SMA was seen in 10.5, 86.8, and 18.4% of SN; 30.8, 97.4, and 38.5% of MT; 54.5, 100.0, and 54.5% of DD; 7.7, 76.9, and 23.1% of CP; and 6.1, 97.0, and 0.0% of SCC, respectively. CK14 immunoreactivity was seen in the periphery of most of the SN component. CK7, CK14, and SMA immunoreactivity was seen in the inner layer, all layers, and the outer layer of DD, respectively. MT and CP showed partial peripheral positivity for CK14 and SMA in microcystic, trabecular, and cribriform-like pseudoglandular structures. BSCCE demonstrates various histopathological and immunohistochemical features including a ductal and cribriform growth pattern.

Evaluation of segmental pancreatic function using 11C-methionine positron emission tomography for safe operation of living donor pancreas transplantation.

For the safe operation of living donor pancreas transplantation, we investigated the utility of 11C-methionine positron emission tomography (PET) to examine the function of the residual pancreatic head in patients with pancreatic disease undergoing distal pancreatectomy and in living donors of pancreas transplantation. After 6 hours of fasting, we intravenously injected 370 to 740 MBq 11C-methionine. PET was scanned 30 minutes after injection. 11C-methionine PET uptake by the pancreatic head versus body/tail was expressed as a standardized uptake value (SUV). The SUVs of the pancreatic head were compared before versus after surgery. The SUVs of the pancreatic head in patients before and after distal pancreatectomy were 15.3 +/- 6.0 and 18.2 +/- 2.4, respectively. The SUVs of the pancreatic head in donors before and after distal pancreatectomy were 16.1 +/- 1.0 and 14.7 +/- 1.4, respectively. Both patients and donors showed no significant difference in SUVs of the pancreatic head before and after surgery. However, the SUVs of the residual pancreatic head were elevated after distal pancreatectomy in 80% of patients and 50% of donors. These data indicated that the function of the pancreatic head may be maintained or improved after distal pancreatectomy. 11C-methionine PET may become a potent modality to evaluate segmental pancreatic function for a safe living donor operation.

Laparoscopy-assisted hepatic lobectomy using hilar Glissonean pedicle transection.

Although many reports have described laparoscopic minor liver resections, major hepatic resection, including right or left lobectomy, has not been widely developed because of technical difficulties. This article describes a new technique for performing laparoscopy-assisted right or left hepatic lobectomy using hilar Glissonean pedicle transection. Laparoscopic mobilization of the right or left hepatic lobe is performed, including dissection of the round, faliciform, triangular, and coronary ligaments. The right or left Glissonean pedicle is encircled and divided laparoscopically. A parenchymal dissection is then performed though the upper median or right subcostal incision, through which the resected liver is removed. We successfully performed this procedure in 6 patients without blood transfusion or serious complications. Laparoscopy-assisted hepatic lobectomy using hilar Glissonean pedicle transection can be feasible and safe in highly selected patients.

Evaluation of esophageal cancers using fluorine-18-fluorodeoxyglucose PET.

UNLABELLED: To evaluate glucose metabolism in esophageal cancer, 48 patients were studied using PET with 18F-2-fluoro-2-deoxy-D-glucose (FDG). METHODS: After transmission scans were obtained, 18F-FDG (148 MBq) was administered intravenously. In 11 patients, a dynamic study was performed to evaluate glucose metabolism. Using the changes of radioactivity in both plasma and tumor, rate constants (k1-k4) defined in the metabolic model for 18F-FDG were calculated. In 48 patients, static PET scans of the tumor (5-min scans) were obtained 60 min after administration. Fluorine-18-FDG activity within each tumor was corrected for physical decay and normalized by dose administration and patient weight to produce a standardized uptake value (SUV). RESULTS: Both the k3 value (n = 11) reflecting hexokinase activity and SUV (n = 13) were well correlated with hexokinase activity from the resected specimen (p < 0.05). Forty-seven of 48 patients before treatment revealed SUV greater than 2.0, but 10 normal control subjects and 1 esophageal benign tumor revealed less than 2.0 (accuracy rate 98.3%). Although clinicopathological findings did not correlate with SUV, except for two patients with carcinosarcoma, 23 patients with an SUV greater than 7.0 had a poor prognosis compared with 25 patients with SUVs less than 7.0. CONCLUSION: These findings suggest that 18F-FDG PET may be useful in distinguishing malignant tumors from benign lesions and in the preoperative evaluation of the prognostic factor.

A feasibility study on L-[1-carbon-11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis by PET.

UNLABELLED: We studied the potential of L-[1-11C]tyrosine ([1-11C]Tyr) and L-[methyl-11C]methionine ([Me-11C]Met) as tracers for measuring protein synthesis rate (PSR) in the liver by PET and proposed their metabolic models. METHODS: In the liver and plasma of control and cycloheximide-treated mice injected with [1-14C]Tyr and [Me-3H]Met, incorporation of the radioactivity into the acid-soluble fraction and chloroform/methanol-extract (CM), RNA and protein fractions were measured. Data were compared with those from rat studies with 11C-labeled analogs and PET. RESULTS: In mice, liver uptake of [Me-3H]Met was over twice as large as that of [1-14C]Tyr. Similar uptake patterns of the 11C-labeled analogs were found in rats by PET. In the mouse liver at 1 to 6 hr after injection, approximately 69%-73% of the 14C was detected in the protein fraction, whereas approximately 65%-70% of the 3H was in the CM fraction, which reflected phospholipid synthesis. In plasma, the percentages of the protein fractions were approximately 73%-76% for 14C and approximately 36%-46% for 3H. Gel-filtration analysis suggested that 80% of the 14C-labeled plasma proteins was albumin originating from the liver, which corresponds to approximately 25% of the total labeled proteins synthesized in the liver at 6 hr. When protein synthesis was inhibited by cycloheximide, the liver uptake of the [1-14C]Tyr and the protein-incorporation of 14C in the liver and in plasma were decreased dose-dependently. On the other hand, uptake of [Me-3H]Met was significantly enhanced in the liver due to increased incorporation into the CM fraction. CONCLUSION: [1-Carbon-11]Tyr can be used for measuring the PSR in the liver by PET. Liver uptake of [Me-11C]Met mainly reflects phospholipid synthesis through the transmethylation process.

Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment.

To evaluate glucose metabolism in patients with tumors involving the liver, 35 patients with liver lesions had PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG (148 MBq) was injected and radioactivity of the tumor was scanned dynamically by PET. The rate constants (k1, k2, k3, k4) of FDG in a metabolic model were calculated. The results were compared to hexokinase activity in the excised tumor specimens. k3 was found to reflect tumor hexokinase activity. When k3 was used as an index (cut-off value: 0.025), it was possible to distinguish benign and malignant tumors. k4 was significantly higher in hepatocellular carcinoma. By using k3 and k4 as indices, one could assess the degree of differentiation of hepatocellular carcinoma. After treatment, k3 decreased according to the effectiveness of therapy and thus may be a useful index for quantitatively assessing tumor viability.

Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer.

BACKGROUND: Despite improvements in surgical techniques and perioperative care, severe complications lead to long hospital stays for some esophageal cancer patients. The purpose of this study was to evaluate the safety and effectiveness of perioperative steroid therapy on the postoperative clinical course. METHODS: Fifty-seven patients operated for esophageal cancer in 1997 and 1998 were treated with perioperative steroid therapy. Fifty consecutive patients operated in 1995 and 1996 served as a control group. In the steroid group, each patient was given 250 mg of methylprednisolone intravenously before operation followed by 125 mg on postoperative days 1 and 2. Serum interleukin-6, polymorphonuclear cell elastase, and C-reactive protein levels, and the postoperative clinical course were compared between the groups. RESULTS: Morbidity rates including hyperbilirubinemia, anastomotic leakage, and liver dysfunction were significantly lower in the steroid group than in the control group. Days until extubation and hospital stay were significantly shorter for the steroid group. Inflammatory mediators, body temperature, heart rate, and respiratory index after the surgical procedure were significantly lower in the steroid group. Adverse effects possibly caused by steroid therapy were not observed. CONCLUSIONS: Perioperative steroid therapy was safe and effective for the inhibition of inflammatory mediators and the improvement of the postoperative clinical course of patients with esophageal cancer.

A patient with rectal ulcer with severe stenosis presenting with perforated peritonitis.

We report a patient with rectal ulcer with severe stenosis, who underwent urgent surgical treatment for perforated peritonitis. The 54-year-old man suddenly developed cramping abdominal pain and fever while hospitalized, with signs of peritoneal irritation. An emergency laparotomy was performed, and severe stenosis of the rectum and a perforated lesion on the oral side approximately 10 cm distant from the stenosis were found, with massive abdominal purulent fluid. He was treated by rectosigmoid colon resection with transverse colon loop colostomy. Histopathologically, the stenosis was caused by ulceration extending to all muscular layers of the rectum, with inflammatory changes. Benign rectal stenosis is so rare that differential diagnosis from malignancy may be difficult when there are inflammatory changes in the surrounding tissues. However, it is necessary to keep in mind the likelihood of this disease in differentiation from rectal cancer.

Clinical significance of serum vascular endothelial growth factor in colorectal cancer patients: correlation with clinicopathological factors and tumor markers.

Vascular endothelial growth factor (VEGF) is known as a potent inducer of angiogenesis in various human cancers. Serum VEGF concentrations of colorectal cancer patients was assessed for their clinical significance as a tumor marker. Serum samples were obtained at admission from 24 healthy volunteers and 111 patients with colorectal cancer. Preoperative serum VEGF concentrations, which are significantly higher than those of healthy controls, reflect clinical stage progression, depth of invasion, liver metastasis, lymph node metastasis and lymphatic invasion. Consequently, detection of VEGF could serve as a clinically useful marker for colorectal cancer progression and metastasis independent of other markers.

Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.

The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.

Chemoradiation for patients with esophageal cancer aged 80 and older.

BACKGROUND: The objectives of this study were to evaluate the efficacy and toxicity of concurrent chemoradiation in patients with esophageal cancer aged 80 and older. PATIENTS AND METHODS: Seven patients with esophageal cancer, aged 80 or more were treated with chemoradiation. Five received a systemic combination of cisplatin and 5-fluorouracil while 2 received daily 5-fluorouracil, concurrent with radiotherapy. The total doses of radiotherapy ranged from 50 to 65 Gy. RESULTS: Complete response was obtained in 3 patients, and partial response and no change in 2 cases each. Esophageal passage improved in 4 patients. The treatment was well-tolerated. There was no death attributable to any adverse treatment effects. None of the patients experienced grade 3 or worse acute toxicities. CONCLUSION: This study demonstrated that advanced age per se is not a sufficient reason to exclude elderly patients from aggressive treatment.

[Evaluation of gastroenterological disease by using 18F-FDG PET--differential diagnosis of malignancy from benignity].

In this study, we used 18F-FDG PET to differentiate gastroenterological malignancy from benignity. We investigated 122 patients with gastroenterological disease before treatment (with lesions exceeding 2.0 cm in diameter only). 60 min after injection of FDG, although 16 cases out of 17 benign disease did not reveal accumulation higher than normal tissue, 105 cases of malignant tumor except some of hepatocellular carcinoma revealed high accumulation of FDG. FDG uptake was expressed as the Ci/Cp ratio, calculated from radioactivity of the tumor (Ci) and the plasma (Cp). 89 cases out of 90 which show more than 2.0 of Ci/Cp ratio were malignant tumor. On the other hand, 32 cases which show less than 2.0 contained 16 cases of benign disease and 15 of hepatocellular carcinoma. FDG PET is a useful tool for differential diagnosis of malignant tumor from benign disease except some of hepatocellular carcinoma.

[Can fluorodeoxyglucose-positron emission tomography evaluate the functional differentiation of hepatocellular carcinoma].

Tumor uptake of 18F-fluorodeoxyglucose (FDG) was studied by dynamic positron emission tomography (PET) in 23 cases of hepatocellular carcinoma. The metabolic rate constants, K1 to K4, were generated by non-linear least square fitting method. We confirmed that K3 from the PET study significantly correlated with directly measured hexokinase activity of the cancer tissue. The region of HCC always had higher K3 values, which represents the hexokinase activity compared with the non-cancerous region. By FDG images, however, in 50% of cases the cancer region could not be clearly defined from the surrounding noncancerous hepatic tissue. These HCC cases without accumulation of FDG had a high ratio of K4/K3 (K4 represents glucose-6-phosphatase activity), which correlated well with the inverse ratio of FDG accumulating images on PET. According to the PET images which is represented by K4/K3 and the hexokinase activity which is represented by K3, we divided these 23 cases into three groups and retrospectively compared their survival rates. The groups with high K4/K3 (greater than or equal to 0.40) had longer survival than other groups. From the view point of glucose metabolism, the value of K4/K3 calculated from dynamic studies of FDG-PET may represent the functional differentiation of HCC.

[Evaluation of clinical usefulness of 11C-methionine positron emission tomography (11C-MET-PET) as a tool for liver functional imaging].

We studied 11C-MET-PET in 17 clinical cases, 10 patients with obstructive jaundice and 7 normal volunteers, and analyzed its efficacy for the evaluation of hepatic functional reserve in major hepatectomy candidates. Differential absorption ratio (DAR) of 11C was compared to the hepatic protein synthesis rate (HPS), which is measured as the incorporation rate of 3H-labeled leucine in protein fraction, using needle biopsied liver specimen obtained from each hepatic segment. In the cases of normal liver function, DAR was well correlated with HPS. Also in jaundice cases with two exceptions, low HPS segment was demonstrated as low DAR segment. Consequently, MET-PET images could clearly provide functional liver imaging. After injection to 11C-MET, the increase in rate of radioactivity of 11C in plasma protein fraction was higher in jaundice cases than in normal volunteers, which is in accord with the results of our former study that cholestatic liver has accelerated protein synthesis rate. In summary, since 11C-MET-PET could demonstrate liver functional imaging, it might be a possible tool for liver function assessment in major hepatectomy candidates.

[Evaluation of the cases of benign disease with high accumulation on the examination of 18F-fluorodeoxyglucose PET].

In this study 39 cases of abdominal benign disease were examined by PET using 18F-fluorodeoxyglucose (FDG), and 11 cases of them (i.e. 4 cases of liver abscess, 1 of pelvic abscess, 1 of omental abscess, 2 of chronic pancreatitis, 1 of inflammatory pseudotumor of liver, 1 of retroperitoneal leiomyoma and 1 of solid and cystic tumor of pancreas) which showed as high accumulation of FDG as malignant lesion were investigated of their clinical and pathological feature. We used Ci/Cp ratio as index to express the accumulation of FDG in the lesion, which was calculated from radioactivities of the lesion (Ci) and the plasma (Cp) at 60 mins after injection of FDG. The Ci/Cp ratio of the 11 cases was 3.64 +/- 0.77. The pathological feature of the 9 inflammatory cases was high accumulation of inflammatory cells and that of the 2 benign tumor cases was solid proliferation of tumor cells. The serum of the 9 inflammatory cases showed high CRP value. It was considered that the high accumulation of FDG in inflammatory lesions was due to piles of FDG uptake of the many inflammatory cells, while the 2 benign tumors of high accumulation were considered that the tumor cell had as high glucose metabolism as malignancies.

[Evaluation of the effect of treatment in patients with liver tumors using 18F-fluorodeoxyglucose PET].

To evaluate the glucose metabolism in the liver tumor, 18FDG PET (Positron Emission Tomography) was performed in 9 patients with primary and metastatic liver tumors. And usefulness of 18FDG PET in clarifying the effect of treatment on liver tumor was examined. Glucose metabolism of tumor was showed in terms of the coefficient 'C' calculated by Patlak's plot. Each tumor's coefficient 'C' was 0.016-0.054 and it decreased after treatment. Compared with pathological findings, the coefficient 'C' of necrosis part of tumor was 0.004 and fibrous change after irradiation was 0.007. It suggested that coefficient 'C' reflected activity of tumor and it was a useful index to know viability of tumors in the treatment for patients with liver tumors.

[Analysis of cases of complete response (CR) in esophageal and gastric cancer].

We investigated 117 patients with advanced esophageal cancer who had undergone radio-chemotherapy from 1990 to 2000 in our department. Concurrent radiotherapy with chemotherapy improved the response rate, and adjuvant surgery improved the prognosis. Future problems are the establishment of a method to estimate the sensitivity of tumors to chemotherapy or radiotherapy, the improvement of diagnostic methods for evaluation of the effect and the development of new therapies and regimens for non-responders in the present radio-chemotherapy group. The CR cases of inoperable, noncurative and recurrent patients with gastric cancer in the past decade were examined. A CR of the lymph nodes was obtained in 5 cases, and that of the hepatic metastasis and peritoneal recurrence was observed in one case each. However, a CR of the primary lesion has not been attained. Though re-swelling of the lymph nodes was not observed in 4 out of 5 CR cases, a maintenance treatment after CR should be established. Topical treatment is promising for the hepatic metastasis and peritoneal seeding. Since it is difficult to attain a CR of the primary lesion, surgical resection is required to prolong the survival time.

[Evaluation of CTA for arterial infusion chemotherapy for liver metastasis from colorectal cancer].

To compare between the arterial blood supply of metastatic liver tumor and effects of intrahepatic arterial infusion chemotherapy (IHAC), we examined 8 patients with 27 liver metastasis from colorectal cancer. They were treated with ADM/lipiodol/5-FU/LV (19 nodules) or 5-FU/LV (8 nodules). To evaluate the arterial blood supply, CT arteriography (CTA) was performed, which classified tumors into 3 grades. Grade (Gr) 0; almost no enhancement, Gr1: less than one-third of tumor, Gr 2; less than two-thirds; Gr 3 over two-thirds (no case). As a result, 3 of NCs and 3 of PDs were Gr 0, 7 of MRs, 3 of NCs and 2 of PDs were Gr 1, and CR, PR and 7 of MRs were Gr 2. These results suggest that the arterial blood supply is necessary for a better response of IHAC and CTA is effective to forecast the response to IHAC.

[Arterial infusion chemotherapy in pelvic space for advanced rectal cancer].

Three rectal cancer patients were treated with arterial infusion chemotherapy through the internal iliac artery. Two patients with pelvic recurrences unresectable after APRA were treated with intensive chemotherapy and the other patient with neoadjuvant chemotherapy. In all cases, 5-FU (500 mg/ body/day) was administered continuously for 5 days or 14 days. We attempted three methods for this procedure which were a bilateral catheterization to the internal iliac artery, a single catheterization with an embolization to the other internal iliac artery and a single catheterization without the embolization. As the result of this treatment, in the resected specimen with neoadjuvant case, histological necrosis was found in 50% in the main tumor and the metastatic lymph nodes. One patient with pelvic recurrence showed a partial response in CT imaging, but died one year later of the recurrence around the external iliac artery. The other patient with pelvic recurrence treated with the bilateral catheterization had no efficacy on CT imaging, but his CEA level has decreased at present. It was concluded that arterial infusion chemotherapy was effective for advanced rectal cancer and the pelvic recurrences. However, the efficacy of this treatment is limited to the area to which the drugs are delivered. Thus, it is important that the method and the location of the catheterization are determined adequately for each case.

[Hepatic arterial infusion chemotherapy (HAI) for advanced hepatocellular carcinoma inefficacious with transcatheter arterial embolization (TAE)].

For 6 patients with advanced hepatocellular carcinoma (HCC) in whom TAE was inefficacious, we tried hepatic arterial infusion chemotherapy. 5-FU 500 mg/day + CDDP 10 mg/day was administered during 5 days. The AFP level was decreased for 4 patients, and 2 patients showed a partial response in CT image. These 2 patients have been alive over 22 and 18 months, respectively. These results suggest that 5-FU + CDDP HAI might be a useful treatment of HCC inefficacious with TAE.