Hisashi Usuki

Hepatic Resection for Metastatic Tumors From Gastric Cancer

ObjectiveTo assess the surgical results and clinicopathologic features of hepatic metastases from gastric adenocarcinoma to identify patients with a better probability of survival. Summary Background DataMany studies have reported the benefit of hepatic resection for metastatic tumors from colorectal cancer. However, indications for a surgical approach for gastric adenocarcinoma involving the liver have not been clearly defined. MethodsNinety (11%) of 807 patients with primary gastric cancer were diagnosed with synchronous (n = 78) or metachronous (n = 12) hepatic metastases. Of these, 19 underwent 20 resections intended to cure the metastatic lesion in the liver. The clinicopathologic features of the hepatic metastases in, and the surgical results for, the 19 patients were analyzed. ResultsThe actuarial 1-year, 3-year, and 5-year survival rates after hepatic resection were, respectively, 77%, 34%, and 34%, and three patients survived for more than 5 years after surgery. Solitary and metachronous metastases were significant determinants for a favorable prognosis after hepatic resection. Pathologically, a fibrous pseudocapsule between the tumor and surrounding hepatic parenchyma was found in 13 of the 19 patients (68%). The presence of a peritumoral fibrous pseudocapsule and a well-differentiated histologic type of metastatic nodule were significant prognostic factors. Factors associated with the primary lesion were not significant prognostic determinants in patients who underwent curative resection of the primary cancer. ConclusionsSolitary and metachronous metastases from gastric cancer should be treated by a surgical approach and confer a better prognosis. A new prognostic factor, the presence of a pseudocapsule, may be helpful in defining indications for postoperative adjuvant treatment.

Long-term survival after resection for small cell carcinoma of the esophagus

We describe the rare case of a patient with esophageal small cell carcinoma who was completely cured. A 77-year-old man had small cell carcinoma of the esophagus with extensive lymph node metastases. Treatment comprised a subtotal esophagectomy and extended lymph node dissection. He has survived for more than 7 years with no evidence of recurrent disease. We suggest that radical operations should be considered for future patients if curative resection can be expected.

18F-fluorodeoxyglucose positron emission tomography in the diagnosis of small pancreatic cancer

AIM To investigate the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis of small pancreatic cancer. METHODS This study involved 31 patients with proven invasive ductal cancer of the pancreas. The patients were divided into 3 groups according to the maximum diameter of the tumor: TS1 (maximum tumor size ≤ 2.0 cm), TS2 (> 2.0 cm and ≤ 4.0 cm) or TS3-4 (> 4.0 cm). The relationships between the TS and various diagnostic tools, including FDG-PET with dual time point evaluation, were analyzed. RESULTS The tumors ranged from 1.3 to 11.0 cm in diameter. Thirty of the 31 patients (97%) had a positive FDG-PET study. There were 5 patients classified as TS1, 15 as TS2 and 11 as TS3-4. The sensitivity of FDG-PET, computed tomography (CT) and magnetic resonance imaging (MRI) were 100%, 40%, 0% in TS1, 93%, 93%, 89% in TS2 and 100%, 100%, 100% in TS3-4. The sensitivity of FDG-PET was significantly higher in comparison to CT and MRI in patients with TS1 (P < 0.032). The mean standardized uptake values (SUVs) did not show a significant difference in relation to the TS (TS1: 5.8 ± 4.5, TS2: 5.7 ± 2.2, TS3-4: 8.2 ± 3.9), respectively. All the TS1 tumors (from 13 to 20 mm) showed higher SUVs in FDG-PET with dual time point evaluation in the delayed phase compared with the early phase, which suggested the lesions were malignant. CONCLUSION These results indicate that FDG-PET with dual time point evaluation is a useful modality for the detection of small pancreatic cancers with a diameter of less than 20 mm.

Neutrophil Elastase Inhibitor (Sivelestat) Preserves Antitumor Immunity and Reduces the Inflammatory Mediators Associated with Major Surgery

PurposeTo examine the effects of the administration of perioperative sivelestat, a selective neutrophil elastase inhibitor, on tumor immunity and inflammatory mediators in patients who undergo major surgery.MethodsThirteen patients admitted to the hospital for elective surgery were equally randomized into one of two groups: the Sivelestat group (n = 6) and the control group (n = 7). Thereafter, the immunosuppressive acidic protein (IAP), serum interleukin-6 (IL-6), and type 1/type 2 T-helper cell balance were all assessed at several time points before and after surgical intervention.ResultsThe serum IL-6 values at 1 and 12 h after surgery and on postoperative days 1 and 3 were all significantly lower in the sivelestat group than in the control group. The IAP values at postoperative days 7 and 28 in the sivelestat group were also significantly lower than those in the control group. There was a significant correlation between the IL-6 level at 1 h after surgery and the IAP level at postoperative days 7 and 28.ConclusionsIn this preliminary study, the perioperative administration of sivelestat was thus suggested to reduce surgical stress by decreasing the cytokine release and preserving the antitumor immunity.

Reduced expression of cell cycle regulator p18INK4C in human hepatocellular carcinoma

Cyclins, cyclin‐dependent kinases (Cdks), and Cdk inhibitors (CdkIs) are frequently altered in human cancer. p18INK4C, a member of the INK4 family of CdkIs, is a potential tumor‐suppressor gene product. However, the expression of p18INK4C in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to examine the expression of p18INK4C in various liver diseases including HCC and to assess its clinical significance in HCC. To that end, we examined the expression of p18INK4C by immunohistochemistry in various liver diseases, including 51 HCCs, and also studied the relationship between p18INK4C expression, the phosphorylation of retinoblastoma protein (pRb), and the activity level of Cdk4 and Cdk6. Immunohistochemical analysis revealed the frequent loss of p18INK4C expression in HCC, especially in poorly differentiated HCC. The loss of p18INK4C expression was shown to be associated with a poor prognosis compared with that associated with p18INK4C‐ positivity. Further, the kinase activity of Cdk4 was found to be higher in p18INK4C‐negative HCCs than in p18INK4C‐ positive HCCs. However, the level of Cdk6 activity was similar in the 2 groups of HCCs. In p18INK4C‐ positive HCCs, p18INK4C dominantly interacted with Cdk4 rather than with Cdk6. pRb phosphorylated at serine(Ser) 780 was detected more frequently in p18INK4C ‐ negative than in p18INK4C ‐ positive HCCs. In conclusion, the loss of p18INK4C expression may play a role in the differentiation and development of HCC through the up‐regulation of Cdk4 activity. (HEPATOLOGY 2004;40:677–686.)

Outer arm fucosylation of N-glycans increases in sera of hepatocellular carcinoma patients.

Serum glycans are promising markers for early-stage cancer detection, but the research remains challenging because low concentrations of serum glycoproteins are secreted from early-stage tumors. We have established an N-glycan profiling method using liquid chromatography electrospray ionization-mass spectrometry with high sensitive derivative, trimethyl(4-aminophenyl)ammonium chloride (TMAPA). The mass sensitivity of TMAPA-labeled oligosaccharides was enhanced more than 50 times compared with 2-aminopyridine (PA) labeled oligosaccharides, and the analytical period was significantly shortened compared with traditional HPLC 2D-mapping. Using this method, we found about 28 major N-linked oligosaccharides in human sera, and we investigated their alterations in patients who developed hepatocellular carcinoma (HCC). We found that outer arm fucosylation (attached GlcNAc via an alpha 1-3/4 linkage) in highly branched oligosaccharides increased significantly in sera of HCC patients. Normalizing the level of outer arm fucosylation by taking into account platelet concentration allowed us to distinguish more clearly between HCC and LC patients.

Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502

While adjuvant chemotherapy is preferable for colon cancer, treatment duration is controversial. This phase III trial is investigated optimal duration of adjuvant chemotherapy for Stage IIB/III colon cancer. Eighteen-month treatment with UFT/LV did not improve DFS compared with 6-month UFT/LV treatment. This study suggests that 6 months treatment duration is enough for Stage IIB/III colon cancer.

Extraperitoneal colostomy in laparoscopic abdominoperineal resection using a laparoscopic retractor

Although extraperitoneal colostomy is often performed to prevent postoperative parastomal hernia formation following an open abdominoperineal resection of lower rectal cancer, it has not been widely employed laparoscopically because of the difficulty associated with the extraperitoneal route. This paper describes a laparoscopic extraperitoneal sigmoid colostomy using the Endo Retract™ Maxi instrument. This surgical technique is easy, and helps to prevent the development of parastomal hernias.

Adrenal metastasis from hepatocellular carcinoma through an adrenohepatic fusion.

To the Editor: Adrenal metastasis most often occurs in patients with lung, kidney, breast, and gastrointestinal carcinomas. Usually, metastasis has been regarded as due to systemic spread. Unilateral adrenal involvement is uncommon and more often noted in the left adrenal gland (60%) compared with the right (40%). Curiously, hepatocellular carcinoma (HCC) metastasizes to the right adrenal gland about twice as frequently as to the left adrenal gland. We describe surgically treated 4 cases with adrenal metastasis from HCC and discuss a possible route of metastasis through an adrenohepatic fusion.

Isolated splenic metastasis of ovarian cancer 20 years after operation: a case report and literature review.

Splenic metastasis reflecting multiple metastases of cancer is often observed in the terminal stage, although solitary splenic metastasis is extremely rare. In addition, late recurrence even after 20 years of operation is very unusual. We report the case of a 52-year-old woman who was admitted to our department with a splenic tumor. She had a past history of total abdominal hysterectomy with bilateral sapingo-oophorectomy for ovarian cancer 20 years ago. Abdominal CT scan revealed a huge mass of 12 × 8 × 5.5 cm between the spleen and the left kidney. Splenectomy was performed with a diagnosis of splenic tumor. Microscopically, the tumor was a poorly differentiated adenocarcinoma including components of poorly differentiated ovarian cancer, and was diagnosed as an ovarian cancer metastasis. The patient showed no evidence of recurrence until 5 years postoperatively. Splenic metastasis is considered a terminal stage of cancer. However, when the lesion is solitary, surgical treatment is recommended. Free full text available at www.tumorionline.it