Improved Long-term Survival after Liver Resection for Hepatocellular Carcinoma in the Modern Era: Retrospective Study from HCV-endemic Areas

Introduction It remains unclear whether recent progress in perioperative management and treatment for recurrent hepatocellular carcinoma (HCC) has improved patient outcomes in hepatitis C virus-endemic areas. Methods The clinicopathologic and follow-up data of 218 consecutive HCC patients who underwent curative resection between 1982 and 2003 were analyzed. Patients were assigned to one of two groups: before 1992 (early group; n = 82) and 1992 and later (late group; n = 136). Factors influencing survival rates were investigated by multivariate analysis. The effects of the period during which the hepatic resection was done on the patients’ outcome were examined with respect to tumor size. Results The 5-year cancer-related and disease-free survival rates were 51.4% and 20.4%, respectively. The late group showed better 5-year cancer-related survival than the early group (64.1% vs. 33.8%), but disease-free survival did not differ significantly between the groups. On multivariate analysis, the period of the hepatic resection was identified as an independent prognostic factor for cancer-related survival (relative risk 0.70, P < 0.01) but not disease-free survival. There were no differences in the cancer-related and disease-free survival rates between the two groups for patients with tumors ≤ 25 mm. In patients with HCCs > 50 mm, both cancer-related and disease-free survival rates were better in patients in the late group. Conclusions During the past two decades, improvements in the treatment of recurrent HCC tumors have contributed to controlling large HCCs but not to controlling the multicentric development of HCCs. It may be important to control multicentric recurrence of HCC to improve patient survival in areas where the hepatitis C virus is endemic.     

Tubular Carcinoma of the Breast: A Histologic Subtype Indicative of Breast-Conserving Therapy

We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5–3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended. Received: January 21, 2000 / Accepted: July 25, 2000     

Addition of epinephrine to epidural bupivacaine infusions following initiation of labor analgesia with epidural fentanyl

Study Objective

To evaluate the analgesic effects of the addition of epinephrine to a bupivacaine epidural infusion in early labor after a fentanyl bolus, following a lidocaine-epinephrine test dose.

Design

Randomized, double-blinded study.

Setting

Labor suite of a tertiary care hospital.

Patients

60 ASA physical status 1 and 2, laboring, nulliparous women.

Interventions

All laboring women received a 3 mL epidural test dose of 1.5% lidocaine with 1:200,000 epinephrine, followed by a fentanyl 100 μg bolus in 10 mL of diluent volume. Patients were randomized to receive one of two continuous epidural infusions: bupivacaine 0.625 mg/mL at 10 mL/hr (control group) or bupivacaine 0.625 mg/mL with epinephrine 5 μg/mL at 10 mL/hr (epinephrine group).

Measurements

Time to re-dose, pain scores, and side effects were recorded.

Main Results

The mean duration of satisfactory analgesia prior to re-dose was 159 ± 62 min for the control group and 221 ± 111 min for the epinephrine group (P < 0.02). Pain scores were significantly higher in the control group than the epinephrine group at two time periods: 2.5 hours and 4.5 hours (P < 0.04).

Conclusions

The administration of 0.625 mg/mL bupivacaine with epinephrine 5 μg/mL at 10 mL/hr, compared with plain 0.625 mg/mL bupivacaine at 10 mL/hr, provided a longer time to re-dose, decreased pain scores at two time intervals, and had no significant difference in duration of labor or side effects.     

早期黏膜下胃癌微转移和微浸润的临床意义

目的 探讨临床早期黏膜下胃癌的淋巴结微转移和原发灶微浸润的临床意义。方法 对79例早期黏膜下胃癌患者手术切除的1945个淋巴结及68例肿瘤原发灶分别进行连续超薄切片,并应用抗细胞角蛋白(CK)单克隆抗体(CAM5．2)进行免疫组化检测并结合临床病理学指标及患者预后进行综合分析研究。结果 常规HE染色时,淋巴结转移率为13％(10／79),而CK染色为34％(27／79)。早期黏膜下胃癌的微转移发生率为25％(17／69)。68例早期黏膜下胃癌患者中,微浸润的发生率为16％(11,／68)。淋巴结微转移分别多发于肿瘤直径大于2cm(43％),凹陷型(48％),淋巴管侵犯(73％)和深度黏膜下侵犯(53％)的肿瘤。微浸润多发于低分化癌(33％)和深度黏膜下侵犯(31％)的肿瘤。5年生存率在没有微转移的患者为100％,有微转移的患者为82％,有微浸润的患者为73％。结论 CK免疫组化检查在诊断微转移和微浸润上明显优于常规HE检查。淋巴结的微转移和原发灶的微浸润明显影响黏膜下胃癌患者预后。     

Natural History of Early Colorectal Cancer

Since superficial tumors have been found, their peculiar pathologic features have evoked questions concerning their biologic behavior, their natural history. The aim of the present study was to elucidate the natural history of colorectal cancers (CRCs) including superficial cancers, using a retrospective radiologic method. Forty nine cancers that had had initial configurations of early cancer seen by previous radiography and that were examined pathologically were the subject of the present study. Growth speeds [doubling time (DT) calculation] and configurational changes at the various stages (invasion depth) were compared between polypoid growth (PG) and nonpolypoid growth (NPG). Growth speeds of mucosal cancer and submucosal cancer were also compared. The results showed that early CRC grows slowly (DT 31.2 months) when the cancer is limited to the mucosa. However, as tumors grow down to the submucosa, their growth speed accelerates (DT 25.8 months). The DT of these early cancers were longer than that of advanced cancers. The pathologic growth pattern (NPG or PG) of the CRCs did not affect the tumor growth speed. In respect to tumor configuration, when the tumor is limited to the submucosa the antecedent growth pattern may be easily deduced. It seems difficult, however, to know the initial growth patterns in advanced cancers because cancers with polyloid growth frequently change to a nonpolypoid growth pattern when in advanced stages. Among 32 advanced cancers, only 6 (19%) derived from IIc/IIc+IIa cancer. The most common (more than 70%) origin of advanced cancer seems to be IIa, Is, and Isp lesions. These results suggest that NPG cancers or superficial depressed cancers are not the main origins of advanced cancers, and that these cancer do not show extraordinarily rapid growth. E-pub: 5 June 2000     

Household Income Is Related to Dietary Fiber Intake and Dietary Acid Load in People with Type 2 Diabetes: A Cross-Sectional Study

Household income was related to habitual dietary intake in general Japanese people. This cross-sectional study investigated the relationship between household income and habitual dietary intake in people with type 2 diabetes mellitus (T2DM). Household income was evaluated using a self-reported questionnaire and categorized into high and low household income. Nutritional status was assessed using a brief-type self-administered diet history questionnaire. Among 128 men and 73 women, the proportions of participants with low household income were 67.2% (n = 86/128) in men and 83.6% (n = 61/73) in women. Dietary fiber intake (11.3 ± 4.2 vs. 13.8 ± 6.0 g/day, p = 0.006) was lower, and dietary acid load, net endogenous aid production score (NEAP) (51.7 ± 10.5 vs. 46.8 ± 10.4 mEq/day, p = 0.014) and potential renal acid load score (PRAL) (9.5 ± 10.7 vs. 3.7 ± 14.1 mEq/day, p = 0.011) were higher in men with low household income than in those without. Multivariable linear regression analyses demonstrated that log (dietary fiber intake) in men with low household income was lower than that in those with high household income after adjusting for covariates (2.35 [2.26–2.44] vs. 2.52 [2.41–2.62], p = 0.010). Furthermore, NEAP (54.6 [51.7–57.4] vs. 45.8 [42.5–49.2], p <0.001) in men with low household income were higher than in those with high household income after adjusting for covariates. Contrastingly, household income was not related to diet quality in women. This study showed that household income was related to dietary fiber intake and dietary acid load in men but not in women.     

Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type

Germline mutations in the RET proto-oncogene are responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Point mutations or in-frame deletions of exons 10, 11, 13, 14 and 16 are associated with sporadic medullary thyroid carcinoma (MTC). To understand further the role of the RET gene in sporadic MTC, we examined mutations in exons 12 and 15 of RET in patients with sporadic MTC. DNAs were extracted from 39 formalin-fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes. DNA sequencing was used to identify mutations in exons 12 and 15 of RET. In this study, one novel somatic mutation was found in exon 12 and five novel mutations or deletions were found in exon 15. Of the patients with mutations, one had an in-frame 12-bp deletion (nt. 2625-2636), one had point mutations in both codons 884 and 908, and the remaining three had point mutations in codons 748, 876 and 901, respectively. Together with our previous identification of somatic mutations in exons 10, 11, 13, 14 and 16, somatic alterations were found in 10 out of 39 (25.6%) sporadic MTCs. There was no association of RET gene mutations with tumor recurrence or prognosis. These results suggest that mutations occur frequently in the RET coding region in addition to the previously reported mutation hot spots, and there is a different spectrum of mutations between sporadic and hereditary MTC.     

Phase II trial of S-1 for neoadjuvant chemotherapy against scirrhous gastric cancer (JCOG 0002)

Background  The prognosis of scirrhous gastric cancer remains poor despite extended surgery or adjuvant or neoadjuvant chemotherapy. A pilot study of S-1 (TS-1; Taiho Pharmaceutical, Tokyo, Japan), an oral 5-fluorouracil derivative, for neoadjuvant chemotherapy unexpectedly showed good response and a promising effect on survival. Therefore, the Japan Clinical Oncology Group conducted a phase II trial to confirm the efficacy of S-1 for neoadjuvant chemotherapy against resectable scirrhous gastric cancer. Methods  Patients were eligible if they had typical scirrhous gastric cancer invading more than half of the stomach, and resectable disease confirmed by laparoscopic staging. The treatment schedule consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 (100–120 mg/body per day), followed by radical surgery. Results  Fifty-five eligible patients were registered. Three completed only one course of the neoadjuvant chemotherapy, whereas 52 completed two courses. Toxicity was acceptable, with a few grade 3 (5.5%) events, but no grade 4 adverse events. The response rate was 32.6% in 43 evaluable patients. Of the 55 patients, 2 refused operation, 1 developed lung metastasis, and 52 underwent laparotomy. The curative resection rate was 80.8%, with acceptable morbidity and no mortality. The survival curve at 2 years’ follow up showed a better survival rate than that of the historical controls, but did not reach the expected survival rate. Conclusion  S-1 neoadjuvant chemotherapy appeared feasible and showed positive effects against scirrhous gastric cancer; however, the survival rate with S-1 did not reach the expected rate required when selecting an agent for a phase III trial to confirm the effectiveness of neoadjuvant chemotherapy against scirrhous gastric cancer. (on behalf of the Gastric Cancer Surgery Study Group of the Japan Clinical Oncology Group)