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We evaluated the morbidity and mortality after anatomical hepatectomy with the Glissonean pedicle approach, and long-term outcomes in relation to the morbidity in patients with hepatocellular carcinoma (HCC).The mortality, morbidity, and long-term outcomes were evaluated retrospectively.A total of 1953 patients with HCC underwent various anatomical hepatectomies with the Glissonean pedicle approach between 1985 and 2014. The mortality (30-day and 90-day) and morbidity (Clavien-Dindo class Ilia or higher) were evaluated among six 5-year eras (1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014).A total of 460 patients (24%) showed morbidity, and the overall 30-day and 90-day mortality rates were 1.8% and 3.3%, respectively. The 30-day (3.9%, 3.0%, 1.8%, 1.3%, 0.3%, 0.5%: P = 0.0074) and 90-day mortality (6.0%, 4.3%, 3.8%, 2.8%, 2.2%, 1.4%: P = 0.0445) significantly improved over the eras. Blood loss2 L (odds ratio: 11.808, P = 0.0244) was an independent risk factor for 30-day mortality, and blood loss2 L (odds ratio: 4.046, P = 0.0271) and bile leakage (odds ratio: 2.122, P = 0.0078) were independent risk factors for 90-day mortality on multivariate analysis. Morbidity was significant independent prognostic factors for overall survival (relative risk: 2.129, P0.0001) and recurrence-free survival (relative risk: 1.299, P0.0001) in patients with HCC.Anatomical hepatectomy with the Glissonean pedicle approach was achieved safely in patients with HCC. For more safety and longer survival, blood loss, bile leakage, and morbidity should be reduced. Longterm outcomes after anatomical hepatectomy with the Glissonean pedicle approach in patients with HCC have been improved over 30 years with gradually less mortality and morbidity due to decreases in blood loss2 L and bile leakage.

Purpose. The aim was to evaluate prognostic factors and factors associated with the resectability of advanced gallbladder cancer (GBC). Methods. This was a single-institution retrospective review of 274 consecutive surgically-treated cases of advanced GBC (excluding incidental GBC and early GBC). Univariate and multivariate analysis were performed to assess prognostic variables. R0 resection and survival rates were investigated for each local extension factor. Results. Long-term survival was uncommon among patients with multiple liver metastases (H2–3: n = 22; 2-year survival, 0 %), dissemination (P1–3: n = 16; 3-year survival, 0 %), invasion through the hepatoduodenal ligament (Binf3: n = 45; 5-year survival, 4.6 %), or group 3 lymph node (LN) metastasis including of the para-aortic LN (N3: n = 52; 13.7 %). Long-term survival rates did not differ significantly between patients who did and did not undergo bile duct resection or pancreaticoduodenectomy. Survival did not differ significantly according to the type of hepatectomy performed. Conclusion. Surgery may not be indicated for patients with multiple liver metastasis, dissemination, Binf3 ,o r visible para-aortic LN metastasis. Furthermore, it is important to achieve R0 surgery in cases of GBC.

We conducted this study to evaluate the optimal hepatic resection for pT2 and pT3 advanced carcinoma of the gallbladder without invasion of the hepatoduodenal ligament. We conducted a questionnaire survey regarding 4,243 cases of carcinoma of the gallbladder treated during the recent 10-year period at 112 institutions belonging to the Japanese Society of Biliary Surgery. The questionnaires included questions on preoperative-diagnosis, complications, treatment, and surgical treatment, procedures of resection, surgical result, path histological findings, mode, and site of recurrence, additional post-operative treatment. They included 293 pT2 and 192 pT3 R0 cases, which were negative for hepatoduodenal ligament invasion, and the cumulative survival rates and sites of postoperative recurrence in the form of liver metastasis, were retrospectively analyzed in these 485 cases. There were no significant differences in survival rate or recurrence rates in the form of liver metastasis between the groups that underwent resection of the gallbladder bed, the group that underwent segmentectomy 4a+5, and the group that underwent hepatectomy in patients with of both pT2 or pT3 gallbladder cancers. Our results also did not show that liver metastasis to segment 4a5 alone was particularly common. For gallbladder cancer, neither with hepatoduodenal ligament invasion nor hepatic invasion, resection of the gallbladder bed is more preferable for surgical hepatic procedure. For gallbladder cancer that invades any hepatic sites, a hepatic surgical procedure that could eliminate surgical margins would be desirable.

Graft survival is affected by various factors, such as preoperative state and the ages of the recipient and donor, as well as graft size. The objective of this study was to analyze the risk factors for graft survival. From September 1997 to July 2005, 24 patients who had undergone living-donor liver transplantation (LDLT) were retrospectively analyzed. Sixteen patients survived and the eight graft-loss cases were classified into two groups according to the cause of graft loss: graft dysfunction without major post-transplantation complications (graft dysfunction group; n = 3), and graft dysfunction with such complications (secondary graft dysfunction group; n = 5). Various factors were compared between these groups and the survival group. Mean donor age was 31.9 years in the survival group and 49.2 years in the secondary graft dysfunction group (P = 0.024). Graft weight/recipient standard liver volume ratios (G/SLVs) were 36.7% in the survival group, and 26.2% in the graft dysfunction group (P = 0.037). The postoperative mean PT% for 1 week was 48.6% in the survival group and 38.1% in the secondary graft dysfunction group (P = 0.05). Our surgical results demonstrated that G/SLV and donor age were independent factors that affected graft survival rates.

Background/Aims: Liver failure after right hepatectomy for hepatocellular carcinoma (HCC) in patients with an indocyanine green retention rate at 15 min (ICGR15) of 10% or higher remains a controversial issue. Methods: Between 1995 and 2004, 98 patients with an ICGR15 of 10% or higher were scheduled to undergo right hepatectomy or tri-sectionectomy for HCC. The hepatic resection volume (HR) excluding the tumor was measured using computed tomography. The allowable HR (AHR) was determined in each patient with a logarithmic graph based on the ICGR15 and the %HR. Liver failure and mortality were evaluated between 54 patients with HR ≤ AHR (low-risk group) and 44 patients with HR > AHR (high-risk group). Results: The number of patients with liver failure was significantly lower in the low-risk group (2%) than in the high-risk group (23%, p = 0.0021). No mortality was observed in the low-risk group, while mortality was seen in the high-risk group (11%, p = 0.016). Multivariate analysis showed that the high-risk group was identified as a significant predictor of liver failure (p = 0.011). Conclusions: In patients with an ICGR15 of 10% or higher, determination of AHR is useful to predict liver failure prior to right hepatectomy or tri-sectionectomy.

Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Surgical indications or method of resection for intraductal papillary mucinous neoplasm of the pancreas (IPMN) are controversial. The aim of the current study was to evaluate surgical indications including cancer prevention and selection of specific surgical procedures. A group of 244 patients who underwent pancreatectomy for IPMN from 1981 to 2005 was examined retrospectively for clinicopathologic features. Carcinomas (carcinoma in situ + invasive carcinoma) were observed in 72% of the patients with main duct IPMN. The mural nodules for patients with carcinomas were larger than 3 mm. The maximum diameter of branch duct IPMN for patients with borderline atypia was larger than 30 mm. Lymph node metastasis and extrapancreatic invasion were observed only in patients with invasive carcinoma. In limited pancreatic resection, pancreatic fistulae were observed in 7.9% of patients. The indication for IPMN resection, including for cancer prevention, is lesions above IPMN with borderline atypia (main duct IPMN, mural nodule ≥3 mm, maximum diameter of branch duct IPMN ≥30 mm). A pancreatectomy with lymph node dissection should be performed for invasive IPMNs and a limited pancreatic resection has a role for noninvasive IPMNs.

From 1979 to 1996, 32 patients underwent at least right hepatic lobectomy with pancreatoduodenectomy (right HPD) for advanced carcinoma of the biliary tract at our institute. Twelve of the 32 patients underwent hepatoligamentopancreatoduodenectomy (HLPD). Curative resection was achieved in 20 (63%) of the 32 patients, but the operative outcomes were not satisfactory. Operative deaths occurred in 15 (47%) of the 32 patients, and postoperative complications in 29 (91%). The overall cumulative 1-, 3-, and 5-year survival rates were 12%, 6%, and 3%, respectively. These results suggested that simultaneous hepatectomy of the right lobe and pancreatoduodenectomy is undesirable, especially when accompanied by vascular resection and reconstruction. Since 1997, we have used partial pancreatectomy and partial duodenectomy instead of pancreatoduodenectomy for access to peripancreatic lesions, and this has markedly improved the operative outcome. From 1997 to 2004, 42 patients underwent resection of the right hepatic lobe, extrahepatic bile duct, and other related organs for advanced carcinoma of the biliary tract. There were postoperative complications in 13 (31%), but no operative death occurred. Recent advances in operative procedures and perioperative management may offer greater safety for right HPD, but the appropriate applications of and the necessity for right HPD are still matters of controversy and require further discussion.

Intrahepatic cholangiocarcinoma (ICC) with lymph node (LN) metastasis is generally associated with a poor prognosis. However, we treated ICC with LN metastasis successfully by surgery and postoperative immunotherapy in a 59-year-old woman. The immunotherapy consisted of CD3-activated T cells and tumor lysate- or peptide-pulsed dendritic cells. Pathological examination confirmed a diagnosis of moderately differentiated adenocarcinoma with LN metastasis and portal vein invasion. The patient has been alive without recurrence for 3 years 6 months since her operation.

Background: Some patients who are seropositive for lectin-reactive α-fetoprotein (AFP-L3) have intrahepatic cholangiocarcinoma (ICC). There have been no studies regarding the features of ICC patients seropositive for AFP-L3. Thus, the purpose of the present paper was to compare the features of ICC patients from the viewpoint of two different tumor markers, AFP-L3 and carbohydrate antigen (CA) 19-9. Methods: The ICC patients who underwent hepatectomy (n = 51) were divided into three groups, and their clinicopathologic features were compared: (i) group A, seropositive for AFP-L3 ≥ 15%; (ii) group B, seropositive for CA 19-9 ≥ 37 U/mL; and (iii) group C, seronegative for both AFP-L3 and CA 19-9. The features of combined hepatocellular and cholangiocarcinoma (n = 11) were also studied. Results: Group A had a higher positivity rate for hepatitis viruses than group B (60%vs 20%, P

Background We sometimes encounter hepatocellular carcinoma (HCC) with a central scar and a scalloped tumor margin resembling focal nodular hyperplasia (FNH) in macroscopic appearance. The fibrolamellar variant sometimes shows this appearance; however, this type of HCC can be clearly differentiated from fibrolamellar variants on the basis of clinical and histopathological findings. The clinical features of patients with this type of HCC need to be clarified. Methods From 1988 to 1999, 1,043 patients with HCC underwent hepatectomy at our institution. Histopathological examinations show that fibrolamellar HCC was not included in the series. We selected HCC with a central scar and a scalloped tumor margin resembling FNH in macroscopic appearance. We refer to such tumors as scalloped HCC. We compared the clinical findings and surgical outcomes between patients with scalloped HCC and patients with simple nodular HCC. Results Of the 1,043 cases of HCC, 31 (3%) and 571 (55%) were scalloped HCC and simple nodular HCC, respectively. The mean age of the patients with scalloped HCC was 60.7 years, and that of the patients with simple nodular HCC was 62.6 years, without significant difference. The rates of hepatitis C virus infection and liver cirrhosis and serum alpha-fetoprotein levels were significantly lower, and Child-Pugh class and surgical outcomes were significantly better in patients with scalloped HCC than in those with simple nodular HCC. In multivariate analysis, Child-Pugh class (P

Purpose: Increased vascular endothelial growth factor (VEGF) expression is associated with colorectal cancer liver metastases. It is reasonable to expect that measurement of VEGF in liver metastases would provide the best prediction of therapy benefit for VEGF-targeted drugs, such as bevacizumab (Avastin). In this study, we evaluated how VEGF mRNA level in primary colorectal cancer was related to that in corresponding liver metastases. Thirty-one pairs of primary colorectal cancer and corresponding liver metastases were analyzed. Experimental Design: Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse transcription. Quantitation of VEGF and internal reference gene (β-actin) was done using real-time PCR (Taqman PCR). Results: There was no difference between median VEGF mRNA levels of primary colorectal cancer and liver metastases (median value 3.79 versus 3.97: P = 0.989). On an individual basis, there was a significant correlation in VEGF mRNA expression between primary colorectal cancer and corresponding liver metastases (rs = 0.6627, P < 0.0001). In addition, the VEGF mRNA levels of the patients who had two or more liver metastatic tumors were significantly higher than those of the patient who had solitary liver metastatic tumor in both primary cancer (5.02 versus 3.34: P = 0.0483) and liver metastases (4.38 versus 3.25: P = 0.0358). Conclusion: Good prediction of VEGF mRNA levels in liver metastases can be obtained by measuring those of primary colorectal cancer. The risk of multiple liver metastatic tumors might be predictable by measuring VEGF mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.

Background/Purpose The effectiveness of systematized hepatectomy with transection of Glisson's pedicle at the hepatic hilus has not been clarified in detail in relation to previous staging systems. Outcomes after systematized hepatectomy in patients with hepatocellular carcinoma (HCC) were examined in relation to our new staging system. Methods We retrospectively studied 955 patients with HCC who underwent hepatectomy from 1989 through 2002. We classified patients with HCC into four groups according to the pathological findings (pathological step [p-step]): p-step 1, HCC with absence of vascular invasion and absence of intrahepatic metastasis; p-step 2, HCC with vascular invasion and/or intrahepatic metastasis; p-step 3, HCC with major vascular invasion and/or intrahepatic metastasis to both lobes of the liver; and p-step 4, HCC with distant metastasis, including lymph node metastasis or ruptured HCC). We separated the liver into three segments (Takasaki's liver segments). Systematized hepatectomy was classified as systematized segmentectomy or larger resection, and partial segmentectomy. Segmentectomy refers to resection of one of Takasaki's segments. Results Systematized segmentectomy did not affect recurrence-free survival, by univariate analysis, in patients with p-step 1, p-step 3, or p-step 4. However, systematized segmentectomy or larger resection was significantly associated with patient recurrence-free survival, by univariate analysis, in patients with p-step 2. Multivariate analysis also showed systematized segmentectomy or larger resection as a significant independent prognostic factor in patients with p-step 2. Conclusions Systematized segmentectomy is suitable for patients with p-step 2 HCC according to this step classification.

Definitive chemoradiotherapy has been performed as a first-line treatment for esophageal cancer, whereas salvage surgery might be the only reliable treatment for patients with recurrence after definitive chemoradiotherapy. We reviewed 38 patients with squamous cell carcinoma who underwent esophagectomy and 6 patients who underwent lymphadenectomy after definitive chemoradiotherapy (≥50 Gy). The median survival time and 5-year survival rate after salvage esophagectomy were 16 months and 27%, respectively. Three of the 7 patients who had cervical esophageal cancer underwent cervical esophagectomy with laryngeal preservation. Two patients (5.2%) who underwent salvage esophagectomy with three-field lymphadenectomy before 1997 died of postoperative complications, but no patient died of complications thereafter. Although the overall survival after salvage esophagectomy was correlated with residual tumor (R) (P = 0.0097), the median survival time of 7 patients with residual tumors (R2) was 7 months. Overall postoperative survival was closely correlated with the response to chemoradiotherapy (P < 0.0001) but was not associated with histologic effects on resected specimens. Survival was significantly correlated with the depth of viable tumor invasion (pT) (P = 0.0013) and with lymph node metastasis (pN) (P < 0.0001). Long-term survival was achieved in 5 of the 6 patients who underwent salvage lymphadenectomy. Salvage surgery should be considered for patients with recurrence after definitive chemoradiotherapy. Salvage lymphadenectomy may be useful for recurrence confined to the lymph nodes whereas postoperative complications of salvage esophagectomy should be warranted.

Objective: In order to assess the usefulness of esophagectomy through mini-thoracotomy/laparotomy as a minimally invasive surgical procedure for esophageal cancer, we compared the results to those of conventional right thoracotomy/laparotomy. Methods: From 1998 to 2002, 40 patients with thoracic esophageal cancer were prospectively assigned to two groups. Twenty patients underwent esophagectomy through mini-thoracotomy/laparotomy (M-group), while the other 20 had conventional thoracotomy/laparotomy (C-group). Surgical complications, the duration of the systemic inflammatory response syndrome (SIRS), postoperative pain, cytokine responses, and respiratory function were compared between the two groups. Results: There was no difference of morbidity between the M- and C-groups after surgery. There were also no differences between the two groups with respect to the operating time, bleeding, and number of dissected lymph nodes. The duration of SIRS was shorter in the M-group than in the C-group (p=0.055). Use of morphine was lower in the M-group than in the C-group with patient-controlled anesthesia (p=0.002) .The interleukin-6 level of the M-group was lower than that of the C-group at 3, 6 hours, and 3 days after the operation. Recovery of vital capacity by the M-group was better than by the C-group after the operation. Postoperative hospital stay of the M-group was significantly shorter than that of the C-group (p=0.014). Long-term survival was not different in the two groups. Conclusion: Mini-thoracotomy/laparotomy reduces invasiveness and pain compared with conventional thoracotomy/laparotomy for esophagectomy without causing any differences of morbidity or long-term survival.

Purpose: Cyclooxygenase-2 (COX-2) is generally elevated in tumors compared with normal tissue and apparently has an important role in tumor development. A number of studies have found high expression of COX-2 to be an unfavorable prognostic factor for overall survival in several cancers. However, the influence of COX-2 expression levels on tumor response to chemotherapy has been relatively little studied. The purpose of this study was to ascertain if COX-2 gene expression is associated with tumor response in the clinical treatment of colorectal cancer with the fluoropyrimidine-based therapy S-1. Experimental Design: Patients with advanced (stage IV) colorectal cancer were treated with S-1 twice daily based on the patient's body surface area (BSA; BSA < 1.25 m2, 80 mg/d; 1.25 m2 ≤ BSA < 1.5 m2, 100 mg/d; BSA ≥ 1.5 m2, 120 mg/d) for 28 days followed by a 2-week period rest. mRNA was isolated from paraffin-embedded pretreatment primary tumor specimens and expression levels of COX-2 relative to β-actin as the internal reference gene were measured using a quantitative reverse transcription-PCR (Taqman) system. Results: The overall response rate in a group of 44 patients treated with S-1 was 40.9%. Sufficient tumor tissue was available from 40 of these patients for COX-2 mRNA quantitation. COX-2 gene expression was significantly lower in the responding tumors compared with the nonresponders (P = 0.012, Wilcoxon test). Patients with COX-2 values above the cutoff value of 3.28 × 10−3 had a significantly shorter survival than those with COX-2 gene expressions below the cutoff value (adjusted P = 0.031). Conclusions: Intratumoral COX-2 gene expression is associated with likelihood of response to chemotherapy with S-1 and is a prognostic factor for survival of patients after the start of S-1 chemotherapy.

Objective: The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods: Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as

‹はじめに›肝細胞癌では病理学的に門脈侵襲, 肝静脈侵襲に比べ, 胆管侵襲は比較的稀である. 胆管侵襲を伴う肝細胞癌症例につき臨床病理学的検討を行った. ‹検討対象›当院で1986年から2002年までの切除肝細胞癌1452例のうち病理学的に胆管侵襲陽性であった40例を対象とした. ‹結果›胆管侵襲を伴う肝細胞癌は以下の特徴を認めた. 1. 肉眼型で単純結節型の割合が少ない. 2. 門脈肝静脈侵襲を保有する率が高い. 3. 被膜形成を伴わないものが多い. 4. 病理診断上, 細胞異型度が低～中分化のみで肉芽様変化や淡明細胞等, 特殊型が多くみられる. 5. リンパ節転移率が高く, 術後のリンパ節再発, 肝外再発が多い. 6. 生存率は不良である. ‹結論›胆管侵襲を伴う肝細胞癌は胆管侵襲を伴わない肝細胞癌と異なる特異な臨床病理学的特徴を有する.

膵管内乳頭粘液性腫瘍 (IPMT) の自然経過を知る上で, 興味深い症例を経験した. 症例は57歳男性. 50歳時まで急性膵炎で他医に入退院を繰り返していた. この際のERCPで, 主膵管の拡張, 陰影欠損を伴う膵頭部分枝膵管の嚢胞状拡張が認められていたが, 外科的処置は行われていなかった. 2001年10月, 他医で慢性膵炎, 閉塞性黄疸と診断され胆嚢摘出術, 胆道バイパス術 (肝管空腸吻合) を施行. その後の当院入院精査で, 胃・十二指腸に瘻孔形成を伴う膵管内乳頭腺癌由来の浸潤癌と診断し, 2001年12月6日, 膵頭十二指腸切除術を施行した. 摘出標本では, 膵頭体部に径6.6×6.1cm, 内部に結節状隆起を伴う嚢胞性腫瘍を認め, 嚢胞内にはゼリー状の粘液が充満していた. 病理組織所見では, 印環細胞を含む粘液結節を広範囲に認めた. 膵管内には粘液産生を伴う乳頭状の腺癌部分がみられ, 浸潤部はほとんど粘液結節として存在し, 膵管内乳頭腺癌由来の浸潤癌 (粘液癌) と診断された.

We prospectively analyzed the clinical significance of transient portal vein stenosis soon after a pancreaticoduodenectomy (PD) as detected on three-dimensional computed tomography (3D-CT) for portography.This study included 20 patients who underwent a generalized pancreatic head resection. A 3D-CT scan was taken seven times up until the eighth postoperative week for each patient. The 3D images were reconstructed by the Voxel Transmission method. The portal vein images were quantified using the portal volume rates (PVR). The relationship between portal vein stenosis and six clinical factors was statistically analyzed.The 3D-CT scans showed portal vein stenosis in all 20 patients. The preoperative mean of these 20 PVR were 100%, and the postoperative values were 76.2%, 64.1%, 69.5%, 75.1%, 84.1%, and 89.8% at weeks 1-4, 6, and 8, respectively. Portal vein stenosis soon after PD reached a peak in the second week and almost disappeared by the eighth postoperative week. Three clinical factors, namely, the main pancreatic duct diameters, pancreatic reconstruction methods, and postoperative prognoses, significantly affected portal vein stenosis.The stenotic changes to the portal vein are considered to be significant prognostic indicators of pancreatic anastomotic trouble and postoperative complications.

Background Although local recurrence of advanced esophageal cancer is frequent after definitive chemoradiotherapy (CRT), the clinical benefit of salvage esophagectomy has not been elucidated. Methods We reviewed 27 patients with squamous-cell cancer who underwent esophagectomy after definitive CRT (≥50 Gy) (salvage group) and 28 patients who underwent planned esophagectomy after neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group). Results The preoperative albumin level and vital capacity were significantly lower in the salvage group than in the neoadjuvant group. Two patients (7.4%) from the salvage group who underwent extended esophagectomy with three-field lymphadenectomy died of postoperative complications, but no deaths occurred after less-invasive surgery. There was no difference of overall postoperative survival between the salvage and neoadjuvant groups. Conclusions The outcome of salvage esophagectomy after definitive CRT was similar to that of planned esophagectomy after neoadjuvant CRT. Less-invasive procedures might be better for salvage esophagectomy because of the high operative risk.

Carcinoma of the gallbladder shows diverse patterns of spread. The most appropriate surgical procedures according to the depth and extent of the spread of the tumor are still controversial. We investigated this surgical problem clinicopathologically, especially regarding the indications for pancreatoduodenectomy (PD), by retrospectively reviewing the clinical records of 216 patients who were surgically treated for advanced gallbladder carcinoma. Detailed studies of resected specimens, in our department, showed that preservation of the pancreas head carried an increased risk of residual microscopic metastases in small peripancreatic lymphatic nodes and ducts. Some patients with curative operations had shown recurrence in lymph nodes around the head of the pancreas within a few years after PD. Therefore, we performed hepatopancreatoduodenectomy (HPD) in 93 patients, some of whom underwent the HPD as a prophylactic dissection of peripancreatic lymph nodes and some of whom underwent the HPD as a curative resection due to invasion to the peripancreatic lymph nodes, duodenum, and pancreas, observed macroscopically. The surgical outcome after PD was compared with that obtained after other curative resections (non-HPD). In patients with microscopically negative lymph node metastasis without hepatoduodenal ligament invasion, PD was not necessary for a complete resection of lymphatic metastases around the pancreas head. The 5-year survival rate of these patients who had HPD was not significantly higher than that for non-HPD resections with curative intent (73% vs 63%), and lymphatic recurrence was not marked. On the other hand, in patients with positive lymph node metastases without hepatoduodenal ligament invasion, PD was necessary for a complete resection. The 5-year survival rate after HPD in these patients was significantly improved compared to that after non-HPD resections with curative intent (87% vs 17%), because lymphatic recurrence was reduced (0% vs 80%). In advanced carcinomas with positive hepatoduodenal ligament invasion, although the basic operative strategy, which inevitably includes right lobectomy, should be curative, PD should not be performed for prophylactic lymphatic resection, because local recurrence in the hepatoduodenal ligament cannot be controlled by PD, and the 5-year survival rate of curative HPD was only 4% (non-HPD resection with curative intent, 18%); moreover, frequent, lethal, major postoperative complications (hepatic failure) occurred after combined right lobectomy.

【目的】胃原発広義GISTの手術適応におけるKITレセプターの臨床的意義を検討した.【対象】1987年～2001年に切除した胃原発広義GIST75例.【方法】LSAB法にてα-SMA, s-100蛋白, KITレセプターの免疫染色を行った.【結果】(1) Rosai分類いずれの群にも悪性例を認めた.(2)腫瘍径4 cm未満の症例に約40%の悪性例を含む.(3)全症例の76%がKITレセプター陽性.(4) KITレセプター陰性例に悪性例なく,陽性例中63%が悪性例.(5)再発8例全例にKITレセプター陽性.【結論】広義の胃GISTは腫瘍径で手術適応を判断してきたが, KITレセプター陰性症例に悪性例を認めない結果より生検可能であればKITレセプター染色性により手術適応を判断でき,特に腫瘍径の小さい粘膜下腫瘍の手術適応の判断に有用である.

症例は75歳の男性で, 外側区の肝細胞癌に対し他医にてTAE, 経皮的エタノール注入療法をくり返し施行されていたが, 再発をくり返すため当院紹介となった. 再TAE施行するも腫瘍の縮小効果が得られず再入院となったが, 入院当日に黒色便と貧血を認め突然の上腹部痛, 嘔気が出現した. 腹部超音波, CT検査にて肝外側区域に胆管内腫瘍栓を認めその末梢胆管の拡張を認めた. 血管造影検査では外側区域に腫瘍濃染像を認め, 経皮経肝胆道造影では左胆管が造影されず総胆管末端に血腫によると思われる透亮像を認めた. 以上より肝細胞癌の胆管内腫瘍栓からの胆道内出血と診断した. 開腹すると左胆管内に腫瘍栓があり腫瘍栓からの出血と胆管内の凝血塊を認め, 肝左葉尾状葉切除, 総胆管血腫掻爬を施行した. 病理組織像はsar-comatous changeを伴う低分化型肝細胞癌であった.

症例は71歳,女性. 1994年右耳下腺癌(腺様嚢胞癌)の診断にて右耳下腺拡大全摘出術を受けた.局所再発を認めず経過したが1998年超音波検査にて肝右葉に10cm大の腫瘍を指摘された.超音波および腹部CT検査にて腫瘍中心部を走行する門脈枝を認め,ドップラー超音波検査にて車軸状血流を認めfocal nodular hyperplasia (以下FNH)が疑われた.腫瘍生検の結果耳下腺癌肝転移と診断され肝拡大右葉切除術が施行された.再発なく経過するも2003年12月超音波検査にて腹腔内腫瘍および肝転移を指摘された.耳下腺癌の化学療法の奏効率は低く切除を考えて開腹したが,腹膜播種の状態にて切除不能であった.本症例は原発巣術後4年で肝転移,さらに5年後に腹膜播種をきたした.長い経過で遠隔転移を呈する耳下腺癌の特徴を考慮し,長期間にわたる慎重な全身follow upの必要性が示唆された.

Background Some cases of mass-forming intrahepatic cholangiocarcinoma (ICC) are diagnosed as hepatocellular carcinoma (HCC) based on preoperative imaging and clinical findings. We investigated the backgrounds of such cases. Methods Sixty-seven patients with mass-forming ICC underwent surgery from 1980 to 2002. Twenty-four of these patients received a diagnosis of HCC preoperatively. We compared the group diagnosed as HCC and that diagnosed as ICC. ICC was diagnosed histopathologically in all 67 patients. Results The specific clinical findings included high rates of associated hepatitis C virus infection, high levels of serum alpha fetoprotein, lower levels of serum CA19-9, small dimension of the tumor, hypervascular staining on angiography or computed tomography, lower rates of lymph node metastasis, and high rates of HCC occurrence in the group diagnosed as HCC. None of the patients underwent extrahepatic bile duct resection and most patients did not undergo lymph node dissection in the group diagnosed as HCC. The rates of mucus secretion and the ductal expression of mucin core protein-1 (MUC1) were significantly different between the subgroups. The cumulative survival rates were significantly better in the group diagnosed as HCC than in the group diagnosed as ICC. Conclusion Patients with ICC given a preoperative diagnosis of HCC had distinct clinical features and could be treated with the same operation as HCC patients. J. Surg. Oncol. 2004;87:80–83. © 2004 Wiley-Liss, Inc.

It has been possible to resect early colorectal cancer by endoscopy due to the progress of colonoscopic diagnosis and technology. Therefore, most cases of colorectal mucosal cancer and benign tumor have been resected by endoscopy only. We report some techniques for endoscopic resection of colorectal tumors. The technique of endoscopic resection: (i) The B-Wave bipolar snare device: It is difficult to resect flat lesions that are not sufficiently elevated to be ligated by a usual snare. The snare of the B-Wave bipolar snare device is coated to prevent slipping on the colorectal mucosa. (ii) ‘Sculpting down’ polypectomy: It is difficult to resect large sessile lesions because the bases of these lesions cannot be well observed endoscopically. ‘Sculpting down’ polypectomy is a useful method for safe resection of such tumors. (iii) Endoscopic resection through a retroflexed scope: Under retroverted colonoscopic observation, submucosal injection and partial resection is performed. Then, under ordinary observation, complete resection of the residual tumor is performed. (iv) Endoscopic mucosal resection using a cap-fitted panendoscope (EMRC): EMRC is useful for lesions located in the lower rectum because there is no risk of free perforation. At first, submucosal injection is performed. The snare is set in the transparent cap and the lesion is aspirated into the cap. Then, it is snared and resected.

Background and Objectives The sensitivity and specificity of the monoclonal antibody Hepatocyte Paraffin 1 (Hep Par 1) for hepatocellular carcinoma (HCC) are very high, and the usefulness for differential diagnosis of hepatic tumors has been reported. However, there are some cases of HCC with negative staining for Hep Par 1. We examined the histopathological features of HCC with negative staining for Hep Par 1. Methods We examined 69 samples of single nodular HCC less than 2 cm in greatest dimension, resected from 1985 to 1994 in our hospital, with immunohistological staining for Hep Par 1, cytokeratin 19 (CK 19), MUC-1 glycoprotein (MUC-1), and epithelial membrane antigen (EMA). Results Hep Par 1 staining was positive in 64 cases (93%) and negative in 5 cases (7%). With regard to the histological structure, 3 of the 5 negative cases were scirrhous HCC. With regard to the grade of histological differentiation, 2 cases were poorly differentiated HCC, 3 cases were moderately differentiated HCC, and no well-differentiated HCC was found in the negative cases. CK 19, MUC-1, and EMA staining were negative in all cases. Conclusions It is necessary to recognize the existence of Hep Par 1 negative HCC, in particular scirrhous HCC. This may be due to a different mechanism in the earlier stage of hepatocarcinogenesis. J. Surg. Oncol. 2004;88:104–107. © 2004 Wiley-Liss, Inc.

Background Control of blood loss is a crucial problem during hepatectomy. Bleeding from the inflow system can be controlled by the Pringle maneuver or selective vascular occlusion. Bleeding from the outflow system is closely related to central venous pressure (CVP). Therefore, in this study, we evaluated whether vascular outflow control by clamping the inferior vena cava (IVC) below the liver (IVC clamping) during hepatectomy is a safe and effective method to reduce blood loss and CVP. Methods We reviewed the outcomes of 103 consecutive patients whose CVP values were >5 cm H 2 O and who had undergone right or left hemihepatectomy between 1995 and 2000. Forty-seven patients who underwent hepatectomy with IVC clamping (Group A) between 1998 and 2000 were compared with the previous 56 patients who underwent hepatectomy without IVC clamping between 1995 and 1997 (Group B). Results The CVP decreased by 3.7 cm H 2 0 after IVC clamping. Estimated blood loss was 910 mL in Group A and 1177 mL in Group B. ( P = .008) No severe renal or cardiovascular damage occurred after IVC clamping. Conclusions IVC clamping is very effective in reducing blood loss during hepatectomy when the CVP is elevated and cannot be reduced pharmacologically or by fluid restriction.

Background:Micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients after surgery. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of gastric cancer patients. Methods:Bone marrow and peripheral blood samples were obtained from 53 gastric cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor and erbB-2/HER2 was examined in the primary tumors. Results:Cytokeratin-positive cancer cells were observed in the bone marrow of 16 (30%) of 53 patients. Among them, two patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with the depth of invasion and lymph node metastasis but was not associated with peritoneal dissemination. Detection of bone marrow micrometastasis was not correlated with vascular endothelial growth factor or HER2 expression in the primary tumors. Four patients with micrometastasis had recurrence in the liver or lungs, but this did not occur in patients without micrometastasis. Conclusions:Detection of cancer cells in the bone marrow might be an indicator of postoperative hematogenous metastasis in gastric cancer patients.

症例は65歳,男性.突然の下腹部痛を訴え救急車にて来院. 4年半前にC型慢性肝炎と巨大肝癌にて右三区域切除施行していた.病理所見は索状型中低分化型肝細胞癌, vp1 vv0 b0 tw0 im2で非癌肝は硬変肝であった.その後に残肝再発に対して1回の再切除と3回の焼灼療法を行っていた.来院時下腹部に圧痛と軽度の膨隆を認めたが反跳痛,筋性防御はなかった. CTにて小骨盤腔に造影効果のある腫瘤と大量の腹水を認めた.その直後出血性ショックとなり緊急手術となった.腹腔内には大量の凝血塊と小骨盤腔内右精嚢腺浸潤する直径3cm大,弾性軟の腫瘍からの出血があり腫瘍摘出術を施行した.術後13日目に軽快退院された.病理組織では好酸性異型細胞が索状に増生する中分化型肝細胞癌で, hepatocyte染色陽性であった.肝細胞癌術後の急激な下腹部痛,腹部膨満感では本症を疑い,適切かつ迅速な診断,治療が重要であると考えられた.

Background: The effectiveness of liver segmentectomy or larger resection in patients with hepatocellular carcinoma (HCC) 2 cm or less in greatest diameter has not been clarified. Methods: From 1985 to 1994, 125 patients with solitary HCC 2 cm or less in greatest diameter underwent curative hepatectomy (liver segmentectomy or larger resection, 94; subsegmentectomy, 31). The relationship between clinicopathological findings and surgical outcomes were examined. Results The 5- and 10-year survival rates were 68% and 47%, respectively. Univariate and multivariate analysis showed the Child-Pugh class to be a significant prognostic factor. However, liver segmentectomy or larger resection did not have any significant effect on long-term survival. Conclusions Our data suggest that no further improvement of the survival rate can be achieved by liver segmentectomy or larger resection, compared with subsegmentectomy in patients with solitary HCC 2 cm or less in greatest diameter.

Background/Purpose: A registry project for cancers of the biliary tract accumulated a total of 11 030 cases for 10 years. In the present study, registered cases were analyzed for information bearing on problems with the treatment of cancer of the biliary tract. The Japanese classification of lymph nodes was also considered on the basis of the results of this study. Methods: In 11 030 cases, the site of cancer was the gallbladder in 4774, the bile duct in 4833, and the papilla of Vater in 1423. Those cases were analyzed with regard to patient survival according to the stage of disease and the extent of lymph node metastasis. Results: More than 11 000 cases of cancer of the biliary tract have been registered to date from 158 member institutions of the Japanese Society of Biliary Surgery. While the 5-year survival rates for stage I gallbladder cancer and cancer of the papilla were 77% and 75%, respectively, those for stage I hilar or upper bile duct cancer and middle or lower bile duct cancer were 47% and 54%. For stage II and stage III disease, the 5-year survival rates were about 50% for gallbladder cancer and 30% or higher for cancer of the papilla, while survival was only 20% to 30% for bile duct cancer, regardless of specific site. For stage IV, the 5-year survival rate was unexpectedly high, being about 10% or higher for cancers at all sites, with 19% for cancer of the papillary region being the highest. Thus, there still seem to remain surgical indications for stage IV cancers. The lymph node metastasis rate was about 40% for cancers at all sites. Changes in surgical procedures to improve the 5-year survival rate in patients with n2 metastasis or less will be needed. Noncurative resection occurred frequently for cancers at all sites, particularly in cancers of the hilar or upper bile duct, accounting for 60% of cases or more. We have to recognize that measures to reduce inadvertent noncurative resection are fundamental to the treatment of cancer. Conclusions: Considering the survival results according to specific lymph nodes involved, we concluded that the Japanese classification of lymph nodes, particularly hepatoduodenal ligament lymph nodes, should be reexamined, while another procedure to remove such lymph nodes completely should be developed.

We describe life-threatening vasculitis of the small bowel following fulminant hepatitis. A 35-year-old man was admitted to our hospital due to consciousness disturbance and jaundice. He was diagnosed with fulminant hepatitis, and recovered after intensive medical care that included corticosteroid administration and artificial liver support. During reduction of the dosage of steroid, massive gastrointestinal hemorrhage occurred from the upper jejunum, revealed by arteriography. The hemorrhage could not be stopped, so a portion of the ileum, including the bleeding point, was excised. However, the intestinal hemorrhage continued from several small ulcers remaining outside the resected area. Pathological findings revealed an ulcerative region that was diagnosed as cytomegalovirus (CMV) vasculitis. His serum level of CMV (measured by real-time-detection polymerase chain reaction [PCR]) was high. Ganciclovir therapy was started, and manifestations of the CMV infection improved. In addition to CMV, PCR assay for hepatitis A virus (HAV), HBV, HCV, Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and herpes simplex virus (HSV) was performed, but no viruses other than CMV were detected. We are the first to report such a case. We conclude that the possibility of CMV enteritis should be considered when patients present with unexplained fever and gastrointestinal hemorrhage following fulminant hepatitis, and we conclude that the early administration of ganciclovir should be considered.

BACKGROUND It has been reported that MUC1 is an important prognostic factor in several cancers. This study investigated the importance of MUC1 as a prognostic factor in mass-forming intrahepatic cholangiocarcinoma (m-ICC). METHODS In 50 patients with m-ICC who had undergone hepatectomy, expression of MUC1 was investigated. Expression of MUC1 was examined by immunohistochemical staining with monoclonal antibody HMPV, which recognizes the MUC1 core peptide. The immunohistochemical staining patterns of MUC1 were classified into three types: ductal type (the luminal surface membrane of neoplastic cells was stained), cytoplasmic type (the cytoplasm of neoplastic cells was stained dominantly), and negative type. RESULTS Expression of MUC1 was detected immunohistochemically in 38 (76%) of 50 cases of m-ICC (ductal type, 18; cytoplasmic type, 20; and negative type, 12). Seventy-five percent of patients with lymph node metastasis had the cytoplasmic type MUC1 expression. Lymph node dissection was performed in only 20 patients, but significant correlation was demonstrated between MUC1 expression and lymph node metastasis (P = 0.0227). The location of MUC1 expression correlated with surgical outcome in m-ICC. Patients with the cytoplasmic type expression showed significantly lower survival rates. Univariate analysis revealed that MUC1 expression was a statistically significant risk factor affecting outcome in m-ICC (P = 0.0028). Furthermore, expression of MUC1 was found to be a statistically significant independent risk factor in multivariate analysis (P = 0.0063). CONCLUSIONS The results suggest that evaluation of MUC1 expression may be very useful in predicting the surgical outcome in m-ICC. Cancer 2002;94:1770–6. © 2002 American Cancer Society. DOI 10.1002/cncr.10398

Background and Objectives Lymph node micrometastasis is frequently detected in resected specimens of esophageal squamous cell carcinoma (ESCC). The goal of this study was to evaluate the clinical implication of micrometastasis in patients with lymph node-negative (pN0) disease. Methods We examined the presence of micrometastasis in 2,511 lymph nodes from 53 patients with pN0 disease who underwent curative esophagectomy. All lymph nodes and the primary tumors were immunostained using an anticytokeratin antibody cocktail (AE1/AE3). Results Micrometastasis was detected in 18 lymph nodes (0.72%) from 14 patients (26.4%). Detection of micrometastasis was not associated with the depth of invasion or the differentiation or lymphatic invasion. Lymph nodes containing micrometastases were widely distributed, but the most frequently involved nodes were located along the lesser curvature of the stomach. Four patients with micrometastasis (29%) and the only two patients without micrometastasis (5%) had recurrence as lymph node metastases (P = 0.036). There were no significant differences in recurrence-free survival and disease-specific survival between patients with micrometastasis and patients without micrometastasis. Conclusions These results show that micrometastasis might increase the risk of lymph node recurrence, but does not influence the survival of patients with pN0 ESCC. J. Surg. Oncol. 2002;79:224–229. © 2002 Wiley-Liss, Inc.

Background: There is a high risk of anastomotic leakage after pancreaticojejunostomy after pancreaticoduodenectomy (PD) in patients with a normal pancreas because of the high degree of exocrine function. These PD are therefore generally performed using a stenting tube (stented method). In recent years, we have performed pancreaticojejunostomy with duct-to-mucosa anastomosis without a stenting tube (nonstented method) and obtained good results. Methods: The point of this technique is to preserve adequate patency of the pancreatic duct by carefully picking up the pancreatic duct wall with a fine atraumatic needle and monofilament thread. The results of end-to-side pancreaticojejunostomy of the normal pancreas were compared between the nonstented method (n = 109) and the stented method (n = 39). Results: There were no differences in background characteristics between the groups, including age, gender and disease. The mean duration to complete pancreaticojejunostomy was 26.6 min in the nonstented group and 29.2 min in the stented group. The mean durations of surgical procedure and intraoperative blood loss were also similar in the groups. Morbidity rates due to early postoperative complications were 20.2 and 23.1%, with pancreatic leakage occurring in 7.3 and 7.7% of patients, respectively. These differences were not statistically significant. One patient in the stented group died of sepsis following leakage of pancreaticojejunostomy. There were also no significant differences in the mean time to initiation of solid food intake or postoperative hospital stay. Conclusion: We conclude that a stenting tube is unnecessary if the duct-to-mucosa anastomosis is completely performed. This operative technique can be considered a basic procedure for pancreaticojejunostomy because of the low risk.

The recurrence rate after surgery in patients with hepatocellular carcinoma (HCC) is very high, while prognosis is quite poor. However, there is no standard treatment to prevent recurrence of HCC after a curative operation. In this study, we investigated the clinical utilization of an autologous tumor lysate-pulsed dendritic cell vaccine plus ex vivo activated T cell transfer (ATVAC) in an adjuvant setting for postoperative HCC as a non-randomized controlled trial. Ninety-four patients with invasive HCC received informed consent information regarding the study, and 42 opted to have the ATVAC after surgery. Their recurrence-free survival (RFS) and overall survival (OS) were measured after 5 years and compared with those of 52 patients who selected to have the curative operation alone. The median RFS and OS were 24.5 months and 97.7 months in the patients receiving adjuvant ATVAC and 12.6 months and 41.0 months in the group receiving surgery alone (P = 0.011 and 0.029). In the treated group, patients with positive delayed-type hypersensitivity (DTH) had a better prognosis (RFS P = 0.019, OS P = 0.025). No adverse events of grade 3 or more were observed. A postoperative dendritic cell vaccine plus activated T cell transfer would be a feasible and effective treatment for preventing recurrence in HCC patients and achieving long-term survival especially in DTH positive patients.