Oncologic Reappraisal of Bile Duct Resection for Middle-Third Cholangiocarcinoma.

BACKGROUND: Although bile duct resection (BDR) in addition to pancreaticoduodenectomy (PD) is considered a surgical approach in patients with middle-third cholangiocarcinoma (MCC), available prognostic information after BDR remains very limited. The aim of this study was to reappraise BDR from the viewpoint of surgical oncology. METHODS: Patients who underwent BDR or PD for MCC between 2001 and 2010 at 32 Japanese hospitals were included. Clinicopathological factors were retrospectively compared according to surgical procedure to identify a subset cohort who benefited most from BDR. RESULTS: During the study, 92 patients underwent BDR (n = 38) or PD (n = 54). BDR was characterized by a shorter operation time, less blood loss, less frequent complications, and lower mortality, than PD. The incidence of positive surgical margins was 26.3% versus 5.6% (P = 0.007). The survival rate after BDR was significantly worse than that after PD: 38.8% versus 54.8% at 5 years (P = 0.035), and BDR was independently associated with deteriorated survival [hazard ratio (HR), 1.76; P = 0.023] by multivariable analysis. In the BDR group, tumor length < 15 mm (HR, 3.38; P = 0.017) and ductal margin length ≥ 10 mm (HR, 2.54; P = 0.018) were independent positive prognostic factors. Stratified by these two favorable factors, the 5-year survival rate was 63.0% in patients with 1/2 factors and 6.7% in those with 0 factors (P < 0.001). CONCLUSION: In patients with MCC, BDR provided a better short-term and a worse long-term outcome than PD. However, patient selection using tumor length and ductal margin length may allow a favorable survival probability even after BDR.

[A case of pancreatic metastasis from breast cancer during multimodality therapy].

We report a case of pancreatic metastasis from breast cancer during multimodality therapy. A 53-year-old woman received right breast-conserving surgery for invasive ductal carcinoma and then chemo-radiotherapy for liver, brain, bone, neck and axillary lymphnodes, mediastinum, pleural, and spinal cord metastasis. Although she then survived in a tumor-free condition, a blood examination performed 4 years after the surgery showed an elevated serum amylase level. Abdominal CT and US revealed swelling of the pancreas head and body with main pancreatic duct dilatation of the pancreatic tail. ERCP showed diffuse stenosis of the extrahepatic bile duct and the main pancreatic duct of the pancreatic head and body. Immunohistochemical staining of the biopsy specimen from the pancreatic head confirmed pancreatic metastasis from breast cancer. Despite the intensive chemotherapy including trastuzumab, she died 2 years after the onset of pancreatic metastasis. Metastatic breast cancer to the pancreas is very rare. However, considering the recent advances of multimodality therapy for breast cancer, this clinical state may become more common.

[Optic lesions in patients with epiphora during S-1 therapy].

PURPOSE: To elucidate the features of optic lesions in patients with epiphora during S-1 therapy. PATIENTS: Twelve patients with epiphora in 123 patients during S-1 therapy. RESULTS: Age range was 38-84 years (mean 68.4 years). There were 4 cases in 81 men (5%) and 8 in 42 women (19%). Epiphora occurred significantly more often in women (p=0.02). The administration period was from 10 days to 36 months. Lesions were superficial punctate keratopathy in 10 cases with cornea and obstruction of inferior punctum in 2, stenosis of nasolacrimal duct in 1 and suspected occlusion of the nasolacrimal duct in 1 with lacrimal duct. Local therapy was eye drops in all cases. Of the whole 12 patients, S-1 was continued or discontinued in 6 each of all 12 cases, in 5 each of 10 cases with superficial punctate keratopathy, and in 2 each of 4 cases with lacrimal duct lesions. Epiphora/optic lesions improved with a range from 10 days to 1.5 months in cases of discontinuation and with that from 2 weeks to 1 month in cases of continuation. DISCUSSION: Our results revealed superficial punctate keratopathy in many cases, lacrimal duct lesions in a few cases, and discontinuation of medication provided improvement of optic events. CONCLUSIONS: When epiphora is observed in patients on S-1 therapy, it is necessary to assess optic disorders by an opthalmologist immediately because of suspicion of injury to the cornea and lacrimal duct.

[A case of recurrent colon cancer with angina pectoris and interstitial pneumonia during cetuximab therapy with death by carcinomatous lymphangiosis].

The case was a man in his 60s with no past history of heart and lung. Chest tightness was felt during the first course of cetuximab therapy for recurrent colon cancer. He was diagnosed as having vasospastic angina, and administration of vasodilatation agents was done. After the therapy, no chest pain attack was seen. Chemotherapy was continued. After 3 courses, fever elevation, chest tightness and dyspnea were seen. Chest X-ray and CT revealed diffuse interstitial pneumonia in bilateral lung. Although steroid pulse therapy and intensive therapy with mandatory ventilation were performed, he died of respiratory failure. Pathological findings of autopsy revealed remarkable metastasis of cancer cells to the bilateral lungs accompanied chiefly with carcinomatous lymphangiosis. Furthermore, acute and subacute interstitial pneumonia with diffuse alveolar damage were seen in the background of the lungs. Cardiopulmonary disorder as well as skin disorder should be considered as possible adverse events of cetuximab therapy.

[Patient of advanced age with synclonus liver metastases from colon cancer effectively treated with intraarterial chemotherapy of 5-FU].

An 85-year-old man received ileocecal resection and cholecystectomy for ascending colon cancer with synclonus liver metastases. After a catheter for intraarterial injection into liver was inserted and it fixed to the gastroduodenal artery, an intraarterial chemotherapy of 5-FU 750 mg/body/5 hr biweekly was performed for liver metastases. He had no system trouble and side effects, and liver metastases had been estimated as stable disease for 23 months. After progression of the disease, other chemotherapies such as intraarterial injection of CPT-11 or oral intake of S-1 were not tolerated due to side effects and were immediately discontinued. He died after 31 months postoperatively. Chemotherapy for elderly patients is a key issue in Japan, which is renowned worldwide for its longevity. Nowadays, the standard chemotherapy for unresectable liver metastases from colorectal cancer is continuous venous injection therapy such as FOLFOX. Although intraarterial injection chemotherapy has a risk of system trouble, this procedure could be acceptable for elderly patients because of less anti-cancer drug toxicity. Thus, it should be considered one of several treatment options for unresectable liver metastases in elderly patients.

Laparoscopic surgery for the treatment of a ruptured aneurysm of the right gastric artery: a case report.

Laparoscopic surgery for the treatment of a ruptured visceral artery aneurysm is recognized as a challenging procedure. Here, we describe our experience with laparoscopic surgery to treat a ruptured aneurysm of the right gastric artery. A 72-year-old woman was diagnosed with intra-abdominal hemorrhage caused by a ruptured aneurysm of the right gastric artery. Transcatheter arterial embolization failed because the right gastric artery could not be cannulated. Therefore, we performed laparoscopic surgery. Using laparoscopy, we detected that the bleeding from the aneurysm had ceased; thus, the planned procedure was successful. The operative time and intraoperative blood loss were 100 min and 5 mL, respectively. The patient was discharged 7 days after surgery. Laparoscopic surgery after the failure of transcatheter arterial embolization is a suitable and safe procedure for ruptured visceral artery aneurysms, provided the circulatory dynamics are stable as a result of the temporary cessation of bleeding from the ruptured aneurysm.

Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer.

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001), lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p<0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8-17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

Optimal schedule of adjuvant chemotherapy with S-1 for stage III colon cancer: study protocol for a randomized controlled trial.

BACKGROUND: Although, in Western countries, oxaliplatin-based regimens have been established as a gold standard treatment for patients with stage III or high risk stage II colon cancer after curative resection, in Japan fluorouracil-based regimens have been widely accepted and recommended in the guidelines for adjuvant settings in patients with stage III colon cancer. S-1, an oral preparation evolved from uracil and tegafur, has equivalent efficacy to uracil and tegafur/leucovorin for treating patients with advanced colorectal cancer and might be a suitable regimen in an adjuvant setting. However, the completion rate of the standard six-week cycle of the S-1 regimen is poor and the establishment of an optimal treatment schedule is critical. Therefore, we will conduct a multicenter randomized phase II trial to compare six-week and three-week cycles to establish the optimal schedule of S-1 adjuvant therapy for patients with stage III colon cancer after curative resection. METHODS/DESIGN: The study is an open-label, multicenter randomized phase II trial. The primary endpoint of this study is three-year disease-free survival rate. Secondary endpoints are the completion rate of the treatment, relative dose intensity, overall survival, disease-free survival, and incidence of adverse events. The sample size was 200, determined with a significance level of 0.20, power of 0.80, and non-inferiority margin of a 10% absolute difference in the primary endpoint. DISCUSSION: Although S-1 has not been approved yet as a standard treatment of colon cancer in an adjuvant setting, it is a promising option. Moreover, in Japan S-1 is a standard treatment for patients with stage II/III gastric cancer after curative resection and a promising option for patients with colorectal liver metastases in an adjuvant setting. However, a six-week cycle of treatment is not considered to be the best schedule, and some clinicians use a modified schedule, such as a three-week cycle to keep a sufficient dose intensity with few adverse events. Therefore, it will be useful to determine whether a three-week cycle has an equal or greater efficacy and tolerance to side-effects compared with the standard six-week cycle schedule, and thus may be the most suitable treatment schedule for S-1 treatment. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000006750.

Simultaneous segmental obstruction of bile duct and portal vein markedly changes a population of biliary and hepatic cells in human liver.

BACKGROUND AND AIMS: No studies have investigated histologic changes caused by simultaneous segmental obstruction of the bile duct and portal vein in human liver. PATIENTS/METHODS: Liver tissues with simultaneous obstruction of the segmental bile duct and portal vein (O(+/+) liver), with segmental bile duct obstruction alone (O(+/-) liver), and without obstruction (O(-/-) liver) were obtained from patients who underwent hepatectomy, and studied morphologically and immunohistochemically. RESULTS: In O(+/+) liver, the proportional area consisting of hepatocytes was significantly less (31.0+/-25.8%) than in O(+/-) liver (78.4+/-18.9%) or O(-/-) liver (86.5+/-9.2%). In contrast, the proportional area consisting of biliary epithelial cells was significantly higher in O(+/+) liver (9.1+/-6.1%) than in O(+/-) liver (1.6+/-1.5%) or O(-/-) liver (0.7+/-0.6%). The proportional area consisting of fibrous tissue also was significantly higher in O(+/+) liver than in the other two groups. In O(+/+) liver, some cells located at the periphery of hepatocyte areas were immunoreactive for both hepatocyte and biliary epithelial cell markers. CONCLUSION: Simultaneous segmental obstruction of the bile duct and portal vein induces a marked ductular increase, periportal fibrosis, and a reduction in the number of hepatocytes in human liver tissue.