[Perioperative Steroid Administration for Colorectal Cancer with Synchronous Unresectable Hepatic Metastases].

PURPOSE: In our institution, steroids are administered before resection of primary colorectal cancer lesions with synchronous unresectable hepatic metastases in order to avoid severe postoperative complications and hepatic failure. We herein report the results of the treatment. PATIENTS AND METHODS: Thirty-eight colorectal cancer patients with synchronous unresectable hepatic metastases were divided into 2 groups: Group S (patients who received steroids in the perioperative period) and Group N (other patients). The clinicopathological features, post-operative course, and survival were compared between the 2 groups. Hydrocortisone sodium succinate was administered twice a day from immediately before laparotomy until the second postoperative day. RESULTS: The number of patients with severe hepatic metastases and extra-hepatic metastases was significantly higher in Group S. No significant differences were observed between the 2 groups regarding the incidence of severe postoperative complications or the overall survival. Among 25 patients with liver dysfunction, the complication rate was significantly lower and survival was significantly longer in Group S compared to Group N. CONCLUSIONS: The perioperative administration of steroids to colorectal cancer patients with synchronous unresectable hepatic metastases may reduce the complication rate and may thus improve survival, especially in patients with liver dysfunction.

[A Case of Early Recurrence after Esophagectomy for Cancer Following Neoadjuvant Chemotherapy Resulting in a Complete Response of the Primary Lesion].

A 78-year-old man presented with a chief complaint of dysphagia. He was diagnosed with an esophageal squamous cell carcinoma and referred to our hospital. A type 3 tumor was identified in the lower thoracic esophagus on endoscopy. A CT scan revealed lymph node metastases at the No. 3 station. The clinical stage of the tumor was T3N1M0, Stage III. The patient was treated with neoadjuvant chemotherapy consisting of2 courses of5 -FU and nedaplatin. He had a partial response and underwent a radical esophagectomy. Histopathological examination revealed a complete response of the primary lesion and viable cancer cells in only one lymph node at the No. 3 station. No adjuvant chemotherapy was administered. Three months after the operation, recurrences in the upper abdominal multiple para-aortic lymph nodes were detected. Although he was treated with chemotherapy, he died 7 months after the operation. Even after a complete response of the primary lesion was achieved using neoadjuvant chemotherapy, esophageal cancer with lymph node metastasis has the potential for an early recurrence. Therefore, we should consider adjuvant therapy in such cases.

[The Different Indications and Treatment Effect between Preoperative Chemotherapy and Preoperative Radiotherapy for Advanced Rectal Cancer].

We evaluated the difference in effectiveness between preoperative radiotherapy (RT) and chemotherapy (C) as part of multimodal therapy for locally advanced rectal cancer. In the RT group, 43 patients were enrolled and preoperative radiotherapy was performed with 42.6 Gy for 4 weeks. In the C group, 16 patients were treated with preoperative chemotherapy consisting of mFOLFOX6/XELOX plus bevacizumab for 3 months. All 43 tumors in the RT group were located in the lower rectum. The C group was composed of 9 in the lower rectum and 7 in the middle or upper rectum. The C group was more advanced than the RT group in terms of depth of invasion, lymph node metastasis, and tumor diameter. The histological treatment response was better after RT (7 with little, 10 with a minor, 24 with a major, and 2 with a complete response) than after C (10 with little, 4 with a minor, 1 with a major, and 1 with a complete response). The tumor reduction ratio by colonography showed 36.5% after RT and 28.7% after C. CEA was reduced by 47.2% after RT and 45.2% after C. Though RT is more effective for local lesions than C, C is expected to be preferred as the local and systemic therapy for locally advanced rectal cancer with pelvic organ involvement or lateral lymph node metastases.

[Surgical Simulation-CT Colonography for Laparoscopic Assisted Sigmoid Colectomy Preserving the Inferior Mesenteric Artery and Vein].

D2 lymph node dissection in laparoscopic surgery for early colon cancer requires selective vessel dissection, making it technically very difficult. Using surgical simulation-CT colonography (simulation-CTC), we could perform laparoscopic assisted sigmoid colectomy preserving the inferior mesenteric artery (IMA) and vein (IMV) more accurately and safely. The case described here was a type 0-Ip sigmoid colon cancer with a tumor size of 13 mm. Endoscopic mucosal resection was performed to confirm a pathological diagnosis of pT1b (4,000 mm) and v1. Sigmoid colectomy was planned, and simulation-CTC was performed, which demonstrated that the cancer was located in the proximal sigmoid colon and supplied by the first sigmoid colon artery (S1). To maintain the blood flow to the distal sigmoid colon, selective S1 resection preserving the IMA and IMV was planned. At the operation, S1, which branches off from the IMA near the bifurcation of the abdominal aorta, was dissected, and the vein accompanying S1, which branches from the IMV in the same area as S1, was dissected. The operation was performed accurately according to the plan, showing that simulation-CTC can be very useful.

[A Case of Anal Canal Carcinoma with Inguinal Lymph Node Metastasis Treated with Laparoscopic Abdominoperineal Resection].

We report a case of anal canal cancer with inguinal lymph node metastasis treated with laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. A 52-year-old woman was diagnosed with anal squamous carcinoma after excision of an anal canal tumor. Further examination revealed right inguinal lymph node metastasis. Chemoradiotherapy was administered but was discontinued because of serious adverse events. We therefore performed laparoscopic abdominoperineal resection combined with inguinal lymph node dissection. The pathological findings revealed residual squamous cell carcinoma at the lymphatic vessels in the rectal wall and lymph nodes, including the right inguinal region. Therapeutic effect of Grade 1a was achieved in spite of interruption of the chemoradiotherapy. She was discharged 17 days after the operation, and no recurrence was observed for 11 months. Radical resection was performed for the anal canal squamous cell carcinoma with the metastasis to the right inguinal lymph node, even after interruption of the chemoradiotherapy.

[Intraperitoneal chemotherapy with CDDP for patients with peritoneal recurrent gastric cancer following surgical intervention].

We evaluated the efficacy of intraperitoneal chemotherapy with cisplatin (CDDP) for peritoneal recurrent gastric cancer following surgical intervention. Twelve patients were enrolled. The combination systemic chemotherapy was S-1 or S-1 plus paclitaxel (S-1+PTX). PTX was administered intravenously at 80 mg/m² on day S-1 and 15. S-1 was administered at 80 mg/ m²/ day for 7 consecutive days, followed by 7 days of rest, and the cycle was repeated. CDDP was administered intraperitoneally at 40 mg/body on day 8. This treatment was repeated every 4 weeks until disease progression was diagnosed. The survival time(ST)and time to treatment failure(TTF)were estimated. The surgical interventions were gastrectomy in 3 patients, colostomy in 8 patients, and enterostomy in 1 patient. Overall, the median TTF and ST were 294 days and 455 days, respectively. When stratified by surgical method and combination chemotherapy, the median TTF and ST were not statistically significant. However, when stratified by performance status (PS), the median TTF was 352 days for patients with PS 0 and 218 days for those with PS 1, 2 (p=0.0029), whereas the median ST was 553 days for patients with PS 0 and 331 days for those with PS 1, 2 (p=0.0198). In conclusion, the data suggest that intraperitoneal CDDP chemotherapy with systemic chemotherapy is effective for the treatment of extensive peritoneal recurrent gastric cancer, especially in patients with good PS.

Diffusion-weighted magnetic resonance imaging for predicting and detecting the early response to chemoradiotherapy of advanced esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to investigate the utility of the apparent diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance imaging (DWMRI) for prediction and early detection of treatment response in advanced esophageal squamous cell carcinoma. METHOD: DWMRI was performed in 27 patients with primary cT4 esophageal carcinoma that were undergoing chemoradiotherapy before treatment and after 20 and 40 Gy. We calculated tumor ADCs and association of the treatment effect between responders and nonresponders. RESULTS: The ADC at the time of 20 Gy was significantly higher in responders compared to nonresponders (1.13 vs. 0.93; p = 0.005). The ADC cut-off value was set at 1.00 × 10(-3) mm(2)/s and the ADC predicted the responders with a sensitivity, positive predictive value and accuracy of 79, 73 and 74%, respectively. The increased rate of the ADC at the time of 20 Gy (ΔADC20) was also significantly higher in responders compared to nonresponders (35.4 vs. 1.5%; p = 0.0007). An ADC cut-off value for ΔADC20 of 15% predicted the responders with a sensitivity, positive predictive value and accuracy of 71, 100 and 85%, respectively. CONCLUSION: The ADC values predicted the prognosis of patients with advanced esophageal squamous cell carcinoma as well as the treatment response.

Role of perfusion CT in assessing tumor blood flow and malignancy level of gastric cancer.

BACKGROUND/AIMS: Intratumoral hemodynamics or tumor perfusion is useful in understanding the pathological background of the cancer. A parameter for a non-invasive, preoperative assessment of tumor perfusion has yet to be developed. METHODS: The study included 50 patients who underwent surgery for gastric cancer. Perfusion computed tomography (P-CT) was performed using a 16-row multidetector CT, and tumor blood flow (ml/min/100 g tissue) values were measured. We compared blood flow with histopathological characteristics and evaluated its correlation with microvessel density and tumor stromal density and calculated the ratio of vessels and stromal tissue. RESULTS: There was a significant decrease in blood flow in advanced tumor depth, peritoneal dissemination and undifferentiated subtypes. Cases with Lauren's diffuse type carcinoma were found to have decreased blood flow compared to the mixed or intestinal type. As for the stromal structure, despite the lack of correlation with microvessel density, blood flow significantly decreased with increased stromal density. CONCLUSIONS: Decreased blood flow value acquired from P-CT may reflect a progressive state of gastric cancer. The pathological background for this relation involves the tumor stroma. Tumor perfusion decreased as the stage and malignant character of the tumor advanced, and therefore P-CT could be a better strategy to estimate the malignancy level of cancer.

[A case of long-term survival after resection for postoperative solitary adrenal metastasis from esophageal adenocarcinoma].

A 71-year-old man presented with chief complains of hoarseness and dysphagia. He was diagnosed to have an advanced esophageal adenocarcinoma in the middle thoracic esophagus for which chemoradiation therapy was started. Partial response was observed and he was referred to our hospital thereafter. After detailed examination, he underwent a subtotal esophagectomy followed by two-field lymphadenectomy in May 2001. Histopathological examination revealed a complete response. Ten months later, hematological examination showed a high serum CEA level and CT scan disclosed mediastinal lymph node recurrences. He received a course of systemic chemotherapy so called FP therapy and five months later, a course of combination chemotherapy with 700 mg/m2 5-FU on days 1-5 and 70 mg/m2 nedaplatin on day 1 was administered. Because the high serum CEA level sustained afterward, FDG-PET was undertaken in March 2003. The right adrenal gland showed an intense abnormal FDG uptake and CT scan detected a low density mass in the area. Since no metastases could be identified in other sites, right adrenalectomy was performed. Pathological finding was poorly-differentiated tubular adenocarcinoma. Five years and eleven months after adrenalectomy, he died of pneumonia with no signs of recurrence. Surgical resection may contribute to improving the prognosis of solitary adrenal metastasis of esophageal cancer without the other noncurative factors.

[Regional treatment of esophageal liver metastasis by intra-arterial low-dose 5-FU therapy].

The prognosis of esophageal liver metastasis remains poor because of the high incidence of synchronous metastasis in other area and insufficient response to systemic chemotherapy. We assessed loco-regional anticancer potential of intra-arterial 5-FU chemotherapy for esophageal liver metastasis aimed at combination with systemic chemotherapy, radiotherapy and ablation therapy as a multidisciplinary treatment. Six patients of esophageal cancer with liver metastasis and without extra-hepatic metastasis were enrolled. Intra-aortic chemotherapy consisted of 5-FU (250 mg/body) in a one-shot infusion or a continuous infusion for 7 days with 2-week intervals until failure. The responses of liver metastasis were 2 cases of CR, 3 of PR and 1 of SD. The response rate and the local control rate were 83% and 100%, respectively. The maximum time to progression was 53 months. Grade 3/4 toxicity was not observed. Two cases had catheter failure and the treatment was interrupted. Liver metastases were controlled well until death in all cases except one. Low-dose intra-aortic 5-FU chemotherapy provided a good regional response and a combination with systemic chemotherapy may prolong survival for the patients of liver metastasis of esophageal cancer.

[Evaluation of hepatic arterial infusion chemotherapy for liver metastasis from gastric cancer].

We performed hepatic arterial infusion (HAI) chemotherapy for 11 patients with liver metastasis from gastric cancer, who had no other metastasis. The main antineoplastic drug was 5-fluorouracil (5-FU). The catheter was inserted into the hepatic artery using the GDA coiling method by interventional radiologic technique in 9 patients, and by operative treatment in 2 patients. The response rate for 10 patients was 91% (CR 3, PR 7, PD 1). The survival time from the beginning of the HAI chemotherapy was 8-34 months. The causes of withdrawal from the chemotherapy were PD in 7 patients and catheter troubles in 4 patients. There was no patient suffering from severe adverse effect. The HAI chemotherapy was effective and useful for patients with liver metastasis of gastric cancer. We thought a gastric cancer patient with liver metastasis who didn't have an uncontrollable other organ metastasis was a good target for this regimen.

[Evaluation of preoperative chemoradiation therapy for lower rectal carcinoma using DWIBS].

We investigated the efficacy of diffusion-weighed whole body imaging with background body signal suppression (DWIBS) in assessing effects of chemoradiation therapy (CRT) on rectal carcinoma. DWIBS was performed in patients (n=12) with primary rectal carcinoma undergoing preoperative CRT before and 3 weeks after the treatment. Each patient received a total irradiation dose of 45 Gy at a single dose of 1.8 Gy administered once daily. Parallel to this, in the 1st, 3rd and 5th weeks 350 mg/m2 5-fluorouracil and 35 mg/m2 l-leucovorin were administered for 5 days. The apparent diffusion coefficient (ADC) was measured by DWIBS and surgical resection of the tumors enabled a correlation of ADC values with the pathological findings. With respect to histopathological grading of regression, two, five and five cases exhibited Grade 3, Grade 2 and Grade 1, respectively. In all patients, ADC values were higher after completion of CRT compared to those before it( 1.23+/-0.26x10(-3) mm2/s vs 0.75+/-0.13x10(-3) mm2/s, p<0.001). After completion of CRT, mean ADC values were 1.71+/-0.38x10(-3) mm2/s, 1.25+/-0.10x10(-3) mm2/s and 1.02+/-0.08x10(-3) mm2/s for Grade 3, Grade 2 and Grade 1, respectively. These preliminary results indicate that DWIBS may be a valuable tool to assess effects of CRT on rectal carcinoma by using appropriate cut-off values.

[Diffusion-weighted MR imaging for postoperative nodal recurrence of esophageal squamous cell cancer in comparison with FDG-PET].

We evaluated the power of DWIBS in patients with postoperative lymph node recurrence of esophageal cancer and compared with FDG-PET findings. Forty-seven suspected lesions by MDCT were enrolled. No significant difference between DWIBS and PET was observed in sensitivity (95% vs 97%), PPV (83% vs 90%) and overall accuracy rate (81% vs 87%). The ADCs (x10(-3) mm2/s) of recurrent nodes, primary cancer and normal esophagus were 1.124, 1.058 and 2.079, respectively. ADCs of recurrent nodes were significantly lower than those of normal esophagus (p<0.0001). The cut-off ADC line of 1.5 revealed 100% overall accuracy for separating the recurrent lesion from normal esophagus. Noninvasive DWIBS may become a valid modality to discriminate nodal recurrence of esophageal cancer by no means inferior to PET.

Lateral lymph node dissection for lower rectal cancer.

BACKGROUND/AIMS: This study was conducted to evaluate the effects of lateral lymph node dissection (LLD) on overall survival, disease-free survival, and local recurrence for the patients with lower rectal cancer. METHODOLOGY: From 1990 through 2000, 169 consecutive patients with T2 (TNM classification) or more advanced, extended lower rectal cancer (located below the peritoneal reflection) underwent curative resection at Kanagawa Cancer Center were reviewed. One hundred and forty-three patients who underwent LLD and the 26 patients who did not were entered in this study. RESULTS: Cox's multivariate regression analysis showed T stage (TMN classification), N stage (TNM classification), and LLD were found to be significantly related to the rates of both cumulative survival and disease-free survival. That mean LLD was identified as a significant prognostic factor. But disease-free survival did not differ significantly between the patients who underwent LLD and those who did not undergo LLD in stage I, II, or III disease (p = 0.3681, p = 0.1815, and p = 0.0896, respectively). The local recurrence rate was similar in patients who received LLD (17.5 percent) and in those who did not receive LLD (23.1 percent; p = 0.498). But 7 patients with lateral lymph node metastasis (33.3 percent) remained disease free. And these patients had local lateral lymph node metastasis and benefited from LLD. CONCLUSIONS: LLD can substantially improve outcomes in selected patients at high risk for lateral lymph node metastasis. A randomized controlled clinical study is necessary to clarify the role of LLD in the treatment of rectal cancer.

Clinicopathological features of skip metastasis in colorectal cancer.

BACKGROUND/AIMS: Japanese general rules for the staging of colorectal cancer conventionally classify lymph node metastasis into three groups according to location with respect to the primary tumor. Skip metastasis, in which distant nodes are positive but regional nodes are negative, is often encountered but poorly understood. We studied the clinicopathological features of skip metastasis in colorectal cancer. METHODOLOGY: The location of positive nodes was classified in 323 patients with Dukes' stage C colorectal cancer. Skip n2 lymph node metastasis was defined as positive N2 metastasis without negative N1 or N3 metastasis. Clinicopathological findings and survival were compared between the patients with skip n2 metastasis (skip n2 group) and those with n1 (n1 group) or n2 metastasis (n2 group). RESULTS: There were 211 patients in the n1 group, 91 in the n2 group, and 21 in the skip n2 group. Pathological examination showed that the skip n2 group had fewer positive nodes than the n1 and n2 groups, but was positioned between these groups with respect to the degree of lymphatic invasion. Cumulative survival was significantly poorer in the n2 group than in the skip n2 group (p = 0.039 by log-rank test). Survival was similar in the skip n2 group and n1 group. There was also no difference in survival between patients in the skip n2 group and patients with one, two, or three N1 metastases. CONCLUSIONS: Lymph nodes with skip n2 metastasis are most likely sentinel nodes of the primary tumor in patients with colorectal cancer. The prognosis of patients with skip n2 metastasis is therefore better than that of patients with n2 metastasis and similar to that of patients with n1 metastasis.