[A Case of Recurred Gastric Cancer of the Anastomosis Completely Responding to Docetaxel, Cisplatin, and S-1 Triplet Therapy].

A 51-year-old man who had undergone distal gastrectomy for gastric cancer was admitted in Kagoshima University Hospital under the diagnosis of anastomotic recurrence of gastric cancer. From abdominal CT results, the recurred tumor was suspected to invade into the pancreas with regional node metastases. Because of the intense radicality of surgical intervention, we planned 3 courses of docetaxel, cisplatin, and S-1 triplet therapy(DCS therapy). After the chemotherapy, the recurred tumor and lymph node metastases shrunk drastically. Segmental gastrectomy with lymph node dissection was performed with curative intent. Final pathology revealed complete regression of both the recurred tumor and lymph node metastases. The patient's postoperative course was uneventful without tumor relapse. DCS therapy seems to be suitable to obtain drastic tumor regression before surgical intervention as a neoadjuvant chemotherapy for locally advanced gastric cancer.

A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients.

The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC.

Anatomical laparoscopic hepatectomy for hepatocellular carcinoma using indocyanine green fluorescence imaging.

PURPOSE: It is important to minimize surgical invasiveness in the therapy of patients with hepatocellular carcinoma (HCC), and consequently laparoscopic hepatic resection is widely performed. However, most anatomical resections, except left lateral sectionectomy, remain difficult technically, and laparoscopy-assisted procedures have been introduced as an alternative approach because of the safety and curative success of the operation. We reported previously pure laparoscopic subsegmentectomy of the liver using puncture of the portal branch under percutaneous ultrasound (US) with artificial ascites. Herein, we describe pure anatomical laparoscopic segmentectomy using the puncture method with indocyanine green (ICG) injection under laparoscopic US. PATIENTS AND METHODS: Pure laparoscopic segmentectomy was planned for 2 patients with HCC of the liver. Identification of the segment was performed by ICG injection for optical imaging using near-infrared fluorescence under laparoscopic US guidance. RESULTS: The procedures were completed successfully, and the postoperative courses were uneventful. CONCLUSIONS: Pure laparoscopic segmentectomy for HCC with a conventional puncture technique by ICG injection under laparoscopic US is considered to be a useful procedure featuring both low invasiveness and curative success.

[Outcomes of advanced gastric cancer patients treated with chemoradiation therapy].

We retrospectively analyzed 20 patients with advanced gastric cancer treated with chemoradiation(CRT). The patients consisted of 16 males and 4 females, 17(85%)of whom received intensive chemotherapy prior to CRT. Radiation was administered concurrently at 40 to 55 Gy according to the purpose of treatment. Sixteen patients received low dose CDDP and S-1. Of 8 patients who had measurable disease, one obtained CR and 3 obtained PR by the CRT. Fifteen percent of the distinct adverse effects of CRT were grade 3 leucopenia and 30% of them were grade 3 nausea. The 2-year-survival of patients who received CRT with curative intent was 91%, significantly higher than the percentage of those with palliative intent. Four patients who received R0 surgery following CRT are postoperatively healthy without symptoms of relapse. In conclusion, even though, 75% of the patients were already given chemotherapy prior to CRT, good outcomes were achieved unexpectedly. The combination of CRT and surgery may be a useful tool for chemo-resistant, locally advanced gastric cancer.

Pure laparoscopic subsegmentectomy of the liver using a puncture method for the target portal branch under percutaneous ultrasound with artificial ascites.

PURPOSE: It is important to minimize surgical invasiveness in the therapy of patients with hepatocellular carcinoma (HCC) and, consequently, laparoscopic hepatic resection is widely performed. However, most anatomic resections, except left lateral sectionectomy, are still difficult technically and, as an alternative approach, laparoscopy-assisted procedures also have been introduced because of the safety and curative success of the operation. Herein, we describe pure laparoscopic subsegmentectomy of the liver using puncture of the portal branch under percutaneous ultrasound (US) with artificial ascites. METHODS: Pure laparoscopic subsegmentectomy of segment 6 (S6) was planned for a patient with HCC of S6 of the liver. The identification of the segment was performed by dye injection under percutaneous US guidance with artificial ascites. RESULTS: The procedure was completed successfully in a minimally invasive manner with an operative time of 260 minutes and with intraoperative blood loss of 10 mL. The difference between the size of the resected specimen and that estimated by 3-dimensional computed tomography was very small. The postoperative course was uneventful and the patient was discharged 10 days after surgery. CONCLUSIONS: Pure laparoscopic subsegmentectomy for HCC with a conventional puncture technique under percutaneous US with artificial ascites is considered to be a useful procedure featuring both low invasiveness and curative success.

Endoscopic versus open radiofrequency ablation for treatment of small hepatocellular carcinoma.

BACKGROUND: Surgical radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is associated with superior oncological outcome in comparison with percutaneous RFA. The present study aimed to retrospectively evaluate the relative perioperative safety and postoperative outcome of the laparoscopic or thoracoscopic approach versus the open approach to RFA for small HCC. METHODS: A retrospective analysis was performed in 55 consecutive patients who underwent open (n = 32) or laparoscopic/thoracoscopic (LTS) RFA (n = 23) for primary unresectable HCC between January 2005 and December 2010. Baseline characteristics, survival/recurrence rates, and complications after treatment were compared between the two groups. RESULTS: There was a trend showing that LTS RFA was performed for tumors located in the anterior segment (e.g., segments III, V, VIII). The LTS RFA group had a significantly lower intraoperative blood loss, shorter operative time, and shorter postoperative hospital stay, compared with the open RFA group. No major postoperative complications occurred in patients who underwent LTS RFA. No significant differences in overall survival, recurrence-free survival and local recurrence rates were observed between the two groups. CONCLUSIONS: In consideration of operative invasiveness and postoperative recovery, LTS RFA is superior to the open approach in patients with small HCC. Moreover, the surgical outcome did not differ between the two approaches. Laparoscopic/thorascopic RFA can be considered to be a useful procedure for ablation therapy.

Significance of M2-polarized tumor-associated macrophage in pancreatic cancer.

BACKGROUND: The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40. RESULTS: High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P=0.0094). Significantly increased LVD (P=0.0175) and a poor prognosis (P=0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages. CONCLUSIONS: M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis.

[A case of curatively resected locally advanced pancreatic cancer after chemoradiation therapy].

A 68-year-old man admitted for pancreatic tumor detected by US was found by computed tomography(CT)to have locally advanced pancreatic cancer invading the portal vein and neural plexus of the superior mesenteric artery without distant metastasis. We conducted preoperative chemoradiation therapy containing S-1 and hyperfractionated accelerated radiation therapy (50 Gy). Reevaluation of CT after chemoradiation therapy showed that the primary tumor reduced 52% without distant metastasis. Based on these findings, we conducted subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection. Pathological examination revealed moderately-differentiated adenocarcinoma. Extensive fibrosis with a small amount of cancer cells was observed in the marginal area of the tumor. The portal vein was surrounded with extensive fibrosis and free from cancer cells. Extrapancreatic nerve plexus invasion and lymph node metastasis were not observed. There were no residual cancer cells (R0). The postoperative course was uneventful, and adjuvant chemotherapy (S-1) was started. The patient remains well without recurrence 12 months after surgery.

Significance of lymphangiogenesis in primary tumor and draining lymph nodes during lymphatic metastasis of pancreatic head cancer.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the significance of lymphangiogenesis in primary pancreatic tumors and in draining lymph nodes during lymphatic metastasis of pancreatic head cancers. METHODS: Specimens were obtained from 70 patients. To evaluate lymphangiogenesis, we measured lymphatic vessel density (LVD) using D2-40 antibody in the primary tumors and in the draining lymph nodes. AE1/AE3 antibody was used to detect tiny, histologically negative metastases in lymph nodes. RESULTS: Patients with high LVD of primary tumors had significantly higher incidence of node metastasis (P = 0.0006) and lower postoperative survival rate (P = 0.0066) than those with low LVD. Intranodal LVDs increased with increasing size of the intranodal metastases. The LVDs of non-metastatic nodes in patients with node metastasis were also significantly higher than those of non-metastatic nodes in patients without node metastasis (P < 0.0001). The LVDs of peripancreatic nodes in patients with paraaortic node metastases were significantly higher than those in patients without paraaortic metastasis (P < 0.0001). CONCLUSIONS: Lymphangiogenesis in primary tumors and draining lymph nodes is essential for efficient spread of tumor cells through the lymphatic system. Thus, inhibition of lymphangiogenesis could limit lymphatic dissemination of tumor cells.

Subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) prevents postoperative delayed gastric emptying.

BACKGROUND AND OBJECTIVES: Delayed gastric emptying (DGE) is one of main complications after pylorus-preserving pancreaticoduodenectomy (PPPD) with regional lymph node dissection (RLND). The aim of this study was to retrospectively investigate whether subtotal stomach-preserving PD (SSPPD) decreased incidence of DGE. METHODS: This study included 112 consecutive patients underwent PPPD (n = 48) or SSPPD (n = 64) with/without RLND. DGE was classified into three categories (grades A, B, and C) according to the guideline proposed by the International Study Group of Pancreatic Surgery. RESULTS: The incidence of DGE grade B/C in SSPPD with RLND (13.0%) was lower compared with that (34.8%) in PPPD with RLND (P = 0.0326). Consequently, the mean length of postoperative hospital stay of SSPPD with RLND group was significantly shorter than that of PPPD with RLND (P = 0.0476). CONCLUSIONS: SSPPD could be substituted for PPPD due to decreased postoperative DGE when RLND is involved. A randomized control trial of SSPPD versus PPPD should be considered.

Asymptomatic somatostatinoma of the pancreatic head: Report of a case.

A 44-year-old man was attending routine follow-up 5 years after colon cancer resection, when ultrasonography detected a pancreatic tumor with a low echoic area. He had no symptoms. Computed tomography (CT) showed a protruding-type tumor, 4 cm in diameter, in the pancreatic head with central necrosis. Angiography revealed that the tumor was hypervascular. The serum somatostatin level was elevated, at 27 pg/ml (normal range, 1.0-12 pg/ml). As somatostatinoma of the pancreas was suspected, we performed pylorus-preserving pancreaticoduodenectomy. Histological and immunohistochemical staining confirmed somatostatinoma of the pancreas without nodal metastasis. Thus, if an endocrine tumor of the pancreas is suspected in a patient with a hypervascular tumor, the possibility of somatostatinoma should be included in the differential diagnosis.

Impact of lymph node micrometastasis in patients with pancreatic head cancer.

PURPOSE: The purpose of this study was to investigate the clinical significance of nodal micrometastasis in patients who underwent a curative operation for pancreatic cancer. EXPERIMENTAL DESIGN: Fifty-eight patients underwent a macroscopically curative resection with extended lymph node dissection for pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944 histologically negative lymph nodes were subjected to immunohistochemical staining to detect occult micrometastases. RESULTS: Nodal micrometastases were detected immunohistochemically in 147 out of 944 resected histologically negative lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23 histologically node-negative patients (56.5%) had nodal micrometastases. Nodal micrometastases existed in the N1 lymph node area most frequently, followed by the N2 and N3 lymph node areas. The distribution was similar to that of histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal micrometastases beyond the histological lymph node status. Three and 5-year survival rates of pN0 patients without lymph node nodal micrometastases were both 60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively. There was statistically significant difference between the both groups (P = 0.041). CONCLUSIONS: Nodal micrometastasis in pancreatic cancer existed in wider and more distant areas than histological lymph node status, and it was an unfavorable predictive factor, even in N0 patients.

Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: its relationship to lymph node metastasis.

PURPOSE: The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF)-C and -D in pancreatic cancer and to reveal its relation to lymph node metastasis. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded blocks were obtained from 58 patients with pancreatic head cancer. All of the patients underwent a curative resection. The total number of resected lymph nodes was 1,058. The expressions of VEGF-C and -D were evaluated by immunohistochemical staining. To evaluate the relation to lymph node metastasis, the expressions of VEGF-C and -D between the marginal and central portions in the tumor were compared. When >25% of the tumor cells showed distinct staining, the portion was judged as high expression. RESULTS: The two groups with high expression of VEGF-C (P = 0.015) and VEGF-D (P = 0.020) in the marginal portion had a significantly higher incidence of lymph node metastasis compared with the groups with low expression, respectively. Furthermore, the group with high expression of both VEGF-C and -D in the marginal portion had a higher incidence of lymph node metastasis compared with the group with low expression (P = 0.007). The 5-year survival rate of patients with high expression of both VEGF-C and -D in the marginal portion was significantly lower than that of patients with low expression of both VEGF-C and -D (P = 0.017). CONCLUSIONS: VEGF-C and -D expression in tumor cells in the marginal portion of the tumor significantly associated with lymphatic metastasis and prognosis in patients with pancreatic head cancer.

Carcinoembryonic antigen messenger RNA expression using nested reverse transcription-PCR in the peripheral blood during follow-up period of patients who underwent curative surgery for biliary-pancreatic cancer: longitudinal analyses.

PURPOSE: Outcome for patients with biliary-pancreatic cancer is still poor, despite curative operation. We investigated the clinical significance of molecular detection of circulating cancer cells in the blood as an early indicator of relapse during follow-up of patients who underwent a curative operation for biliary-pancreatic cancer. PATIENTS AND METHODS: We followed 53 patients who underwent a curative operation for biliary-pancreatic cancer between 1996 and 2001. We used reverse transcription-PCR in the peripheral blood to evaluate carcinoembryonic antigen (CEA) mRNA expression for molecular detection of circulating cancer cells. Follow-up examinations every 3 months after surgery included CEA mRNA expression in the blood, serum CEA, serum carbohydrate antigen 19-9 (CA19-9), and computed tomography or magnetic resonance imaging. RESULTS: Sixteen of 53 patients (30.2%) were diagnosed with a recurrence by imaging studies. The CEA mRNA detection rate in the peripheral blood of these 16 patients was 75% compared with 5.4% in the 37 patients without relapse (P < 0.001). Sensitivity of CEA mRNA, CEA, and CA19-9 serum levels was 75.0%, 50.0%, and 68.8%, respectively. Similarly, specificity was 94.6%, 64.9%, and 81.1%, respectively. CEA mRNA was expressed in the blood, even though tumor markers CEA and CA19-9 were within the normal range in patients with relapse. CEA mRNA expression in the blood, as well as the serum level of CA19-9, tended to be detected a few months earlier than detection by imaging modalities. CONCLUSIONS: During the follow-up of patients who undergo a curative operation for biliary-pancreatic cancer, CEA mRNA expression in the peripheral blood might be a useful and early indicator of relapse.