Masaaki Motoori

Feasibility of a Lateral Region Sentinel Node Biopsy of Lower Rectal Cancer Guided by Indocyanine Green Using a Near-Infrared Camera System

A lateral pelvic lymph node dissection (LPLD) for lower rectal cancer may be beneficial for a limited number of patients. If sentinel node (SN) navigation surgery could be applied to lower rectal cancer, then unnecessary LPLDs could be avoided. The aim of this study was to investigate the feasibility of lateral region SN biopsy by means of indocyanine green (ICG) visualized with a near-infrared camera system (Photodynamic Eye, PDE). This study investigated the existence of a lateral region SN in 25 patients with lower rectal cancer. ICG was injected around the tumor, and the lateral pelvic region was observed with PDE. With PDE, the lymph nodes and lymph vessels that received ICG appeared as shining fluorescent spots and streams in the fluorescence image. This allowed the detection of not only tumor-negative SNs but also tumor-positive SNs as shining spots. The lateral SNs were detected in 6 of 6 T1 and T2 diseases and 17 of 19 T3 diseases. The lateral SNs were successfully identified in 23 (92%) of the 25 patients. The mean number of lateral SNs per patients was 2.1. Of the 23 patients, 6 patients underwent LPLD. Of the 3 patients who had a tumor-negative SN, all dissected lateral non-SNs were negative in all 3 cases. We could detect the lateral SNs, not only in T1 and T2 disease, but also in T3 disease. Although this is only a preliminary study, the detection of lateral SNs in lower rectal cancer by means of the ICG fluorescence imaging system is considered to be a promising technique that may be used for determining the indications for performing LPLD.BackgroundA lateral pelvic lymph node dissection (LPLD) for lower rectal cancer may be beneficial for a limited number of patients. If sentinel node (SN) navigation surgery could be applied to lower rectal cancer, then unnecessary LPLDs could be avoided. The aim of this study was to investigate the feasibility of lateral region SN biopsy by means of indocyanine green (ICG) visualized with a near-infrared camera system (Photodynamic Eye, PDE).MethodsThis study investigated the existence of a lateral region SN in 25 patients with lower rectal cancer. ICG was injected around the tumor, and the lateral pelvic region was observed with PDE.ResultsWith PDE, the lymph nodes and lymph vessels that received ICG appeared as shining fluorescent spots and streams in the fluorescence image. This allowed the detection of not only tumor-negative SNs but also tumor-positive SNs as shining spots. The lateral SNs were detected in 6 of 6 T1 and T2 diseases and 17 of 19 T3 diseases. The lateral SNs were successfully identified in 23 (92%) of the 25 patients. The mean number of lateral SNs per patients was 2.1. Of the 23 patients, 6 patients underwent LPLD. Of the 3 patients who had a tumor-negative SN, all dissected lateral non-SNs were negative in all 3 cases.ConclusionsWe could detect the lateral SNs, not only in T1 and T2 disease, but also in T3 disease. Although this is only a preliminary study, the detection of lateral SNs in lower rectal cancer by means of the ICG fluorescence imaging system is considered to be a promising technique that may be used for determining the indications for performing LPLD.

Multicenter Phase I/II Study of Docetaxel, Cisplatin and Fluorouracil Combination Chemotherapy in Patients with Advanced or Recurrent Squamous Cell Carcinoma of the Esophagus

Objective: Esophageal squamous cell carcinoma (ESCC) is refractory to current therapeutic regimens and more effective therapies are imperative. To this end, we conducted a multicenter phase I/II trial of docetaxel, cisplatin, and fluorouracil (DCF) combination chemotherapy for ESCC. Methods: The study subjects were 46 patients with advanced or recurrent ESCC. Treatment included docetaxel at 60, 70, and 75 mg/m2, cisplatin at 70 mg/m2 on day 1, and daily fluorouracil at 700 mg/m2 on days 1 through 5. The recommended dose of docetaxel was determined in phase I, while the response rate (RR) and progression-free survival rates were analyzed in phase II. Results: The recommended dose was determined to be 70 mg/m2 in phase I. In phase II, the RR was 72.5%. Interim analysis showed median and 1-year progression-free survival of 14 months and 55.6%, respectively. Grade 3/4 toxicities of leukopenia and neutropenia occurred in 72.5 and 90% of patients, respectively. No treatment-related death was recorded. Surgical resection was subsequently performed in 20 patients after chemotherapy, and curative resection was achieved in 19. Conclusion: DCF was tolerable and effective for advanced and recurrent ESCC. Such findings might encourage a change in the treatment strategy for ESCC.

Comparison between definitive chemoradiotherapy and esophagectomy in patients with clinical stage I esophageal squamous cell carcinoma.

OBJECTIVES:Chemoradiotherapy (CRT) has been proposed as an alternative therapy to esophagectomy for esophageal cancer, because of its favorable survival rate and mild toxicity. However, no comparative studies of esophagectomy and CRT have been reported in patients with clinical stage I esophageal squamous cell carcinoma.METHODS:A total of 54 patients with clinical stage I esophageal squamous cell carcinoma were treated with definitive CRT and 116 patients with esophagectomy at Osaka Medical Center for Cancer and Cardiovascular Diseases between 1995 and 2008, and were included in the analysis. Overall survival and recurrence rates were evaluated.RESULTS:Complete follow-up data were available for 169 of the 170 patients (99%). The median (range) observation period was 67 (10–171) months in the esophagectomy group and 30 (4–77) months in the CRT group (P<0.0001). The 1- and 3-year overall survival rates were 97.4% and 85.5%, respectively, in the esophagectomy group and 98.1% and 88.7%, respectively, in the CRT group (P=0.78). Cox proportional hazards modeling showed that the overall survival was comparable between the two groups after adjusting for age, sex, and tumor size. The hazard ratio of CRT for overall survival was 0.95 (95% confidence interval 0.37–2.47). The incidence of local recurrence, including metachronous esophageal cancer, was significantly higher in the CRT group than in the esophagectomy group (P<0.0001). Most local recurrences in the CRT group were intramucosal carcinomas, and were cured after salvage treatment, mainly using endoscopy.CONCLUSIONS:The overall survival rate of patients with clinical stage I esophageal cancer treated with CRT was comparable to that in those treated with esophagectomy, despite a high local recurrence rate. Locally recurrent carcinoma was endoscopically treatable in most patients, with no effect on overall survival. CRT seems to be a viable alternative to esophagectomy in patients with clinical stage I esophageal cancer.

Laparoscopic detection of sentinel node in gastric cancer surgery by indocyanine green fluorescence imaging

BackgroundIndocyanine green (ICG) fluorescence imaging is a promising technique for detection of sentinel node (SN) as it avoids unnecessary resection. However, the ICG fluorescence imaging system cannot be used in laparoscopic surgery because of technological difficulties.MethodsA prototype laparoscopic detection system comprising an electron multiplier charge-coupled device (EM-CCD) as the detector and a xenon lamp as the light source was developed. The CCD camera head was attached to the end of a specially designed laparoscope that could transmit ICG fluorescence. The system allows visualization of both color and fluorescence images. Laparoscopic surgery in ten patients with gastric cancer included SN biopsy using ICG dye, ICG fluorescence images using our system, and laparoscopy-assisted gastrectomy (LAG) with lymphadenectomy. SNs were sliced into 2-mm sections for histological examination and imprint cytology.ResultsImmediately after intraoperative ICG injection by endoscopy, the laparoscopic ICG fluorescence imaging system allowed easy visualization of the lymphatic vessels draining from the primary gastric tumor toward the lymph nodes and traced the moving injected dye, whereas lymph vessels and nodes were hardly recognized by ICG green color through a standard laparoscope. Surgeons could confirm the removed lymph nodes stained with ICG by fluorescent imaging. SNs were successfully detected in all patients. Three patients had suspicious metastases in the SNs; two patients had lymph node metastases only in the SNs.ConclusionsOur newly developed laparoscopic ICG fluorescence imaging system is promising in the detection of SNs in laparoscopic gastric cancer surgery. The preliminary results suggest an easier and shorter learning curve of dye-guided SN biopsy in laparoscopic gastric surgery.

Randomized study of clinical effect of enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

BACKGROUND & AIMS Enteral nutrition (EN) is provided for patients with cancer. However, Little is known about the clinical efficacy of EN support during chemotherapy in patients with cancer. METHODS Ninety-one patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin and adriamycin) for esophageal cancer were enrolled to receive either EN (n = 47) or PN (n = 44) at random. The primary endpoint was the incidence of chemotherapy-related toxicities during chemotherapy. RESULTS Total and dietary intake calories during chemotherapy were equal in the two groups. There were no significant differences in serum albumin level and body weight change after chemotherapy between the two groups. There was no significant difference in tumor response to chemotherapy between the two groups (EN: 51%, PN: 55%, p = 0.886). Leukopenia and neutropenia of grade 3 or 4, defined according to the Common Toxicities Criteria of the National Cancer Institute, were significantly less frequent in the EN group than PN group (leukopenia: 17% vs 41%, p = 0.011, neutropenia: 36% vs 66%, p = 0.005). Lymphopenia and thrombocytopenia tended to be less frequent in the EN group, albeit insignificantly. CONCLUSIONS Compared with PN support, EN support during neoadjuvant chemotherapy reduced the incidence of chemotherapy-related hematological toxicities in patients with esophageal cancers.

Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma

BACKGROUND Pancreatic fistula (PF) is a common complication after pancreatectomy. Previous reports indicate that preoperative irradiation decreases the risk of PF after pancreatoduodenectomy. In this context, the impact of preoperative chemoradiation therapy (CRT) on PF formation after distal pancreatectomy is of interest. METHODS Fifty-eight patients with pancreatic adenocarcinoma who underwent distal pancreatectomy, including 28 patients with preoperative gemcitabine-based CRT and 30 patients without preoperative treatment, were assessed in this study. The incidence and severity of postoperative PF, assessed according to the definition of the International Study Group on Pancreatic Fistula, were compared between the 2 groups. RESULTS In the CRT group, 86% of patients did not develop PF, whereas grades A and B PF were observed in 1 and 3 patients, respectively. In the non-CRT group, 33% of patients did not develop a PF, whereas grades A and B PF were observed in 9 and 11 patients, respectively. The incidence of clinically significant PF, defined as either grade B or grade C PF, was less in the CRT group (P = .031). The amylase activities in the draining fluid on postoperative days 1 and 3 were both less in the CRT group (P = .003 and P = .006, respectively). CONCLUSION Preoperative CRT significantly decreases the incidence of PF after distal pancreatectomy, which potentially provides another benefit to patients in addition to its original advantages (ie, locoregional effect and patient selection effect), allowing more opportunities for the immediate initiation of postoperative adjuvant treatment.

Impact of perioperative administration of synbiotics in patients with esophageal cancer undergoing esophagectomy: A prospective randomized controlled trial

BACKGROUND The clinical value of synbiotics in patients undergoing esophagectomy remains unclear. This study investigated the effects of synbiotics on intestinal microflora and surgical outcomes in a clinical setting. METHODS We studied 70 patients with esophageal cancer who were scheduled to undergo esophagectomy. They were randomly allocated to 2 groups: 1 group received synbiotics before and after surgery, and the other did not. Fecal microflora and organic acid concentrations were determined. Postoperative infections, abdominal symptoms, and duration of systemic inflammatory response syndrome (SIRS) were recorded. RESULTS Of the patients, 64 completed the trial (synbiotics, 30; control, 34). The counts of beneficial bacteria and harmful bacteria in the group given synbiotics were significantly larger and smaller, respectively, than those in the control group on postoperative day (POD) 7. The concentrations of total organic acid and acetic acid were higher in the synbiotics group than in the control group (P < .01), and the intestinal pH in the synbiotics group was lower than that in the control (P < .05) on POD 7. The rate of infections was 10% in the synbiotics group and 29.4% in the control group (P = .0676). The duration of SIRS in the synbiotics group was shorter than in the control group (P = .0057). The incidence of interruption or reduction of enteral nutrition by abdominal symptoms was 6.7% in the synbiotics group and 29.4% in the control group (P = .0259). CONCLUSION Perioperative administration of synbiotics in patients with esophagectomy is useful because they suppress excessive inflammatory response and relieve uncomfortable abdominal symptoms through the adjustment of the intestinal microfloral environment.

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high‐throughput quantitative RT‐PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good‐signature or poor‐signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan‐Meier analysis revealed significant difference between the good‐signature and the poor‐signature group (p = 0.0125). Especially in patients with smaller tumor (≤ 5 cm), less developed LN metastasis (N0,1), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Staging laparoscopy using ALA‐mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer

This study evaluated the usefulness of photodynamic diagnosis (PDD) using oral 5‐aminolevulinic acid (ALA) for the detection of peritoneal metastases in advanced gastric cancer.

Ten cases of gastro‐tracheobronchial fistula: a serious complication after esophagectomy and reconstruction using posterior mediastinal gastric tube

Gastro-tracheobronchial fistula (GTF) is a rare but life-threatening complication specifically observed after esophagectomy and reconstruction using posterior mediastinal gastric tube. Ten cases of GTF were encountered in three hospitals in 2000-2009. Their clinicopathological, surgical, and postoperative care are summarized, together with a review of previously reported cases. GTF was classified as anastomotic leakage (n= 5), gastric necrosis (n= 4), and gastric ulcer type (n= 1). The anastomotic leakage type appeared about 2 weeks (postoperative day [POD]: 8-35) after esophagectomy, was located in the cervical or higher thoracic trachea. Breathing and pneumonia were controlled by tracheal tube placed in the distal of fistula. The gastric necrosis type was noted in patients who developed necrosis of the upper part of the gastric tube and abscess formation behind the tracheal wall, at POD 20-36 around the carina, the site of pronounced ischemia. Due to the large fistula around the carina, emergency surgery with muscle patch repair was frequently required for the control of aspiration pneumonia. Patients of the gastric ulcer type had peptic ulcer in the lesser curvature of the gastric tube, which perforated into the right bronchus long after surgery (POD 630). With respect to tracheobronchial factors, preoperative chemoradiation (three cases) and pre-tracheal node dissection (three cases) tended to increase the risk of GTF. Closure of GTF by surgery (muscle patch repair) was successful in four cases and by nonsurgical treatment in three cases. In one case, stable oral intake was achieved by bypass operation without closure of GTF. Hospital death occurred in three cases. Understanding the pathogenesis and treatment options of GTF is important for surgeons who deal with esophageal cancer.