Hitoshi Tonouchi

Bioresorbable Hyaluronate-Carboxymethylcellulose Membrane (Seprafilm) in Surgery for Rectal Carcinoma: A Prospective Randomized Clinical Trial

PurposeTo evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy.MethodsA total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA−). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome.ResultsSeprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates.ConclusionSeprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery.

Operative Morbidity Associated with Groin Dissections

Purpose.Groin dissection remains the treatment of choice for malignant neoplasms of the skin in the lower extremities and perineum. We sought to quantify the hospital complications after groin dissection, and to identify the patient- and procedure-related factors affecting these complications.Methods.We reviewed 20 consecutive patients who underwent a collective 25 groin dissections for malignant neoplasms of the skin between 1996 and 2002 to determine the incidence and degree of morbidity, and to analyze the clinical factors associated with morbidity. An S-shaped incision was used for the first 8 procedures, whereas a straight incision was used for the next 17.Results.The overall incidences of complications were 24% for wound infection, 52% for skin flap problems, 32% for seromas, 40% for edema, and 4% for hemorrhage, whereas the incidences of moderate to severe complications were 16% for wound infection, 16% for skin flap problems, 12% for seromas, 4% for edema, and 4% for hemorrhage. The incidence of wound infection tended to be higher after S-shaped incisions than after straight incisions (P = 0.059), and the incidence of leg edema was significantly higher after S-shaped incisions than after straight incisions (P = 0.028).Conclusion.S-shaped incisions more often resulted in lymphatic collection and stagnation, with a higher incidence of wound infections and leg edema than straight incisions. Therefore, we now perform straight incisions to minimize the risk of wound infections and leg edema.

Laparoscopic Lymphatic Mapping and Sentinel Node Biopsies for Early-stage Gastric Cancer: The Cause of False Negativity

Sentinel node (SN) biopsies might be useful for performing minimally invasive surgery without interrupting surgical curability. This study examined the cause of false negativity during laparoscopic lymphatic mapping and SN biopsies for early-stage gastric cancer. Thirty-seven patients with gastric cancer (preoperative stage T1-2 or N0) who underwent laparoscopic lymph node mapping and SN biopsies between March 2001 and June 2004 were enrolled in this study. The tracer, patent blue and technecium-99m-labeled tin colloid, was injected endoscopically. Blue-stained or radioactive nodes were defined as SNs. Gastrectomy with lymphadenectomy was performed then the results of the SN biopsies were compared with the final diagnosis of the removed lymph nodes in permanent sections. Sentinel nodes were successfully identified in 35 patients (94.6%), and they were positive in 3 of 4 patients with metastatic lymph nodes; sensitivity was 75% and specificity was 100%. Sentinel node status could therefore be used to diagnose lymph node status with 97.1% accuracy. Of 6 SNs with metastasis, 5 showed radioactivity, and only 2 were blue stained. In the false negative case, a radioactive SN with metastasis in the right paracardial region was missed during laparoscopic mapping. An error in laparoscopic intracorporeal detection of the radioactive node with metastasis occurred because we could not eliminate the shine-through effect. We found that during laparoscopic SN mapping there is a high risk of false negativity with SNs located in the right paracardial region. To apply laparoscopic SN mapping to early-stage gastric cancer patients, the shine-through effect must be eliminated because radiotracers are essential for this method.

Randomized clinical trial comparing intravenous antimicrobial prophylaxis alone with oral and intravenous antimicrobial prophylaxis for the prevention of a surgical site infection in colorectal cancer surgery.

PurposeThe use of preoperative oral antibiotics during preparation for elective colorectal surgery remains controversial. This was a prospective randomized clinical trial to compare the efficacy of intravenous antimicrobial prophylaxis alone with combined oral and intravenous antimicrobial prophylaxis for surgical site infection (SSI) in patients undergoing elective colorectal surgery.MethodsFive hundred patients were enrolled in this study. Of these, 491 were randomly assigned to receive either intravenous antimicrobial prophylaxis or combined oral and intravenous antimicrobial prophylaxis. The primary outcome was the incidence of SSI within 6 weeks of elective colorectal surgery.ResultsThe incidence of SSI was similar in the two treatment groups: intravenous alone, 10.7%; and oral and intravenous, 7.0% (difference 3.7%; 95% confidence interval −4.8% to 5.6%). No critical adverse events were reported.ConclusionThe addition of oral antibiotics to intravenous antimicrobial prophylaxis showed no advantage in the prevention of SSI.

Randomized clinical trial of single‐ versus multiple‐dose antimicrobial prophylaxis in gastric cancer surgery

The optimum duration of antimicrobial prophylaxis in elective gastric cancer surgery is still open to question. This multicentre randomized clinical trial compared a single‐dose with a multiple‐dose regimen of antimicrobial prophylaxis for prevention of surgical‐site infection.

Lymphatic Mapping and Sentinel Node Biopsy during Laparoscopic Gastrectomy for Early Cancer

Background/Aims: Intraoperative lymphatic mapping and sentinel node (SN) biopsy can potentially be combined with minimally invasive surgery, but there are few reports of laparoscopic lymphatic mapping for gastrointestinal cancer. We examined the feasibility and accuracy of laparoscopic lymphatic mapping in predicting lymph node status in patients with gastric cancer. Methods: Seventeen patients with gastric cancer invading the mucosal or submucosal layers (T1) underwent laparoscopic gastrectomy with lymphatic mapping between March 2001 and May 2002. The day before surgery, a technetium-99m-labelled tin colloid solution was injected endoscopically around the tumor. Immediately after the pneumoperitoneum, patent blue was injected. Gastrectomy was performed in all patients, and blue-stained or radioactive nodes were defined as SNs. Fresh SNs were immediately processed for frozen-section examination by hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining. All non-SNs harvested from resected specimens were subjected to histological examination with H&E. Results: SNs were detected in all patients by combination of the two kinds of tracers. Three patients had lymph node metastases in their final examination, and SNs in these 3 were operatively diagnosed as positive by H&E or IHC staining. Lymphatic mapping and SN biopsy under laparoscopic surgery were performed with 100% accuracy. Conclusion: Our preliminary study shows the feasibility of intraoperative lymphatic mapping in laparoscopic gastrectomy for T1 gastric cancer.

Circulating level of hepatocyte growth factor as a useful tumor marker in patients with early‐stage gastric carcinoma

Background: Although conventional tumor markers including carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19‐9) have been used in gastric cancer patients, clinically useful markers of early gastric cancer have not been identified. The present study was designed to clarify the clinical significance of the circulating level of hepatocyte growth factor (HGF) as a tumor marker, especially in early‐stage gastric cancer patients. Methods: Preoperative serum HGF levels were measured with an enzyme‐linked immunosorbent assay in 30 early‐stage and 42 advanced‐stage gastric cancer patients. Results: The mean value of serum HGF in 72 patients was significantly higher than that in the normal subjects. There was a significant increase in serum HGF levels in both advanced‐stage and early‐stage patients compared with normal subjects. The positivity rates of HGF in early disease cases were higher than those of CEA and CA19‐9. The serum HGF level was significantly higher in patients with vessel invasion than in those without invasion. In smaller early gastric cancers, serum HGF elevation was associated with lymphatic invasion. Conclusions: The serum HGF level may be a clinically significant tumor marker in patients with early‐stage, as well as advanced‐stage, gastric cancer. HGF elevation in early‐stage patients may help us to predict the risk of lymph node metastasis of early gastric tumors, even of smaller tumor size. HGF may be a useful indicator for appropriate lymphadenectomy in early gastric cancer.

Prospective Study of Arterial Infusion Chemotherapy Followed by Radiofrequency Ablation for the Treatment of Liver Metastasis of Gastric Cancer

This prospective study was conducted to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) with use of an implanted port followed by radiofrequency (RF) ablation for the treatment of liver metastasis of gastric cancer. Seven patients without extrahepatic metastasis were enrolled. The maximum tumor size was less than 3 cm in one patient and 3.2-6.0 cm in the other six patients (mean, 4.4 cm +/- 1.5). Two patients had single lesions and the other five patients had two to six lesions each. The maximum tumor size was reduced to 3 cm or less (mean, 2.4 cm +/- 0.4; P < .03) after HAIC in all patients. The total number of tumors was reduced from 25 to 16. RF ablation was performed for all residual liver tumors, resulting in complete tumor necrosis. All but one patient are still living without intrahepatic recurrence, with a median survival time of 16.5 months.

Profile of Monocyte Chemoattractant Protein-1 Circulating Levels in Gastric Cancer Patients

Background : Monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. It acts as an important factor in the cytokine network, which regulates tumor proliferation, whereas the association between serum MCP-1 level and gastric cancer has not yet been clarified. Methods : The serum concentration of MCP-1 in 76 gastric cancer patients and in 45 normal controls was determined using an immunoradiometric assay. The concentration of MCP-1 in the 47 cancer tissue samples was also determined. Results : The serum concentration of MCP-1 in patients with advanced carcinoma was significantly lower than that in controls. The serum concentration of MCP-1 in patients with advanced carcinoma was significantly lower than that in patients with early carcinoma. The serum concentration of MCP-1 was associated with clinicopathological factors including lymph node metastasis, serosal invasion and histological differentiation of the tumor. In patients who underwent palliative surgery, the serum MCP-1 level significantly decreased postoperatively, whereas in patients who underwent curative surgery the serum MCP-1 level tended to increase. The 4-year survival rate in patients whose serum MCP-1 levels were lower than or equal to the median value was significantly lower than that in patients whose MCP-1 levels were higher than the median value. The tissue concentration of MCP-1 in the cancer tended to decrease in accordance with disease progression. Conclusions : The serum level of MCP-1 decreased in accord with disease progression, which reflects local consumption in gastric cancer. Serum MCP-1 may be a useful marker that reflects the hosts local resistance to the tumor.

Apolipoprotein C-II Modifications Associated with an Infusion of Artificial Lipid Particles

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.