[A Case of Two-Stage Radical Resection with Neoadjuvant Chemotherapy for Cecal Cancer with Synchronous Peritoneal Metastasis(P3)].

A 63-year-old female patient was diagnosed with cecal cancer(cT3, N2a, M0)and underwent surgery for the first time. Only laparoscopic ileocecal resection(D3 dissection)was performed because intraperitoneal observation revealed peritoneal metastasis around the tumor and uterus. We decided to perform a radical resection because the peritoneal metastasis was localized by FDG-PET/CT. Five courses of neoadjuvant chemotherapy(mFOLFOX6)were performed to shrink the tumor. Unrecognized peritoneal metastases were found in other areas during the second surgery. Although the extent of the peritoneal metastasis was P3, all lesions had been resected. No perioperative complications occurred, and adjuvant chemotherapy was administered to the patient. Recurrence was not observed until 6 months postoperatively.

[A Case of HER2-Positive Inflammatory Breast Cancer for Which Preoperative Chemotherapy with Pertuzumab Resulted in a Pathological Complete Response].

A 52-year-old woman presented with redness and swelling with a peau d'orange appearance in the whole right breast. Ultrasound revealed elevated subcutaneus fat density and a diffuse hypoechoic area. She was diagnosed with inflammatory breast cancer(T4dN2M0, Stage III B of the HER2 subtype). After 4 courses of EC treatment as primary systemic therapy, the hypoechoic area was still present. Subsequent chemotherapy with pertuzumab, trastuzumab, and docetaxel was effective, as hypoechoic area was not observed on ultrasound. She underwent mastectomy and axillary dissection, and pathological examination revealed pCR. At present, 2 years after surgery, the patient is alive with no reccurence.

Laparoscopic sigmoidectomy using a hemi-double-stapling technique.

BACKGROUND: The double-stapling technique (DST) is frequently used in laparoscopic sigmoidectomy. Unfortunately, anastomotic leakage after laparoscopic intracorporeal colorectal anastomosis with DST is seen with some frequency. METHODS: We performed DST on 40 patients (June 2007 to August 2008) and hemi-DST on 50 patients (September 2008 to December 2011) undergoing laparoscopic sigmoidectomy. RESULTS: There were no occurrences of anastomotic leakage in the hemi-DST group, and 2 instances of anastomotic leakage in the DST group were observed. In these patients, the leakage appeared at the lateral intersecting anastomotic margins. CONCLUSIONS: Using the hemi-DST for laparoscopic intracorporeal colorectal anastomosis will make laparoscopic sigmoidectomy a safer procedure.

Clinical significance of the gene expression profile in residual tumor cells after neoadjuvant chemo-radiotherapy for esophageal cancer.

Recurrence after neoadjuvant chemo-radiotherapy (CRT) followed by surgery is high in patients with esophageal cancer. No standard second line therapy is currently available for patients with recurrence. This study aimed to evaluate the expression of chemo-radiosensitive genes after neoadjuvant CRT in residual tumor cells. Thirteen patients with esophageal squamous cell carcinoma underwent 5-fluorouracil (5-FU) and cisplatin (CDDP) based CRT followed by surgery. Total RNA was successfully obtained from 6 formalin-fixed paraffin-embedded (FFPE) specimens using proteinase K digestion and phenol chloroform extraction. TS and DPD as the 5-FU pathway gene, ERCC1 as the CDDP pathway gene, and EGFR, VEGF, HIF1a as radioresistant genes were measured using real-time reverse transcription polymerase chain reaction; comparing the mRNA level of each gene in pre-CRT biopsy with that in post-CRT FFPE specimens. Five patients had less than one-third residual tumor cells in resected specimens histopathologically; eight had more than two-thirds residual tumor cells. There were significant increases in TS (p=0.02) and DPD (p=0.01) levels in residual tumor cells after CRT. Significant decreases in ERCC1 (p=0.03), EGFR (p=0.01), VEGF (p=0.003) and HIF1a (p=0.003) levels were observed. 5-FU and CDDP based CRT up-regulated 5-FU pathway genes and down-regulated CDDP pathway and radioresistant genes. The expression of chemo-radiosensitive genes was significantly changed in residual tumor cells after CRT. Gene expression analysis of residual tumor cells in FFPE specimens may be useful when selecting a second line chemotherapy regimen for recurrent esophageal cancer after CRT.

Neurotrophic receptor, tropomyosin-related kinase B as an independent prognostic marker in gastric cancer patients.

BACKGROUND AND OBJECTIVES: Neurotrophic receptor tyrosine kinase TrkB has been associated with clinical outcome and chemotherapy resistance in neuroblastoma and certain human malignancies. Recent studies have focused on the association between metastatic potential and TrkB expression in tumor cells. METHODS: To determine the role of TrkB in gastric cancer, we analyzed TrkB mRNA levels by real-time reverse transcription polymerase chain reaction in 90 patients with gastric cancer. TrkB levels were correlated with clinicopathological variables. The association between TrkB and overall survival was evaluated by univariate and multivariate analyses. RESULTS: The mean TrkB level in gastric cancer tissue was 2.96 (range, 0-27.1). Thirty-eight (42%) of 90 patients showed detectable TrkB levels, whereas the remainder had no detectable TrkB. There was no significant association between clinicopathological variables and TrkB positivity. TrkB level was significantly associated with extent of lymph node metastasis in node positive patients (P = 0.03). TrkB positivity (n = 38) was significantly correlated with worse patient survival (P = 0.03). Multivariate analysis showed TrkB to be an independent prognostic parameter for overall survival (P = 0.04). CONCLUSIONS: TrkB is an independent prognostic marker in patients with gastric cancer and appears to be associated with metastatic potential.

Clinicopathological features and prognosis of gastric cancer patients > or =75 years of age after laparotomy.

The aim of this study was to clarify whether gastric cancer in elderly patients warrants surgical resection. Of 320 patients who underwent laparotomy for gastric cancer, 36 were older (elderly group) and 286 were younger than 75 years (control group). Clinicopathological features, mortality, morbidity, and survival were compared between the two groups. There were no differences between the two groups regarding clinicopathological features. There were no significant differences in mortality, morbidity, and the disease-specific 5-year survival rate between the two groups (elderly, 2.9%, 36.1%, and 65.7%, respectively; control, 0.7%, 24.6%, and 80.6%, respectively). The percentage of death from other diseases was 38.5% in the elderly group and 9.1% in the control group; the result was significantly higher in the elderly group (P = 0.0017). Our findings support that gastric cancer in elderly patients warrants surgical resection because the benefits with regard to early and long-term outcomes are the same as for younger patients.

Excision-repair cross-complementing 1 predicts response to cisplatin-based neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Low excision repair cross-complementing 1 (ERCC1) has been associated with a favorable response to cisplatin (CDDP) in several types of malignancies. The present study aimed to investigate whether ERCC1 predicts the response to CDDP-based chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the association between ERCC1 and platinum drug sensitivity in ESCC cell lines. ERCC1 mRNA levels in pre- and post-treatment tumoral and normal biopsies of 16 ESCC patients receiving CDDP-based CRT and in 4 ESCC cell lines were examined using real-time reverse transcription polymerase chain reaction. Pre-treatment tumoral ERCC1 was compared with clinicopathological variables and response to CRT. Responses to CDDP and oxaliplatin (OXA) in ESCC cell lines were evaluated using the WST-8 colorimetric assay by comparing ERCC1 levels. ERCC1 was significantly higher in cancer tissue compared to normal tissue (p<0.01). Tumoral ERCC1 significantly decreased after CRT to normal levels (p<0.05). ERCC1 levels in patients with a partial response were significantly lower than levels in patients who did not respond to CRT (p<0.05). ESCC cell lines with lower ERCC1 showed significantly greater sensitivity to clinically relevant concentrations of CDDP and OXA compared to lines with higher ERCC1 (p<0.01). In conclusion, low ERCC1 levels were associated with platinum drug sensitivity in ESCC cell lines. Pre-treatment tumoral ERCC1 may be used as a predictive marker for identifying patients who respond to CRT.

Postoperative weight loss during hospital stays in patients with gastric cancer undergoing surgical resection.

BACKGROUND/AIMS: The timing of sampling weight loss in the patients with gastric cancer undergoing surgical resection can be divided into 2 categories: prior to operation and postoperative follow-up as an outpatient. In this study, a third timing is proposed; the postoperative period during hospital stay. The purposes of this report were to identify the clinical variables related to postoperative weight loss during the hospital stay in gastric cancer patients and to investigate the influence of the weight loss on the long-term survival. METHODOLOGY: Records of 313 patients who underwent gastrectomies for cancer between 1992 and 2003 were reviewed retrospectively. Patients were divided into 2 groups according to the median value of the rate of weight loss. Overall survival was estimated by the Kaplan-Meier Method. RESULTS: The postoperative hospital stays were significantly longer in the serious weight loss group than in the mild weight loss group. Developing complication, extended lymph node dissection, and operation time had the impact independently of the rate of weight loss. The overall survival was not different between the serious weight loss and the mild weight loss groups by a log-rank test (5-year survival, 70.1% vs. 70.5%, p = 0.82). CONCLUSIONS: Although the serious weight loss during hospital stay means the true surgical damage in gastric cancer patients, it has no influence on the long-term survival.

Incidence and risk factors for hospital-acquired pneumonia after surgery for gastric cancer: results of prospective surveillance.

BACKGROUND: Postoperative hospital-acquired pneumonia (HAP) is recognized as a major risk associated with surgery. Although upper abdominal surgery is known to have the highest incidence of postoperative HAP, little is known about the risk factors that contribute to HAP after gastric cancer surgery. The aim of this study was to determine the incidence and risk factors for HAP after elective surgery for gastric cancer. METHODS: We conducted prospective surveillance of all elective gastric resections by surgeons in ten affiliated hospitals, including ours, from May 2001 to May 2005. The outcome of interest was postoperative HAP. Univariate and multivariate analyses were performed to determine the predictive significance of variables in gastric cancer surgery. RESULTS: A total of 529 patients undergoing elective operations for gastric cancer were admitted to the program. Postoperative HAP was identified in 20 patients (3.6%). Univariate and multivariate analyses showed that male gender and intra- and/or postoperative blood transfusion were independently predictive of postoperative HAP. CONCLUSIONS: Male gender and intra- and/or postoperative blood transfusion were independent risk factors for the development of HAP after elective resection of gastric cancer. Surgeons should keep these risk factors in mind when managing postoperative patients.

Ultrasonically activated shears in gastrectomy for large gastric cancers.

PURPOSE: High-frequency ultrasound energy was introduced in gastrointestinal surgery to improve dissection and coagulation. We assessed the safety and efficacy of ultrasonic dissection compared with standard electrosurgery in gastrectomy for large gastric cancers, which is associated with high morbidity. METHODS: The subjects of this retrospective study were 52 patients who underwent gastrectomy for gastric cancers, > or =7 cm in diameter. Gastrectomy was performed with ultrasonically activated shears (UAS) between January 2005 and June 2006 (UAS group, n = 26) and with standard electrosurgery between July 2003 and December 2004 (control group, n = 26). We compared morbidity, operating time, and intraoperative blood loss between the two groups. RESULTS: The mean operating time and intraoperative blood loss were significantly lower in the UAS group than in the control group. Morbidity in the UAS group was also lower, but the difference was not significant. CONCLUSION: Our findings showed that UAS gastrectomy was safe, with significantly shorter operating times and less intraoperative blood loss than standard electrosurgery.

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.

PURPOSE: The 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. METHODS: Five 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. RESULTS: The 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. CONCLUSION: The addition of oral antibiotics to intravenous antimicrobial prophylaxis showed no advantage in the prevention of SSI.

Laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection for early gastric cancer.

BACKGROUND: There has been a trend toward minimally invasive treatment of early gastric cancer. We report the preliminary results of laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection. METHODS: Six patients underwent laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection between February 2002 and October 2005 at Mie University Hospital. These patients first underwent laparoscopic sentinel lymph node biopsy and then laparoscopy-assisted distal gastrectomy with lymphadenectomy. RESULTS: No patient underwent conversion to open surgery during the operation. None of the patients had any postoperative complications. The mean length of postoperative hospital stay was 11.3 days. Sentinel lymph nodes were identified laparoscopically in five patients. There were 20 sentinel and 85 nonsentinel lymph nodes in the six patients. Postoperatively, tissue sections showed that none of the lymph nodes were metastasized. Immunohistochemistry with D2-40 antibody showed that there were normal lymphatics in the submucosal layer with mucosal defects at the endoscopic mucosal resection site. No patients had any tumor recurrence during followup. CONCLUSIONS: Laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection was a safe and curative procedure. Endoscopic mucosal resection before sentinel lymph node biopsy was acceptable for early gastric cancer.

Diagnostic sensitivity of contrast swallow for leakage after gastric resection.

INTRODUCTION: We examined the clinical manifestations and computed tomography findings of patients with leakage after gastrectomy for cancer and determined the sensitivity of the contrast swallow for the leakage diagnosis. METHODS: The medical records of 331 consecutive patients undergoing gastrectomy between January 1992 and December 2003 were reviewed. Routine contrast swallow was performed in all patients before oral intake. Once leakage was suspected, an emergency contrast swallow was performed and its diagnostic sensitivity determined. RESULTS: In total, leakage was diagnosed 9 of 17 times by the contrast swallow, for a diagnostic sensitivity of 53%. The clinical signs or another imaging modality often corrected the misdiagnosis. CONCLUSIONS: The diagnostic sensitivity of contrast swallow for leakage after gastrectomy was low. Therefore, if we employ the contrast swallow technique, we should keep in mind its low sensitivity.

Hemidouble stapling for esophagogastrostomy during laparoscopically assisted proximal gastrectomy.

In esophagogastrostomy during laparoscopically assisted proximal gastrectomy, some problems have occurred; the main ones being reflux esophagitis and the technical difficulty in anastomosis. We have had good results with a hemidouble stapling technique; the center rod of circular stapler is pierced through the left end of the staple line of the stomach. The longest distance from the pylorus to the esophagogastrostomy can be fired in this position. The distance is longer, so alkaline esophagitis is rarer. When the center rod is pierced through the anterior or posterior gastric wall, the operator may be worried about ischemia of the area surrounded by the linear stapler and circular stapler. In hemidouble stapling, an ischemic area is not created at all structurally. Any surgeon can perform a reproducible anastomosis because the place pierced with the center rod is fixed. This technique is easy and safety to operate via minilaparotomy.

Laparoscopic intragastric surgery using GelPort.

In laparoscopic intragastric surgery for early gastric cancer and submucosal tumors, three trocars are routinely inserted in the gastric lumen. We placed a GelPort hand assist device through a 5-cm transverse incision in the upper abdomen, and inserted the trocars into the gastric lumen through the gel seal cap, snapping the gel seal cap on and off during the operation. This makes it possible to use an open technique in which trocars are inserted into the gastric lumen, and to close the trocar sites in the gastric wall. We believe that the technique described here is easier and saves time compared with inserting trocars and closing trocar sites laparoscopically.

Fatal and non-fatal complications after surgical resection for gastric cancer.

BACKGROUND/AIMS: We divided overall complications after surgical resection for gastric cancer into fatal and non-fatal, and examined them in view of risk factors. Next we examined the meaning of dividing complications into two groups. METHODOLOGY: Records of 331 patients who underwent gastrectomies for cancer between 1992 and 2003 were used. Any postoperative overall complications were divided into fatal and non-fatal according to the association with mortality. RESULTS: Leakage and respiratory complication were defined as fatal complications. Tumor size (cm) (OR=1.14, 95% CI 1.05-1.25, p=0.003) and patient age (OR=1.06, 95% CI 1.06-1.10, p=0.007) were shown to be risk factors for fatal complications. Total gastrectomy (vs. distal gastrectomy) was a risk factor for non-fatal complications (OR= 1.63, 95% CI 0.99-2.7, p=0.05). Extended lymphadenectomy was a further possible risk factor for non-fatal complications (OR=1.71, 95% CI 0.98-3.0, p=0.06). On the other hand, intra-operative blood loss (mL) was only a risk factor for overall complications (OR=1.001, 95% CI 1.0-1.001, p=0.009). CONCLUSIONS: Independent risk factors for fatal complications and those for non-fatal complications did not include that for overall complications. To divide overall complications into fatal or non-fatal was useful for finding the real reason for complications. We could not prepare preventive measures for complications until analyzing the divided groups.

Evaluation of tap water for surgical handwashing.

PURPOSE: In Japan, sterile water is used for rinsing in surgical handwashing, whereas in Western countries tap water is generally used. We conducted this study to examine the conditions and the equipment that affect bacterial contamination in tap water and to determine whether the tap water in our institute is suitable for surgical handwashing. METHODS: First, we examined the water pipes and measured the free chlorine content in the tap water in the operating room. Next, we recruited 40 volunteers and conducted preliminary tests with sterile water. Thirty of these subjects participated in a handwashing test using tap water. RESULTS: The mean free chlorine levels in the tap water and the sterile water were 0.30 +/- 0.05 and 0.07 +/- 0.03 mg/l, respectively. The handwashing test using tap water showed immediate, persistent, and cumulative bacteria activity within the minimum limits set by the Food and Drug Administration (FDA). CONCLUSION: The free chlorine levels in the tap water in our institute satisfied Japanese health regulations. Moreover, the handwashing test met the criteria of the FDA. Thus, we conclude that this tap water is safe to use for rinsing in surgical handwashing.

Administration sequence-dependent antitumor effects of paclitaxel and 5-fluorouracil in the human gastric cancer cell line MKN45.

BACKGROUND: The clinical outcome of gastric cancer patients has been improved by combination of 5-fluorouracil (5-FU) and paclitaxel (PXL). However, the optimal schedule of this combination has not been determined. METHODS: The efficacies of sequential administrations of 5-FU and PXL on the gastric cancer cell line MKN45 were investigated using a WST-8 colorimetric assay. The cell cycle distribution of each drug was evaluated by flow-cytometry. Furthermore, the mechanism of antitumor activity enhancement by the administration sequence was investigated by western blotting. RESULTS: MKN45 cell growth was significantly inhibited by each drug in a dose- and time-dependent manner. The cytotoxicities of PXL followed by 5-FU were significantly greater than those of 5-FU followed by PXL. The flow-cytometric analysis revealed that PXL exposure caused viable cell accumulation in G2/M phase in a dose-dependent manner. Western blotting showed that PXL exposure followed by 5-FU up-regulated Chk1 and Wee1 protein expressions until PXL removal and 5-FU exposure, when these expressions gradually decreased to their basal levels. 14-3-3sigma protein expression was significantly up-regulated upon PXL treatment followed by 5-FU. Interestingly, Mad2 protein expression with PXL treatment followed by 5-FU gradually increased after the PXL removal and 5-FU exposure. CONCLUSIONS: PXL followed by 5-FU administration may be the optimal sequence for treatment of gastric cancer. The enhanced viable cell accumulation after PXL pretreatment may be related to G2 arrest. After PXL removal and 5-FU exposure, the cells progressing to M phase may undergo cell death by mitotic catastrophe due to DNA damage caused by 5-FU exposure.

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.

Bioresorbable hyaluronate-carboxymethylcellulose membrane (Seprafilm) in surgery for rectal carcinoma: a prospective randomized clinical trial.

PURPOSE: To 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. METHODS: A 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. RESULTS: Seprafilm 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. CONCLUSION: Seprafilm 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.