Prospective feasibility study to evaluate neoadjuvant-synchronous S-1 + RT for locally advanced rectal cancer: a multicenter phase II trial (UMIN ID: 03396).

In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. However, in Japan, the treatment results without preoperative chemoradiotherapy are by no means inferior; therefore, extrapolation of the results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative chemoradiotherapy with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy using S-1 in patients with locally advanced rectal cancer. The primary endpoint is the rate of complete treatment of neoadjuvant chemoradiotherapy. Secondary endpoints are the response rate of neoadjuvant chemoradiotherapy, short-term clinical outcomes, rate of curative resection and pathological evaluation. The short-term clinical outcomes are adverse events of neoadjuvant chemoradiotherapy and surgery-related complications. Thirty-five patients are required for this study.

Totally laparoscopic colectomy with intracorporeal anastomosis achieved using a laparoscopic linear stapler: experience of a single institute.

PURPOSE: Laparoscopic colonic surgery is now widely accepted. We assessed the safety and effectiveness of using a total intracorporeal surgical strategy to perform intracorporeal functional end-to-end anastomosis with an endoscopic linear stapler to treat colon cancer. METHODS: Forty-three selected patients underwent elective laparoscopic colon resection for carcinoma. A total intracorporeal colon resection was performed in all patients, using a functional end-to-end anastomosis with an endoscopic linear stapler. RESULTS: Good results were achieved in all 43 patients, none of whom required conversion to open surgery with extracorporeal anastomosis. There have been no intraoperative complications related to this technique and no instances of postoperative anastomotic leakage, intra-abdominal abscess, or wound infection. CONCLUSION: Intracorporeal functional end-to-end anastomosis using a linear stapler can be performed safely and easily for the resection of any part of the colon. We consider it an effective modality for totally laparoscopic colon resection. Favorable results have been achieved by this method, particularly for small tumors, since natural-orifice transluminal endoscopic surgery remains a challenging method to perform.

Peroral placement of a self-expandable covered metallic stent using an overtube for malignant gastroduodenal obstructions.

PURPOSE: To evaluate the technical feasibility and safety of overtube-guided covered metallic stent placement as palliative treatment for patients with inoperable malignant gastric outlet obstructions. METHODS: To relieve the symptoms of severe nausea and recurrent vomiting in five patients with inoperable gastric cancer, we used an overtube (Long overtube; Sumitomo Bakelite, Tokyo, Japan) to place large-diameter, self-expandable, covered esophageal Ultraflex stents (inner diameter 22-28 mm, length 10 or 12 cm; Boston Scientific, Watertown, MA, USA). Success was defined both technically and clinically. RESULTS: The stent placement was technically successful in all patients and resulted in improvement of symptoms in all five patients, four of whom were thereafter able to ingest solid food. The remaining patient, a 94-year-old man, was unable to ingest food because of dysmasesis. During the mean follow-up of 17 weeks, there was no stent reocclusion and no life-threatening complications developed. CONCLUSIONS: The placement of a large diameter, self-expandable, covered esophageal stent using an overtube appears to be effective for the palliative treatment of malignant gastric outlet obstruction.

Intraoperative cholangiography using an endoscopic nasobiliary tube during a laparoscopic cholecystectomy.

PURPOSE: The goals of this report are to present the characteristics of biliary complications associated with laparoscopic cholecystectomies (LC) performed at a single center, and to evaluate the efficacy of intraoperative cholangiography (IOC) using an endoscopic nasobiliary tube (ENBT) during an LC in order to prevent biliary complications. METHODS: A retrospective audit was conducted on a total of 657 patients who underwent either LC or open cholecystectomies (OC). There were 19 patients who developed bile duct injury (BDI; n = 9) or bile leakage (BL; n = 10) during an LC and were actively treated. After May of 1999, the patients with a higher risk of developing biliary complications were selected for preoperative placement of an ENBT, and IOC was performed. RESULTS: Intraoperative cholangiography using ENBT was performed on 93 (27.1%) out of 343 patients who underwent either LC or OC after May of 1999. An LC was performed in 335 cases (97.7%), and a conversion from an LC to OC was necessary in only three cases. Even though BDI never occurred, BL from the cystic duct and gallbladder bed were recognized in five cases. CONCLUSIONS: The selective use of IOC using ENBT may help to prevent BDI during LC, thereby expanding the indications for LC, while also reducing the rate of conversion to open procedures.

Laparoscopic surgery for the diagnosis and treatment of a paracecal hernia repair: Report of a case.

Internal hernias are relatively rare viscous protrusions through a defect in the peritoneal cavity. Paracecal hernia is one of the least common types, and only a few cases have been reported to date. We herein present the case of a 43-year-old woman, who was preoperatively diagnosed to have a small bowel obstruction caused by a paracecal hernia resulting from intestinal protrusion and invagination into a paracecal pouch. Laparoscopic surgery was performed for definitive diagnosis and treatment. The surgery achieved a good outcome and the patient experienced an uneventful perioperative course.

Surgical treatment of cecal cancer in a patient with Glanzmann's thrombasthenia: report of a case.

Glanzmann's thrombasthenia (GT) is a rare inherited platelet disorder with no specific treatment. Prophylactic and therapeutic platelet transfusions work only as supportive treatments. To date, there has been no report of surgical treatment for malignant disease in GT patients. We herein report the case of a 43-year-old woman presenting with cecal cancer with accompanying GT. The patient underwent a laparotomic procedure under general anesthesia for resection of the tumor. A good perioperative course was achieved by the transfusion of ABO-identical and antihistocompatibility locus antigen-matched platelets, without causing any accidental bleeding.

Long-term outcomes of neoadjuvant-synchronous S-1 plus radiotherapy for locally advanced rectal cancer: a multi-institutional prospective phase II study.

OBJECTIVES: This study aimed to evaluate the long-term outcomes of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. METHODS: A multi-institutional, prospective, phase II trial was conducted between April 2009 and August 2011. The study enrolled 37 patients with histologically proven rectal carcinoma (T3-4 N0-3 M0) who underwent neoadjuvant chemoradiotherapy with S-1. Total mesorectal excision with D3 lymphadenectomy was performed 4-8 weeks after completion of neoadjuvant chemoradiotherapy with S-1 in 36 patients. We then analyzed late adverse events, overall survival, and disease-free survival. RESULTS: The median patient age was 59 years (range: 32-79 years); there were 24 men and 13 women. Ten patients had Stage II disease, and 27 had Stage III disease. Severe late adverse events occurred in 7 patients (18.9%). The 5-year disease-free survival was 66.7%, and the 5-year overall survival was 74.7%. The median follow-up period was 57 months. Local recurrences developed in 5 patients (13.5%), and distant metastases developed in 8 (21.6%). CONCLUSION: Neoadjuvant-synchronous chemoradiotherapy with S-1 for locally advanced rectal cancer is feasible in terms of adverse events and long-term outcomes. (UMIN Clinical Trial Registry: UMIN000003396).

[The efficacy and safety of docetaxel for elderly advanced breast cancer patients].

We studied the efficacy and safety of docetaxel (DOC) for elderly breast cancer patients. Between September 1997 and June 2003, five consecutive women with advanced breast cancers who were 75 years of age or older received DOC at a dose of 60 mg/m(2) every three weeks. No premedications to prevent hypersensitive reactions and fluid retention by DOC were given. The number of DOC dosages per case was 5-16 times (12 times the median) and the relative dose intensity (RDI) was 80-100% (95% of medians). Objective partial responses were observed in all patients. The median time to partial response was 21 days (range: 21-50 days). The median time to treatment failure was 12 months (range: 5-22 months). The grade and the frequency of major side effects were the following: leukocytopenia of grade 3 (80%), edema of grade 2-3 (40%), and alopecia of grade 2 (100%). It was concluded from these findings that DOC could be safely and effectively administered to elderly advanced breast cancer patients.

A prospective feasibility study to evaluate neoadjuvant-synchronous S-1 with radiotherapy for locally advanced rectal cancer: A multicentre phase II trial.

Treatment results of locally advanced rectal cancer without preoperative chemoradiotherapy (CRT) in Japan do not differ from those of Western countries. Preoperative CRT with new anticancer agents may decrease local recurrence rate and prevent distant metastases, thus improving survival. We conducted a trial to evaluate feasibility of neoadjuvant CRT using S-1 in patients with locally advanced rectal cancer. A multi-institutional (17 specialized centres), interventional, phase II trial was conducted from April 2009 to August 2011. Patients fulfilling the following requirements before neoadjuvant CRT were included: histologically proven rectal carcinoma; tumour in the upper or lower rectum; cancer classified as T3-4 N0-3 M0. Neoadjuvant CRT with S-1 (80 mg/m2/day on days 1-5, 8-12, 22-26, and 29-33) and irradiation (total 45 Gy/25 fr, 1.8 Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision with D3 lymphadenectomy was performed during weeks 4 and 8 after completion of neoadjuvant CRT. The primary endpoint was completion rate of neoadjuvant CRT. Secondary endpoints were response rate to neoadjuvant CRT, short-term clinical outcomes, curative resection rate, and pathologic response (grade 2/3). Of the 37 patients included, 86.5% completed neoadjuvant CRT (95% CI, 75.5-97.5%), and 10.8% (4) experienced an adverse event (grade 3/4). Response rate (RECIST 1.0) was 56.8% (95% CI, 40.8-72.7%), and pathologic response rate was 48.6% (95% CI, 32.5-64.8%). This study demonstrated that neoadjuvant-synchronous S-1+radiotherapy for locally advanced rectal cancer was feasible in terms of pathologic response and adverse events. Registration number: UMIN-CTR, No. C003396.

A randomized controlled trial comparing open vs laparoscopy-assisted distal gastrectomy for the treatment of early gastric cancer: an interim report.

BACKGROUND: The application of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer remains controversial among gastric surgeons. The purpose of this study was to compare LADG with open distal gastrectomy (ODG) regarding clinical outcome and postoperative parameters, including postoperative pain and pulmonary function. METHODS: From October 1998 to March 2001, 28 patients with early gastric cancer were randomly assigned to an LADG (n = 14) or ODG group (n = 14) with Billroth I reconstruction. Postoperative pain during resting, coughing, and walking were evaluated by a visual analog scale (VAS). Pulmonary functions such as forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) measured on the third postoperative day were compared with preoperative functions. RESULTS: Patients in the 2 groups were comparable for age, gender, height, weight, staging, and location of gastric cancer. The mean blood loss was significantly less in the LADG than in the ODG group (P <.05). Histologic examinations of resected specimens revealed that these 2 operations were identical from the standpoint of curability. Patients in the LADG group recovered both bowel movement and walking ability earlier than did patients in the ODG group (P <.05). The postoperative VAS pain score during rest was lower for 3 days after LADG than ODG (P <.05) and for 1 day during coughing or walking (P <.05). The pulmonary functions such as FVC and FEV1 values were reduced on the third day after LADG and ODG. However, the FVC value on the third day after LADG was lower than after ODG (P <.05). CONCLUSIONS: This study demonstrates that LADG has several advantages including an earlier recovery, less pain, and less impaired pulmonary function after gastric surgery when compared with ODG; furthermore, no reduction in curability was observed.

A convenient murine model for the study of intra-abdominal lymph node metastasis.

Lymph node metastasis is one of the most important prognostic factors for cancer patients. There are few animal models of lymph node metastasis. The purpose of this study was to develop a simple animal model without surgical trauma. B16F10 melanoma (1 x 10(6) cells in 0.1 ml phosphate-buffered saline) were slowly injected into the retroperitoneal space followed by direct puncture at the position between the anus and tail of 50 female C57BL6 mice. At 1-week intervals for 4 weeks after the procedure, we examined the retroperitoneal tumor and intra-abdominal lymph nodes. There was no morbidity and no mortality. At 2 weeks after inoculation, the retroperitoneal tumor was visible macroscopically at the position between the rectum and the sacrum, and histological examination showed the occurrence of intra-abdominal lymph node metastasis in all mice. The number of positive nodules was increased and was affected by the amount of cancer cells inoculated and the interval from inoculation to lymph node metastasis. A convenient murine model for the study of lymph node metastasis has been developed. Our animal model does not involve surgical trauma and may be useful in the analysis of the association between surgical stress and lymph node metastasis and in the elucidation of the mechanism and prevention of lymph node metastasis.

Length of laparotomy incision and surgical stress assessed by serum IL-6 level.

BACKGROUND: Because surgical stress is thought to have an effect on morbidity, mortality, and remnant tumour progression after surgery, diminishing surgical stress is important. The purpose of this study was to assess in a murine model whether the length and type of laparotomy incision influence surgical stress. METHODS: Serum IL-6 concentrations were measured sequentionally in 220 male BALB/c mice who were assigned to different basic laparotomies, (1-cm versus 2-cm versus 3-cm laparotomy with or without caecal resection), other types of laparotomy (3-cm, 1-cm x 3, 3-cm transverse, 3-cm laparotomy with rapid closure), or 3-cm skin incision with or without laparotomy. The serum level of IL-6 was measured by ELISA. RESULTS: Serum IL-6 levels at 3 and 6h after surgery were significantly higher in the 3-cm laparotomy group (1,680+/-802pg/ml and 1,066+/-507pg/ml, respectively), than in the 1-cm laparotomy group (797+/-427pg/ml and 515+/-212pg/ml, respectively). When caecal resection was added, the serum IL-6 level at 6h was significantly higher in the 3-cm laparotomy group (2,844+/-134pg/ml) than in the 1-cm laparotomy group (2,200+/-379pg/ml). Although the type of laparotomy incision was not associated with the serum level of IL-6, the serum IL-6 level after midline skin incision without laparotomy (245+/-142pg/ml) was significantly lower than that after 3-cm laparotomy (1,680+/-802pg/ml). CONCLUSIONS: The length of laparotomy incision was correlated with the serum level of IL-6 in a murine model. The surgical stress related to abdominal procedures might be decreased when laparotomy wounds are kept as small as possible.

Less impaired cell-mediated immune response in the murine peritoneal cavity after CO(2) pneumoperitoneum.

PURPOSE: We compared changes in the populations of peritoneal T lymphocytes and natural killer (NK) cells after CO(2) pneumoperitoneum and laparotomy to clarify whether pneumoperitoneum affects cell-mediated immune responses in the peritoneal cavity. METHODS: We analyzed and compared populations of T lymphocytes and NK cells among peritoneal exudative cells (PECs) collected from 185 female mice subjected to pneumoperitoneum, laparotomy, or anesthesia only. PECs were collected postoperatively, and the populations of T lymphocytes and NK cell subsets were analyzed by flow cytometry. The NK cell cytotoxicity (NKCC) of PECs and splenocytes was measured. RESULTS: The populations of CD3(+), CD4(+), and CD8(+) lymphocytes in the PECs continued to increase up until postoperative day (POD) 7 after laparotomy. The CD4/8 ratio on POD 3 was significantly lower after laparotomy than after pneumoperitoneum. The percentages of NK cells in the pneumoperitoneum group were significantly lower than those in the laparotomy group. On POD 1, the NKCC of splenocytes was less impaired in the pneumoperitoneum group than in the laparotomy group (10.3% vs 5.0%, P << 0.05). CONCLUSION: Laparoscopic surgery is preferable to open surgery because it results in less impairment of systemic and intraperitoneal cell-mediated immune responses.

Superficially spreading cancer of the stomach.

BACKGROUND: Superficially spreading cancer (SSC) of the stomach is rare and extends widely along the mucosa or submucosa of the stomach. This study was conducted to clarify the clinicopathologic characteristics and prognosis of patients with SSC. METHODS: SSC was defined as a tumor invading the mucosa or submucosa and measuring > or =5 cm in size. The clinicopathologic findings and outcomes of 36 patients with SSC were compared with those of 300 patients with early gastric cancer (EGC) measuring < or =5 cm and 271 with advanced gastric cancer measuring > or =5 cm. RESULTS: SSC was significantly different from ordinary EGC in tumor size, frequency of lymph node metastasis, lymphatic invasion, venous invasion, and stage II, III, and IV disease. The frequency of serosal invasion, lymph node metastasis, and lymphatic and venous invasions in cases of SSC was significantly lower than with advanced gastric cancer. Although tumor size of SSC evaluated before operation was smaller than that on the resected specimen, the 10-year survival rate was not different between SSC and ordinary EGC. CONCLUSIONS: SSC was characterized by high frequency of lymph node metastasis and preoperative underestimation of tumor size. SSC should be treated by a gastrectomy and lymphadenectomy with sufficient resection margin.