Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC-06).

BACKGROUND: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. METHODS: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. RESULTS: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. CONCLUSIONS: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. CLINICAL TRIALS REGISTRATION: UMIN000007368.

Correction to: Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC­06).

The correct name of the twelfth author should be ''Yasuhiro Yuasa", and not ''Yasuhiko Yuasa'' as given in the original publication of the article.

Lobulated esophageal schwannoma resected with concurrent approach from the thorax and cervix.

BACKGROUND: Esophageal schwannomas are rare esophageal submucosal tumors. We herein report a case of a lobulated esophageal schwannoma resected with concurrent approach from the thorax and cervix. CASE PRESENTATION: A 74-year-old woman visited our hospital with complaint of loss of consciousness, and a lobulated mediastinal tumor was discovered by chance in computed tomography. Upper gastrointestinal endoscopy showed a smooth elevated lesion at a position of 23-28 cm from the incisor teeth. A hypermetabolic appearance was noted on positron emission tomography. Based on these data, a gastrointestinal stromal tumor was suspected. The tumor was enucleated at the thoracic cavity while being pushed from the cervical incision. Pathological examination showed an esophageal schwannoma. CONCLUSIONS: We experienced a case of lobulated esophageal schwannoma with fluorodeoxyglucose accumulation. We resected the tumor with concurrent approach from the thorax and cervix.

A case of carcinoma of the papilla of Vater in a young man after subtotal colectomy for familial adenomatous polyposis.

BACKGROUND: Carcinoma and adenoma of the duodenum, including the papilla of Vater, are problematic diseases in patients with familial adenomatous polyposis (FAP). CASE PRESENTATION: A 36-year-old man underwent a periodic medical examination for early colon cancer originating from FAP for which laparoscopic-assisted subtotal colectomy with a J-shaped ileal pouch-rectal anastomosis was performed 3 years earlier. A tumor was detected at the papilla of Vater along with elevation of total bilirubin and hepatobiliary enzymes. Although cytology did not determine the tumor to be an adenocarcinoma, we suspected adenocarcinoma due to its hypervascularity shown by contrast-enhanced computed tomography. Pylorus-preserving pancreaticoduodenectomy with modified Imanaga reconstruction and regional lymph node dissection (D2) was performed. The pathological study showed that the tumor was a papillary and moderately differentiated tubular adenocarcinoma. The patient is currently in good health without recurrence, weight loss, or severe diarrhea at 12 months after surgery. CONCLUSIONS: Awareness of biliary-pancreatic symptoms and periodic gastroduodenoscopy might contribute both to the early detection of duodenal or periampullary polyps and cancer and to the radical treatment of FAP. Modified Imanaga reconstruction has the potential to become one of the more effective procedures for providing good quality of life to FAP patients with duodenal or periampullary cancer.

Concomitant pancreatic and duodenal metastases 12 years after nephrectomy for renal cell carcinoma: a case report.

In selected patients with metastatic renal cell carcinoma, metastasectomy can achieve prolonged survival. Herein we report a patient with concomitant pancreatic and duodenal metastases occurring 12 years after total right nephrectomy for a renal cell carcinoma. The metastases were successfully treated by a pancreas-sparing duodenectomy and distal pancreatectomy. A 66-year-old man was referred to our hospital with a chief complaint of right upper abdominal pain. He had undergone laparoscopic total right nephrectomy for renal cell carcinoma 12 years before. Enhanced computed tomography showed hypervascular tumors in the pancreatic body and the descending duodenum near the papilla of Vater. Histopathological examination of endoscopic ultrasonography-guided fine needle aspiration cytology specimens revealed metastatic clear cell renal cancer. The patient underwent pancreas-sparing duodenectomy and distal pancreatectomy. He developed a pancreatic fistula after surgery that improved with conservative treatment, and has been free of evidence of recurrence up to 20 months postoperatively.

Right paraduodenal hernia presenting with strangulated obstruction with intestinal malrotation: a case report.

A paraduodenal hernia is a rare cause of an internal hernia that may require massive bowel resection; prompt diagnosis and surgical treatment are essential. In cases of malrotation, strangulation may occur both inside and outside the hernial sac. Strangulation outside the hernial sac makes the preoperative diagnosis more difficult. Herein, we report a patient with a right paraduodenal hernia, intestinal malrotation, and strangulation outside the hernia. An 86-year-old woman was admitted to our hospital with abdominal pain. Enhanced computed tomography showed a closed-loop obstruction of the hypo-enhancing small bowel and absence of a horizontal duodenal leg. The patient underwent an emergency laparotomy and was diagnosed with strangulated bowel obstruction due to a right paraduodenal hernia and malrotation. The patient underwent resection of the ischemic ileum, closure of the hernial orifice, and repositioning of the intestine. The postoperative course was uneventful. The patient reported no abdominal discomfort after 7 months of follow-up.

V-shaped lymph node dissection in laparoscopic distal gastrectomy; new technique of intra-abdominal dissection and surgical outcomes.

BACKGROUND: Recently, laparoscopic-assisted distal gastrectomy (LADG) has become popular for the treatment of early gastric cancer. Furthermore, the use of totally laparoscopic gastrectomy (TLG), a more difficult procedure than LADG, has been increasing in Japan. Laparoscopic-assisted distal gastrectomy is currently performed more frequently than laparoscopic distal gastrectomy (LDG) in hospitals in Japan. METHOD: Reconstruction after LDG is commonly performed extra-abdominally and lymph node dissection of the lesser curvature is performed at the same time. We have developed a new method of intra-abdominal lymph node dissection for the lesser curvature. RESULTS: Our technique showed positive results, is easy to perform, and is reasonable in terms of general oncology theory. CONCLUSION: In oncological therapy, this technique could be a valuable surgical option for totally laparoscopic surgery.

A patient with spontaneous rupture of the esophagus and concomitant gastric cancer whose life was saved: case of report and review of the literature in Japan.

A 71-year-old man suddenly developed abdominal pain and vomiting on drinking soda after a meal, and visited a physician. Cervical subcutaneous and mediastinal emphysemas were observed on CT, and the patient was transferred to the emergency medical center of our hospital on the same day. Esophagography was performed at our department. A ruptured region was identified on the left side of the lower thoracic esophagus, and surgery was emergently performed employing sequential left thoracoabdominal incision. The chest wall was adhered due to inflammation, and large amounts of residual food and sloughing were present in the thoracic cavity and mediastinum. Moreover, necrotic changes were noted in the superior through inferior mediastinum. An about 2-cm rupture site was confirmed on the left side of the lower thoracic esophagus and closed by suture and filling with pediculate omentum. The presence of a tumorous lesion located mainly in the body of the stomach and lymph node enlargement were also diagnosed before surgery, for which gastric and intestinal fistulae were inserted to prepare for the second-stage surgery. The patient was admitted to an ICU after surgery. ARDS and MRSA-induced pneumonia and enteritis concomitantly developed but remitted. Curative surgery for gastric cancer was performed at 40 POD. Spontaneous rupture of the esophagus is relatively rare and that complicated by gastric caner is very rare, with only six cases being reported in Japan. Herein, we report the case.

Spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip: A case report.

INTRODUCTION AND IMPORTANCE: Spontaneous esophageal rupture is a life-threatening condition caused by a sudden increase in the intraesophageal pressure. While surgery is the mainstay of management for spontaneous esophageal ruptures, in recent years, an increasing number of patients have been managed with endoscopic interventions. We report a case of spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip (Ovesco Endoscopy AG, Tübingen, Germany). CASE PRESENTATION: A 68-year-old female presented with epigastric pain and left-sided back pain following vomiting. A computed tomography scan revealed mediastinal emphysema and an esophagogram showed leakage from the left side of the lower thoracic esophagus into the mediastinum. The patient was diagnosed with spontaneous esophageal rupture localized to the mediastinum and was treated conservatively. However, she had persistent fever and continuing esophageal leakage on the esophagogram. On the 12th day of admission, a gastrointestinal endoscopy was performed, which found a 10-mm full-thickness longitudinal laceration on the left side of the lower esophagus. Endoscopic closure using an over-the-scope clip was performed. The next day, the patient became afebrile. One week later, esophagogram revealed slight residual leakage and an additional endoscopic closure using an over-the-scope clip was performed; the patient subsequently had an uneventful recovery and was discharged on the 44th day of admission. CLINICAL DISCUSSION: Endoscopic closure using an over-the-scope clip led to a good outcome in this patient with spontaneous esophageal rupture. CONCLUSION: Endoscopic closure using an over-the-scope clip is an effective and minimally invasive technique for selected patients with spontaneous esophageal rupture.

[A case of advanced colon cancer with metastases to both supraclavicular and para-aortic lymph nodes effectively treated by radiation and S-1 therapy].

We report the case of a 60-year-old woman with multiple lymph node metastases after ascending colon cancer who received radiation therapy and then chemotherapy with S-1. She was diagnosed with lymph node metastasis of the para aorta and left upper clavicle 10 months after surgery. We performed radiation therapy for the left upper clavicle (64 Gy)and para aorta (40 Gy). Consequently, we administered S-1(100mg/day)orally. After three months, the upper clavicle lymph nodes had disappeared and the para-aortic lymph nodes reduced. All metastatic lesions disappeared after 10 months. She survived for 32 months after the radiation therapy.

[Three cases of gastric cancer with para-aortic lymph node metastases succesfully treated by S-1/CDDP combination therapy followed by curative resection].

Due to advanced gastric cancer with abdominal para-aortic lymph node metastases, we performed a curative operation in three cases in which S-1/CDDP combination therapy proved effective. In case 1, after only one course of this chemotherapy, the reduction of the primary lesion was slight, but para-aortic metastatic lymph nodes were remarkably reduced. We performed a curative operation with complete D3 lymph node dissection. In case 2, after two courses the reduction of the primary lesion was remarkable, and para-aortic metastatic lymph nodes almost disappeared. Therefore, we performed a curative operation with D2 lymph node dissection. In case 3, after two courses the reduction of the primary lesion was cicatrized. Although para-aortic metastatic lymph nodes were gradually reduced, one of them increased after the third period of treatment. Therefore, we performed a curative operation with complete D2 lymph node dissection and 16b1 lateral lymph node dissection. All underwent postoperative adjuvant chemotherapy, and have been surviving for 58 months, 42 months, and 18 months, respectively. In advanced gastric cancer with para-aortic lymph node metastases without other non-curative factors, long-term survival can be expected by combining a curative operation with S-1/CDDP combined therapy.

Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial.

PURPOSE: S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings. PATIENTS AND METHODS: This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; ß = .2). RESULTS: The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test, P < .001), and enrollment was terminated as recommended by the independent data and safety monitoring committee. Incidences of grade 3 or greater adverse events, particularly neutropenia and leukopenia, were higher in the S-1 plus docetaxel group, but all events were manageable. CONCLUSION: Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.

[Percutaneous cryoablation therapy under local anesthesia for unresectable metastatic liver tumors].

Even though liver resection is the first choice against metastatic liver tumors, oncologists are often obliged to include other treatment modalities depending on metastatic tumor size, number of metastatic nodules, location of tumors, patient's general condition, and so on. Among others we selected cryoablation therapy against unresectable tumors and examined its usefulness clinically in 5 patients. Under local anesthesia, the cryoprobe, which was 3 mm in diameter, was introduced into the center of the tumor by use of an ultrasonographic guiding technique. In the middle of the freezing process, through ultrasonography we could clearly monitor the target tumor, which would change into an ice ball. It was noteworthy that not only the treated tumor but also untreated tumors were reduced in 2 cases. Because of extra-hepatic metastases, 3 patients died within 1 year after the therapy, while 2 patients are alive. This modality was easily repeatable and was minimally invasive with little toxic effect. In addition, it did not worsen quality of life (QOL). The above results indicate that cryoablation therapy could be a feasible modality against unresectable metastatic liver tumors.

Giant left-sided inguinoscrotal hernia containing the cecum and appendix (giant left-sided Amyand's hernia).

KEY CLINICAL MESSAGE: The present case involved a 62-year-old male with a large left-sided inguinoscrotal hernia. A CT scan and a clinical examination led to a diagnosis of a giant left-sided Amyand's hernia. The hernia was repaired using the ULTRAPRO Hernia System (UHS), and the patient exhibited an uneventful postoperative course.

A case of esophageal adenocarcinoma arising from the ectopic gastric mucosa in the thoracic esophagus.

A 75-year old man was detected with a pediculate tumor in the upper esophagus. A biopsy determined that it was an adenocarcinoma. A subtotal esophagectomy with dissection of three-fields of lymph nodes was selected. The pathological study revealed it to be an esophageal adenocarcinoma arising from ectopic gastric mucosa of the fundus of the stomach. His post-operative course was uneventful and without sign of recurrence for 3.5 years.

Large solitary fibrous tumor of the retroperitoneum: report of a case.

We report an unusual case of a large solitary fibrous tumor (SFT) in the retroperitoneum. A 53-year-old man was referred to our hospital for surgical treatment of a swelling in the right flank with dull pain. Abdominal computed tomography (CT) and echograms showed a large encapsulated tumor compressing the right kidney and liver. At laparotomy, the tumor was found to be encapsulated but fixed to the capsule of the right kidney within a small area. Therefore, complete removal was achieved. The resected specimen was an encapsulated elastic hard tumor, 14 x 13 x 10 cm in size. Immunohistochemical studies revealed reactivity for CD34 and vimentin, but no staining for keratin, S-100, or alpha-smooth muscle actin, confirming a diagnosis of SFT. Although SFT is usually associated with a favorable prognosis, close follow-up is recommended because of the limited information on its long-term behavior.

Evaluation of treatment for synchronous hepatic metastases from gastric cancer with special reference to long-term survivors.

PURPOSE: The purpose of this study was to determine the most effective means of treating liver metastases from gastric cancer. METHODS: We retrospectively examined 43 patients with liver metastases, but without peritoneal dissemination, who had received different forms of treatment. RESULTS: The crude 5-year survival rates of patients who underwent gastrectomy with complete hepatectomy (curative gastrectomy), noncurative gastrectomy, and no gastrectomy were 33.3%, 3.7%, and 0%, respectively. The curative gastrectomy group showed the highest survival rate (not significant). The median survival of patients given hepatic artery infusion (HAI), systemic chemotherapy, and no chemotherapy were 353, 189, and 61 days, respectively. The patients given chemotherapy survived significantly longer than those not given chemotherapy. Three patients survived for more than 5 years without any signs of recurrence. The long-term survivors all had primary lesions without serosal invasion (T2) and no other noncurative factors. Two patients underwent curative gastrectomy and one underwent noncurative gastrectomy. All were given postoperative chemotherapy; as HAI in two cases, and as systemic chemotherapy in one case. CONCLUSION: These findings suggest that curative gastrectomy combined with HAI or systemic chemotherapy should be attempted for patients with primary tumors without serosal invasion or any other noncurative factors.