Effect of the number of cycles of docetaxel + S-1 therapy on long-term survival in adjuvant chemotherapy for stage III gastric cancer. A pooled analysis of the OGSG0604 and OGSG1002 trials.

BACKGROUND: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. RESULTS: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5-90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. CONCLUSION: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. TRIAL REGISTRATION: Registration number: UMIN00000714 and UMIN000004440.

Five-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy (OGSG1002).

BACKGROUND: Adjuvant S-1 monotherapy is standard of care for stage II and III gastric cancer (GC), but there is still a need to improve the efficacy of treatment for stage III disease. We conducted phase II study of eight cycles of S-1 plus docetaxel (DS) followed by S-1 monotherapy for up to 1 year after D2 gastrectomy for stage III GC. PATIENTS AND METHODS: Sixty-two patients with stage III GC were enrolled. They received oral S-1 (80 mg/m2/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks for 8 cycles, followed by S-1 until 1 year postgastrectomy. Treatment safety, tolerability, and survival were evaluated. RESULTS: The completion rate for eight cycles of DS therapy was 77.4% [95% confidence interval (CI) 65.0-87.1%]. Subsequent S-1 monotherapy for 1 year was feasible in 71.0% (95% CI 58.1-81.8%) of patients. The incidence of neutropenia, leukopenia, anorexia, and fatigue of grade 3 or higher was 10% or higher. There were no treatment-related deaths. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72.4% (95% CI 62.1-84.5%) and 60.0% (95% CI 48.8-73.9%), respectively. Subgroup analyses by disease stage showed 5-year OS and DFS rates of 74.5% (95% CI 60.7-91.5%) and 59.3% (95% CI 43.8-80.2%) for stage IIIA and 70.0% (95% CI 55.4-88.5%) and 60.0% (95% CI 44.8-80.4%) for stage IIIB, respectively. CONCLUSIONS: Adjuvant eight cycles of DS therapy might be safe and manageable and has promising OS and DFS for stage III GC.

[Consideration of Nutritional Support for Decreased Caloric Intake in Patients with Severe Weight Loss after Esophageal Cancer Surgery].

OBJECTIVE AND METHODS: We evaluated factors that caused the decrease in caloric intake early after surgery, which led to weight loss after esophageal cancer surgery. We selected 35 patients whose weights at 1 year after surgery were ≥10% lower than their preoperative weights. In these patients, the caloric intake and nutritional support received at discharge and 1 month after operation were investigated. At discharge, the caloric intake of 25 patients was lower than the required caloric intake, which was <85% in 17 patients. However, among the 17 patients, only 2 received nutritional support with increased enteral nutrition. One month later, the number of patients with caloric intake less than and <85% of the required caloric intake increased to 29 and 23, respectively. In addition, none of the patients received increased enteral nutrition at home. Many complained of gastrointestinal symptoms after surgery and while receiving enteral nutrition, even under weight loss status. In these patients, oral intake at discharge was inadequate and the caloric intake via enteral nutrition was also not adjusted enough to meet the nutritional requirement. On the basis of this study, flexible nutritional management for oral intake and enteral nutrition is deemed necessary for severe weight loss early after esophageal cancer surgery.

Feasibility of International Proposed Standardized Enteral Connector for Semi-Solid Formula Feeding.

BACKGROUND/AIMS: The current study was undertaken to assess if the semi-solid formulas could be used with a new ENFit connector with similar force to current percutaneous endoscopic gastrostomy (PEG) tubes. METHODS: Experiment 1: We measured the applied pressure (force) needed to compress the syringe containing 7 viscous semi-solid formulas with a 20 Fr PEG tube and low-profile tube through the ENFit connector or the current connector. Experiment 2: This experiment was conducted to evaluate the compression force through 2 connectors in 3 infusion velocity, 7 PEG tube types with 2 semi-solid formulas. RESULTS: Experiment 1: The force needed to compress the syringe through the ENFit connector was higher in 3 semi-solid formulas with a 20 Fr low-profile tube; otherwise, there were no significant differences. Experiment 2: Each formula required a higher force in the ENFit connector in 6 settings out of 21. CONCLUSIONS: The ENFit connector will likely not show any remarkable change in the force to administer the semi-solid formula. However, a higher force was required under some conditions in the prototype ENFit connector. Further investigation of sensory test is needed to confirm the feasibility of the ENFit connector for using the semi-solid formulas.

[Relationship between Nutritional Biochemical Parameters and Body Weight Loss in Patients with Esophageal Cancer Up to One Year after Surgery].

SUBJECTS AND METHODS: The subjects comprised 21 patients with esophageal cancer who underwent surgery, without adjuvant chemotherapy. Caloric intake, body weight loss, and biochemical parameters(serum albumin[Alb], hemoglobin[Hb], transthyretin[TTR], and total cholesterol[T-Cho])were measured up to 1 year after surgery, and relationships between all parameters were investigated. RESULTS: The caloric intake dropped to about 87% of base-line intake at 1 month after surgery and recovered to 100% at 1 year after the operation. Body weight also dropped to about 89% of baseline at 6 months after surgery and then was relatively stable. Caloric intake was significantly positively correlated with TTR(r=0.82, p=0.02), and it also tended to be positively correlated with T-Cho(r=0.70, p=0.14). Body weight loss was significantly negatively correlated with Alb(r=-0.82, p=0.01)and Hb(r=-0.87, p=0.01). CONCLUSION: Alb and Hb were recovered in the early postoperative period when body weight was still decreased. However, TTR appeared to be a good parameter of caloric intake in the short-term, postoperatively.

[Sequential Post-Operative Nutrition Care at Home for Patients Receiving Surgical Treatment for Esophageal Cancer].

OBJECTIVE AND METHODS: We evaluated the outcomes of sequential nutrition care provided at home to patients who had undergone surgery for esophageal cancer. For 44 such patients, we investigated caloric intake(kcal), percentage of preoperative body weight(%), and requests and complains related to home nutrition care every 3 months for 1 year after surgery. RESULTS: Duringthe observation period, the mean postoperative caloric intake decreased to a minimum level at 1 month, but nearly recovered to the baseline at 12 months. The percentage of preoperative body weight decreased postoperatively, and this decrease was maintained. The average weight percentage reached 87%at 6 months after surgery, and recovered to only 89% at 12 months. Regarding requests and complaints, many reports of digestive symptoms related to gastrointestinal surgery were reported up to 3 months postoperatively. Additionally, the large number of requests for cancellation of enteral support indicates the difficulty in managing home enteral nutrition. On the other hand, guidance about dietary quality with oral intake enhancement increased at 6 months postoperatively. CONCLUSION: The aims of postoperative nutrition care should change over time with the patient's postoperative progress. In the early stage, weight loss management is important. In addition to dietary guidance with regard to digestive reconstruction, nutrition support with acceptable enteral nutrition is recommended. Guidance regarding problems with dietary behavior is needed for every patient when the digestive adaptation has advanced.

[A Case of Recurrent Gastric Cancer with Recurrent Celiac Lymph Node Metastasis Successfully Treated with Chemoradiotherapy and CPT-11 plus CDDP Therapy].

Chemotherapy is performed for the recurrence of gastric cancer in many cases. We report a case of recurrent lymph node metastasis successfully treated with chemoradiotherapy and chemotherapy. A man in his 60s underwent total gastrectomy and D2 dissection in 2009. The pathological diagnosis was poorly differentiated adenocarcinoma, T4a, int, INF b, ly2, v2, LN#2: 2/3, #3: 1/4, #7, 8, and 9: 3/4, stage III B. Although we administered S-1/UFT as postoperative adjuvant chemotherapy, a strong rash appeared and the patient ceased chemotherapy. Eight months later, the rash had disappeared. We started chemotherapy with paclitaxel(PAC). CT performed 1 year postoperatively showed celiac lymph node(#9)metastasis. Chemoradiotherapy( RT+PAC)and additional CPT-11(98mg)and CDDP(49mg)treatment were administered. The lymph node (#9)was cicatrized after 8 cycles. Forty-two months after the end of treatment, the patient has had no recurrence. It is thought that chemoradiotherapy is an effective cure for local recurrence of gastric cancer.

[Investigation of the Safety of and Patient Satisfaction with iEat®, the Support Food for the Recovery of Eating Function in Patients with Carcinomatosis - Related Gastrointestinal Passage Disorder].

OBJECTIVE: iEat®, a support food for the recovery of eating function, is food that can be easily masticated with little power and has suitable fluidity for enzyme processing, regardless of its normal appearance. We provided iEat® to 5 patients with carcinomatosis-related gastrointestinal passage disorder who could take fluid foods and investigated the stability of iEat® and patient satisfaction with the food. METHODS: We provided regular diets for lunch on the first and 7th day, and provided iEat® from the 2nd to the 6th day. The stability of iEat(R) was evaluated based on the presence and grade of abdominal pain, diarrhea, sense of abdominal distension, nausea, and vomiting, according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0, JCOG). The patients assessed their satisfaction by using 6 grades of taste, appearance, amount, difficulty of intake, and overall valuation. RESULTS: One patient could not continue the study because of vomiting from overeating of iEat(R). In the other patients, iEat(R) induced approximately the same adverse events as did the regular diets. All of the patients expressed better satisfaction with iEat® than with the regular diets. CONCLUSION: Although patient management for overeating is necessary, iEat® might provide good quality of life in terms of eating satisfaction to the patients with carcinomatosis-related gastrointestinal passage disorder.

[A Case of Small Intestinal Cancer Repeating an Ileus Symptom Complicated with Refractory Arrhythmia].

A 56-year-old man had been treated for hypertrophic cardiomyopathy since childhood. He had been treated for refractory ventricular tachycardia (VT) with interventricular septum cauterization, catheter ablation, and implantation of a defibrillator. He had been treated at home for several years. The ileus that developed in July 2014 was relieved by conservative medical treatment once, but it recurred after oral intake of food a short time later. The obstruction was due to a small intestine cancer that was diagnosed by enteroscopy. After considering the risks of surgery due to the cardiac problem and the quality of life due to ileus caused by the mass, we resected it. This surgery was not a radical resection because of peritoneal dissemination. He started oral food intake postoperatively, and returned to home care. Three months after surgery, oral chemotherapy was administered after considering his stable cardiac function in addition to his coherent mental status. An adverse event of severe watery diarrhea developed, and VT caused by dehydration occurred. After the chemotherapy was discontinued, he recovered in intensive care. He returned to home care at his prior status for 9 months postoperatively.

[A Case of Carcinosarcoma of the Esophagus Treated with Chemoradiotherapy].

Carcinosarcoma of the esophagus is a rare malignant neoplasm. We report a case of an 87-year-old man treated with chemoradiotherapy. The main presenting complaint was hiccups. Histological analysis of a biopsy from the tumor demonstrated a carcinosarcoma. The clinical diagnosis was T2N0M0, cStageⅡ. In consideration of his advanced age, a past history of cerebral infarction, high blood pressure, aortic valve sclerosis, and chronic renal failure (Cr 1.5-1.8 mg/dL), chemoradiotherapy consisting of TS-1 40 mg/day with radiotherapy of 66 Gy was administered to the patient. The carcinosarcoma decreased in size on endoscopic examination in response to the chemoradiotherapy. Surgery with extended lymphadenectomy for esophageal carcinosarcoma is the standard treatment, but chemotherapy may be a good choice for local control for patients who cannot undergo surgical resection.

Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy.

BACKGROUND: We have previously reported the superior feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer during a prospective phase II study. We report 3-year follow-up data on patients enrolled in this study. PATIENTS AND METHODS: Fifty-three patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled into this study. They received oral S-1 (80 mg/m(2)/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m(2)) on day 1, repeated every 3 weeks (one cycle). Treatment was initiated within 45 days after surgery and repeated for four cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. Three-year overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: The OS rate at 3 years was 78.4 % [95 % confidence interval (CI), 67.9-90.6 %] and the DFS rate at 3 years was 66.2 % (95 % CI, 54.4-80.7 %). Subgroup analyses according to disease stage showed a 3-year OS and DFS rate of 85.7 % (95 % CI, 74.9-98.1 %) and 70.8 % (95 % CI, 57.1-87.8 %) for stage IIIA, and 62.5 % (95 % CI, 42.8-91.4 %) and 56.2 % (95 % CI, 36.5-86.7 %) for stage IIIB, respectively. CONCLUSIONS: On the basis of 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel yielded promising OS and DFS in stage IIIA gastric cancer patients who had undergone D2 gastrectomy. We believe that this regimen is a candidate for future phase III trials studying the optimal adjuvant chemotherapy regimen for stage III gastric cancer.

[Nutritional support to establish refeeding in a patient with acute gastrointestinal graft-versus-host disease - a case report].

A patient with acute myeloid leukemia having acute gastrointestinal graft-versus-host disease(aGVHD)was provided nutritional support. Oral intake was not permitted owing to the gastrointestinal injury induced by aGVHD. Our goal was to achieve oral feeding by the time of discharge. The initial aim in reinitiating eating was to stimulate intestinal adaptation to the mucosal injury. Via total parenteral nutrition(TPN), the patient was provided food in the form of a semisolid jelly, which passed through the intestinal tract slowly. After interviewing the patient and ascertaining that no complications had arisen owing to eating, a regular diet was initiated. Considering the unstable nature of the gastrointestinal condition and the associated long-term hospitalization, it is important to ensure that the meal contents comply with the patient's taste, while considering the patients'uneasiness and fear of progress to oral intake. It is difficult to predict improvement of aGVHD. Therefore, it is essential that patients are offered meals via TPN, suitable to their intestinal condition and mental status.

[Background of patients receiving peripheral parenteral nutrition after discharge from Minoh City Hospital].

After much debate about the nutritional management of patients at the time of discharge, the number of discharged patients receiving peripheral parenteral nutrition has increased. We investigated the nutritional management on discharge and the background of 2,636 patients discharged from Minoh City Hospital over 7 years from 2006. Of these, 55 patients (2%)received peripheral parenteral nutrition after discharge. In the years preceding 2010, ≤7 patients per year received peripheral parenteral nutrition after discharge, but this number increased to >10 after 2010. More than 60% of the patients were aged ≥80 years; more than 80% were discharged to a hospital. These patients had terminal-stage cancer or high-grade dysphagia, and they required end-of-life medical care. The patients' condition, knowledge of their care, and their view of life and death as well as the medical treatment environment influenced the choice of nutritional support. Correct information is necessary to take appropriate decisions regarding nutritional support.

[The influence of counseling for patients with cancer on their discharge from the palliative care support department of the community health care service of Minoh City Hospital].

Counseling for patients with cancer by a certified nurse in palliative care began in April 2011 in Minoh City Hospital. Counseling was provided immediately after a patient was informed by the treating physician of a primary diagnosis of cancer, a metastatic recurrence, or a decision to terminate cancer therapy. We examined the patient's support system after the counseling ended. The number of patients receiving end-of-life support with home or hospital care rapidly increased from 118 prior to the program's beginning to 186. The number of patients counseled was comparable to the rapid increase in their number(n=68). New cases in the outpatient department comprised 59% of all patients, of which, 45% began supportive counseling, with 43%of them ultimately returning home. Of the new cases receiving counseling in the hospital, 34%eventually returned home after discharge, and the highest percentage of discharges were to a palliative care unit or hospice program (48%). The initiation of counseling in the outpatient department allowed us to provide sufficient time to make decisions about appropriate places for end-of-life care. Cooperation with the patients' physicians was necessary to provide counseling from the outpatient department. Our findings suggest the importance of sharing the patients' medical and social information among the staff when necessary.

[A case of resection of pancreatic head lymph node metastasis of rectal carcinoid].

An 80-year-old woman was treated with low anterior resection and D3 lymph node dissection for rectal carcinoid in August 2007. Pathological diagnosis was a tumor 23 × 22 mm in size with muscularis propria invasion, ly1, v0, n1 (No. 251[1/12]). Partial hepatectomy was performed for liver metastasis in March 2010 and September 2011. In June 2013, an isolated tumor of 17 mm in diameter was detected between the inferior vena cava and the stomach using abdominal ultrasonography. The tumor was diagnosed as pancreatic head lymph node metastasis using abdominal enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and positron emission tomography (PET); fluorodeoxyglucose (FDG) uptake was noted at the site of the tumor, but not at other parts of the body. Curative resection was the chosen treatment option. Open surgery was performed in September 2013, and a tumor 30 mm in diameter located at the ventral side of the inferior vena cava, lateral side of the portal vein, and cranial side of duodenum was resected. No surrounding tissue infiltration was found. Pathological analysis of the resected specimen indicated lymph node metastasis of the rectal carcinoid. The patient has been disease free for 9 months after surgery.

[A case of gastric cancer with multiple liver metastases that was successfully treated by chemotherapy].

A man in his 60s received SP (S-1+CDDP) therapy for gastric cancer with multiple liver metastases. After completion of 3 courses, liver metastases had reduced significantly, and the paraaortic lymph nodes, which had swelled previously, had reduced in size. Furthermore, the serum carcinoembryonic antigen (CEA) level had also improved to the standard value from 814.3 ng/mL. The patient was able to discontinue the opioid he had needed for pain control. The chemotherapy was continued for 18 courses, with the dose reduced at the time of the adverse events along the way. By completion of the 18 courses, we recognized regrowth of the primary lesion and a rise in the serum CEA over the standard value. There was no sign of the regrowth of liver metastases and distant lymph nodes according to examinations for enhanced computed tomography (CT) and ¹8F-fluorodeoxyglucose positron-emission tomography (FDG-PET) CT.The patient received distal gastrectomy. The CEA level decreased in standard value or less after surgery and we believed the cancer was limited to the primary stomach lesion.

Recurrent Stroke with Rapid Development of Intracranial Artery Stenosis and Subsequent Successful Mechanical Thrombectomy in Essential Thrombocythemia.

Essential thrombocythemia is a myeloproliferative neoplasm. Ischemic stroke is frequently the first manifestation of essential thrombocythemia. We herein report a patient with JAK2V617 mutation-positive essential thrombocythemia who developed recurrent ischemic stroke with rapid development of intracranial artery stenosis and subsequently underwent successful mechanical thrombectomy. The high JAK2V617F allele burden in our patient (58.4%) may have affected the patient's condition. We discuss similar reports in the literature and the possible pathophysiologic mechanism of large artery involvement in these patients.

[Recurrent gastric cancer treated with fourth-line chemotherapy consisting of capecitabine and cisplatin leading to partial response].

A 70-year-old man with advanced gastric cancer was treated with neoadjuvant chemotherapy consisting of S-1 plus cisplatin( CDDP). He exhibited symptoms of cerebral infarction during the second course of chemotherapy. Distal gastrectomy was performed and the histological diagnosis was pT3N3aM0, pStage IIIB. Adjuvant chemotherapy was administered; however, after the second course, gastric cancer recurred in the lymph nodes. Second-line chemotherapy with irinotecan (CPT-11) and CDDP was initiated. Thereafter, third-line chemotherapy with docetaxel was performed. However, the response to treatment was progressive disease (PD). Subsequently, fourth-line chemotherapy was performed with capecitabine and CDDP (XP chemotherapy). After the fourth course of XP chemotherapy, the response was partial response (PR). Moreover, PR was maintained after 20 courses of chemotherapy.

[Coordination to assist with hospital-to-home discharge after cerebral hemorrhage--perspectives of a patient's family and nurse].

Discharge support, although provided for a limited time, is of vital importance in the acute phase care period. Such support is necessary to ensure continuity of care and treatment even after being discharged from the hospital. I acquired both the viewpoints of the family and the nurse of a patient who was about to be discharged from the hospital after cerebral hemorrhage. However, the patient's family and I were not able to decide on a home care plan or hospital-to-home transfer ahead of time because of the unstable condition of the patient, limited care power of the family, and varying discharge plans among the family members. I intended to help in the decision-making process, taking into consideration the patient's best interest. I evaluated the viewpoint of the family and was able to understand situations in which a family member, who assumes the role of a primary care giver, would need guidance in providing home care to the patient.