Prospective Randomized Trial of Early Postoperative Enteral and Total Parenteral Nutrition for Treating Esophageal Cancer.

BACKGROUND/AIM: Surgical stress significantly decreases serum diamine oxidase (DAO), a marker of intestinal mucosal maturation and integrity. This study aimed to determine the effects of postoperative enteral and total parenteral nutrition (EN and TPN, respectively) in patients with esophageal cancer. PATIENTS AND METHODS: This prospective randomized trial compared serum DAO activities, nutritional states, trace elements and complications between patients who underwent esophagectomy and received EN or TPN for seven days thereafter. RESULTS: Fifty-one patients were randomized to receive EN or TPN. The rates of change in serum DAO activity from the day before surgery were 0.79, 0.89 and 0.91 on postoperative days (POD) 1, 3 and 7, respectively, in the EN group, and 0.64, 0.76 and 1.06, respectively, in the TPN group, with no significant differences. Furthermore, the rates of changes in indicators of nutritional status, namely total protein, albumin, total cholesterol, trace element concentrations and infectious and non-infectious complications did not significantly differ between the groups. CONCLUSION: EN and/or TPN can be administered for early nutritional management until resumption of oral intake after esophagectomy according to the postoperative status of individual patients with esophageal cancer.

Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib.

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.

Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy.

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.

Traditional Japanese herbal medicine rikkunshito increases food intake and plasma acylated ghrelin levels in patients with esophageal cancer treated by cisplatin-based chemotherapy.

BACKGROUND: Cisplatin (CDDP) is an important chemotherapeutic drug for treating esophageal cancer that often induces nausea and vomiting. Rikkunshito (RKT), a traditional Japanese herbal medicine, can increase levels of plasma ghrelin, which is an orexigenic gut hormone that can alleviate chemotherapy-induced nausea and vomiting (CINV) and anorexia. METHODS: This prospective randomized crossover study included 20 patients with esophageal cancer who were administered with CDDP-based chemotherapy. Ten of them were assigned to group A [1st course: with RKT 7.5 g/day on days 1-14; 2nd course: without RKT (control)] and 10 were assigned to group B [1st course: without RKT (control); 2nd course: with RKT 7.5 g/day on days 22-35]. Food intake and levels of plasma acylated ghrelin (AG) were compared between the control and RKT courses. RESULTS: Data from 18 patients were included in this analysis, as chemotherapy was immediately stopped due to deteriorating renal function in one patient and intracerebral bleeding in another. The median rate at which food intake decreased between days 4 and 6 was considerably lower in the course with, than without RKT (2% vs. 30%; P=0.02). Median levels of AG significantly increased from days 3 to 8 in patients in both courses with and without RKT (9.6 to 15.7 fmol/mL, P<0.0001; control, 10.2 to 17.8, P=0.0002). The rate at which median plasma AG levels increased from days 3 to 8 tend to be higher in the RKT, than in the control course (68% vs. 48%, P=0.08). CONCLUSIONS: RKT can improve CDDP-induced, delayed-onset anorexia and increase plasma AG levels among patients with esophageal cancer who undergo highly emetogenic chemotherapy (HEC).

Long-term results of neoadjuvant chemoradiotherapy using cisplatin and 5-fluorouracil followed by esophagectomy for resectable, locally advanced esophageal squamous cell carcinoma.

This study retrospectively evaluated the long-term results of neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy for the patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC). Altogether, 49 patients treated from 2008 to 2012 were analyzed. Chemotherapy consisted of 5-fluorouracil and cisplatin. Radiotherapy was performed with a total dose of 40 Gy in 20 fractions for primary tumor, metastatic lymph nodes, and elective nodal area. Subsequently, transthoracic esophagectomy with extensive lymphadenectomy was performed. The median follow-up time for the survivors was 86 (range, 55-111) months. Pathological complete response from NCRT was observed in 17 (35%) patients. The 5-year overall survival and relapse-free survival rates were 56% [95% confidence interval (CI): 43-71%] and 55% (95% CI: 41-69%), respectively. The 5-year locoregional control rate was 84% (95% CI: 74-95%). Multivariate analyses revealed body mass index, N-factor, and %ΔSUVmax as significant factors for overall survival. Recurrences and within-irradiation field failure were observed in 16 (31%) and 4 (8%) patients, respectively. Toxicities of NCRT were generally mild. Postoperative Grade IIIb or worse complications were seen in 14% of patients, including one Grade V case (2%). The 5-year incidence rate of late complications of Grade 3 or worse was 22% (95% CI: 7-36%). The cumulative 5-year incidence rate of metachronous malignancies was 13% (95% CI: 1-26%). NCRT followed by esophagectomy for patients with resectable, locally advanced ESCC showed favorable locoregional control and overall survival, with acceptable postoperative complications. Long-term careful follow-up for late complications and metachronous malignancies is needed.

[BRONCHOPLASTY FOR LUNG CANCER].

Bronchoplasty for patients with lung cancer is basically designed to achieve radical cure with the preservation of lung function. Functional lung parenchyma can be preserved, and the reimplanted lobes contribute to postoperative quality of life. Pneumonectomy is associated with a higher occurrence of postoperative complications, poor quality of life, and cardiopulmonary dysfunction as compared with lobectomy. In addition, long-term complications (i.e., late pulmonary hypertension, respiratory failure, or so-called postpneumonectomy syndrome) are sometimes seen after pneumonectomy but seldom after lobectomy. Thus pneumonectomy itself is considered a disease. Sleeve lobectomy, or lobectomy with bronchoplasty, which allows the preservation of functional lung parenchyma with the possible advantages of lower mortality and morbidity rates, is a valid alternative to pneumonectomy and has recently been accepted as a standard treatment in noncompromised patients with lung cancer. Atypical bronchoplasties such as double-sleeve and extended-sleeve lobectomy, and sleeve segmentectomy are also performed at present. This article describes the surgical techniques for bronchoplastic procedures and compares the surgical outcomes of sleeve lobectomy with those of pneumonectomy reported in the literature.

Results of Neoadjuvant Chemoradiotherapy With Docetaxel and 5-Fluorouracil Followed by Esophagectomy to Treat Locally Advanced Esophageal Cancer.

BACKGROUND: Esophageal cancer is most frequently treated with platinum-based chemoradiotherapy (CRT). We previously described a phase I study of definitive CRT with docetaxel (DOC) and 5-fluorouracil (5FU) in patients with advanced esophageal cancer. This regimen had low toxicity and was effective without platinating agents. The present study aims to determine the antitumor effects of neoadjuvant CRT with DOC and 5FU and surgical outcomes. METHODS: We reviewed data from 38 patients with locally advanced cancer of the esophagus or esophagogastric junction who underwent trimodality therapy comprising neoadjuvant CRT with DOC and 5FU followed by esophagectomy between 2003 and 2008. RESULTS: Esophagitis was the most common toxicity associated with neoadjuvant CRT (grade 3; 26.3%), and hematologic toxicity was mild. Transthoracic esophagectomy and pharyngolaryngoesophagectomy proceeded in 36 (94.7%) and 2 (5.3%) patients, respectively, and 35 (92.1%) underwent R0 resection. Five (13.2%) patients had complete pathologic responses (pCR) of the primary tumor, and 23 (60.5%) had pathologic reductions of over two-thirds of the primary tumor. The T or N status was also down-staged in 26 (68.4%) patients. Overall postoperative morbidity developed in 21 (55.3%) patients, and mortality due to postoperative morbidity was zero. The 5-year recurrence-free and overall survival rates were 39.5% and 44.7%, respectively. CONCLUSIONS: The rates of neoadjuvant CRT toxicity and postoperative complications were acceptable, and the complete resection rate and survival data were favorable. This regimen is promising as neoadjuvant CRT for esophageal cancer and very useful as an alternative regimen for treating patients with esophageal cancer who cannot tolerate cisplatin.

The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial.

BACKGROUND: It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. PATIENTS AND METHODS: From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. RESULTS: The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. CONCLUSION: Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens.

Fibrinogen/thrombin-based collagen fleece (TachoComb(R)) promotes regeneration in pulmonary arterial injury.

OBJECTIVES: To repair unexpected damage of the pulmonary artery (PA) during thoracic surgery, fibrinogen/thrombin-based collagen fleece (TachoComb(®) [TC]) can be applied as a haemostatic material. The progression of vessel restoration with TC has not been elucidated. In this study, we investigate details of the healing process with TC after PA injury using a canine model. METHODS: Left thoracotomy was performed on female beagles under general anaesthesia. PA injury was induced and repaired using TC. Repair sites were histologically evaluated 2, 4 and 8 weeks after surgery (n = 3 in each group). RESULTS: Haemostasis of PA injury was achieved promptly after TC application. After surgery, no bleeding was found in the thoracic cavity, and no repair sites revealed stenosis, thrombi or false aneurism formation. Two weeks after surgery, inflammatory cells had infiltrated around the vascular defect, and vascular endothelium had regenerated on the innermost surface of TC applied to the defect. At Week 4, elastic and smooth muscle fibres had begun to extend into the defect between the endothelial layer and collagen fleece. By Week 8, elastic fibres and smooth muscle had completely regenerated in the medial layer. The adventitial layer had also fully regenerated. CONCLUSIONS: Haemostasis of injured PA using TC was safe and reliable. TC provided a mechanical scaffold on which vascular regeneration occurred. Three layers reconstructed in the PA defect were identical to those in normal structures.