A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.

BACKGROUND: We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 + oxaliplatin + bevacizumab). METHODS: This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m2/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m2 on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. RESULTS: All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. CONCLUSIONS: Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 + oxaliplatin + bevacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

Single-arm confirmatory trial of laparoscopy-assisted total or proximal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group study JCOG1401.

BACKGROUNDS: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer is safe and feasible. In contrast, no prospective study evaluating the safety and efficacy of laparoscopy-assisted total gastrectomy (LATG) or laparoscopy-assisted proximal gastrectomy (LAPG) has been completed. We conducted a single-arm confirmatory trial to evaluate the safety of LATG/LAPG for clinical stage I (T1N0/T1N1/T2N0) proximal gastric cancer. METHODS: The extent of lymphadenectomy was selected based on the Japanese Gastric Cancer Treatment Guidelines. The mini-laparotomy incision was required to be ≤ 6 cm. The primary endpoint was the proportion of grade 2-4 (CTCAE ver. 4.0) esophagojejunal anastomotic leakage. The planned sample size was 245 considering a threshold of 8% and one-sided alpha of 2.5%. RESULTS: Between April 2015 and February 2017, 244 eligible patients were enrolled. LATG/LAPG was performed in 195/49. The proportion of conversions was 1.7%. Clinical T1N0/T1N1/T2N0 was 212/9/23. The extents of lymphadenectomy were as follows: D1+: 229; D2: 15. The median operation time was 309 min (IQR 265-353). The median blood loss was 30 ml (IQR 10-86). Grade 2-4 esophagojejunal anastomotic leakage was 2.5% (6/244; 95% CI 0.9-5.3). The overall proportion of in-hospital grade 3-4 adverse events was 29% (71/244). The proportions of intraabdominal abscess and pancreatic fistula were 3.7% and 2.0%, respectively. There were no treatment-related deaths. CONCLUSIONS: This trial confirmed the safety of LATG/LAPG. After the non-inferiority of LADG is confirmed in our phase III trial (JCOG0912), LATG/LAPG is expected to be established as one of the standard treatments for clinical stage I gastric cancer.

[Effectiveness of Ramucirumab Therapy for Advanced Gastric Cancer after Stent Placement for Esophagogastric Junction Carcinoma Obstruction-A Case Report].

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.

Propensity score-matched study of laparoscopic and open surgery for colorectal cancer in rural hospitals.

BACKGROUND AND AIM: Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. METHODS: This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. RESULTS: In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. CONCLUSIONS: Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.

[A Case of Complete Pathological Response in a Patient with Locally Advanced Sigmoid Colon Cancer after FOLFOX IRI Chemotherapy].

A 61-year-old man with advanced sigmoid colon cancer was admitted to our hospital. Abdominal computed tomography (CT) revealed locally advanced sigmoid colon cancer, with suspected invasion of the bladder and small intestine. The clinical stage of the disease was T4b, N1, M0, and Stage III a, with wild-type KRAS expression. A transverse colostomy was performed because of the presence of a bowel obstruction. The patient received 4 courses of Leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI). The size of the tumor and lymph nodes decreased noticeably after chemotherapy and laparoscopic high anterior resection with lymph node dissection. During this phase, the pathological stage of the disease was ypT0, N0, and Stage 0(no viable carcinoma cells, Grade 3). This result suggested that preoperative FOLFOXIRI chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.

[A case of gastric cancer in which grade 2 treatment effects were obtained with preoperative two-week S-1 administration].

In our hospital, a clinical trial on the effects of preoperative 2-week S-1 administration for advanced gastric cancer is being conducted. A7 5-year-old man presented to our hospital with a type 2 tumor(poorly differentiated adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c-T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently administered for 14 days. On day 15, we performed laparoscopy-assisted distal gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the primary tumor and metastatic lymph nodes, confirmed the effect of the treatment as Grade 2, and revealed a type 2 gastric cancer of 30×20mm in size; this tumor was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with perioperative S-1 were observed, and the postoperative course was good. At the latest follow-up(6 years after treatment), no recurrence was observed.

[Approximately four years of survival benefits for a case of gastric cancer postoperative carcinomatous peritonitis by combined modality therapy].

Carcinomatous peritonitis may develop after operation for gastric cancer. As ascites are difficult to control, especially for gastric cancer postoperative carcinomatous peritonitis, many cases are difficult to treat. The present case was a female patient with carcinomatous peritonitis that occurred 2 years post-surgery. Administration of docetaxel (DOC)and S-1 combination therapy achieved a complete response. However, she had a relapse of carcinomatous peritonitis 3 years post-surgery. She underwent bypass operation, followed by DOC and S-1 combination therapy again. She achieved a good quality of life for more than two years. As side effects in patients worsen with the repeated exposure to chemotherapy, continuing the same treatment is difficult. Therefore, we changed the therapy method to irinotecan(CPT-11)/cisplatin(CDDP)therapy, weekly paclitaxel(PTX)and methotrexate(MTX)/5-fluorouracil(5-FU)therapy, and bypass operation when necessary. Rapid progression of her condition was sequentially suppressed, allowing her to continue her everyday life. Overall, this treatment method provided survival benefits of approximately four years following the recurrence of carcinomatous peritonitis.

Effects of chemotherapy on quality of life and night-time sleep of colon cancer patients.

Background : The aim of this study was to investigate quality of life (QOL) and night-time sleep disturbance in colon cancer patients with middle risk chemotherapy for proper antiemetic therapy. Methods : The study enrolled 139 patients with colorectal cancer. All patients received oxaliplatin or irinotecan-based chemotherapy. Patients completed a questionnaire about chemotherapy-induced nausea and vomiting and sleep disturbance. Sleep disturbance was checked, and the relationship between sleep disturbance and nausea was analyzed. Results : The prevalence of nausea was 48.9% (68 / 139). The degree of the nausea was slight / moderate / severe in 51 / 11 / 6 patients, and 12 patients had vomiting. Appetite showed no change / slightly decreased / half / one-fourth / none in 51 / 34 / 33 / 6 / 7 patients. There were significant differences in the mental component summary (MCS) score and the role-social component score (RCS). (MCS : nausea(+) vs nausea(-) 46.4 ±â€…1.1 vs 54.1 ±â€…1.1 p < 0.01 RCS : nausea(+) vs nausea(-) 33.1 ±â€…2.1 vs 41.6 ±â€…2.1 p < 0.01). Using the MCS with a cut-off score of 50, patients were divided into two groups, and nausea was significantly correlated with a low MCS score. Furthermore, patients were divided into two groups using a Pittsburgh Sleep Quality Index cut-off score of 6, and sleep disturbance was correlated with old age and second-line chemotherapy. Conclusions : Nausea affects QOL and night-time sleep of colon cancer patients with middle risk chemotherapy. J. Med. Invest. 67 : 338-342, August, 2020.

Thoracoscopic Oesophagectomy Using Prone Positioning for Oesophageal Cancer With Right Aortic Arch: A Case Report.

BACKGROUND/AIM: Right aortic arch (RAA) is a rare abnormality of the aortic arch that forms a vascular ring. Oesophageal cancer (EC) accompanied with RAA is even rarer, and in such cases, it is very important to understand the anatomical structure in the upper mediastinum in order to perform a safe and curative operation. PATIENTS AND METHODS: A 67-year-old man who presented with pharyngeal discomfort was admitted to our hospital. Further examinations revealed advanced thoracic EC accompanied with RAA and aortic diverticulum. RESULTS: After neoadjuvant chemotherapy, we successfully and safely performed thoracoscopic oesophagectomy and lymphadenectomy using the prone positioning. CONCLUSION: There exist only a few reports of thoracoscopic oesophagectomy for EC with RAA. Sufficient preoperative preparation and sharing an adequate strategy for the surgical approach with the surgical team are definitely necessary. Although the thoracoscopic approach for EC with RAA is useful, more considerations are needed for some issues.

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.

[A case of disseminated bone marrow carcinosis with disseminated intravascular coagulation successfully controlled with S-1 after total gastrectomy for advanced gastric cancer].

Bone marrow carcinosis due to gastric cancer with disseminated intravascular coagulation(DIC)occurs suddenly, progresses rapidly, and has a very poor prognosis. In addition, physical status tends to be bad at the time of the episode, and palliative care is generally selected as the treatment method. The case was a 70-year-old woman who underwent total gastrectomy for scirrhous stomach cancer five years previously. She recently noticed gingival hemorrhage, and was referred to our hospital by a nearby doctor. As a result of her examination, she was diagnosed with disseminated bone marrow carcinosis as a postoperative recurrence of gastric cancer that resulted in DIC. We transfused blood platelets and fresh frozen plasma into her, and controlled the bleeding tendency temporarily. She was started on oral administration of S-1 for improvement of DIC, and the therapy was successful without loss of QOL. It is easy to continue S-1 therapy as chemotherapy in the outpatient department, because it is a matter of internal medicine.

Proteomic alteration in gastic adenocarcinomas from Japanese patients.

BACKGROUND: Gastric adenocarcinomas comprise one of the common types of cancers in Asian countries including Japan. Comprehensive protein profiling of paired surgical specimens of primary gastric adenocarcinomas and nontumor mucosae derived from Japanese patients was carried out by means of two-dimensional gel electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as putative clinical biomarkers and molecular targets for chemotherapy. RESULTS: Relatively common alterations in protein expression were revealed in the tumor tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG-1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II, glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa stomach-specific protein with putative tumor suppressor activity, were detected. RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression in tumor tissues. CONCLUSION: A possible pathological role for down-regulation of FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific decreases in gene and protein expression of FOV in patients may be utilized as clinical biomarkers for effective diagnosis and assessment of gastric cancer.

Short-Term Outcomes of Laparoscopic Distal Gastrectomy for Advanced Gastric Cancer.

The purpose of this study was to investigate the oncologic outcomes of laparoscopic distal gastrectomy (LDG) for advanced gastric cancer (AGC). Between April 2003 and March 2014, LDG was performed for 392 patients, 91 patients (23.2%) had histopathologically diagnosed AGC beyond T2 depth. The clinicopathological features, postoperative outcomes, mortality, morbidity, recurrence rate, and survivals of those patients were reviewed. The TNM stages of the tumor were IB in 26 patients (28.5%), IIA in 20 (21.9%), IIB in 18 (19.7%), IIIA in 13 (14.2%), IIIB in 6 (6.5%), IIIC in 6 (6.5%), and IV in 2 (2.1%). Major morbidity occurred in 14 patients (15.3%), with no postoperative mortality. Median follow-up was 24.5 months; 10 patients developed recurrence during the follow-up period, and 10 patients died, including 6 cancer deaths. The 5-year overall and disease-free survival rates were 76.8% and 72.6%, respectively. By stage, OS/DFS was 92.3%/91.8% in stage IB, 85.4%/85.4% in stage II, and 49.3%/26.9% in stage III. Oncologic outcomes were good in patients with AGC, especially with stage IB-IIB, who underwent LDG. LDG appears to be an effective approach for treating stage IB and II gastric cancer.

Mesh-Airtight-Preperitoneum: a simple method for confirming mesh placement in transabdominal preperitoneal repair of inguinal hernia.

We devised a method for confirming the position of mesh placed during transabdominal preperitoneal repair (TAPP) of an inguinal hernia. The preperitoneum is sufficiently detached, and the mesh is fixed in place as usual. Before completely closing the peritoneum, pressure is applied from outside the body and inside the abdominal cavity to remove as much air as possible from the detached preperitoneum; the peritoneum is then sutured using a V-Loc(TM) closure device so that it does not constrict. By releasing the pressure all at once, the airtightness of the preperitoneum is maintained, and the position of the mesh can be observed through the translucent peritoneum. This method, called Mesh-Airtight-Preperitoneum (MAPP), could become widely used as a simple technique for confirming mesh position in TAPP. J. Med. Invest. 63: 270-273, August, 2016.

Three-dimensional CT for preoperative detection of the left gastric artery and left gastric vein in laparoscopy-assisted distal gastrectomy.

INTRODUCTION: We evaluated 3-D CT imaging for preoperative classification of the left gastric artery and vein in patients with early gastric cancer and estimated its clinical benefit. METHODS: Between April 2009 and March 2014, 279 patients underwent preoperative 3-D CT using a 64-row multi-detector CT scanner, followed by laparoscopy-assisted distal gastrectomy. The 3-D CT images of the arterial and portal phases were reconstructed and fused. The operative outcomes were compared between patients who had not undergone 3-D CT (2007-2008) and who had undergone 3-D CT (2009-2011). RESULTS: According to Adachi's classification, the numbers of type I, II, III, IV, V, and VI arterial patterns were 253, 15, 1, 3, 3, and 1, respectively. Three cases could not be classified. According to the Douglass classification, the left gastric vein flowed into the portal vein, splenic vein, junction of the portal vein and splenic vein, and left branch of the portal vein in 119, 111, 36, and 5 patients, respectively. The left gastric vein could not be visualized in six patients, and two patients could not be classified. In addition, the relation was absent for an Adachi type I vein and one of the "other" types of veins. The total operative time was significantly shorter with 3-D CT than without it (P = 0.01), and the degree of lymph-node dissection was significantly higher (P = 0.01). Inflammatory parameters and operative morbidity tended to decrease with 3-D CT. CONCLUSION: Three-dimensional CT is a useful modality to visualize the vessel anatomy around the stomach, and it improves clinical effectiveness and reduces the invasiveness of surgery.

[A case of rectal cancer treated by preoperative chemoradiation].

Fifty-one-year-old male visited our hospital suffering from anal pain and subileus. Further examination revealed that advanced rectal cancer which invaded to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We administered neo-adjuvant chemoradiotherapy for fear of non curative resection of the rectum. The regimen was once weekly administration of intravenous CPT-11 40 mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4 weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first administration, a partial response was confirmed on CT, and so we carried out an abdominoperineal resection. The postoperative course is almost uneventful without a little perineal infection. The specimen revealed that no malignant lesion remained, which changed to necrotic tissue. The side effects were not so severe. For example, diarrhea, nausea, and mucosal dysfunction were each less than grade 2, and there was much tolerate for renal, liver, and bone marrow function. This combination chemoradiotherapy is considered to be effective for locally advanced rectal cancer.

A treatment using STI571 for jejunal gastrointestinal stromal tumor (GIST) accompanied with liver metastasis and peritoneal dissemination.

A 64-year-old man with a chief complaint of melena visited our emergency outpatient clinic. After several examinations, he was diagnosed as a gastrointestinal stromal tumor (GIST) with liver metastasis. Surgical resection of the jejunal lesion and postoperative adjuvant therapy with STI571 for one year was performed. Due to recent immunohistological studies and introduction of STI571, the diagnosis, treatment, and prognosis of GIST are about to change profoundly. Further accumulation of cases is necessary to investigate the diagnosis, treatment, and prognosis of GIST.

[A case of pneumoconiosis in a dental technician].

We report a case of pneumoconiosis in a dental technician. He was a 33-year-old man who had worked in a dental clinic as a dental technician for 12 years. In October 1999, he visited to the National Zentsuji Hospital complaining of progressive cough and sputum over a three-year period. Although he received medication, his condition did not improve. He visited the same hospital again on May 8, 2000. His chest radiographs and CT films showed massive shadows in both upper lung lobes. Pneumoconiosis was diagnosed from the pathological findings in a lung specimen obtained by video-assisted thoracic surgery (VATS). There are few reports of pneumoconiosis of dental technicians diagnosed by VATS.

The effect of nutritional support on the immune function in the acute postoperative period after esophageal cancer surgery: total parenteral nutrition versus enteral nutrition.

BACKGROUND: Enteral nutrition (EN) is now used more frequently than total parenteral nutrition (TPN) for nutritional support after resection for esophageal cancer. But consensus regarding which type of nutrition should be used does not exist. We studied the effect of TPN and EN on patients' nutritional status and immune function in the immediate postoperative period after esophageal cancer resection. METHODS: We enrolled 30 patients (27 men and 3 women) who underwent subtotal esophagectomy. The patients were randomly assigned to TPN or EN group. Either TPN or EN was begun on postoperative day 1. On postoperative days 1, 3, and 7, three endpoints were measured: albumin, C-reactive protein, and Th1/Th2 balance. RESULTS: All patients completed the study. Anastomotic leaks occurred in 6 patients in the TPN group and 7 patients in the EN group. Albumin, Th1/Th2 balance, and C-reactive protein did not differ between the groups. Th1/Th2 balance was not different regardless of the preoperative treatment or complications. CONCLUSIONS: No differences in immune function, nutritional state, or inflammatory response were seen between patients supported with TPN and those supported with EN. The results of our study suggest that perioperative nutritional support can be safely performed either with TPN or EN.