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Purpose: In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer. Patients and Methods: Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers. Results: As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8–34.5], and the median PFS was 3.7 months (95% CI, 2.7–4.8). The DCR was 79.4% (95% CI, 62.1–91.3), and the CBR was 32.4% (95% CI, 17.4–50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response. Conclusions: E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.

Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced esophageal cancers. During neoadjuvant therapy, tumor-induced esophageal stenosis or adverse events often cause weight loss. However, little is known about the effects of weight loss during neoadjuvant therapy on postoperative complications or prognosis. We investigated the association between weight loss during neoadjuvant chemotherapy, postoperative infectious complications, and prognosis.Data from OGSG1003, a randomized phase-II trial comparing two regimens of neoadjuvant chemotherapy, cisplatin and fluorouracil plus Adriamycin and cisplatin and fluorouracil plus docetaxel, for locally advanced esophageal squamous cell carcinoma were used. Body weight was measured before neoadjuvant chemotherapy and esophagectomy. Multivariate analysis for infectious complications and prognosis was performed.The study included 134 patients. The median weight loss during neoadjuvant chemotherapy was 2.83% (-2.07% to 6.29%). Postoperative infectious complications were observed in 37 patients who had a significantly higher weight loss during neoadjuvant chemotherapy (5.18% vs. 1.90%, P = 0.002). Multivariate analysis revealed that 5% of weight loss during neoadjuvant chemotherapy was the only independent factor associated with postoperative infectious complications (odds ratio 2.69, 95% confidence interval 1.12-6.46, P = 0.027). Weight loss during neoadjuvant chemotherapy was significantly associated with worse recurrence-free survival in the univariate analysis (log-rank test, P = 0.002), but this association was marginal in the multivariate analysis (hazard ratio 1.73, 95% confidence interval 0.98-3.08, P = 0.058).Severe weight loss during neoadjuvant chemotherapy was an independent risk factor for postoperative infectious complications. Weight maintenance during neoadjuvant chemotherapy may reduce the incidence of postoperative infectious complications.

The aim of this study was to evaluate the efficacy of preoperative chemotherapy for stage II-III esophageal squamous cell carcinoma based on an objective computed tomography method.A total of 82 patients who underwent preoperative chemotherapy followed by surgery for advanced esophageal squamous cell carcinoma from January 2006 to June 2019 were included. Treatment effect was evaluated by measuring the esophageal wall thickness before and after neoadjuvant chemotherapy using contrast-enhanced thoracoabdominal computed tomography. The percentage decrease in esophageal wall thickness was calculated using the following formula: reduction (%)=(wall thickness before preoperative chemotherapy - wall thickness after preoperative chemotherapy)/(wall thickness before preoperative chemotherapy)×100. We demonstrated the efficacy of this measurement method and then analyzed which patient factors might affect the treatment effect.Receiver operating characteristic analysis showed the percentage tumor reduction to be a good predictor of histological therapeutic effect (grade ≥2) (area under the curve=0.727). In the multivariate analysis, tumor location (lower versus upper esophagus) was identified as an independent factor associated with tumor reduction (odds ratio=0.15; 95% confidence interval=0.03-0.79; p=0.025).We demonstrated an association between the reduction of esophageal wall thickness in the tumoral area and the histological therapeutic effect of chemotherapy. Secondary analysis showed poorer tumor reduction in patients with lower esophageal cancer than in those with upper esophageal cancer.

Supplementary Figure S5 shows pharmacodynamic changes in biomarkers over time (A) and changes by best overall response (B) in all study 114 cohorts.

Supplementary Table S3 provides a summary of infusion-related reactions during cycle 1, per premedication.

Purpose:In the dose-expansion part of this open-label, phase I study, we explored the efficacy and safety of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced gastric cancer.Patients and Methods:Patients with advanced gastric cancer who had been previously treated with ≥2 lines of chemotherapy received E7389-LF 2.0 mg/m2 every 3 weeks (the previously determined maximum tolerated dose, the primary objective of Study 114). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), and safety; exploratory objectives included disease control rate (DCR) and clinical benefit rate (CBR), as well as pharmacodynamic measurements of serum biomarkers.Results:As of June 24, 2021, 34 patients were enrolled and treated (10 from the original dose-expansion cohort, expanded to include 24 additional patients). Six patients had partial responses, for an ORR of 17.6% [95% confidence interval (CI), 6.8–34.5], and the median PFS was 3.7 months (95% CI, 2.7–4.8). The DCR was 79.4% (95% CI, 62.1–91.3), and the CBR was 32.4% (95% CI, 17.4–50.5). Overall, 32 patients (94.1%) experienced treatment-related adverse events, and 26 patients (76.5%) experienced grade ≥3 events, most commonly neutropenia (41.2%) and leukopenia (29.4%). Of the 8 endothelial cell/vasculature markers tested in this study, 7 were significantly increased among patients treated with E7389-LF; these changes were generally consistent regardless of best overall response.Conclusions:E7389-LF 2.0 mg/m2 every 3 weeks was tolerable and showed preliminary activity for the treatment of patients with gastric cancer.

The impact of thoracic duct (TD) resection on prognosis is controversial. This study aimed to examine the impact of TD resection. In this six-institution, matched-cohort study, 2269 consecutive patients with esophageal squamous cell carcinoma who underwent esophagectomy between 2000 and 2017 were enrolled for analysis of long-term outcomes, including overall survival (OS), disease-free survival (DFS), cause-specific survival (CSS), and recurrence patterns. Based on a propensity score, 642 TD-resected and 642 TD-preserved patients with all stages of disease were selected. At 5 years, the TD-resected group had an OS of 57.7%, a DFS of 50.9%, and a CSS of 62.2%. These rates were significantly higher than the corresponding rates of 48.7% (p = 0.0078), 41.0% (p = 0.0297), and 55.3% (p = 0.0473) in the TD-preserved group. The OS in the TD-preserved and TD-resected groups was similar for the patients with cStage 1 or 2 (p = 0.6265), but it was significantly higher in the TD-resected group for the patients with cStage 3 or 4 (p = 0.0052). The incidence of total recurrence did not differ between the two groups. However, the incidence of hematogenous recurrence in the TD-resected group (19.0%) was significantly lower than in the TD-preserved group (26.2%) (p = 0.0021). For cT4a tumors, the incidence of local recurrence in the TD-resected group (2.4%) was significantly lower than in the TD-preserved group (18.4%) (p = 0.0183). Performance of TD resection may help to improve prognosis, especially for patients with advanced esophageal squamous cell carcinoma, by reducing hematogenous and local recurrence. Prospective trials are needed to determine whether prophylactic TD resection has a positive impact on the prognosis of patients with esophageal cancer.

Although the standard treatment for intramucosal esophageal cancer without lymph node metastasis is endoscopic submucosal dissection (ESD), we sometimes encounter patients who are not able to undergo a transoral endoscopic examination. Here, we report a surgical procedure consisting of transgastric retrograde ESD to treat early esophageal cancer (T1a-EP, N0, M0) because of a stricture after hypopharyngeal cancer surgery. This retrograde ESD procedure can be a safe and effective treatment option for early esophageal cancer. This is the first report of a surgical retrograde ESD method for esophageal cancer.

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.

An 85-year-old woman who visited the hospital with sores on the perianal skin was diagnosed with squamous cell carcinoma of the anal canal(cT3N1aM0, cStage ⅢC). She received chemoradiotherapy(radiation total 54 Gy/30 Fr, mitomycin C/capecitabine). The tumor initially shrank, but regrowth of the primary lesion, extensive perianal skin infiltration, and the appearance of para aortic lymph node metastases was observed 6 months later. Laparoscopic abdominoperineal resection was performed to mitigate strong local symptoms. The perineal defect was repaired with bilateral gluteus maximus flap(V- Y flap). The operation prevented anal pain and improved ADL. The patient is currently undergoing chemotherapy 7 months after surgery. We report the case with a review of the literature in which ADL was improved by salvage surgery for tumor regrowth with severe local symptoms and distant metastases after chemoradiotherapy for squamous cell carcinoma of the anal canal.

In this open-label, Phase 1 study, we explore the safety and efficacy of E7389-LF (liposomal formulation of eribulin) in Japanese patients with advanced solid tumors.This open-label, Phase 1 study enrolled Japanese adult patients to receive E7389-LF for the treatment of advanced solid tumors. Treatment with E7389-LF 2.0 mg/mAs of October 16, 2020, 43 patients were enrolled (adenoid cystic carcinoma, n = 12; gastric cancer, n = 10; esophageal cancer, n = 11; small cell lung cancer, n = 10). Thirty-three patients experienced a Grade ≥3 treatment-related treatment-emergent adverse event, most commonly neutropenia (53.5%). Additionally, the incidence of hypersensitivity did not appear to change with a reduced number of infusion steps (2 vs. 4) and patients who were administered prophylactic pegylated granulocyte-colony stimulating factor had a noticeably lower incidence of Grade 3-4 neutropenia (although this did not have a proper control). The overall objective response rate was 11.6% (95% confidence interval: 3.9-25.1), corresponding to two partial responses in patients with adenoid cystic carcinoma, two partial responses in gastric cancer, and one partial response in esophageal cancer. Median progression-free survival was longer in the adenoid cystic carcinoma population (16.6 months) than in others.E7389-LF 2.0 mg/m

A metachronous neoplasm can develop in a gastric conduit used for reconstruction after esophagectomy for thoracic esophageal cancer. Surgical resection is sometimes necessary to treat this neoplasm. We report a method for performing minimally invasive gastrectomy with preservation of the proximal residual stomach through laparotomy for cancer in the distal side of gastric conduit after Ivor-Lewis esophagectomy. Furthermore, Roux-en-Y reconstruction was performed after gastrectomy. This minimally invasive partial gastrectomy for early gastric conduit cancer and followed Roux-en-Y reconstruction may lead to a favorable clinical outcome.

A 60-year-old man was referred to our hospital for the evaluation and treatment of general malaise. Contrast-enhanced computed tomography detected sigmoid colon cancer that had invaded the bladder, multiple liver metastases, and a small intestinal tumor. Hartmann's procedure was performed, with partial bladder and small bowel resection. A pathological examination revealed that the patient had sigmoid colon cancer and a gastrointestinal stromal tumor. The biopsy findings of a tumor in segment 8 of the liver indicated the presence of adenocarcinoma, thereby indicating the origin of multiple liver metastases from sigmoid colon cancer. On chemotherapy, the tumors in liver segments 2/3 and 8 shrank. However, the tumor in segment 6 enlarged. Since radical resection of all metastatic liver tumors was possible, hepatectomy was performed 10 months after the initial surgery. A pathological examination revealed that the tumors in segments 2/3, 4, and 8 were adenocarcinomas and the tumors in segments 4, 6, and 7 had originated from the gastrointestinal stromal tumor. This suggested the coexistence of liver metastases from sigmoid colon cancer and the gastrointestinal stromal tumor. In cases involving multiple primary tumors, it is necessary to consider the possible coexistence of multiple metastases from different primary tumors.

A metachronous neoplasm can develop in a gastric conduit used for reconstruction after esophagectomy for thoracic esophageal cancer. Surgical resection is sometimes necessary to treat this neoplasm. We report a method for performing minimally invasive gastrectomy with preservation of the proximal residual stomach through laparotomy for cancer in the distal side of gastric conduit after Ivor-Lewis esophagectomy. Furthermore, Roux-en-Y reconstruction was performed after gastrectomy. This minimally invasive partial gastrectomy for early gastric conduit cancer and followed Roux-en-Y reconstruction may lead to a favorable clinical outcome.

Aim In response to the rising use of laparoscopic surgery, recent studies have shown that laparoscopic multivisceral resections for locally advanced colon cancer are safe, feasible, and provide acceptable oncological outcomes. However, the usefulness of laparoscopic multivisceral resection remains controversial. Here, we aimed to compare short‐term and long‐term outcomes between laparoscopic and open multivisceral resection approaches for treating locally advanced colon cancer. Methods We retrospectively collected data on 1315 consecutive patients admitted to the National Hospital Organization, Osaka National Hospital, for surgical treatment of colorectal cancer between 2010 and 2017. We assessed invasiveness in terms of operating times, blood loss, and complications. Oncological outcomes included 5‐year survival rates and recurrences. Results We included 85 patients that underwent a colectomy with a multivisceral resection for locally advanced colon cancer; of these, 38 were treated with a laparoscopic approach and 47 were treated with an open approach. Compared to the open surgery group, the laparoscopic group had significantly less blood loss (median volume: 25 vs 140 mL, P, A laparoscopic approach for locally advanced colon cancer could be less invasive than an open approach without affecting oncological outcomes. Our findings suggested that laparoscopic multivisceral resection is a promising option, even when the tumor has progressed locally.

A 62-year-old woman was diagnosed with gastric cancer, Type 4, cT4b(LN, mesentery of transverse colon), N1 M1H0P1CY1, cStage ⅣB. S-1 and L-OHP(SOX)were administered for 4 courses and clinical response was SD. She interrupted the treatment because of practicing folk therapy. She had an emergency hospitalization due to pyloric stenosis, vomiting, and an umbilical tumor with pain. She was treated with 1 course of mFOLFOX6(5-FU, L-OHP, l-LV)followed by palliative surgery(laparoscopy assisted distal gastrectomy, Roux-en-Y reconstruction, resection of umbilical tumor, and bypass for transverse colon stenosis due to dissemination). The pathological diagnosis was L, Circ, Type 4, 126×89 mm, porsig, pT4b(SI, mesentery of transverse colon), pN3a(12/13), H0P1CY1, pStageⅣ, and metastatic umbilical tumor. Following surgery, oral administration of mFOLFOX6 is continued. Umbilical metastasis(Sister Mary Joseph's nodule)is associated with poor prognosis, however, appropriate management including symptom control by palliative surgery and continuation of chemotherapy may lead a better prognosis.

The incidence of perineal wound complications after extended pelvic surgeries for locally advanced or locally recurrent cancer is high. The management of these refractory complications is usually difficult. Extended pelvic surgeries are commonly associated with severe infectious complications owing to pre-operative chemoradiation therapy, the tissue damage during surgery, and the dead space after radical resections. Negative pressure wound therapy(NPWT)is widely used for the management ofseveral wounds. Recently, the utility ofNPWT has been reported on the management ofinf ectious wound complications post-surgery. Some authors reported the drainage effect of NPWT on pelvic abscess after surgery. However, so far, only a few reports have been published on the usefulness of NPWT in the management of perineal wound disruption or pelvic abscess. We performed NPWT on patients with perineal wound disruption or intractable lymphorrhoea. In these cases, NPWP was effective in early successful treatment. In summary, NPWT is an effective treatment option for perineal disruption and pelvic abscess after surgery for locally advanced or locally recurrent cancers.

A 52-year-old man underwent total gastrectomy for advanced gastric cancer. The postoperative diagnosis was por1mucpor2tub2, pT4a(SE)N3bM0H0P0CY0, pStage ⅢC. He underwent 6 courses of adjuvant chemotherapy with capecitabine plus oxaliplatin. Six months after the surgery, CT showed 2 recurrent lesions: a tumor behind the esophago-jejunal anastomosis and another in the mesentery around the jejuno-jejunal anastomosis. Endoscopy showed intrajejunal invasion. Second-line therapy with paclitaxel and ramucirumab were administered for 3 courses, resulting in rapid progression of the disease. Palliative radiotherapy(39.6 Gy/22 Fr)for both lesions was performed for local control. Sequential administration of nivolumab was started 9 days after terminating radiotherapy. After 6 courses, both tumors markedly reduced PR, and the oral intake of food improved. After 10 courses, there was hyper-progression of the tumor behind the esophago-jejunal anastomosis and shrinkage of the other tumor. Surgery (left upper abdominal exenteration and enucleation of the tumor in the mesentery)was performed to release the jejunal limb obstruction. The tumor behind the esophago-jejunal anastomosis was a poorly differentiated adenocarcinoma, and no viable cancer cells were seen in the tumor in the mesentery. Radiotherapy and immune checkpoint inhibitors may be effective for gastric cancers, although the mechanism of action should be elucidated.

We reported a case of a 30s woman who underwent Hartmann's surgery for sigmoid cancer. Her pathological stage was Stage Ⅳ(pT4b, N1b, M1b[liver and lung]). Postoperatively, 10 courses of systemic chemotherapy with FOLFOX plus cetuximab( Cmab)or bevacizumab(Bmab)were administered. After the chemotherapy, partial liver dissection and radiofrequency ablation(RFA)for multiple liver metastasis were performed. After 2 years of systemic chemotherapy with FOLFIRI plus ramucirumab(RAM), no liver or lung metastasis was observed; however, left supraclavicular lymph node and para-aortic lymph node metastases existed and gradually increased. For the purpose of local control, the para-aortic lymph node metastasis was treated with cervical dissection and carbon ion radiotherapy. Therefore, carbon ion radiotherapy was a useful treatment for local control.

Background/Aims: Since the risk of cancer cells seeding the peritoneum after perforation during endoscopic submucosal dissection (ESD) is unclear, we retrospectively examined peritoneal relapse after gastric perforation during ESD for gastric cancer at a single institution. Methods: Of 876 patients who underwent ESD for early gastric cancer between January 2002 and December 2015, 22 patients (2.5%) experienced gastric perforation during ESD at the Osaka National Hospital in Osaka, Japan. Clinical data from these 22 patients were reviewed for information on pathology, clinical course, and evidence of peritoneal dissemination. Results: Patients were followed for a median of 55 (range 2–108) months. Two patients had peritoneal seeding following perforation during ESD. Multivariate analysis to explore the influence of clinical factors on the peritoneal seeding revealed that an intra-abdominal fluid collection on the CT imaging just after ESD, tumor location at the upper lesion of stomach, and pathologically marginal invasion were independently associated with an incidence of peritoneal relapse. Conclusion: Although rare, we should recognize the possibility of cancer cells seeding the peritoneum after perforation during gastric ESD.

Pelvic exenteration (PE) for locally advanced or recurrent colorectal cancer is often used to secure negative resection margins. The aim of this study was to evaluate the feasibility of laparoscopic PE.The clinical records of 24 patients (9, open; 15, laparoscopic) who underwent total or posterior PE for locally advanced or recurrent colorectal cancer between July 2012 and April 2016 at Osaka National Hospital were retrospectively reviewed. Operative factors were compared between the 2 groups.The R0 resection rate was 100% in the laparoscopic group and 89% in the open group. The operative time and the incidence of postoperative complications were not significantly different between the 2 groups. The laparoscopic group showed less intraoperative blood loss (P=0.019), a lower C-reactive protein elevation on postoperative day 7 (P=0.025), and a shorter postoperative hospital stay (P=0.0009).Laparoscopic PE is a safe and feasible procedure to reduce postoperative stress.

The patient, a woman in her 70s, was diagnosed with occlusive ileus caused by sigmoid colon cancer.She underwent transanal stent placement to release the occlusion.Subsequent detailed testing revealed a 70×60mm mass on the dorsal side of the pancreas and PET-CT indicated an SUVmax 18.2 FDG uptake. EUS-FNA was performed twice.However, the mass was unable to be definitively diagnosed.The patient was then referred to our hospital.She underwent laparoscopic sigmoid colectomy and laparoscopic biopsy of the mass for sigmoid colon cancer.The patient progressed well postoperatively and was discharged home on postoperative day 9.The postoperative diagnosis was colon cancer(S, Type 2, 58×50 mm, tub2, pT4a [SE], pN1, Stage Ⅲa)and the biopsied mass was found to be a nodal marginal zone B-cell lymphoma according to histopathological testing.After undergoing chemotherapy at our hematology department, she has experienced no recurrence.

We report a case of recurrent pancreatic cancer in the remnant pancreas after pancreatoduodenectomy(PD)that was successfully treated by surgical resection. A woman in her 70s who was treated for multiple lung metastases of breast cancer was referred to our hospital because of obstructive jaundice. A low-density area in the pancreas head(19mm in diameter) and dilatation of the main pancreatic duct were observed on abdominal CT. She was diagnosed with pancreatic head cancer and underwent PD. Twenty months after PD, abdominal CT revealed a tumor in the pancreas tail, and she started receiving chemotherapy containing gemcitabine(GEM)for the diagnosis of recurrent pancreatic cancer in the remnant pancreas. Twelve months after the induction of chemotherapy, we performed surgical resection of the tumor(total pancreatectomy). The pathological diagnosis was moderately differentiated adenocarcinoma, which was similar to the primary lesion, and the tumor was confirmed as recurrence of pancreatic cancer. Although she died of multiple lung metastases of breast cancer 62 months after the total pancreatectomy, the recurrence of pancreatic cancer was not observed without adjuvant therapy during that time.

A man in his 70s was diagnosed with gastric cancer and underwent total gastrectomy with D2 lymphadenectomy. The final diagnosis was T3(SS)N2M0, Stage ⅢA. After surgery, S-1 was administered for 1 year. One year and 6 months after surgery, abdominal computed tomography showed a single liver tumor(S4: 30mm). Based on overexpression of the human epidermal growth factor receptor 2(HER2)protein in the primary tumor, we selected capecitabine plus cisplatin plus trastuzumab as the combination chemotherapy. After the second course, the therapeutic response was stable. S4 partial liver resection was performed. The liver tumor was histologically evaluated as Grade Ⅰb metastatic gastric adenocarcinoma. After surgery, capecitabine plus trastuzumab was administered for 1 year. One year after resection of liver metastasis, the patient is alive without any relapse.

An 82-year-old man receiving oral administration of warfarin for atrial fibrillation underwent distal gastrectomy for advanced gastric cancer. The postoperative diagnosis was pT3(SS)N2M1H1P0CY0, pStage Ⅳ,(HER2, score 3+)gastric cancer. He received chemotherapy for the treatment of multiple liver metastases, following which, he developed lymph node metastases. Grade 3 anemia was observed at 46 months after initiation of chemotherapy when he was treated with third-line irinotecan plus cisplatin. Abdominal CT showed that CR for liver metastases and SD for lymph node metastases were maintained. Esophagogastroduodenoscopy and colonoscopy showed no intraluminal bleeding. As the anemia progressed, blood transfusion was required repeatedly instead of withdrawal of chemotherapy and replacement therapy of iron and vitamin B12. Double- balloon endoscopy revealed hemorrhagic tumor at duodenal stump. We diagnosed tumor bleeding from metastatic lymph node around pancreatic head invading to duodenum. Palliative radiotherapy(40 Gy/20 Fr)for hemostasis was performed. Finally, hemostasis and tumor shrinkage were achieved.

Here, we report a long-term survival case treated with docetaxel and S-1 combination therapy(DS therapy)for peritoneal dissemination of gastric cancer. A 58-year-old man was diagnosed with gastric cancer in 2006. Distal gastrectomy, D2 dissec- tion, and RY reconstruction were performed. The pathological diagnosis was gastric cancer, por2, pT3(SS), pN3a(8/27), pStage ⅢB. S -1 monotherapy was administered as an adjuvant chemotherapy for 1 year from 3 months after surgery. Five years after surgery, peritoneal dissemination and bladder recurrence caused rectal stenosis and hydronephrosis. We performed ileostomy and left nephrostomy. DS therapy was started 5 years and 2 months after the initial surgery. A complete clinical remission was observed 2 years and 10 months after starting DS therapy(23 courses). Multiple lymph node metastasis and bone metastasis were confirmed at 5 years and 5 months(57 courses). Even though irinotecan monotherapy was performed for five courses, the bone and lymph node metastasis increased at 5 years and 9 months after starting DS therapy, and the patient died at 69 years of age. DS therapy may be a useful option for peritoneal metastasis of gastric cancer.

Objective: Imatinib is a standard treatment for metastatic gastrointestinal stromal tumor (GIST). Imatinib resistance is mostly caused by secondary mutations in C-KIT. The antitumor effect of second-line agents is correlated with the type of secondary mutation: indeed, sunitinib is effective against tumors with C-KIT exon 13 or 14 mutations. We investigated whether secondary C-KIT mutations can be detected in circulating tumor DNA (ctDNA) from peripheral blood. Methods: This study included 4 patients who underwent resection of imatinib-resistant GIST. Tumor-specific mutations in each tumor were determined by Sanger sequencing. ctDNA was extracted from peripheral blood obtained before and after the treatment of imatinib-resistant lesions. Each of the secondary target mutations in ctDNA was investigated, using a next-generation sequencer. Results: Imatinib-resistant lesions had single-nucleotide substitutions in C-KIT exon 13 in 3 patients and exon 18 in 1 patient. Identical secondary C-KIT mutations could be detected in ctDNA with a mutant fraction range of 0.010-9.385%. One patient had growth of an imatinib-resistant tumor containing a C-KIT exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. Conclusion: Detection of secondary C-KIT mutations in ctDNA could be useful for the selection of targeted agents and prediction of antitumor effects.

We report a case of peritoneal metastasis of bile duct cancer that was successfully treated by surgical resection. A 70s man underwent pancreatoduodenectomy(PD)for bile duct cancer, and abdominal CT revealed a tumor in the peritoneum along the right kidney at 55 months after PD. As FDG uptake was seen at the lesion on PET-CT, he was diagnosed as recurrence of bile duct cancer or primary malignant tumor in the retroperitoneum. Because the tumor was solitary on CT and PET-CT, we conducted surgical resection of the tumor. Pathological diagnosis was well differentiated adenocarcinoma that was similar to the primary lesion, and the tumor was confirmed as recurrence of bile duct cancer. He remains alive without 2nd recurrence for 60 months since tumor resection(117 months since PD).

The patient is a 65-year-old woman with anemia. The multiple liver tumors detected by ultrasonography, it was diagnosed as neuroendocrine tumor(NET), G2 by biopsy. There was an ulcer at the bulb of the duodenum, so we diagnosed liver metastasis of duodenum NET. Because the liver tumors spreaded to both right and left lobes, we carrying out a transcatheter arterial embolization(TAE)twice to liver metastasis, and chemotherapy by octreotide was performed. 20 months after the beginning of treatment, a 4 cm tumor was remained in the left lobe but others were not detected by computed tomography, so we performed cytoreductive surgery. Duodenum bulb resection and left hepatectomy was performed and the specimens were NET, G2 in the pathological findings. We detected a lot of tumors less than 1 cm in the right lobe during the operation, so TAE was carried out for the right lobe after surgery. The disease showed no progression for 28 months after the first admission(post operation5 months).

Here we report a case of a hemorrhagic gastric cancer patient with severe coronary artery disease, in whom the cancer was successfully resected with the support of intra-aortic balloon pumping(IABP). An 80-year-old man was referred to our hospital for further examination of his anemia and tumor around the pancreatic head. He was diagnosed with type 3 gastric cancer with multiple bulky lymph node metastases invadingto the pancreas(cT4b[LN-Panc], N3a, M1[LYM No.16a2int], cStage IV ). Tarry stools continued and blood transfusion was repeatedly required. To control tumor bleeding, we considered that gastrectomy should be performed prior to chemotherapy. Since he had a history of acute myocardial infarction, coronary angiography was performed, which showed severe coronary stenosis in 3 vessels. Preoperative percutaneous coronary intervention or coronary artery bypass grafting were inappropriate because of tumor bleeding. We performed palliative distal gastrectomy under the support of IABP. The postoperative course was uneventful and he could initiate subsequent chemotherapy smoothly. IABP may be a useful option for hemorrhagic gastric cancer patients with severe coronary stenosis.

Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA.

Computed tomography (CT) is the major diagnostic tool for clinical management of gastric cancer. However, minimal residual disease and peritoneal dissemination, the most frequent recurrent patterns in gastric cancer, are typically difficult to detect with CT. Circulating tumour DNA (ctDNA)—fragmented DNA released from cancer cells into the bloodstream—is an emerging candidate marker to follow disease progression (Schwarzenbach et al, 2011). Previous studies have indicated that ctDNA levels correlate with tumour burden in colon cancer (Diehl et al, 2008) and breast cancer (Dawson et al, 2013). However, no comparative studies have been conducted in gastric cancer, and it is necessary to examine the possibility that ctDNA can be used for monitoring disease status, especially minimal residual disease and peritoneal dissemination. We previously developed a system to detect EGFR mutations in the plasma of lung cancer patients using a massively parallel sequencer (Kukita et al, 2013) and applied it to monitor advanced gastric cancer.

The most frequent relapse site of gastrointestinal stromal tumors(GIST)is the liver. We encountered a patient with longterm survival treated with multidisciplinary treatment, including4 hepatectomies for liver metastases. The patient was a woman aged 69 years at the time of the first medical treatment. She underwent total gastrectomy and S6 segmental hepatec- tomy for a stomach GIST with a hepatic metastasis. The tumor diameter was 24 cm and the mitotic figure was 65/50 HPF. According to the guidelines, it was diagnosed as a high risk GIST based on strong positive immunostaining for CD34 and c-kit. The tumor had metastasized to the liver and greater omentum. She took imatinib in the year following surgery. Because the GIST had spread to the lung1 8 months after the operation, she took imatinib again. Two years after the operation the pulmonary metastasis showed a clinical complete response(cCR)and the CR lasted for 4 years. Six years after the surgery she had a hepatic recurrence in S5, and she underwent an S5/4 partial hepatic resection. Seven years after the first operation, a liver S7 metastasis developed and she underwent S7 partial hepatectomy. Ten years after the first surgery, the GIST relapsed in liver S6 with right adrenal gland permeation. She underwent partial S6/7 liver resection and a right adrenal gland resection. She resumed takingimatinib after this surgical resection. Now, 11 years after the first operation, she is alive with an S1 hepatic recurrence taking sunitinib. Therefore, multidisciplinary treatment with surgical resection prolongs the survival of patients with resectable liver metastases of GIST.