Doublet chemotherapy, triplet chemotherapy, or doublet chemotherapy combined with radiotherapy as neoadjuvant treatment for locally advanced oesophageal cancer (JCOG1109 NExT): a randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Neoadjuvant therapy is the standard treatment for patients with locally advanced oesophageal squamous cell carcinoma (OSCC). However, the prognosis remains poor and more intensive neoadjuvant treatment might be needed to improve patient outcomes. We therefore aimed to compare the efficacy and safety of neoadjuvant doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy plus radiotherapy in patients with previously untreated locally advanced OSCC. METHODS: In this randomised, open-label, phase 3 trial, patients aged 20-75 years with previously untreated locally advanced OSCC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 44 centres across Japan. Patients were randomly assigned (1:1:1) centrally via a web-based system to receive neoadjuvant doublet chemotherapy (two courses of fluorouracil [800 mg/m2 per day intravenously on days 1-5] and cisplatin [80 mg/m2 per day on day 1] separated by an interval of 3 weeks [NeoCF]), triplet chemotherapy (three courses of fluorouracil [750 mg/m2 per day on days 1-5], cisplatin [70 mg/m2 per day on day 1], and docetaxel [70 mg/m2 per day on day 1] repeated every 3 weeks [NeoCF+D]), or doublet chemotherapy (two courses of fluorouracil [1000 mg/m2 per day on days 1-4] and cisplatin [75 mg/m2 per day on day 1] separated by an interval of 4 weeks) plus 41·4 Gy radiotherapy [NeoCF+RT]) followed by oesophagectomy with regional lymph node dissection. Randomisation was stratified by T stage and institution. Participants, investigators, and those assessing outcomes were not masked to group assignment. The primary endpoint was overall survival, analysed by intention to treat. Analysis of safety included all patients who received at least one course of chemotherapy, and analysis of surgical complications included those who also underwent surgery. This study is registered with the Japan Registry of Clinical Trials, jRCTs031180202, and the trial is complete. FINDINGS: A total of 601 patients (529 male individuals and 72 female individuals) were randomly assigned between Dec 5, 2012, and July 20, 2018, with 199 patients in the NeoCF group, 202 patients in the NeoCF+D group, and 200 patients in the NeoCF+RT group. Compared with the NeoCF group, during a median follow-up period of 50·7 months (IQR 23·8-70·7), the 3-year overall survival rate was significantly higher in the NeoCF+D group (72·1% [95% CI 65·4-77·8] vs 62·6% [55·5-68·9]; hazard ratio [HR] 0·68, 95% CI 0·50-0·92; p=0·006) but not in the NeoCF+RT group (68·3% [61·3-74·3]; HR 0·84, 0·63-1·12; p=0·12). Grade 3 or higher febrile neutropenia occurred in two (1%) of 193 patients in the NeoCF group, 32 (16%) of 196 patients in the NeoCF+D group, and nine (5%) of 191 patients in the NeoCF+RT group. Treatment-related adverse events leading to termination of neoadjuvant therapy were more common in the NeoCF+D group (18 [9%] of 202 participants) than in the NeoCF+RT group (12 [6%] of 200) and NeoCF group (eight [4%] of 199). There were three (2%) treatment-related deaths during neoadjuvant therapy in the NeoCF group, four (2%) deaths in the NeoCF+D group, and two (1%) deaths in the NeoCF+RT group. Grade 2 or higher postoperative pneumonia, anastomotic leak, and recurrent laryngeal nerve paralysis were reported in 19 (10%), 19 (10%), and 28 (15%) of 185 patients, respectively, in the NeoCF group; 18 (10%), 16 (9%), and 19 (10%) of 183 patients, respectively, in the NeoCF+D group; and 23 (13%), 23 (13%), and 17 (10%) of 178 patients, respectively, in the NeoCF+RT group. The in-hospital deaths following surgery included three deaths in the NeoCF group, two deaths in the NeoCF+D group, and one in the NeoCF+RT group. INTERPRETATION: Neoadjuvant triplet chemotherapy followed by oesophagectomy resulted in a statistically significant overall survival benefit compared with doublet chemotherapy and might be the new standard of care for locally advanced OSCC who are in good condition in Japan. Neoadjuvant doublet chemotherapy plus radiotherapy did not show significant improvement of survival compared with doublet chemotherapy. FUNDING: Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund.

Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1.

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni-adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P < .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.

Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma.

BACKGROUND & AIMS: Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC. METHODS: Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/m2) on days 1-4 and cisplatin (70 mg/m2) on day 1 every 4 weeks with concurrent radiation (60 Gy). RESULTS: From December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [<1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm. CONCLUSIONS: CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

Laparoscopic Synchronous Resection for Descending Colon Cancer and Tailgut Cyst.

A 67-year-old woman underwent polypectomy for a tumor at the descending colon. Pathologically, the tumor was diagnosed as adenocarcinoma with an invasion of 2000 µm. Computed tomography showed a swollen paracolic lymph node and a mass lesion in the presacral space. Magnetic resonance imaging revealed a multio-cular cystic lesion. On diagnosis of descending colon cancer and tailgut cyst, she underwent synchronous lapa-roscopic resection. Histopathologically, the colon cancer was diagnosed as pT1bN1M0, pStage IIIa. The pre-sacral cystic lesion was diagnosed as a nonmalignant tailgut cyst with negative surgical margin. The patient is currently doing well without recurrence at 28 months.

[Successful Resection Using a Posterior Approach of a Tailgut Cyst in the Retrorectal Space].

We present the case of a Tailgut cyst occurring in the retrorectal space that was curatively resected using a posterior approach. A 40-year-old man presented to the Kochi Health Sciences Center with the chief complaint of perineal incongruity. Pelvic magnetic resonance imaging revealed a multilocular cystic lesion in the retrorectal space, with high signal intensity on T2-weighted imaging. After diagnosing a Tailgut cyst, we performed resection of the tumor using a posterior approach. The lesion was removed en bloc with the coccyx. Histopathologically, the lesion was diagnosed as a non-malignant Tailgut cyst, and the surgical margin was negative. The patient is currently doing well without recurrence at 20 months.

A Surgical Case of Inferior Mesenteric Arteriovenous Malformation.

The treatment option for inferior mesenteric arteriovenous malformations is under debate because of the number of cases. We, herein, report about a 35-year-old man with congenital inferior mesenteric artery malformation (AVM) presenting with mucous stool and severe abdominal pain. The radical operation, after building the diverting stoma, minimized the extent of the resection. This is the first reported case where surgical management was used to control severe symptoms induced by inferior mesenteric AVM.

Safety and Efficacy of the Surgical Management of Hemodialysis Patients with Gastric Cancer.

This retrospective study evaluated the short- and long-term outcomes after surgical management for gastric cancer in hemodialysis patients compared to non-dialysis patients. Twelve hemodialysis patients were compared with a propensity score-matched cohort of 39 gastric cancer patients who had not undergone hemodialysis. Short- and long-term outcomes along with scores estimating physiological ability and surgical stress were evaluated in both groups. The incidence of postoperative morbidity according to the Clavien-Dindo classification was higher in the hemodialysis gastric cancer group than in the non-dialysis gastric cancer group. The 5-year overall survival rate in the non-dialysis group was 69.2% after surgical resection for gastric cancer and 22.2% in the hemodialysis group. Patients with preoperative risk scores≥0.48 had significantly poorer survival outcomes compared to those with preoperative risk scores<0.48 (5-year survival rate, 83.3% vs. 39.4%, respectively). Our analyses suggest that hemodialysis patients undergoing surgery for gastric cancer have a significantly poorer postoperative prognosis and an elevated risk of postoperative complications.

Role of a Water Network around the Mn4CaO5 Cluster in Photosynthetic Water Oxidation: A Fourier Transform Infrared Spectroscopy and Quantum Mechanics/Molecular Mechanics Calculation Study.

Photosynthetic water oxidation takes place at the Mn4CaO5 cluster in photosystem II. Around the Mn4CaO5 cluster, a hydrogen bond network is formed by several water molecules, including four water ligands. To clarify the role of this water network in the mechanism of water oxidation, we investigated the effects of the removal of Ca(2+) and substitution with metal ions on the vibrations of water molecules coupled to the Mn4CaO5 cluster by means of Fourier transform infrared (FTIR) difference spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations. The OH stretching vibrations of nine water molecules forming a network between D1-D61 and YZ were calculated using the QM/MM method. On the the calculated normal modes, a broad positive feature at 3200-2500 cm(-1) in an S2-minus-S1 FTIR spectrum was attributed to the vibrations of strongly hydrogen-bonded OH bonds of water involving the vibrations of water ligands to a Mn ion and the in-phase coupled vibration of a water network connected to YZ, while bands in the 3700-3500 cm(-1) region were assigned to the coupled vibrations of weakly hydrogen-bonded OH bonds of water. All the water bands were lost upon Ca(2+) depletion and Ba(2+) substitution, which inhibit the S2 → S3 transition, indicating that a solid water network was broken by these treatments. By contrast, Sr(2+) substitution slightly altered the water bands around 3600 cm(-1), reflecting minor modification in water interactions, consistent with the retention of water oxidation activity with a decreased efficiency. These results suggest that the water network around the Mn4CaO5 cluster plays an essential role in the water oxidation mechanism particularly in a concerted process of proton transfer and water insertion during the S2 → S3 transition.

Surgical Management in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience.

BACKGROUND: We have revisited prognostic outcomes and recurrence patterns in patients with gastrointestinal stromal tumors (GISTs) who underwent complete surgical resection at a single institution. PATIENTS AND METHODS: Patients who underwent curative surgical treatment were divided into two groups: those with high-risk GISTs (high-risk group) and those with very low-, low-, and intermediate-risk GISTs (lower-risk group). RESULTS: A total of 109 patients who underwent surgery as an initial treatment for GIST were studied. The overall 5- and 10-year survival rates after surgery were 90.3 and 71.1%, respectively. The 5-year survival rate in high-risk group patients was 88.1%, and their overall survival rate did not vary significantly from that of the lower-risk group (5-year survival rate, 91.3%). The recurrence rate in patients with high-risk GISTs gradually increased without reaching a plateau, with a cumulative rate of GIST recurrence of 26.4 and 48.9% at 5 and 10 years after surgical treatment, respectively. CONCLUSIONS: Our data suggest that the repeat surgical management in metastatic GIST is of clinical usefulness whatever the risk and improves survival.

A randomized controlled Phase III trial comparing 2-weekly docetaxel combined with cisplatin plus fluorouracil (2-weekly DCF) with cisplatin plus fluorouracil (CF) in patients with metastatic or recurrent esophageal cancer: rationale, design and methods of Japan Clinical Oncology Group study JCOG1314 (MIRACLE study).

Chemotherapy with cisplatin plus fluorouracil is the current standard treatment for metastatic or recurrent esophageal cancer. We have developed a 2-weekly docetaxel combined with CF regimen and conducted a Phase I/II trial for metastatic or recurrent esophageal cancer (JCOG0807). Promising efficacy and safety were shown in JCOG0807, and we have commenced a Phase III trial in September 2014 to confirm the superiority of 2-weekly DCF to CF for patients with metastatic or recurrent esophageal cancer. A total of 240 patients will be accrued from 41 Japanese institutions over a period of 4 years. The primary end point is overall survival. The secondary end points are progression-free survival, response rate and proportion of adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000015107 (http://www.umin.ac.jp/ctr/index.htm).

Goblet cell carcinoid of the appendix: Six case reports.

BACKGROUND: Goblet cell carcinoid (GCC) of the appendix is a rare tumor characterized by neuroendocrine and adenocarcinoma features. Accurate preoperative diagnosis is very difficult, with most patients complaining mainly of abdominal pain. Computed tomography shows swelling of the appendix, so diagnosis is usually made incidentally after appendectomy based on a preoperative diagnosis of appendicitis. Even if a patient undergoes preoperative colonoscopy, accurate endoscopic diagnosis is very difficult because GCC shows a submucosal growth pattern with invasion of the appendiceal wall. CASE SUMMARY: Between 2017 and 2022, 6 patients with GCC were treated in our hospital. The presenting complaint for 5 of these 6 patients was abdominal pain. All 5 patients underwent appendectomy, including 4 for a preoperative diagnosis of appendicitis and the other for diagnosis and treatment of an appendiceal tumor. The sixth patient presented with vomiting and underwent ileocecal resection for GCC diagnosed from preoperative biopsy. Although 2 patients with GCC underwent colonoscopy, no neoplastic changes were identified. Two of the six patients showed lymph node metastasis on pathological examination. As of the last follow-up (median: 15 mo), all cases remained alive without recurrence. CONCLUSION: As preoperative diagnosis of GCC is difficult, this possibility must be considered during surgical treatments for presumptive appendicitis.

Efficacy of Olanzapine in Addition to Standard Triplet Antiemetic Therapy for Cisplatin-Based Chemotherapy: A Secondary Analysis of the J-FORCE Randomized Clinical Trial.

Importance: It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin. Objective: To examine the add-on effect of olanzapine according to risk factors for CINV. Design, Setting, and Participants: This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020. Interventions: Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy. Main Outcomes and Measures: The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed. Results: Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher. Conclusions and Relevance: Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676.

[Marked response to oral administration of UFT and leucovorin for liver metastases from colon cancer in an elderly patient].

A83 -year-old man was admitted to our hospital for the treatment of advanced ascending colon cancer with liver metastases. He had initially undergone an ileocecal resection for ascending colon cancer. Subsequently, we started oral administration of UFT/LV(UFT 400mg/day, LV 75 mg/day, and 4 weeks of therapy followed by a week suspension of treatment). After 3 courses, his tumors responded well to treatment, and CT showed marked regression of liver metastases. After 10 courses, liver metastases had almost disappeared. Two years passed without any adverse events since UFT/LV therapy was started. These findings suggest that UFT/LV therapy is very safe and effective for elderly patients with unresectable colorectal cancer.

A case of Epstein Barr virus-associated primary squamous cell carcinoma of stomach.

BACKGROUND: Primary squamous cell carcinoma (SCC) of stomach is extremely rare. The pathogenesis of SCC of stomach remains unclear. There is only one report that Epstein Barr virus (EBV) infection may be involved in the pathogenesis of SCC arising in the stomach ever before. Here, we report a case of Epstein Barr virus infection-associated primary SCC of stomach in a 70-year-old woman. She was presented to the referring hospital with hematemesis. Initial endoscopy revealed a bleeding gastric ulcer in the upper part of gastric corpus and the coagulation therapy was followed. After a 3-month follow-up, endoscopy revealed a submucosal tumor-like protrusion instead of an ulcer. Computed tomography revealed a mass in the upper part of stomach and swollen lymph nodes along with the lesser curvature and para-aortic lymph node. Biopsy could not confirm the definitive diagnosis. We performed total gastrectomy with para-aortic lymph node sampling. Histological analysis revealed squamous cell carcinoma with EBV infection with lymph node metastases. Tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. The postoperative course was uneventful and the patient was discharged on day 11 after the operation. CapeOX was started as adjuvant chemotherapy, and the patient remains alive without recurrence 7 months after surgery. CONCLUSION: This is the first case report of EBV infection-associated primary SCC of the stomach diagnosed by in situ hybridization of EBER. EBV infection may be related to the pathogenesis of primary SCC. Further evidence and studies are required to establish optimal strategy for this rare disease.

Hydrogen bond interactions of the pheophytin electron acceptor and its radical anion in photosystem II as revealed by Fourier transform infrared difference spectroscopy.

The primary electron acceptor pheophytin (Pheo(D1)) plays a crucial role in regulation of forward and backward electron transfer in photosystem II (PSII). It is known that some cyanobacteria control the Pheo(D1) potential in high-light acclimation by exchanging the D1 proteins from different copies of the psbA genes. To clarify the mechanism of the potential control of Pheo(D1), we studied the hydrogen bond interactions of Pheo(D1) in the neutral and anionic states using light-induced Fourier transform infrared (FTIR) difference spectroscopy. FTIR difference spectra of Pheo(D1) upon its photoreduction were obtained using three different PSII preparations, PSII core complexes from Thermosynechococcus elongatus possessing PsbA1 as a D1 subunit (PSII-PsbA1), those with PsbA3 (PSII-PsbA3), and PSII membranes from spinach. The D1-Gln130 side chain, which is hydrogen bonded to the 13(1)-keto C=O group of Pheo(D1) in PSII-PsbA1, is replaced by Glu in PSII-PsbA3 and spinach PSII. The spectrum of PSII-PsbA1 exhibited 13(1)-keto C=O bands at 1682 and 1605 cm(-1) in neutral Pheo(D1) and its anion, respectively, while the corresponding bands were observed at frequencies lower by 1-3 and 18-19 cm(-1), respectively, in the latter two preparations. This larger frequency shift in Pheo(D1)(-) than Pheo(D1) by the change of the hydrogen bond donor was well reproduced by density functional theory (DFT) calculations for the Pheo models hydrogen bonded with acetamide and acetic acid. The DFT calculations also exhibited a higher redox potential for Pheo reduction in the model with acetic acid than that with acetamide, consistent with previous observations for the D1-Gln130Glu mutant of Synechocystis. It is thus concluded that a stronger hydrogen bond effect on the Pheo(-) anion than the neutral Pheo causes the shift in the redox potential, which is utilized in the photoprotection mechanism of PSII.

A case of stage IV gastric cancer with para-aortic lymph node metastasis showing pathological complete response after neoadjuvant chemotherapy.

BACKGROUND: Stage IV advanced gastric cancer with para-aortic lymph node metastasis (PALM) is considered unresectable. Systemic chemotherapy is the treatment of choice for such tumors, while conversion surgery may be a treatment option in the case chemotherapy is effective but R0 resection is possible. We report a case of stage IV gastric cancer with PALM that showed pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) using S-1, oxaliplatin, and trastuzumab (SOX+HER). CASE PRESENTATION: A 69-year-old woman who was diagnosed with type 4 stage IV gastric cancer with PALM underwent five courses of NAC with the SOX+HER regimen. The primary tumor and the PALM shrank after treatment, suggesting that the NAC induced a partial response. We performed a total gastrectomy plus distal pancreaticosplenectomy with para-aortic lymph node dissection. Histological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. The postoperative course was uneventful, and the patient was discharged on day 14 after the operation. S-1 was started as adjuvant chemotherapy, and the patient remains alive without recurrence 2 months after surgery. CONCLUSION: This case shows the possibility of conversion surgery after SOX+HER therapy for stage IV advanced gastric cancer with PALM.

A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis in Heart and Kidney Transplant Recipients in Japan.

BACKGROUND: Recently, chronic hepatitis E has been reported in solid organ transplant (SOT) recipients in European countries. Previously, we clarified the prevalence of hepatitis E virus (HEV) infection in Japanese liver transplant recipients and identified 2 chronic hepatitis E patients infected by blood transfusion. However, the rate of HEV infection in recipients of SOTs other than liver in Japan remains unclear, so we conducted a nationwide survey to clarify the prevalence of chronic HEV infection in Japanese heart and kidney transplant recipients. METHODS: A total of 99 heart and 2526 kidney transplant recipients in 17 hospitals in Japan were examined for the presence of the IgG class of anti-HEV antibodies as well as for serum HEV RNA. RESULTS: The prevalence of anti-HEV IgG among heart and kidney transplant recipients was 7.07% (7/99) and 4.08% (103/2526), respectively. One heart transplant patient (1.01%) and 11 kidney transplant patients (0.44%) were found to be positive for HEV RNA. The HEV isolates from all viremic patients were typed as genotype 3. Four patients developed chronic hepatitis E after transplantation. Three patients were treated with ribavirin; their liver enzymes normalized, and HEV RNA became negative immediately. Sustained virologic response was achieved in all cases. CONCLUSIONS: This is the first nationwide survey of HEV infection in Japanese heart and kidney transplant recipients. The prevalence of anti-HEV IgG and HEV RNA in heart and kidney transplant recipients in Japan was lower than that in European countries. Of note, 42% of viremic transplant patients developed chronic hepatitis.

Efficacy of lenvatinib in a patient with anaplastic thyroid cancer.

We experienced a case of an 82-year-old woman who presented to our hospital with a 1-month history of dysphagia and dyspnea. Cervical contrast-enhanced computed tomography revealed diffuse thyroid neoplasms causing significant tracheal stenosis with tumors, particularly of the superior mediastinum, which were associated with an embolism of the brachiocephalic vein and suspected invasion to the bilateral common carotid arteries. Anaplastic thyroid cancer (ATC) was diagnosed by fine-needle aspiration; thus, emergency tracheostomy and gastrostomy were performed. We made a definitive diagnosis of ATC (T4bN0M0 Stage IVB) and initiated continuous lenvatinib administration at 24 mg/day. Although several adverse events occurred, the tumor size reduced remarkably over a short period. However, the patient died from rupture of the common carotid artery 30 days after treatment initiation. Here, we report our experience with lenvatinib therapy for ATC and include a literature review. LEARNING POINTS: Lenvatinib is extremely effective for ATC.Lenvatinib has a much greater cytoreductive effect than traditional therapies, but it needs dose reduction or withdrawal because of treatment-related side effects.Lenvatinib may cause treatment-related carotid blowout syndrome, resulting in death for patients with invasion to the carotid artery.

[Two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP].

We report two resected cases of advanced gastric cancer with peritoneal dissemination after successful treatment with TS-1 plus low-dose CDDP. Patient 1 presented with right hypochondralgia and underwent laparotomy with diagnosis of type 4 gastric cancer by gastrointestinal fiberscopy. However, the tumor was judged to be unresectable due to peritoneal dissemination, and chemotherapy was performed. At the completion of course 1, he underwent laparotomy again. Although the tumor involved the body of the pancreas and transverse colon, there was no peritoneal dissemination. Therefore, a total gastrectomy was performed with distal pancreatectomy, partial colectomy, cholecystectomy, and D2 lymph node dissection. Patient 2 presented with anorexia and was diagnosed with type 3 gastric cancer by gastrointestinal fiberscopy. CT revealed the tumor was unresectable due to peritoneal dissemination, and so chemotherapy was performed. He underwent laparotomy at the completion of course 3. There was no peritoneal dissemination, so a total gastrectomy was performed with cholecystectomy and D2 lymph node dissection. Both patients remain alive and in good condition without any signs of recurrence after surgery.

Formation and reinforcement of clusters composed of C60 molecules.

We carry out two experiments: (1) the formation of clusters composed of C60 molecules via self-assembly and (2) the reinforcement of the clusters. Firstly, clusters such as fibres and helices composed of C60 molecules are produced via self-assembly in supercritical carbon dioxide. However, C60 molecules are so weakly bonded to each other in the clusters that the clusters are broken by the irradiation of electron beams during scanning electron microscope observation. Secondly, UV photons are irradiated inside a chamber in which air is filled at 1 atm and the above clusters are placed, and it was found that the clusters are reinforced; that is, they are not broken by electron beams any more. C60 molecules located at the surface of the clusters are oxidised, i.e. C60On molecules, where n = 1, 2, 3 and 4, are produced according to time-of-flight mass spectroscopy. It is supposed that oxidised C60 molecules at the surface of the clusters may have an important role for the reinforcement, but the actual mechanism of the reinforcement of the clusters has not yet been clearly understood and therefore is an open question.