A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study).

Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

Prognostic nutritional index is a prognostic factor for patients with gastric cancer and esophagogastric junction cancer undergoing proximal gastrectomy with esophagogastrostomy by the double-flap technique: A secondary analysis of the rD-FLAP study.

PURPOSE: Although proximal gastrectomy (PG) is commonly used in patients with upper gastric cancer (GC) and esophagogastric junction (EGJ) cancer, long-term prognostic factors in these patients are poorly understood. The double-flap technique (DFT) is an esophagogastrostomy with anti-reflux mechanism after PG; we previously conducted a multicenter retrospective study (rD-FLAP) to evaluate the short-term outcomes of DFT reconstruction. Here, we evaluated the long-term prognostic factors in patients with upper GC and EGJ cancer. METHODS: The study was conducted as a secondary analysis of the rD-FLAP Study, which enrolled patients who underwent PG with DFT reconstruction, irrespective of disease type, between January 1996 and December 2015. RESULTS: A total of 509 GC and EGJ cancer patients were enrolled. Univariate and multivariate analyses of overall survival demonstrated that a preoperative prognostic nutritional index (PNI) < 45 (p < 0.001, hazard ratio [HR]: 3.59, 95% confidential interval [CI]: 1.93-6.67) was an independent poor prognostic factor alongside pathological T factor ([pT] ≥2) (p = 0.010, HR: 2.29, 95% CI: 1.22-4.30) and pathological N factor ([pN] ≥1) (p = 0.001, HR: 3.27, 95% CI: 1.66-6.46). In patients with preoperative PNI ≥45, PNI change (<90%) at 1-year follow-up (p = 0.019, HR: 2.54, 95%CI: 1.16-5.54) was an independent poor prognostic factor, for which operation time (≥300 min) and blood loss (≥200 mL) were independent risk factors. No independent prognostic factors were identified in patients with preoperative PNI <45. CONCLUSIONS: PNI is a prognostic factor in upper GC and EGJ cancer patients. Preoperative nutritional enhancement and postoperative nutritional maintenance are important for prognostic improvement in these patients.

Head and Neck Arteriovenous Malformations: Clinical Manifestations and Endovascular Treatments.

Arteriovenous malformations (AVMs) are vascular malformations that present high-flow direct communication between the arteries and veins, not involving the capillary beds. They can be progressive and lead to various manifestations, including abnormal skin or mucosal findings, ischemia, hemorrhage, and high-output heart failure in severe cases. AVMs often involve the head and neck region. Head and neck AVMs can present region-specific clinical manifestations, angioarchitecture, and complications, especially in cosmetic appearance and ingestion, respiratory, and neuronal functions. Therefore, when planning endovascular treatment of head and neck AVMs, physicians should consider not only the treatment strategy but also the preservation of the cosmetic appearance and critical functions. Knowledge of the functional vascular anatomy as well as treatment techniques should facilitate a successful management. This review summarizes AVMs' clinical manifestations, imaging findings, treatment strategy, and complications.

Value of fat-suppressed T2-weighted imaging for predicting short-term pain relief after sclerotherapy for venous malformations in the extremities.

PURPOSE: This study aimed to evaluate the value of fat-suppressed T2-weighted imaging (FS-T2WI) for predicting short-term pain relief after polidocanol sclerotherapy for painful venous malformations (VMs) in the extremities. MATERIALS AND METHODS: This retrospective study included patients with painful VMs in the extremities between October 2014 and September 2021, had their first sclerotherapy without history of surgical therapy, and underwent magnetic resonance imaging before sclerotherapy. Pain relief was assessed 2 months after 3% polidocanol sclerotherapy and was categorized as follows: progression, no change, partial relief, or free of pain. The associations between pain relief and imaging features on FS-T2WI were analyzed. RESULTS: The study included 51 patients. The no change, partial relief, and free of pain groups included 6 (11.8%), 25 (49.0%), and 20 (39.2%) patients, respectively. No patient experienced progressive pain. The lesion diameter was ≤ 50 mm in 13 (65.0%) patients in the free of pain group, whereas it was > 50 mm in all patients in the no change group (p = 0.019). The lesions showed well-defined margin in 15 (75.0%) patients in the free of pain group, whereas they showed ill-defined margin in 5 (83.3%) patients in the no change group (p = 0.034). The most common morphological type was cavitary in the free of pain group (14 [70.0%] patients), whereas there was no patient with cavitary type lesion in the no change group (p = 0.003). Drainage vein was demonstrated in 6 (100%), 22 (88.0%), and 11 (55.0%) patients in the no change, partial relief, and free of pain group, respectively (p = 0.011). CONCLUSION: A lesion size of 50 mm or less, a well-defined margin, a cavitary type, and no drainage vein on FS-T2WI were significant features for predicting short-term pain relief after polidocanol sclerotherapy for painful VMs in the extremities.

Incidence of Metachronous Remnant Gastric Cancer after Proximal Gastrectomy with the Double-flap Technique (rD-FLAP-rGC Study): A Multicenter, Retrospective Study.

BACKGROUND: Although proximal gastrectomy (PG) with the double-flap technique (DFT) is a function-preserving surgery that prevents esophagogastric reflux, there is a risk of developing metachronous remnant gastric cancer (MRGC). Moreover, details of MRGC and appropriate postoperative follow-up after PG with DFT are unclear. METHODS: We reviewed the medical records of 471 patients who underwent PG with DFT for cancer in a preceding, multicenter, retrospective study (rD-FLAP Study). We investigated the incidence of MRGC, frequency of follow-up endoscopy, and eradication of Helicobacter pylori (H. pylori) infection. RESULTS: MRGC was diagnosed in 42 (8.9%) of the 471 patients, and 56 lesions of MRGC were observed. The cumulative 5- and 10-year incidence rates were 5.7 and 11.4%, respectively. There was no clinicopathological difference at the time of primary PG between patients with and without MRGC. Curative resection for MRGC was performed for 49 (88%) lesions. All patients with a 1-year, follow-up, endoscopy interval were diagnosed with early-stage MRGC, and none of them died due to MRGC. Overall and disease-specific survival rates did not significantly differ between patients with and without MRGC. The incidence rate of MRGC in the eradicated group after PG was 10.8% and that in the uneradicated group was 19.6%, which was significantly higher than that in patients without H. pylori infection at primary PG (7.6%) (p = 0.049). CONCLUSIONS: The incidence rate of MRGC after PG with DFT was 8.9%. Early detection of MRGC with annual endoscopy provides survival benefits. Eradicating H. pylori infection can reduce the incidence of MRGC.

Super-selective and staged glue embolization for labral AVMs using ultra-thin microcatheters: report of two cases.

BACKGROUND: Treating arteriovenous malformation (AVM) is challenging because of the high recurrence rate and because incomplete resection or embolization can induce aggressive growth. However, a standard strategy is not fully established. Although transcatheter arterial embolization (TAE) is currently almost always part of the treatment, in many cases, single treatment is not curative and only palliative. Additionally, the success and complication rates associated with TAE alone are unclear, and there has been limited study of staged TAE for facial AVMs. Furthermore, few reports have described the details of the procedure. CASE-PRESENTATION: We report two cases of AVM of the upper lip in patients who were successfully treated by staged super-selective TAE at several-month intervals using ultra-thin microcatheters and n-butyl-2-cyanoacrylate. CONCLUSION: Staged and super-selective TAE may prevent complications and provide high curability and might be a useful treatment in cases of AVM.

Stent graft placement guided by intravascular ultrasound for subclavian artery dissecting aneurysm.

Subclavian artery dissecting aneurysm is relatively rare and can be caused by traumatic, nontraumatic, and iatrogenic etiologies. Surgical management of subclavian artery dissecting aneurysm has been sparsely reported. Recently, due advances in endovascular techniques making them less invasive, these approaches have become more standard as treatments. Subclavian artery dissecting aneurysm management usually depends on whether there is ischemia of the tissues supplied by the subclavian artery. Furthermore, treatment strategies depend on which section of the artery is involved. In particular, treatment is difficult if the dissecting aneurysm has branching vessels. In this case report, we show that endovascular repair using a covered stent graft is a promising approach to repair a subclavian artery dissecting aneurysm. In this case, the stent graft was highly effective, and follow-up examinations showed good patency of the subclavian artery. Additional use of IVUS (Volcano Inc.; Rancho Cordova, CA, USA) is helpful to obtain the precise location of the true lumen of a dissecting aneurysm.

Comparative Treatment Outcome in T3N0 Glottic Cancer With and Without Vocal Fold Fixation Receiving Radiation Therapy and Concurrent Low-Dose Intra-Arterial Cisplatin Infusion.

OBJECTIVES: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. METHODS: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. RESULTS: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). CONCLUSIONS: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.

Conversion surgery of Stage IV gastric cancer with peritoneal dissemination after nivolumab.

A 69-year-old man was clinically diagnosed as stage IV gastric cancer with peritoneal dissemination. We performed systemic chemotherapy consisting of S-1 plus oxaliplatin as a first line, and ramucirumab plus nab-paclitaxel as a second line. However, CT and EGD revealed growth of the primary tumor and the lymph nodes along the lesser curvature and adjacent to the cardia. In addition, CT revealed ascites in the rectovesical pouch. Therefore, treatment was switched to nivolumab. After 3 treatment courses, CT revealed shrinkage of lymph nodes and disappearance of ascites. After 12 courses of nivolumab, however, EGD revealed growth of the tumors in the stomach with minor hemorrhage, prompting the consideration of gastrectomy. At the time of laparotomy, the peritoneal dissemination had completely disappeared, and peritoneal cytology was negative. Therefore, total gastrectomy with D2 and paraaortic lymphadenectomy was performed, after 21 months following the initial diagnosis. To our knowledge, there are no previous reports that have demonstrated the disappearance of peritoneal dissemination and ascites in response to nivolumab, resulting in curative gastrectomy.

Efficacy and Safety of Ramucirumab/nab-paclitaxel for Previously Treated Advanced Gastric Cancer in Community Hospitals.

As the nanoparticle albumin-bound paclitaxel (nab-PTX) is free of ethanol and premedication, the duration of administration is shorter and patients can drive themselves to and from the hospital. In the 2018 Japanese gastric cancer treatment guidelines, ramucirumab (RAM) plus weekly nab-PTX is conditionally recommended for previously treated patients with advanced gastric cancer. Here, we retrospectively analysed the efficacy and safety of RAM+nab-PTX for such patients in community hospitals. From January 2018 to December 2019, 43 patients with metastatic and recurrent gastric cancer received RAM+nab-PTX treatment. Six patients (13.9%) were older than 80 years and 9 patients (20.9%) showed ECOG-PS 2. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were reviewed retrospectively. Median PFS was 114 days (95% confidence interval [CI]: 84-190) and median OS was 297 days (95% CI: 180-398). ORR and DCR were 32.4% and 72.2%, respectively. The incidence rates of ≥grade 3 neutropenia and febrile neutropenia were 53.5% and 2.3%, respectively. No treatment-related deaths occurred. RAM plus nab-PTX combination therapy demonstrated manageable toxicity even patients who were elderly or had an ECOG-PS 2. This treatment is useful in community hospital settings.

Predictive value of CD8/FOXP3 ratio combined with PD-L1 expression for radiosensitivity in patients with squamous cell carcinoma of the larynx receiving definitive radiation therapy.

BACKGROUND: Little is known about immune-related radiosensitivity in patients with squamous cell carcinoma of the larynx (SCC-L) treated with radiation therapy (RT). METHODS: We retrospectively reviewed 91 patients with SCC-L treated with RT or chemoradiation therapy and performed immunohistochemical examination to analyze PD-L1 level on tumor cells, CD4+ tumor-infiltrating lymphocytes (TILs), CD8+ TIL, and FOXP3+ TIL using pretreated biopsy specimens. The association between these immune-related parameters and radiosensitivity was evaluated. RESULTS: Multivariate analyses showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression was an independent and significant favorable predictive factor for local control, compared with the other groups. CONCLUSIONS: We showed that high CD8/FOXP3 ratio combined with negative PD-L1 expression might be a useful biomarker of radiosensitivity in patients with SCC-L receiving definitive RT. We propose that coassessment of CD8/FOXP3 ratio and PD-L1 expression level in tumor cells can help predict potential radiosensitivity in patients with SCC-L.

Follow-up non-contrast MRA after treatment of intracranial aneurysms using microcoils with prominent metallic artifact: a comparative study of TOF-MRA and Silent MRA.

PURPOSE: Some of the detachable microcoils are associated with the prominent metallic artifact. We have applied Silent MRA to reduce the artifact. In this study, we present a retrospective study in which Silent MRA is used for cases showing prominent metallic artifact on conventional TOF-MRA due to a detachable bare platinum microcoil (Barricade coil). MATERIALS AND METHODS: Fifteen patients, who had undergone endosaccular embolization using Barricade coil and other detachable microcoils up to 3 days previously, were scanned with TOF-MRA and silent MRA at the same time. The treatment DSA and follow-up MRA images were graded by two experienced neuroradiologists, focusing on the visibility of residual aneurysm and parent arterial lumen. RESULTS: DSA images showed residual aneurysm (RA) in four, residual neck (RN) in six, and complete occlusion (CO) in five patients. TOF-MRA images showed RN in five, CO in four, mild defect (MD) in one, severe defect (SD) in three, and complete defect in two. In contrast, on Silent MRA, the grades were RA in two, RN in five, CO in five, and MD in three. CONCLUSION: Barricade coils are associated with prominent metallic artifact on TOF-MRA. Silent MRA is useful for follow-up MRA after embolization using Barricade coils. The metallic artifacts were compared between TOF-MRA and Silent MRA in patients treated by using Barricade coils. Barricade coils are associated with more metallic artifact on TOF-MRA than Silent MRA. Silent MRA is useful for follow-up MRA after embolization using Barricade coils.

Organ preservation following radiation therapy and concurrent intra-arterial low dose cisplatin infusion for advanced T2 and T3 laryngeal cancer: Long-term clinical results from a pilot study.

BACKGROUND: This pilot study evaluated the long-term outcomes of patients with advanced T2 or T3 squamous cell carcinoma of the larynx (SCC-L) who were treated with selective intra-arterial cisplatin and concomitant radiotherapy (RADPLAT). METHODS: We retrospectively investigated the data of 49 patients with advanced T2 or T3 SCC-L who received a RADPLAT regimen with low-dose cisplatin. RESULTS: The 5-year locoregional control, disease-specific survival, and overall survival rates were 83.3%, 88.1%, and 82.6%, respectively, while the 5-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates were 89.6%, 79.4%, and 77.1%, respectively. The incidences of grade 3-4 hematologic and nonhematologic toxicities were 18% and 6%, respectively. Although two patients (4%) developed late toxicities within 5 years following RADPLAT, no other events were noted beyond 5 years. CONCLUSION: This pilot study demonstrated that RADPLAT is feasible and safe and yielded favorable survival outcomes and functional laryngeal preservation in patients with advanced T2 or T3 SCC-L. LEVEL OF EVIDENCE: 3.

[Cancer of the Ascending Colon Diagnosed at the Same Time as Breast Cancer Following Leukemia Treatment for Which Laparoscopic Surgery Was Performed-A Case Report].

An 83-year-old woman received 8 courses of chemotherapy(mogamulizumab)for adult T cell leukemia in the hematolo- gy department of our hospital, after which she achieved complete remission and was followed up with chemotherapy(VP/ MST: sobuzoxane/etoposide)as an outpatient. Later, diarrheal symptoms appeared, and detailed examinations led to a diagnosis of cancer of the ascending colon. Although no distal metastasis was found, breast cancer was also revealed in the C area of the right breast. The general status of the patient was favorable; thus, right pectoral muscle-conserving mastectomy and concomitant sentinel lymph node biopsy were performed through laparoscope-assisted extended right hemicolectomy. The postoperative course was favorable, and she was discharged on hospital day 7. The excised tumors were pathologically diagnosed as stageⅠ breast cancer and stage Ⅲa colorectal cancer. Chemotherapy(VP/MST)was administered without adjuvant chemotherapy. Presently, 18 months after surgery, complete remission of adult T cell leukemia has been maintained, without metastasis and recurrence of cancer of the ascending colon and breast cancer.

Multicenter retrospective study to evaluate the efficacy and safety of the double-flap technique as antireflux esophagogastrostomy after proximal gastrectomy (rD-FLAP Study).

AIM: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. METHODS: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. RESULTS: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). CONCLUSION: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

A Rare Case of Cerebral Air Embolism Caused by Pulmonary Arteriovenous Malformation After Removal of a Central Venous Catheter.

Cerebral air embolism following central venous catheter (CVC) removal is extremely rare. We report a case of cerebral air embolism with loss of consciousness after removal of CVC caused by pulmonary arteriovenous malformation (PAVM). Computed tomography revealed air bubbles in the internal carotid arteries along the sulci in the cerebral hemispheres, as well as a PAVM. The cerebral air embolism was treated with hyperbaric oxygen and intravenous thrombolytic therapy, and transcatheter embolization of the PAVM was performed. When inserting/removing CVC in a patient with a small PAVM, treatment of the PAVM, irrespective of its size, could prevent the type of complication that occurred in our present case.

A multi-institution phase II study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer (DASH study).

BACKGROUND: Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated. METHODS: This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m2 on day 1 of each cycle. S-1 was administered at a dosage based on body surface area for 14 days in a 3-weekly cycle. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%). CONCLUSION: Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

Expression and functional analysis of apple MdMADS13 on flower and fruit formation.

Apple MdMADS13 has a transcription factor with MADS domain. Moreover, it is expressed specifically at petals and carpels. The product forms a dimer with MdPISTILLATA (MdPI) protein as a class B gene for floral organ formation. Reportedly, in parthenocarpic cultivars of apple (Spencer Seedless, Wellington Bloomless, Wickson and Noblow) the MdPI function is lost by genome insertion of retrotransposon, which cultivars show a homeotic mutation of floral organs, petals to sepals and stamens to carpels. Apple fruit is pome from receptacle tissue, and MdSEPALLATA (MdMADS8/9) and AGAMOUS homologues MdMADS15/22 involved in the fruit development, the transgenic apple suppressed these gene showed poor fruit development and abnormal flower formation. This article describes that the MdMADS13 retained expression after blossom and small fruits of parthenocarpic cultivars. Yeast two-hybrid experiment showed specific binding between MdPI and MdMADS13 proteins. Furthermore, transgenic Arabidopsis with 35S::MdMADS13 have malformed stamens and carpels. These results suggest strongly that MdMADS13 is related to flower organ formation as a class B gene with MdPI.