HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug–drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3–‍34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9–‍81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1–NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. FIH study, NCT02564900; DDI study, NCT03383692

Aim: The objective of this retrospective, single‐institution study was to assess the safety and feasibility of reconstruction using subtotal stomach (SS) with esophagectomy for patients with esophageal cancer (EC). Although several different gastric‐tube‐making and anastomotic methods have been reported, the incidence rate of anastomotic leakage with EC surgery is generally reported over 10%. Complications should be avoided, and patient quality of life (QOL) should be maintained postoperatively. We have used SS reconstruction and hand‐sutured cervical esophagus‐subtotal gastric anastomosis at the neck wound in EC surgery. Short‐ and long‐term outcomes in cases using SS are not well known.Methods: Between January 2008 and September 2019, 300 patients underwent esophagectomy for EC and reconstruction using SS. The primary endpoint was the rate of anastomotic leakage. Secondary endpoints were postoperative morbidities, QOL, and changes in patients’ body weight and skeletal muscle weight.Results: Anastomotic leakage was observed in two patients (0.67%), and pneumonia was observed in nine patients (3.0%). Fifteen patients (5.0%) had an anastomotic stenosis requiring a bougie. Nausea occurred in 11 patients (3.7%), and dumping syndrome occurred in seven patients (2.3%). Dysphagia and early feeling of abdominal fullness scores tended to be high after surgery but gradually decreased after 6 months. Good results were obtained for reflux feeling scores. Body weight changed with an average decrease of −2 ± 3.71 kg (P = .071) over 5 years.Conclusion: Reconstruction using SS resulted in an extremely low rate of anastomotic leakage and good QOL postoperatively in patients with EC.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO) has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS) production and apoptotic rate, and upregulated the caspase-3/7 pathway. Furthermore, these effects of 7KCHO were abolished by pre-incubation of the cells with N-acetylcysteine (NAC), an ROS inhibitor. Also, 7KCHO enhanced the mRNA expression of two endoplasmic reticulum (ER) stress markers; CHOP and GRP78, in MC3T3-E1 cells. Pre-incubation of the cells with NAC suppressed the 7KCHO-induced upregulation of CHOP, but not GRP78. In conclusion, we demonstrated that 7KCHO induced apoptosis of MC3T3-E1 cells associated with ROS generation, ER stress, and caspase-3/7 activity, and the effects of 7KCHO were abolished by the ROS inhibitor NAC. These findings may provide new insight into the relationship between oxysterol and pathophysiology of osteoporosis seen in T2DM.

Background: We report two rare cases of retroperitoneal schwannoma completely resected by a laparoscopic medial-retroperitoneal approach aided by virtual navigation. Three-dimensional images have been used in liver and lung surgery, but there are few prior reports on retroperitoneal surgery. Case presentation: These two case reports are of a 60-year-old man and a 40-year-old man with asymptomatic retroperitoneal schwannoma. In both cases, the tumors were located in the right renal hilum and were close to the duodenum, right ureter, and inferior vena cava. Simulation using three-dimensional images was performed before surgery, and a medial-retroperitoneal approach was performed to secure a wide surgical field. During the operation, we confirmed the location of the main feeder and the relationship between the tumor and organs with those shown on the three-dimensional images and performed total laparoscopic resection. Conclusion: The medial-retroperitoneal approach provides operative safety. Preoperative simulation and intraoperative navigation with three-dimensional images, which can be freely rotated and interactively visualized from any angle, are useful methods to enhance the surgeon’s understanding of a patient’s specific anatomy and are especially effective when resecting a retroperitoneal tumor that is located in an anatomically deep and complex location.

Background: Even if 3D angiographic images of preoperative contrast-enhanced computed tomography (CT) are created, the coronal and axial sections can be unclear, and thus, it is difficult to achieve projection awareness similar to that of actual laparoscopic images. In recent years, the technology of analyzing and applying medical images has advanced, and surgical simulation and navigation have been widely used to improve the safety of surgical operations. It is important to understand pelvic anatomy in the area of rectal cancer, and use of the SYNAPSE VINCENT makes it possible to simulate the anatomy before surgery, which is very useful in educating surgeons and their assistants.Materials and methods: An important objective in surgery is to understand the anatomy of the external/internal iliac arteries and lymph nodes in lateral lymph node dissection (LLD) for rectal cancer. In this study, we explored the accuracy and usefulness of SYNAPSE VINCENT images of pelvic anatomy (especially vascular anatomy) analyzed preoperatively in two cases of LLD for rectal cancer in our department.Results: The patients were two men aged 73 and 57 years, respectively. Both patients underwent robotic abdominal perineal resection and LLD with neoadjuvant chemoradiotherapy. The operating times for LLD were 138 and 106 min, estimated blood loss was less than 10 mL and 20 mL, and the harvested lymph nodes were nos. 21 and 22, respectively. The SYNAPSE VINCENT could be used for simulation and navigation before and during surgery. For experienced surgeons, the system helped them carry out operations more accurately.Conclusion: In the future, surgical support using virtual reality, augmented reality, and mixed reality based on medical images will be useful and is expected to improve the safety, accuracy, and efficiency of surgery, which is extremely useful for both young and skilled surgeons preparing for difficult operations.

With recent advances in endoscopic treatment, many T1 colorectal carcinomas (CRCs) are resected endoscopically with a negative margin. However, some lesions exhibit skip lymphovascular invasion (SLVI), which is defined as the discontinuous foci of the tumor cells within the colon wall. The aim of the present study was to reveal the clinicopathological features of T1 CRCs with SLVI and validate the Japanese guidelines regarding SLVI. A total of 741 patients with T1 CRCs that were resected surgically between April 2001 and October 2016 in our hospital were divided into two groups: With SLVI and without SLVI. Clinicopathological features compared between the two groups were patient's gender, age, tumor size, location, morphology, lymphovascular invasion, tumor differentiation, tumor budding and lymph node metastasis. The incidence of T1 CRCs with SLVI was 0.9% (7/741). All cases with SLVI were found in the sigmoid colon or rectum. T1 CRCs with SLVI showed significantly higher rates of lymphovascular invasion than those without SLVI (P<0.01). In conclusion, lymphovascular invasion was a significant risk factor for SLVI in T1 CRCs, and for which surgical colectomy was necessary. The Japanese guidelines are appropriate regarding SLVI. Registered in the University Hospital Medical Network Clinical Trials Registry (UMIN000027097).