CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers. We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR). Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018). This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

C-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

Recurrent laryngeal nerve palsy remains a significant complication following minimally invasive esophagectomy for esophageal cancer. Despite advancements in surgical techniques and lymphadenectomy precision, the incidence of recurrent laryngeal nerve palsy has not been improved. Recurrent laryngeal nerve palsy predominantly affects the left side and may lead to unilateral or bilateral vocal cord paralysis, resulting in hoarseness, dysphagia, and an increased risk of aspiration pneumonia. While most cases of recurrent laryngeal nerve palsy are temporary and resolve within 6 to 12 months, some patients may experience permanent nerve dysfunction, severely impacting their quality of life. Prevention strategies, such as nerve integrity monitoring, robotic-assisted minimally invasive esophagectomy, and advanced dissection techniques, aim to minimize nerve injury, though their effectiveness varies. The management of recurrent laryngeal nerve palsy includes voice and swallowing rehabilitation, reinnervation techniques, and, in severe cases, surgical interventions such as thyroplasty and intracordal injection. As recurrent laryngeal nerve palsy can lead to significant postoperative respiratory complications, a multidisciplinary approach involving surgical precision, early detection, and comprehensive rehabilitation is crucial to improving patient outcomes and minimizing long-term morbidity in minimally invasive esophagectomy. This review article aims to inform esophageal surgeons and other clinicians about strategies for the prevention and management of recurrent laryngeal nerve palsy in esophagectomy.

Superior posterior pulmonary vein anomaly in the right upper lobe (anomalous V2), which is one of the anomalies of the right superior pulmonary vein (RSPV), runs behind the right main or intermediate bronchus. Although this rarely occurs, attention should be given to this venous anomaly during thoracoscopic esophagectomy with subcarinal lymph node dissection. Here, we report a case of thoracoscopic esophagectomy with subcarinal lymph node dissection in the prone position for lower thoracic esophageal cancer with anomaly of the superior posterior pulmonary vein in the right lobe (anomalous V2). A 61-year-old man was diagnosed as having lower esophageal cancer with swelling of multiple lymph nodes in the mediastinum and abdomen. His clinical diagnosis based on the eighth TNM classification system was cT3 N2 M0 stage IIIB. In addition, an anomalous V2 was recognized on preoperative computed tomography imaging before the operation. The vein ran behind the intermediate bronchus and drained into the RSPV located at the area of the subcarinal lymph node. We performed preoperative simulation by using virtual thoracoscopic imaging with the same view as that during operation to help us better dissect the lymph nodes. As a result, thoracoscopic esophagectomy and subcarinal lymph node dissection were performed in the prone position without injuring the anomalous V2. Severe complications did not occur in the postoperative course except for paralysis of the left recurrent laryngeal nerve. The patient was discharged on postoperative day 17. Injury to an anomalous V2 can cause severe hemorrhage during subcarinal lymph node dissection in esophagectomy. Preoperative simulation by using virtual thoracoscopic imaging is useful to avoid this complication in patients with an anatomical anomaly.

Pancreatic cancer with distant metastases is classified as “unresectable,” for which the standard treatment is systemic chemotherapy. The effectiveness of radical resection for pancreatic cancer with distant metastases is unknown. Here, we report a case of long term survival treated with conversion surgery following chemotherapy after diagnostic metastasectomy for pancreatic cancer with synchronous liver metastasis. A 73-year-old man was referred to our hospital to examine and treat for cancer of the pancreatic body. Computed tomography (CT) scan revealed a 26-mm hypovascular tumor in contact with the common hepatic artery (CHA) (> 180°), the celiac artery (< 180°), and portal vein at the pancreatic body. Resectability was determined as “borderline resectable.” Two courses of gemcitabine plus S-1 combination therapy (GS) were administered as neoadjuvant chemotherapy (NAC). CT scan showed tumor shrinkage (21 mm), determined as stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST). Although the abdomen was opened for radical resection, a small nodule on the liver was detected and removed. Since the nodule was diagnosed as adenocarcinoma by intraoperative frozen section, resection of the primary tumor was not performed. After three subsequent courses of GS therapy, no distant metastases were detected under radiological findings. Distal pancreatectomy with celiac artery resection (DP-CAR) was performed as radical surgery 6 months after the initial diagnosis. Histological diagnosis was well-differentiated tubular adenocarcinoma, showing ypT1 ypN1 M1 stage IV, negative surgical margin (R0), and grade III in the Evans classification. S-1 was administered every other day from 6 months after resection up to the present. The patient has been alive with no recurrence for 5 years after the initial diagnosis and 4.5 years after the resection. There is a case that received survival benefits from conversion surgery following chemotherapy after diagnostic metastasectomy in pancreatic cancer with synchronous liver metastasis.

Von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas-sparing resection should be considered for patients with pancreatic neuroendocrine tumors and complete cystic replacement of the pancreas to preserve quality of life after surgery.