Takayoshi Kishino

Diagnosis and Surgical Outcomes for Primary Malignant Melanoma of the Esophagus: A Single-Center Experience

BACKGROUND We summarize the experience of diagnosis and surgical therapy for primary malignant melanoma of the esophagus (PMME). METHODS Clinical data of 13 patients diagnosed as having PMME treated by surgery as their primary therapy from 2000 to 2012 were retrospectively analyzed, and survival information was collected through follow-up. RESULTS The average age (±standard deviation) of participants in this study was 66.4±7.6 years, and 84.6% were male. Overall, 61.5% of tumors were located in the lower thoracic esophagus. The accuracies of clinical T stage, N stage, and TNM stage were 53.9%, 46.2%, and 38.5%, respectively, compared with pathological staging (kappa=0.252, p=0.023). Surgical mortality and morbidity were 7.7% and 53.9%, respectively. The incidence of lymph node metastasis for patients with tumor invading within the mucosa was 0, but increased to 42.9% (3 of 7) with tumor invading to the submucosal layer. Primary malignant melanoma of the esophagus in the mid third of the thoracic esophagus had a greater chance to metastasize to perigastric lymph nodes (2 of 5) than to middle mediastinal lymph nodes (1 of 5). For PMME located at the lower third of the thoracic esophagus, upper mediastinal lymph node metastasis was more likely to occur (2 of 4) with tumor invasion penetrating the proper muscle layer. Recurrence occurred within 1 year in all patients with tumor later than Stage Ib. The most common recurrent organ was the liver. The overall 1-year and 5-year postoperative survival rates were 54.0% and 35.9%, respectively, and lymph node metastasis was the independent predictive factor for postoperative survival (p=0.013; odds ratio, 15.05). CONCLUSIONS Despite the similarity in lymph node metastatic patterns to squamous cell carcinoma, PMME is more inclined to distant metastasis. Clinical staging was inconsistent with pathological staging for PMME based on endoscopy and computed tomography. Surgical therapy was the optimal treatment for PMME at an earlier stage. Early diagnosis and aggressive lymph node dissection were beneficial for accurate staging, potentially reducing recurrence and thus improving survival.

Prognostic analysis of salvage esophagectomy after definitive chemoradiotherapy for esophageal squamous cell carcinoma: The importance of lymphadenectomy

OBJECTIVES The objective of this study was to review the prognostic factors for increased survival after salvage esophagectomy after definitive chemoradiotherapy for esophageal squamous carcinoma and determine the importance of lymphadenectomy from a prognostic view. METHODS Clinical data for all patients from January 1999 to December 2012 who underwent salvage esophagectomy for residual tumor or tumor recurrence after definitive chemoradiotherapy were retrospectively collected. Survival was determined and prognostic factors were analyzed with univariate and multivariate analyses. RESULTS Survival after 1, 3, and 5 years postoperatively was 74.4%, 39.8%, and 29.5%, respectively. The independent predictive factors for increased postoperative survival were tumor recurrence rather than residual tumor as the indication for salvage surgery (P < .001; odds ratio [OR], 0.292); complete tumor resection (P < .001; OR, 4.520); N category (P = .089; OR, 1.304); M category (P = .081; OR, 2.215), and total mediastinal dissection with 15 or more dissected mediastinal lymph nodes (P = .034; OR, 0.546). CONCLUSIONS Salvage indications of recurrence, earlier disease, and complete tumor resection are related to longer survival. The total area of mediastinal dissection with a sufficient number of dissected mediastinal lymph nodes improves survival. Additional neck dissection does not add benefit. The optimal procedure for lymph node dissection in salvage esophagectomy should be established in future studies.

Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues

Significance The relative importance of genetic and epigenetic alterations in normal tissues on cancer risk was clearly different between esophageal squamous cell and gastric cancers, implying a variety of differences in various types of cancers. The difference observed was well explained by known etiologies: tobacco mutagens for esophageal cancer and chronic inflammation for epigenetic alterations in gastric cancer. The study showed that, if epigenetic and genetic alterations in normal tissues are combined, reflecting their relative contributions, patients with cancer can be precisely discriminated, opening up an avenue to precision cancer risk diagnosis. The study also indicated that for effective cancer prevention, allocation of resources and efforts against genetic and epigenetic alterations should consider their relative contributions. Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69–89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52–23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.

Integrated analysis of DNA methylation and mutations in esophageal squamous cell carcinoma

The recent development of next‐generation sequencing technology for extensive mutation analysis, and beadarray technology for genome‐wide DNA methylation analysis has made it possible to obtain integrated pictures of genetic and epigenetic alterations, using the same cancer samples. In this study, we aimed to characterize such a picture in esophageal squamous cell carcinomas (ESCCs). Base substitutions of 55 cancer‐related genes and copy number alterations (CNAs) of 28 cancer‐related genes were analyzed by targeted sequencing. Forty‐four of 57 ESCCs (77%) had 64 non‐synonymous somatic mutations, and 24 ESCCs (42%) had 35 CNAs. A genome‐wide DNA methylation analysis using an Infinium HumanMethylation450 BeadChip array showed that the CpG island methylator phenotype was unlikely to be present in ESCCs, a different situation from gastric and colon cancers. Regarding individual pathways affected in ESCCs, the WNT pathway was activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). The p53 pathway was inactivated by TP53 mutations (70%), and potentially by aberrant methylation of its downstream genes. The cell cycle was deregulated by mutations of CDKN2A (9%), deletions of CDKN2A and RB1 (32%), and by aberrant methylation of CDKN2A and CHFR (9%). In conclusion, ESCCs had unique methylation profiles different from gastric and colon cancers. The genes involved in the WNT pathway were affected mainly by epigenetic alterations, and those involved in the p53 pathway and cell cycle regulation were affected mainly by genetic alterations.

Recurrent advanced colonic cancer occurring 11 years after initial endoscopic piecemeal resection: a case report

BackgroundThe high frequency of local recurrence occurring after endoscopic piecemeal resection (EPMR) for large colorectal tumors is a serious problem. However, almost all of these cases of local recurrence can be detected within 1 year and cured by additional endoscopic resection. We report a rare case of recurrent advanced colonic cancer diagnosed 11 years after initial EPMR treatment.Case presentationA 65-year-old male was diagnosed with a sigmoid colon lesion following a routine health check-up. Total colonoscopy revealed a 12 mm type 0-Is lesion in the sigmoid colon, which was diagnosed as an adenoma or intramucosal cancer and treated by EPMR in 1996. The post-resection defect was closed completely using metallic endoclips to avoid delayed bleeding. In 2007, at the third follow up, colonoscopy revealed a 20 mm submucosal tumor (SMT) like recurrence at the site of the previous EPMR. The recurrent lesion was treated by laparoscopic assisted sigmoidectomy with lymph node dissection.ConclusionWhen it is difficult to evaluate the depth and margins of resected tumors following EPMR, it is important that the defect is not closed in order to avoid tumor implantation, missing residual lesions and to enable earlier detection of recurrence. It is crucial that the optimal follow-up protocol for EPMR cases is clarified, particularly how often and for how long they should be followed.

A Retrospective Study on Nonmalignant Airway Erosion After Right Transthoracic Subtotal Esophagectomy: Incidence, Diagnosis, Therapy, and Risk Factors

BACKGROUND This study investigated the incidence, diagnosis, treatment, and risk factors for nonmalignant airway erosion after subtotal esophagectomy for thoracic esophageal carcinoma. METHODS Clinical data from all patients with thoracic esophageal carcinoma who underwent right transthoracic subtotal esophagectomy from 2000 to 2012 at our institution were retrospectively reviewed, and the clinical course and outcome of those who developed airway erosion were investigated in detail. Risk factors for airway erosion were calculated by multivariate analysis. RESULTS Of 1,091 patients enrolled, 15 patients (1.4%) developed nonmalignant airway erosion, which occurred at postoperative day (POD) 7 to 92 (median, 24). Anastomotic leakage or gastric-tube necrosis was detected prior to airway erosion in 14 cases (93.3%). Endoscopic and surgical therapy was administrated to 3 patients. Airway erosion was cured in 9 patients (60.0%). Five patients died from airway erosion directly (mortality, 33.3%). Alimentary leakage or necrosis (p<0.001), preoperative radiotherapy (p=0.004), and reconstruction through the posterior mediastinal route (p=0.051) were independent risk factors for airway erosion development. CONCLUSIONS Airway erosion is a fatal complication after subtotal esophagectomy. Preoperative radiotherapy dramatically increases the risk of developing airway erosion and reduces the probability of spontaneous healing. Aggressive treatment of alimentary leakage or necrosis and reconstruction through the anterior route help to decrease the risk of airway erosion, especially in high-risk patients.

Esophageal cancer associated with a sarcoid-like reaction and systemic sarcoidosis in lymph nodes: supportive findings of [18F]-fluorodeoxyglucose positron emission tomography–computed tomography during neoadjuvant therapy

BackgroundIn patients with esophageal cancer, differentiation between lymph node metastasis and lymphadenopathies from sarcoidosis or sarcoid-like reactions of lymph nodes is clinically important. Herein, we report two esophageal cancer cases with lymph node involvement of sarcoid-like reaction or sarcoidosis.Case presentationOne patient received chemotherapy and the other chemoradiotherapy as initial treatments. In both cases, [18F]-fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET/CT) was performed before and after chemo(radio)therapy. After the treatment, FDG uptake was not detected in the primary tumor, but it was slightly reduced in the hilar and mediastinal lymph nodes in both cases. These non-identical responses to chemo(radio)therapy suggest the presence of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of the esophagus. Curative surgical resection was performed as treatment.ConclusionsThese FDG-PET/CT findings may be helpful to distinguish between metastasis and sarcoidosis-associated lymphadenopathy in esophageal cancer.

Pure laparoscopic pancreas parenchymal dissection using CUSA for distal pancreatectomy

Abstract Although stapler dissection and closure is commonly used for laparoscopic distal pancreatectomy (LDP), it is risky in patients with thick pancreatic parenchyma or titanium allergy. We performed laparoscopic pancreatic parenchymal dissection with cavitron ultrasonic surgical aspirator (CUSA) successfully in a patient with titanium allergy. Slinging the pancreas with nylon tape delineates the surgical plane. Pancreatic parenchyma was transected by CUSA in an almost bloodless field. Pancreatic duct branches and vessels were adequately exposed and dissected with a vessel sealing system. The main pancreatic duct was closed with Hem-O-lock. CUSA is an alternative to stapler dissection during LDP in select patients.

Hybrid approach to laparoscopic decapsulation combined with splenic artery balloon occlusion in a patient with carbohydrate antigen 19-9 producing splenic cysts

Carbohydrate antigen 19‐9 producing splenic cysts are relatively rare and usually occur in women and young individuals. This report describes the use of a novel splenic‐preserving surgical approach in the hybrid operating room to reduce the risk of bleeding.

Multiple gastric gastrointestinal stromal tumors treated by laparoscopic-endoscopic cooperative surgery: A case report.

The typical treatment of choice for gastrointestinal stromal tumors (GIST) is surgical resection. Here we report a case of three GIST lesions resected safely by laparoscopic‐endoscopic cooperative surgery (LECS). A 78‐year‐old woman was referred to our hospital for further treatment of an enlarging gastric submucosal tumor. Esophagogastroduodenoscopy and endoscopic ultrasonography revealed two gastric submucosal tumors. Endoscopic ultrasonography‐guided fine needle aspiration was subsequently performed. The patient underwent LECS in accordance with therapeutic guidelines for GIST. Assisted by a laparoscope and using three trocars, a full‐thickness resection was performed endoscopically for the 3‐cm lesion and its nearby submucosal tumor, which was newly detected intraoperatively. The other lesion was also resected with an autosuture device under laparoscopy. No intraoperative or postoperative complications were observed. In LECS, endoscopic observation and resection can minimize gastric deformation and preserve gastric function. To the best of our knowledge, this is the first case of LECS performed on multiple GIST.