Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

A case of sigmoid colon perforation due to segmental absence of intestinal musculature (SAIM) accompanied by vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Segmental absence of intestinal musculature (SAIM) is a partial defect of the intrinsic muscular layer of the intestinal tract. In this report, we describe a case of perforation of the sigmoid colon due to SAIM accompanied by vascular Ehlers-Danlos syndrome (vEDS), which was successfully treated by surgical therapy. CASE PRESENTATION: A male in his 30 s was being followed up for vEDS diagnosed by genetic testing. He had undergone two major vascular surgeries, abdominal aortic artery revascularization and thoracic endovascular aortic repair for a residual dissection and enlarging abdominal aortic aneurysm. On postoperative day 11, the patient developed perforation of the sigmoid colon for which intraperitoneal lavage and drainage, Hartmann surgery, and transverse colostomy were performed. Histological findings showed no disturbance of blood flow or diverticulum but did show a defect in the intrinsic muscular layer around the perforation site, leading to the pathological diagnosis of SAIM and associated perforation of the sigmoid colon. Postoperatively, the patient had no complications and was discharged on postoperative day 18. The patient is being followed as an outpatient and has experienced no relapse. CONCLUSIONS: Both SAIM and vEDS, which may be related diseases, are associated with the presence of tissue fragility and have a high potential to cause intestinal perforation Caution should be exercised during surveillance in patients with constipation and examinations that cause increased intestinal pressure.

Recurrence of gastric gastrointestinal stromal tumor 12 years after repeat hepatectomies for liver metastases: report of a case.

No consensus has been reached on the postoperative treatment and follow-up duration for high-risk malignant gastrointestinal stromal tumor (GIST). We herein report a case of recurrent liver metastasis from gastric GIST in a patient who had been receiving adjuvant chemotherapy with imatinib mesylate for 10 years. A 78-year-old woman underwent local gastrectomy for a 20-cm gastric GIST with a mitotic index of 25/50 high-power fields (HPF) 17 years before. Partial hepatectomy for recurrent liver metastases was repeatedly performed 14 and 12 years before. After the second hepatectomy, postoperative adjuvant chemotherapy with imatinib mesylate was given for 10 years, during which no recurrence was observed. Two years after the completion of adjuvant chemotherapy, computed tomography revealed a 2-cm hepatic tumor; thus, laparoscopic partial hepatectomy was performed. Histopathological findings revealed a liver metastasis of gastric GIST with a mitotic count of 20/50 HPF and MIB-1 labeling index of 20%. Mutation analysis of the KIT gene revealed an exon 11 mutation. The patient is currently undergoing postoperative adjuvant chemotherapy with imatinib mesylate. The combination of surgery and long-term adjuvant chemotherapy for high-risk malignant GIST and liver metastases may be effective to achieve a good prognosis.

[Long‒Term Survival after Lung Resection for Lung Metastasis of Pancreatic Cancer-A Report of Two Cases].

Some reports have shown that the prognosis of recurrent lung metastases after resection of pancreatic cancer is better than that for other organs. We report on 2 cases of long‒term survival after lung resection for lung metastases from pancreatic cancer. Case 1: A 73‒year‒old man underwent distal pancreatectomy for pancreatic body cancer. Adjuvant chemotherapy of S‒1 was administered for 6 months. At 3 years after surgery, 2 small metastatic nodules were detected in the right lung, and the patient underwent thoracoscopic right upper lobectomy. At 5 years and 9 months after the initial surgery, he is alive without recurrence. Case 2: An 81‒year‒old woman underwent pylorus‒preserving pancreatoduodenectomy for pancreatic head cancer. Adjuvant chemotherapy of S‒1 was administered for 4 months. At 1 year and 9 months after surgery, a metastatic nodule was detected in the left upper lung, and the patient underwent thoracoscopic left upper lobectomy. At 4 years and 6 months after initial surgery, radiation therapy was performed for localized bone metastasis. At 5 years and 1 month after the initial surgery, she is alive without other recurrences. In conclusion, recurrent lung metastases of pancreatic cancer with a small number of metastases may result in long‒term survival following resection.

Clinical significance of sarcoid-like reaction in lymph nodes of gastric cancer patients.

BACKGROUND: Although granulomatous formation (sarcoid-like reaction [SR]) similar to sarcoidosis occasionally occurs in regional lymph nodes of malignant tumors, the pathological significance of SR is unknown. We aimed to elucidate the clinicopathological significance and prognostic relevance of SR in gastric cancer. METHODS: We evaluated 391 patients who underwent curative gastrectomy for gastric cancer between 2007 and 2016 at our hospital. The patients were divided into two groups according to presence of SR in lymph nodes, and clinicopathological factors and prognosis were compared between the two groups. RESULTS: SR was found in 67 (17.1%) of the 391 patients, and 332 (3.3%) of 10,149 lymph nodes examined. Regarding clinicopathological factors, SR-positive group showed significantly higher average age (p < 0.01) and numbers of differentiated tumors than SR-negative group (p < 0.05). Three-year overall survival rate in elderly patients aged ≥75 years was significantly more favorable in SR-positive group (n = 27, 85.2%) versus SR-negative group (n = 97, 63.4%) (p < 0.05). Immunohistochemical studies showed the predominant presence of CD68-positive macrophages for SR, with CD4/CD8-positive T cells and interleukin-10 also positive. CONCLUSION: The presence of SR in gastric cancer is frequent in elderly patients and might be a favorable indicator of prognosis. SR is suggested to reflect immune activation in the host.

Intraperitoneal Phototherapy Suppresses Inflammatory Reactions in a Surgical Model of Peritonitis.

BACKGROUND: Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments. MATERIALS AND METHODS: Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated. RESULTS: As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1ß were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability. CONCLUSIONS: Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.

Laparoscopic two-stage operation for rectal cancer with refractory obstructive colitis after kidney transplantation: a case report.

BACKGROUND: Although obstructive colitis with colon cancer is not a rare disease, most cases can be improved with conservative therapy. We report a case of a patient who underwent a laparoscopic two-stage operation for rectal cancer with refractory obstructive colitis after kidney transplantation. CASE PRESENTATION: The patient was a 71-year-old man taking immunosuppressants who had previously undergone right living kidney transplantation for chronic nephritis. He presented to hospital complaining of abdominal pain and was diagnosed as having rectal cancer with obstructive colitis. Although conservative therapy by fasting was continued for 5 weeks, his obstructive colitis did not improve. Therefore, we decided to perform a two-stage operation. First, we performed a laparoscopic Hartmann's operation. It took 6 months for his obstructive colitis to improve after this operation, and then we performed a laparoscopic colorectal anastomosis. There were no postoperative complications in either operation. CONCLUSION: A laparoscopic two-stage operation could be one of the operative options to reduce postoperative complications in patients with comorbidities such as taking immunosuppressants.

[IPMC of the pancreas with enlarged para-aortic lymph nodes with a high accumulation of FDG-PET:a case report].

A 74-year-old man was admitted for evaluation of a pancreatic tumor. Abdominal CT revealed a multilocular cystic tumor with thickened septal walls and an enhanced mural nodule in the head of the pancreas, as well as enlarged para-aortic lymph nodes. FDG-PET revealed FDG accumulation in the nodule and in the para-aortic nodes. The tumor was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with para-aortic lymph node metastases. After 2 courses of chemotherapy with gemcitabine and nab-paclitaxel, the tumor decreased slightly in size, but the lymph nodes did not change. Surgery was then performed. Intraoperative pathology examination confirmed that the para-aortic lymph nodes had only inflammatory swelling. Accordingly, pylorus-preserving pancreaticoduodenectomy was performed. Histopathology examination revealed atypical cells without invasion, and IPMC (TisN0M0;stage 0) was diagnosed. It is thus important for selection of the appropriate treatment approach to determine if enlarged para-aortic lymph nodes are benign or malignant.