堀江 久永

INTRODUCTION AND IMPORTANCE: Brain and thyroid metastasis from rectal cancer are uncommon, and the prognosis is poor. We report a patient with rectal cancer who developed metachronous lung, brain and thyroid metastases. Each metastatic lesion was curatively resected resulting in prolonged survival. CASE PRESENTATION: A 60-year-old male underwent rectal cancer resection, and the pathological diagnosis was tubular adenocarcinoma, pT2,pN1a,M0, pStageⅢa. Ten years after rectal resection, a solitary tumor in the left lung was detected. The tumor was resected thoracoscopically and the pathological diagnosis was metastatic tumor. Three years after the pulmonary resection, a solitary brain tumor was detected. The tumor was removed surgically, and the pathology was metastatic tumor. Two years after brain resection, a thyroid mass was detected. A partial thyroidectomy was performed and the pathology with immunohistochemical staining confirmed the thyroid lesion as a metastasis from the previous rectal cancer. Four years after thyroid resection (19 years after the initial rectal resection), he died from multiple lung and bone metastases. CLINICAL DISCUSSION: Colorectal metastases to the brain and thyroid gland are uncommon and are usually found with other distant metastases. Overall survival has been reported to be extremely poor. In this patient, lung, brain, and thyroid metastases were solitary and metachronous, and each lesion was curatively resected. Surgical treatment might contribute to prolonged survival. CONCLUSION: The treatment strategy of each patient should be individualized and depends on the timing of metastasis development. Selected patients with complete resection of metachronous metastases may have prolonged survival.

BACKGROUND: Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of colonic polyps, and extracolonic manifestations are likely to occur. Pancreatic tumors are rare extracolonic manifestations in patients with FAP, among which solid-pseudopapillary neoplasm (SPN) are extremely rare. We report here a patient with an SPN of the pancreas found during the follow-up of FAP. CASE PRESENTATION: A 20-year-old woman was diagnosed with FAP 3 years previously by colonoscopy which revealed less than 100 colonic polyps within the entire colon. She complained of left upper abdominal pain and a 10-cm solid and cystic pancreatic tumor was found by computed tomography scan. Solid and cystic components within the tumor were seen on abdominal magnetic resonance imaging. Simultaneous laparoscopic resection of the distal pancreas and subtotal colectomy was performed. Histopathological findings confirmed the pancreatic tumor as an SPN without malignancy. Abnormal staining of beta-catenin was observed by immunohistochemical study. Multiple polyps in the colorectum were not malignant. Molecular biological analysis from peripheral blood samples revealed a decrease in the copy number of the promoter 1A and 1B region of the APC gene, which resulted in decreased expression of the APC gene. CONCLUSIONS: A rare association of SPN with FAP is reported. The genetic background with relation to beta-catenin abnormalities is interesting to consider tumor development. So far, there are few reports of SPN in a patient with FAP. Both lesions were treated simultaneously by laparoscopic resection.

Fecalomas most commonly occur in constipated patients and are rarely reported after colectomy. A 55-year-old Japanese female presented with a fecaloma after colectomy, which was impacted at a functional end-to-end anastomosis (FEEA) site. Four and a half years ago, she underwent sigmoidectomy for colon cancer. A follow-up computed tomography (CT) scan revealed an 11 cm incidental fecaloma. The patient was advised to undergo surgery, but she desired nonoperative management because of minimal symptoms, and was referred to our institution. On the day of admission (day 1), mechanical fragmentation of the fecaloma was attempted during the first colonoscopy. Although a large block of stool was evacuated after a second colonoscopic fragmentation on day 8, the third colonoscopy on day 21 and CT scan on day 22 showed no significant change in the fecaloma. Frequent colonoscopic fragmentation was performed, with a fourth, fifth, and sixth colonoscopy on days 24, 29, and 31, respectively. After the size reduction was confirmed at the sixth colonoscopy, the patient was discharged home on day 34. The fecaloma completely resolved after the seventh colonoscopic fragmentation on day 44. Sixteen months after treatment, there is no evidence of recurrent fecaloma. According to the literature, risk factors for fecaloma after colectomy include female gender, left-side colonic anastomosis, and FEEA. FEEA might not be recommended for anastomoses in the left colon, particularly in female patients, to avoid this complication. Colonoscopic fragmentation is recommended for fecalomas at an anastomotic site after colectomy in patients without an absolute indication for surgery.

Aim: PD-1/PD-L1 blockade therapy is now widely used for the treatment of advanced malignancies. Although PD-L1 is known to be expressed by various host cells as well as tumor cells, the role of PD-L1 on non-malignant cells and its clinical significance is unknown. We evaluated cell type-specific expression of PD-L1 in colorectal cancer (CRC) specimens using multicolor flow cytometry. Methods: Single cell suspensions were made from 21 surgically resected CRC specimens, and immunostained with various mAbs conjugated with different fluorescent dyes. Tumor cells, stromal cells, and immune cells were identified as CD326(+), CD90(+) and CD45(+) phenotype, respectively. CD11b(+) myeloid cells, CD19(+) B cells and CD4(+) or CD8(+) T cells were also stained in different samples, and their frequencies in the total cell population and the ratio of PD-L1(+) cells to each phenotype were determined. Results: PD-L1 was expressed by all the cell types. The ratio of PD-L1(+) cells to CD326(+) tumor cells was 19.1% ± 14.0%, lower than those for CD90(+) stromal cells (39.6% ± 16.0%) and CD11b(+) myeloid cells (31.9% ± 14.3%). The ratio of PD-L1(+) cells in tumor cells correlated strongly with the ratio in stromal cells, while only weakly with that in myeloid cells. Tumor cells were divided into two populations by CD326 expression levels, and the PD-L1 positive ratios were inversely correlated with the rate of CD326 highly expressing cells as well as mean fluorescein intensity of CD326 in tumor cells, while positively correlated with the frequencies of stromal cells or myeloid cells in CRC. Conclusion: PD-L1 is differentially expressed on various cell types in CRC. PD-L1 on tumor cells may be upregulated together with CD326 downregulation in the process of epithelial mesenchymal transition. Quantification of cell type-specific expression of PD-L1 using multicolor flow cytometry may provide useful information for the immunotherapy of solid tumors.

BACKGROUND: Repeat intraperitoneal (IP) chemotherapy has been successfully used for treatment of peritoneal metastases (PM) from gastric cancer (GC). Exosomes play important roles not only in tumor progression but also in chemoresistance via transfer of microRNAs (miRNAs). However, there is little evidence of an effect of miRNAs in peritoneal exosomes on chemosensitivity of peritoneal lesions. METHODS: In 74 patients with advanced GC who underwent staging laparoscopy, exosomes were isolated from peritoneal fluid and expression levels of miR-21-5p, miR-223-3p, and miR-29b-3p determined using TaqMan Advanced miRNA assays. In 43 patients with PM treated with combination chemotherapy, S-1 plus Oxaliplatin together with IP Paclitaxel, the relationship between their relative expression levels and outcomes was examined. RESULTS: The ratios of miR-21-5p/miR-29b-3p and miR-223-3p/miR-29b-3p were significantly upregulated in patients with PM, especially in patients with high serum CA125 levels. They showed a mild association with Peritoneal Cancer Index (PCI) score and ascites. More impressively, the ratios were significantly higher in 16 patients with progression of PM within 1 year compared with 27 patients with an excellent tumor response (miR-21-5p/miR-29b-3p: median 17.49, range 1.83-50.90 vs. median 4.64, range 0.40-38.96, p = 0.0015, miR-223-3p/miR-29b-3p: median 1.02, range 0.23-25.85 vs. median 0.21, range 0.01-50.07, p = 0.0006). Overall survival of patients with high miR-21/miR-29b or miR-223/miR-29b ratios was significantly worse than in patients with low ratios (p = 0.0117, p = 0.0021). CONCLUSIONS: The ratios of miRNAs in peritoneal exosome correlate with survival of the patients with PM from GC and suggest the possibility that they modify the chemosensitivity against IP chemotherapy.

Accumulating evidence suggests that metformin reduces the incidence and mortality of colorectal cancer (CRC). However, underlying mechanisms have not been fully clarified. The aim of this study was to examine the pathological characteristics of resected CRC from patients treated with metformin for type 2 diabetes mellitus (DM). In total, 267 patients with DM underwent curative colectomy for Stage I-III CRC and 53 (19.9%) patients had been treated medically including metformin. Pathological N-stage was significantly lower in metformin-treated patients (P < .05) with prolonged disease-free survival (DFS) (P < .05). Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (P < .05). The density of tertiary lymphoid structures (TLS) in tumor stroma was markedly increased in metformin-treated patients (P < .001). In those tumors, there were more CD68(+) tumor-associated macrophages (TAM) infiltrated (P < .05), while the ratio of CD163(+) M2-phenotype was markedly reduced (P < .001). Stromal fibrosis tended to be suppressed by metformin intake (P = .051). These findings suggested that metformin drastically changes the characteristics of infiltrating immune cells in CRC and reprograms the tumor microenvironment from immunosuppressive to immunocompetent status, which may lead to suppression of microscopic tumor spread and improve the outcomes of patients with CRC and type 2 DM.

Traumatic injury to the main pancreatic duct requires surgical treatment, but optimal management strategies have not been established. In patients with isolated pancreatic injury, the pancreatic parenchyma must be preserved to maintain long-term quality of life. We herein report a case of traumatic pancreatic injury with main pancreatic duct injury in the head of the pancreas. Two years later, the patient underwent a side-to-side anastomosis between the distal pancreatic duct and the jejunum. Eleven years later, he presented with abdominal pain and severe gastrointestinal bleeding from the Roux limb. Emergency surgery was performed with resection of the Roux limb along with central pancreatectomy. We attempted to preserve both portions of the remaining pancreas, including the injured pancreas head. We considered the pancreatic fluid outflow tract from the distal pancreatic head and performed primary reconstruction with a double pancreaticogastrostomy to avoid recurrent gastrointestinal bleeding. The double pancreaticogastrostomy allowed preservation of the injured pancreatic head considering the distal pancreatic fluid outflow from the pancreatic head and required no anastomoses to the small intestine.