A Case of Long-Term Survival with Recurrent Liver Metastases from Gastric Cancer Treated with Nivolumab.

Introduction: Improvements in overall survival from advanced gastric cancer have recently been reported with nivolumab. However, few reports have described long-term survival after discontinuing treatment. Case Presentation: A 67-year-old man diagnosed with advanced gastric cancer and abdominal aortic aneurysm initially underwent distal gastrectomy with D2 dissection. Histological examination revealed tub2 and T2N1M0 stage IIA. One month later, endovascular aneurysm repair was performed. Six weeks after gastrectomy, adjuvant chemotherapy with S-1 was started. Six months later, liver metastases were identified and liver segments S1 and S7 were resected. S-1 and oxaliplatin were added postoperatively, but multiple liver metastases recurred. Paclitaxel and ramucirumab, irinotecan, and docetaxel were administered. Liver metastases showed a temporary reduction in size, then enlarged again. Nivolumab was therefore administered and the liver metastases showed a significant reduction in size. The interval between doses gradually increased due to persistent general fatigue. At 28 months after starting nivolumab therapy, bronchitis and adrenal insufficiency appeared, so treatment was discontinued. As of 3.5 years after cessation of nivolumab immunotherapy, tumor regression continued to be maintained. The patient remains alive as of 8 years after recurrence of liver metastases. Conclusion: We encountered a case in which the patient received nivolumab therapy for recurrent liver metastases from gastric cancer and survived long term after discontinuing treatment.

Mucinous cystadenoma of the pancreas associated with pancreatic pseudocyst.

Mucinous cystadenoma of the pancreas is considered as a premalignant lesion, and resection is recommended. The majority of pancreatic cystic lesions are pancreatic pseudocysts, so differentiation between mucinous cystadenoma and pseudocyst is frequently required. We report a rare case of mucinous cystadenoma of the pancreas coexisting with pseudocyst. A 43-year-old woman presented with abdominal pain. Imaging examinations showed a large cystic lesion in the tail of the pancreas, and distal pancreatectomy and splenectomy were performed. Pathological examination revealed that the majority of the cystic wall comprised thick collagen fibrous connective tissue, while part of the cystic wall represented a single layer of columnar, mucin-producing epithelium without atypia. Those findings suggested mucinous cystadenoma with an inflammatory pseudocyst. The mixture of mucinous cystadenoma and pseudocyst within the same cystic lesion appears to be very rare. Complete resection of the cystic lesion seems to allow an excellent prognosis.

Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone.

BACKGROUND: The number of ulcerative colitis (UC) patients is increasing in Japan and other countries. Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn (JIMRO, Takasaki, Japan) was introduced as a nonpharmacologic treatment strategy in UC patients in 2000. GMA has been reported to be effective in clinical trials; however, the effect of concomitant prednisolone (PSL) on GMA needs to be clarified. METHODS: Thirty-nine patients with active UC were treated with GMA at our institute between June 2009 and September 2018. All patients received GMA therapy once or twice a week with the Adacolumn. Conventional medication was to be continued during the whole GMA treatment course. The clinical response was retrospectively evaluated. RESULTS: According to the partial Mayo score, remission was 33.3%, significant efficacy 25.6%, effective 25.6%, and no response 15.4%. The average partial Mayo score was 6.2 ± 1.4 at entry and significantly declined to 1.8 ± 1.8 after GMA sessions (p < 0.0001). The average number of bowel movements was 9.5 ± 5.6 at entry and significantly declined to 3.0 ± 2.8 after GMA sessions (p < 0.0001). In a comparison between the group treated with concomitant PSL and the group without PSL, the change in partial Mayo score or the number of bowel movements from entry to after GMA sessions was not significantly different. Among 24 patients treated by GMA with concomitant PSL, 75% (18/24) became steroid free. CONCLUSIONS: The effect of GMA with concomitant PSL and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis.

PURPOSE: Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot's triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery. METHODS: Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed. RESULTS: LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43-82 years). The median operative time was 125 min (range 60-215 min) and the median postoperative inpatient stay was 6 days (range 3-21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study. CONCLUSIONS: LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.

Number of Lymph Nodes in Rectal Cancer is Correlated with Response to Preoperative Chemoradiotherapy but is not Associated with Patient Survival.

BACKGROUND/AIMS: We aimed to clarify the oncological significance of the number of lymph nodes in rectal cancers treated with preoperative chemoradiotherapy. METHODOLOGY: We studied 126 curatively operated patients with clinical T3-T4 and M0 rectal cancers. The number of lymph nodes and clinicopathological features were compared between the patients treated with surgery alone (OP group, n = 45) and those treated with preoperative chemoradiotherapy (50-50.4 Gy in 25-28 fractions with tegafur-uracil and leucovorin, CRT group, n = 81). Factors influencing lymph node count and its prognostic significance were analyzed. RESULTS: The CRT group had significantly fewer lymph nodes than the OP group (12.4 vs. 21.1, P < 0.0001). High histological regression of rectal lesions was significantly correlated with decreased lymph node count in the CRT group. In the OP group, the 5-year cancer-specific survival rate of the patients with 12 or more lymph nodes was significantly better than those with fewer than 12 lymph nodes (75.1% vs. 33.3%, P = 0.02); in the CRT group, on the other hand, these survival rates did not differ (84.5% vs. 77.5%, P = 0.6). CONCLUSIONS: The number of lymph nodes in rectal cancer was correlated with the response of primary rectal lesions to chemoradiotherapy, and was not associated with patient survival.

[Usefulness of CTCs in tumor drainage vein blood as a biomarker for prognosis in colorectal cancer patients with Dukes' stage B and C].

We aimed to clarify the clinical significance of circulating tumor cells (CTCs) in the tumor drainage vein blood of colorectal cancer(CRC) patients with Dukes' stage B and C. This study included 111 patients with Dukes' stage B and 86 patients with Dukes' stage C. We selected multiple genetic markers, including the cancer-associated marker (CEA), epithelial markers(CK19 and CK20), and cancer stem-like cell marker(CD133), and the mRNA levels of these genes were detected by quantitative real-time reverse transcription-polymerase chain reaction assays. In Kaplan-Meier survival curve analysis, overall survival(OS) and disease-free survival(DFS) of Dukes' stage B and C patients who were positive for CEA, CK19, CK20, and/or CD133 (CEA/CK/CD133) were significantly worse than that in patients who were negative for these markers. By Cox progression analysis, it was demonstrated that CEA/CK/CD133 mRNA in tumor drainage vein blood was an independent prognostic factor for OS and DFS in these patients. These results suggest that CEA/CK/CD133 mRNA detection in tumor drainage vein blood is a useful tool for the determination of high-risk CRC patients with Dukes' stage B and C who are in need of postoperative adjuvant therapy.

Neonatal iliopsoas abscess.

Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22 after birth, his family noticed that his right thigh was swollen. Abdominal computed tomography showed a mass extending to the right iliopsoas from the right thigh with thick septa. Puncture to the right groin yielded purulent fluid, and so a diagnosis of abscess was made. The puncture was followed by surgical drainage through a small inguinal incision, and the abscess cavity was irrigated thoroughly using normal saline. Culture of abscess fluid was positive for Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The postoperative magnetic resonance imaging indicate that the IPA was derived from arthritis of the hip, and the patients received Riemenbügel for the incomplete hip dislocation. He is doing well at 2 years of age.

Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes' stage of colorectal cancer patients.

Down-regulation of the novel tumor suppressor gene programmed cell death 4 (PDCD4) was demonstrated in several types of cancer and regulation by micro-RNA is gaining attention. However, the clinical significance of the PDCD4 gene in colorectal cancer (CRC) patients still remains unclear. In particular, the significance of PDCD4 mRNA expression in each tumor stage has not been reported. In this study, we evaluated the prognostic value of PDCD4 expression in each Dukes' stage of CRC patients. Furthermore, relationships between the PDCD4 mRNA and microRNA-21 (miR-21) were evaluated. Tumor tissues and normal adjacent tumor tissues from 326 patients with CRC (Dukes' stage A, 44 cases; Dukes' B, 118 cases; Dukes' C, 100 cases; Dukes' D, 64 cases) were examined. The PDCD4 mRNA was investigated by the quantitative real-time RT-PCR method and miR-21 was examined by TaqMan microRNA assays. The overall survival rates (OS) and disease-free survival rates (DFS) of low PDCD4 patients were significantly worse than those of patients with high expression. In analysis of each tumor stage, OS and DFS of patients with low PDCD4 levels were significantly worse than those with high PDCD4 levels in Dukes' stage B and C. In Dukes' stage D, patients with low PDCD4 expression showed a significant worse OS compared to those of patients with high PDCD4 expression. In contrast, no significant differences were seen between these groups in patients with Dukes' stage A. PDCD4 expression in CRC tissues was an independent prognostic factor in Dukes' stage B, C and D. Significant inverse correlations were demonstrated between PDCD4 and miR-21. The reduced PDCD4 mRNA expression is associated with poor prognosis in CRC patients with Dukes' stage B, C and D. Furthermore, PDCD4 mRNA levels were negatively regulated by miR-21in each tumor stage of CRC.

Prognostic significance of CTCs and CSCs of tumor drainage vein blood in Dukes' stage B and C colorectal cancer patients.

The clinical significance of circulating tumor cells (CTCs) including cancer stem cells (CSCs) (CTC/CSC) in the tumor drainage vein blood of patients with colorectal cancer (CRC) is unclear. In this study, we investigated the prognostic value of CTC/CSC that express carcinoembryonic antigen (CEA) cytokeratin 19 (CK19), CK20 and/or CD133 (CEA/CK/CD133) mRNA in the tumor drainage blood of CRC patients with Dukes' stage B and C. We examined tumor drainage blood from 197 patients with Dukes' stage B and C CRC. CTCs that expressed CEA, CK19, CK20 and CD133 mRNA were detected using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Each mRNA level was normalized with GAPDH mRNA levels. In the relationship between the expression of CEA/CK/CD133 in the tumor drainage blood and clinicopathological factors, a significant correlation was observed between CEA/CK/CD133 expression and Dukes' stage (p<0.041). In CRC patients with Dukes' stage B and C, disease-free (DFS) and overall survival (OS) of patients with CEA/CK/CD133 positive in the tumor drainage blood were significantly worse than that of marker gene negative patients. In contrast, in patients with Dukes' stage A, no significant differences were shown between these groups. By Cox progression analysis, it was shown that CEA/CK/CD133 mRNA in tumor drainage blood was an independent prognostic factor for DFS and OS in patients with Dukes' stage B and C. These results suggest that detecting CEA/CK/CD133 mRNA in tumor drainage blood by the real-time RT-PCR method would have a prognostic value in CRC patients with Dukes' stage B and C.

Radiation-induced apoptosis of peripheral blood lymphocytes is correlated with histological regression of rectal cancer in response to preoperative chemoradiotherapy.

PURPOSE: The response of rectal cancer to preoperative chemoradiotherapy (PRT) varies widely among patients, and predictors of the response remain to be elucidated. The purpose of this study is to investigate whether radiation-induced apoptosis (RIA) of peripheral blood lymphocytes (PBLs) reflects the underlying intrinsic radiosensitivity of rectal cancer. METHODS: Forty-one patients with clinical T3-4, M0 low rectal cancers, treated with PRT and curative surgery, were retrospectively studied. PBLs were obtained from blood samples of the patients, irradiated at 0, 2, 8, and 16 Gy in vitro, and analyzed for RIA by flow cytometry using Annexin V (AV) and propidium iodide (PI). The correlation of the RIA of PBLs and histological regression of rectal cancer in response to PRT was examined. RESULTS: Both the proportions of AV+/PI- PBLs (early apoptosis) and AV+/PI + PBLs (late apoptosis) were significantly higher in patients with high histological regression than in those with low histological regression. Age, sex, tumor size, and clinical T and N stages did not affect the RIA of PBLs. CONCLUSIONS: This study showed that the RIA of PBLs is correlated with the histological regression of rectal cancer in response to PRT and suggested that the radiosensitivity of rectal cancer might be estimated by the RIA of PBLs.

Tumor location is a prognostic factor in poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma of the colon.

PURPOSE: Cancers which arise in the proximal and distal colon are suggested to be different clinically, pathologically, and genetically. The aim of this study is to clarify whether clinical behavior of colonic poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-cell carcinoma (Por/Muc/Sig cancers), minor and aggressive subpopulation in colonic cancers, differs in accordance with the tumor location. METHODS: A total of 3,175 patients with curatively resected colonic cancers were studied. Clinical and pathological features were compared between Por/Muc/Sig cancers and well or moderately differentiated adenocarcinomas (Wel/Mod cancers) and between proximal and distal cancers in each histologic type. RESULTS: Por/Muc/Sig cancers (n = 213) were more advanced in the TNM stage and showed worse disease-specific survival than Wel/Mod cancers (n = 2,692). In Por/Muc/Sig cancers, but not in Wel/Mod cancers, proximal cancers showed significantly better disease-specific survival than distal cancers (88.9% vs. 76.5%, p = 0.0234), and a multivariate analysis showed that proximal tumor location was an independent predictor of fair prognosis (hazard ratio (HR), 0.458; 95% confidence interval (CI), 0.218-0.961; p = 0.0390). In addition, female gender also was an independent predictor of fair prognosis in Por/Muc/Sig cancers (HR, 0.373; 95% CI, 0.151-0.922) and not in Wel/Mod cancers. CONCLUSIONS: Proximal Por/Muc/Sig cancers were suggested to be a distinct subpopulation with a favorable oncologic outcome. Tumor location and gender might be helpful in the risk stratification after curative surgery for Por/Muc/Sig cancers.

Acute respiratory distress syndrome after gastrointestinal surgery.

BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) occasionally occurs after gastrointestinal surgery involving severe inflammation such as diffuse peritonitis. Management of this condition has been difficult and effective therapies have not yet been established. In the present study the management for ARDS after gastrointestinal surgery was evaluated. METHODOLOGY: A total of 15 patients developed ARDS after gastrointestinal operations performed in our institution. The mean patient age was 75.4±11.1 years. Onset of ARDS occurred ≤24 hours postoperatively in 12 patients and 3- 11 days postoperatively in 3 patients. Treatment for ARDS comprised continuous hemodiafiltration (CHDF), high-dose glucocorticoid therapy or administration of a neutrophil elastase inhibitor (sivelestat). RESULTS: Four patients died 3-45 days after onset of ARDS (mortality rate, 26.6%). CHDF was performed in 12 patients, 8 patients received highdose glucocorticoid therapy and 11 patients received sivelestat. No differences in severity scores and clinical data were noted between survivors and non-survivors. PaO2/FiO2 ratio was significantly lower in non-survivors than in survivors from 5 days after starting treatment, whereas no difference was apparent at the onset of ARDS. CONCLUSIONS: Multimodal therapies for ARDS were effective. Longitudinal fluctuation in PaO2/ FiO2 ratio after starting treatment appears to offer a prognostic factor for ARDS.

Skin metastasis from sigmoid colon cancer.

Skin metastases from visceral cancers are rare and the reported incidence from all visceral cancers is 1.4% to 10%. Skin metastases from colorectal cancers account for only 5% of metastatic skin cancers, among which scalp metastases are very rare. We describe a 53-year-old man with scalp metastasis derived from sigmoid colon cancer that was diagnosed and surgically resected in 2005. Metastatic lung tumors that developed thereafter were surgically resected and then chemotherapy was administered. However, metastatic brain tumors occurred in 2008, and these were treated by gamma-knife radiosurgery. Around the same time, a raised lesion that appeared on the scalp was diagnosed as skin metastasis and treated with best supportive care. Thereafter, the brain metastases continued to spread, and the patient died in October 2008.

A case of marked response to preoperative chemoradiotherapy for rectal cancer with para-aortic lymph node metastasis.

A 67-year-old man had rectal cancer with para-aortic lymph node metastasis. Prior to surgical resection, tegafur-uracil and leucovorin had been administered orally as chemotherapy, and radiotherapy (50.4 Gy) was applied for the rectum and para-aortic lymph nodes. Low anterior resection was then performed, followed by 45 cycles of chemotherapy in total. Enlargement of the left axillary lymph nodes was noted during treatment, but nodes shrank in response to treatment with bevacizumab + FOLFIRI (i.e., irinotecan + 5-fluorouracil/leucovorin). As of the time of writing, 36 months after diagnosis, no swelling of the para-aortic lymph nodes was evident and chemotherapy was being continued. This patient was alive after achieving response to neoadjuvant therapy comprising chemotherapy and irradiation of the para-aortic lymph nodes, along with postoperative chemotherapy. This therapeutic approach of preoperative chemotherapy plus irradiation of the primary lesion and para-aortic lymph nodes has potential as an effective treatment.

Severance of a ventriculoperitoneal shunt catheter implanted between the cerebral ventricle and peritoneal cavity, resulting in protrusion from the anus.

One rare complication of a ventriculoperitoneal (VP) shunt is perforation of the gastrointestinal tract by the catheter. We report a case in which the catheter severed spontaneously inside the peritoneal cavity, creating a communication between the intestinal tract and the peritoneal cavity. The patient was a 41-year-old man who presented with a VP shunt catheter protruding from the anus. Computed tomography showed that the VP shunt catheter, which had been put in place 25 years earlier, had severed spontaneously. The distal end had then perforated and entered the intestinal tract. The patient was hospitalized and emergency surgery was performed to repair the intestinal tract perforation caused by the end of the VP shunt catheter. Laparotomy revealed that the catheter had perforated the sigmoid colon. The VP shunt catheter was removed, and the perforation in the intestinal tract was closed by suturing. The patient was discharged on postoperative day 20.

A case of lung squamous cell carcinoma with metastases to the duodenum and small intestine.

Gastrointestinal metastasis of lung cancer is fairly rare, and metastasis to the duodenum is very uncommon. We report a case of duodenum and small intestine metastases of lung squamous cell carcinoma. The patient was a 66-year-old man. He was diagnosed with lung squamous cell carcinoma (T4N3M1 [mediastinum, cervical lymph node, and duodenum metastases], stage IV). He noted a sense of abdominal fullness on the evening of the day chemoradiotherapy was given, and emergency surgery was performed for suspected perforation of the digestive tract. Intraoperative findings included a tumor in the small intestine with a perforation at the tumor site; partial resection of the small intestine, including the tumor, was performed. Small intestine metastasis of lung cancer was diagnosed following histopathologic examination. When lung cancer patients complain of abdominal symptoms, it is important to consider gastrointestinal metastases in diagnosis and treatment.

Invasive micropapillary carcinoma of the ascending colon--a report of a case.

Micropapillary carcinoma (MC) has been recently recognized to be a rare but distinctive variant of adenocarcinoma. At present, only a limited number of colorectal MC cases have been reported. We present a case of MC of the ascending colon with distant metastasis. A 61-year-old female patient was hospitalized with a complaint of abdominal pain. A diagnostic work-up revealed cancer of the ascending colon with multiple lung metastases. The patient underwent a right hemicolectomy with lymph node dissection. A peritoneal nodule was observed in the abdominal cavity during surgery, and this nodule was also resected. The pathologic findings of the colon tumor revealed components of conventional tubular adenocarcinoma and micropapillary carcinoma. Lymph nodes and a peritoneal nodule revealed tubular adenocarcinoma. MC is a rare disease but has high malignant potential. In the present case the tumor was small in size, but the patient had a peritoneal and multiple lung metastases.

Perforation of the small bowel due to metastasis from tongue cancer.

Distant small bowel metastases from head and neck squamous cell carcinomas are extremely rare, and tongue cancer metastasizing to the small bowel has not been previously reported. We describe a 40-year-old male patient who underwent subtotal gross laryngectomy for squamous cell carcinoma of the tongue in February 2007 and then presented in November 2008 with severe abdominal pain. Abdominal computed tomography (CT) and X-rays revealed free air, suggesting intestinal perforation. Emergency surgery revealed a 10-mm perforation at the ileum and a palpable hard tumor at the perforation site. The ileum was resected, and pathologic findings showed squamous cell carcinoma at the perforation site, which was consistent with metastasis from tongue cancer.