[A Case of Adenocarcinoma of Pancreatic Head of Liver Disfunction after Pancreaticoduodenectomy with Celiac Artery Stenosis Treated by Urgent Median Arcuate Ligament Release].

This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned. A blood test on the 1st day after the operation showed elevated levels of AST 537 U/L, ALT 616 U/L, and 7 hours later blood sampling showed further increases in AST 1,455 U/L, ALT 1,314 U/L. After a detailed review of the preoperative CT, celiac artery stenosis due to compression of the arcuate ligament was suspected, and urgent median arcuate ligament release was performed on the same day. Dissection of the arcuate ligament significantly improved the pulsation of the common hepatic artery and proper hepatic artery. Postoperatively, hepatic enzymes improved and ISGPS showed Grade B pancreatic juice leakage, but the patient was discharged from the hospital on the 49th postoperative day without any other complications. He took S-1 as adjuvant chemotherapy, and no signs of recurrence have been observed 9 months after the operation.

[A Case of Strangulated Bowel Obstruction after a Laparoscopic Hartmann's Operation for Rectal Cancer].

A 98-year-old woman presented with hematochezia and a circumferential type 2 tumor in the rectum Rb identified on fiberoscopy. We a performed laparoscopic Hartmann's operation and D2 lymphadenectomy for advanced rectal cancer. A sigmoid colostomy was created via the intraperitoneal route. On the postoperative day 12, the patient experienced abdominal pain. Computed tomography showed that the small intestine formed a closed loop in the pelvic space. The patient was diagnosed with a strangulated bowel obstruction of the small intestine for which an emergency exploratory laparotomy was performed. The small intestine, which had passed through a defect between the lifted sigmoid colon and the left abdominal wall, was strangulated by the lifted sigmoid colon. We performed partial resection of the small intestine. The patient died on postoperative day 32 of acute deterioration of aortic valve stenosis. There have been few reports of strangulated bowel obstruction resulting from internal hernia associated with colostomy. These findings demonstrate that it is important to select the appropriate route for colostomy creation in each case.

Diagnosis of Depth of Submucosal Invasion in Colorectal Cancer with AI Using Deep Learning.

The submucosal invasion depth predicts prognosis in early colorectal cancer. Although colorectal cancer with shallow submucosal invasion can be treated via endoscopic resection, colorectal cancer with deep submucosal invasion requires surgical colectomy. However, accurately diagnosing the depth of submucosal invasion via endoscopy is difficult. We developed a tool to diagnose the depth of submucosal invasion in early colorectal cancer using artificial intelligence. We reviewed data from 196 patients who had undergone a preoperative colonoscopy at the Osaka University Hospital and Osaka International Cancer Institute between 2011 and 2018 and were diagnosed pathologically as having shallow submucosal invasion or deep submucosal invasion colorectal cancer. A convolutional neural network for predicting invasion depth was constructed using 706 images from 91 patients between 2011 and 2015 as the training dataset. The diagnostic accuracy of the constructed convolutional neural network was evaluated using 394 images from 49 patients between 2016 and 2017 as the validation dataset. We also prospectively tested the tool from 56 patients in 2018 with suspected early-stage colorectal cancer. The sensitivity, specificity, accuracy, and area under the curve of the convolutional neural network for diagnosing deep submucosal invasion colorectal cancer were 87.2% (258/296), 35.7% (35/98), 74.4% (293/394), and 0.758, respectively. The positive predictive value was 84.4% (356/422) and the sensitivity was 75.7% (356/470) in the test set. The diagnostic accuracy of the constructed convolutional neural network seemed to be as high as that of a skilled endoscopist. Thus, endoscopic image recognition by deep learning may be able to predict the submucosal invasion depth in early-stage colorectal cancer in clinical practice.

[A Case of Liver Metastasis Complete Resection for Concurrent Overlapping Cancer of the Transverse Colon and Renal Cell Carcinomas that were Difficult to Differentiate from Hepatocellular Carcinoma].

A 79-year-old man visited the hospital because of constipation. Colonoscopy showed a transverse colon carcinoma. Dynamic CT showed a renal neoplastic lesion and 2 lesions in the liver with early staining and late wash out, and the liver lesions showed ring enhancement on EOB-MRI. The preoperative diagnosis was either transverse colon cancer, renal cell carcinoma, hepatocellular carcinoma, or metastatic liver cancer. The patient underwent partial transverse colon resection, partial right nephrectomy, and partial hepatic resection. Additional to the 2 liver lesions in S6, an intraoperative ultrasound showed 1 tumor in S5; therefore, 3 partial hepatectomies were performed. Histopathological findings revealed that the tumors in S5 and S6 were liver metastases of transverse colon cancer and renal cell carcinoma, respectively. The final diagnosis was transverse colon cancer, pT4a, pN0, pM1, pStage Ⅳa and papillary renal cell carcinoma, pT1a, pN0, pM1, pStage Ⅳ. For 9 months postoperatively, there was no apparent recurrence.

[A Case of Retroperitoneal Leiomyosarcoma Resected Radically by Pancreaticoduodenectomy with Vascular Resection].

A 54-year-old woman visited to a doctor nearby medical clinic complaining of loss of appetite. She was diagnosed with right hydronephrosis on abdominal ultrasonography, and referred to our hospital for further examination. Contrast abdominal computed tomography(CT)revealed that a 6.2 cm tumor with a contrast-enhancing effect inside in the retroperitoneum near the lower pole of the right kidney. She was diagnosed with hydronephrosis due to infiltration of the right kidney of a retroperitoneal tumor. The tumor was suspected of invading the duodenum and inferior vena cava, but no obvious lymph node or distant metastasis was observed. Abdominal MRI revealed a tumor showed hyperintensity on T2-weighted and diffusion-weighted images. We performed pancreaticoduodenectomy with inferior vena cava resection and right nephrectomy. The pathological diagnosis was leiomyosarcoma originating from retroperitoneum and pT2, pN0, pM0, pStage ⅢA. The postoperative course was good, and she was discharged 10 days after the operation. Thoracoabdominal CT showed a tumor 4 cm at the hepatic hilum three months after surgery, and EOB-MRI showed many tumors other than the same site, so multiple liver metastases were diagnosed as recurrence. Doxorubicin has been started and is still being treated.

[A Resected Case of Gallbladder Neuroendocrine Cancer Found as a Liver Mass].

Our patient was a 72-year-old man in whom a liver mass was identified on abdominal ultrasonography at the examination for which he was referred to our hospital. Contrast-enhanced CT showed that the liver mass was a hemangioma with a surrounding AP shunt. Gallbladder wall thickening could not be ruled out as gallbladder cancer; however, a high possibility of adenomyomatosis was considered. EOB-MRI determined that the gallbladder wall thickening was adenomyomatosis and liver mass was a metastatic malignant tumor of unknown primary origin. Our policy was to resect gallbladder adenomyomatosis and the liver tumor for diagnostic purposes. Cholecystectomy plus hepatic S4a subsegmental resection and hepatoduodenal mesenteric lymph node dissection were performed. The histopathological diagnosis was neuroendocrine cancer of the gallbladder. A similar histology of the liver mass suggested continuity from the gallbladder tumor and was considered direct infiltration. Fifteen months after the operation, no recurrence was observed.

[A Case of Rapidly Progressing Colon NEC Treated with Laparoscopic Colectomy and Completely Cured].

We experienced a case of rapidly progressing transverse colon NEC that was treated with laparoscopic right hemispherectomy. A 72-year-old man underwent a follow-up lower gastrointestinal endoscopy at another hospital after a polyp resection. The examination showed a surrounding mass with stenosis of the intestinal tract of the transverse colon. A biopsy led to a diagnosis of poorly differentiated adenocarcinoma. A laparoscopic right hemicolectomy was performed of the transverse colon tumor. He was discharged on postoperative day 13 without complications, and NEC was diagnosed. We decided to administer postoperative adjuvant chemotherapy, starting with cisplatin plus etoposide. Four courses of postoperative adjuvant chemotherapy were completed. Approximately 1 year has passed since the operation, and progress has been observed in the outpatient department without recurrence.

Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer.

PURPOSE: Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities. METHODS: We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period. RESULTS: Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17-0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths. CONCLUSION: Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab. CLINICAL TRIAL REGISTRATION: UMIN000011485 DATE OF REGISTRATION: Sep 1st, 2013.

The meiosis-specific cohesin component stromal antigen 3 promotes cell migration and chemotherapeutic resistance in colorectal cancer.

Chromosome instability is one of the hallmarks of cancer. Stromal antigen (STAG) 3 is a core component of the meiosis-specific cohesin complex, which regulates sister chromatid cohesion. Although aberrantly activated genes encoding the cohesin complex have been identified in cancers, little is known about the role of STAG3 in colorectal cancer (CRC). Here, we evaluated the prognostic impact and role of STAG3 in CRC. Analysis of 172 CRC surgical specimens revealed that high STAG3 expression was associated with poor prognosis. STAG3 knockdown inhibited cell migration and increased drug sensitivity to oxaliplatin, 5-fluorouracil, irinotecan hydrochloride hydrate, and BRAF inhibitor in CRC cell lines. The enhanced drug sensitivity was also confirmed in a human organoid established from a CRC specimen. Moreover, suppression of STAG3 increased γH2AX foci. Particularly, in BRAF-mutant CRC cells, STAG3 silencing suppressed the expression of snail family transcriptional repressor 1 and phosphorylation of extracellular signal-regulated kinase via upregulation of dual-specificity phosphatase 6. Our findings suggest that STAG3 is related to poor clinical outcomes and promotes metastasis and chemotherapeutic resistance in CRC. STAG3 may be a novel prognostic marker and potential therapeutic target for CRC.

Dipeptidyl Peptidase 9 Increases Chemoresistance and is an Indicator of Poor Prognosis in Colorectal Cancer.

BACKGROUND: In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. METHODS: Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance. Moreover, the effects of the DPP9 inhibitors talabostat and vildagliptin in CRC cell lines and primary cultured cells were assessed. RESULTS: High expression of DPP9 was associated with worse prognosis in 196 patients with CRC. Cell viability was markedly inhibited in CRC cell lines transfected with DPP9 small interfering RNA or small hairpin RNA. Talabostat suppressed proliferation in CRC cell lines and primary cultured cells, and increased their sensitivity to chemotherapy. Vildagliptin, a DPP family inhibitor currently administered for diabetes, also increased the sensitivity of CRC cells to anticancer drugs. CONCLUSION: DPP9 was a poor prognostic factor for CRC and could be a new therapeutic target, while vildagliptin could be used as a repositioned drug for CRC treatment.

The inflammation-nutrition score supports the prognostic prediction of the TNM stage for colorectal cancer patients after curative resection.

PURPOSE: Inflammation and the nutritional and immunologic status are known to be associated with the prognosis of malignant tumors. We aimed to examine inflammation-nutrition scores and predict the prognosis of colorectal cancer (CRC) patients by integrating nutritional and immunologic factors and tumor stage. METHODS: This study investigated 511 patients with CRC from 2007 to 2013: 380 in a training set (TS) and 131 in a validation set (VS). The Osaka Prognostic Score (OPS) used comprised 1 point each for C-reactive protein > 1.0 mg/dL, albumin (< 3.5 g/dL), and lymphocyte count < 1600. Patients were classified according to the total points. The modified Glasgow Prognostic Score and the Prognostic Nutritional Index were also examined. A nomogram for predicting the disease-free survival (DFS) and overall survival (OS) was constructed based on the OPS and TNM stage. RESULTS: In the TS, a high OPS and high TNM stage were significant predictors of the DFS and OS. The C-indexes of the OPS for the DFS and OS were higher than those of other reported scoring systems. The C-index of the nomogram for the DFS was 0.762 in the TS and 0.675 in the VS. The C-index of the nomogram for the OS was 0.805 in the TS and 0.743 in the VS. CONCLUSION: Integrating the TNM stage and OPS accurately predicted the prognosis of patients with CRC.

Development of Novel Prognostic Prediction Models including the Prognostic Nutritional Index for Patients with Colorectal Cancer after Curative Resection.

OBJECTIVES: It has been reported that there is an association between the nutritional condition and the prognosis of cancer. Here, we evaluated the relation between the prognostic nutritional index (PNI) and colorectal cancer (CRC). METHODS: A total of 184 patients with CRC who underwent curative surgery from October 2011 to December 2012 at the Osaka University Hospital were investigated. According to the median PNI value of our data set, patients were classified into a high-PNI (≥46) group and a low-PNI (<46) group. The relationship between the PNI and the disease-free survival (DFS) and overall survival (OS) was analyzed by a Cox regression model. RESULTS: A low PNI was significantly associated with poor DFS (P = 0.006) and OS (P < 0.001). A multivariate analysis showed that low PNI, venous invasion (present), and tumor location (rectum) were independent risk factors for recurrence. Low PNI, advanced age, and venous invasion were found to be independent risk factors for mortality. Using these clinicopathological factors, we developed nomograms to predict DFS and OS. The concordance index was 0.828 for DFS and 0.756 for OS. CONCLUSIONS: A low PNI is a prognostic indicator for recurrence and mortality in CRC. Nomograms constructed by clinicopathological factors including the PNI can provide individual prognostic outcomes.

Erratum: A novel prognostic prediction model for recurrence in patients with stage II colon cancer after curative resection.

[This corrects the article DOI: 10.3892/mco.2018.1733.].

New marking method involving a light-emitting diode and power source device to localize gastrointestinal cancer in laparoscopic surgery.

Although the preoperative endoscopic marking method using dye is widely used, the dye can spread into the tissue or abdominal cavity, inducing the inflammation and leading to the wrong dissection. We developed a novel marking method using an endoscopic clip with a light emitting diode (LED) and a power source device to detect the accurate location of the site of interest. We performed this new marking method in three patients with gastrointestinal cancers. We placed an endoscopic clip with an LED on the gastrointestinal mucosa and used a power source device outside of the human body to detect the LED. We detected the clip with the LED using the power source device. We also confirmed the usefulness of this clip in three of three (100%) patients with colorectal and gastric cancer. We developed a novel marking device using an LED to identify an objective location successfully.

A novel prognostic prediction model for recurrence in patients with stage II colon cancer after curative resection.

The present study aimed to clarify the risk factors for recurrence of stage II colon cancer in patients and to determine possible treatment options for postoperative adjuvant chemotherapy. A prediction model for recurrence in patients with stage II colon cancer after curative surgical resection was developed. The present study retrospectively investigated 436 patients who underwent curative resection for stage II colon cancer at Osaka International Cancer Institute and Yao Municipal Hospital between 2004 and 2012. Several clinicopathological factors were examined and the Cox regression model was used to develop a prediction model for recurrence. The prediction model was validated in an independent group of 213 patients who underwent surgery at Osaka University Hospital between 2001 and 2012. Univariate analysis revealed that preoperative serum carcinoembryonic antigen level, preoperative obstruction, tumor invasion, lymphatic invasion and venous invasion were significantly correlated with disease-free survival. Using these variables, a classification and regression tree was constructed as a prediction model. The prediction models were validated by external datasets in an independent patient group. The concordance indices for DFS after current surgical resection were 0.675 in the learning set and 0.552 in the validation set. To conclude, a novel, reliable and personalized prognostic model was developed to predict recurrence in patients with stage II colon cancer, which may help clinicians to determine and perform adjuvant chemotherapy.

[A Case of Metachronous Liver Metastases of Gall Bladder Cancer Successfully Treated by Liver Resection].

A 73-year-old woman was diagnosed with gall bladder cancer by contrast enhanced CT images.The tumor was detected at the fundus of the gall bladder and enhanced heterogeneously.She underwent radical cholecystectomy including Japanese D2 lymph node dissection for gall bladder cancer.After 4 courses of oral S-1(80mg/m2 administered for 4 weeks and then stopped for 2 weeks)as adjuvant chemotherapy, a liver metastasis at segment 5 appeared 11 months postoperatively.It showed a ring enhanced tumor on contrast enhanced CT images.FDG accumulated in a similar lesion on PET-CT images.The patient successfully underwent partial hepatectomy of segment 5 of the liver.However, another liver metastasis at segment 7 appeared 5 months after the second operation, but it was resected successfully.The primary lesion and both liver metastases showed similar microscopic appearances.Seven courses of gemcitabine therapy(gemcitabine 1,000mg/m2 once every week for 3 weeks and then stopped for 1 week)were administered as adjuvant chemotherapy.She is now doing well without any sign of recurrence 2 years after the initial operation and 14 months after the secondary liver resection.

[A Case of Gastric Cancer with Multiple Liver Metastases Treated with XP Chemotherapy and RFA Resulting in a Complete Response for a Long Time].

A 60-year-old man underwent total gastrectomy with Japanese D2 lymph node dissection for advanced gastric cancer. The resected specimen was diagnosed as well-differentiated tubular carcinoma, pT3, pN1, cM0, and the final stage was considered as ⅡB. During adjuvant chemotherapy with S-1 (120 mg/day, administered for 4 weeks and then stopped for 2 weeks), multiple liver metastases were detected by contrast-enhanced CT images 6 months after the operation. Eight courses of XP therapy (capecitabine 1,600 mg/m2/day: day 1-14, cisplatin 70 mg/m2/day: day 1, then stopped until days 15-21) were administered in consideration of the recurrence during adjuvant chemotherapy with S-1, resulting in a partial response. Adverse events such as grade 1-2 abdominal pain, general fatigue, and the resultant deterioration of ADL led to discontinuation of chemotherapy. The residual liver metastasis was treated with RFA therapy, causing it to disappear completely. Serum CEA level was 5.5 ng/mL postoperatively, elevated to 13.9 ng/mL at the time of recurrence and 2.4 ng/mL after XP and RFA therapy. He is doing well without any recurrence 2 years and 6 months later.

[A Case of Pancreatic Cancer with Multiple Liver Metastases That Developed Postoperatively and Showed a Complete Response with S-1 Monotherapy].

We encountered a case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy for a long time. A pancreaticoduodenectomy was successfully performed on an 80- year-old man. Multiple liver metastases developed 6 months postoperatively. Microscopically, the primary lesion was diagnosed as adenosquamous carcinoma with anaplastic carcinoma component, and the final diagnosis was considered to be Stage Ⅲ disease. S-1monotherapy (80 mg/day, administered for 4 weeks and then stopped for 2-weeks) was effective. A partial response was noted after 3 months, and 9 months after the initial administration of S-1, a complete response was achieved, which persisted for more than 12 months, according to contrast-enhanced CT evaluations.Serum CEA and CA19-9 levels, which became slightly elevated at the time of liver metastasis development, normalized promptly and remained within normal limits. Adverse effects of chemotherapy of more than grade 2 severity were not apparent, and the patient tolerated the 11th course of S-1 administration, consistently. A standard therapeutic strategy and its outcomes in cases of pancreatic cancer recurrence are not clearly outlined in the Japanese Guideline for the Treatment of Pancreatic Cancer. A case of pancreatic cancer with multiple liver metastases that developed postoperatively and showed a complete response with S-1 monotherapy is reported in this paper.

[A Case of Unresectable Rectal Cancer Associated with Hemorrhage of the Primary Tumor after Chemotherapy].

A 47-year-old man visited our hospital with complaints of abdominal pain and hematuria.He was diagnosed with unresectable rectal cancer invading the urinary bladder with multiple liver metastases. Systemic chemotherapy with mFOLFOX6 and panitumumab was started soon after sigmoid colostomy. Three months later, both the primary tumor and the liver metastases had partially responded. Another 2 months later, he complained of terrible abdominal pain. CT images revealed a huge primary tumor and hemorrhage in the sigmoid mesocolon occupying the pelvic cavity. A salvage operation was performed and the primary tumor was palliatively resected. Soon after the operation, a local recurrence appeared and grew rapidly. He died 8 months after diagnosis. Rapid growth of the primary tumor seemed a limiting factor for the prognosis.

[A Case of Recurrence of Rectal Cancer with Para-Aortic Lymph Node Metastases Successfully Resected Resulting in Long Term Survival].

Laparoscopy-assisted low anterior resection (Japanese D3 lymph node dissection) was performed to treat a 68-year-old man for rectal cancer. Microscopically, the resected specimen was diagnosed as a moderately differentiated adenocarcinoma and the final stage was considered as pT3, pN1, cM0, pStage Ⅲa. He was administered capecitabine for 6 months as adjuvant chemotherapy. Then, enlarged para-aortic lymph nodes, indicated by follow up CT at 1 year and 11 months postoperatively developed behind the left renal artery. FDG accumulated in it, consistent with the CT images. Para-aortic lymph node dissection was performed after the diagnosis of solitary lymph node metastases. Microscopically, the resected lymph nodes showed features similar to the primary lesion. He is doing well without recurrence for 4 year and 6 months, without any adjuvant chemotherapy. Para-aortic lymph node metastases are frequently associated with other distant metastases; if not, a complete cure may be possible by curative resection for solitary metastases.