[A case of gastric perforation that occurred during the incubation period for infectious mononucleosis in an adolescent patient].

A 17-year-old young man visited our hospital because of severe upper abdominal pain and was diagnosed with acute peritonitis caused by gastrointestinal perforation. Emergent surgical treatment was performed, and the perforated lesion of the stomach was repaired. He recovered and was discharged without any complication at 14 days postoperatively. However, he had intermittent fever 2 days after discharge and visited our hospital again. He was diagnosed with infectious mononucleosis (IM), derived from Epstein-Barr virus (EBV) initial infection, on biochemical examination that was positive for anti-EBV VCA-IgG and negative for EBV nuclear antigen, although he was ameliorated conservatively. This pathophysiology raised a possibility that EBV infection had induced acute gastritis or gastric ulcer leading to the penetration of the stomach. Six weeks postoperatively, esophagogastroduodenoscopy showed a gastric ulcer in the vestibular part of the stomach. Pathologic examination of the stomach revealed mucosal erosion with B-cell infiltration into the lamina propria;however, Epstein-Barr viral infection was unclear by EBV-encoded small RNA in situ hybridization. Here, we report a rare case of gastric perforation that occurred during the incubation period of IM with a review of the relevant literature.

[A Case of Duodenal Adenocarcinoma in the Third Portion Treated with Partial Duodenectomy].

A 85-year-old man was admitted due to vomiting. Abdominal CT showed the remarkable expansion of the stomach and the stenotic lesion in the third portion of the duodenum. Duodenal endoscopy showed a circular tumor of the third potion of the duodenum, and biopsy disclosed tubular adenocarcinoma. Operation was performed on the basis of a diagnosis of primary duodenal cancer of the third portion. Liver metastasis, peritoneal dissemination, and apparent lymph node enlargement were not observed. The tumor was present in the third portion of the duodenum and partial duodenectomy was performed. Reconstruction was achieved by side to side anastomosis of the duodenum and the jejunum. Histopathological diagnosis was well differentiated tubular adenocarcinoma, SS, ly1, v1. Primary duodenal cancer is a relatively rare disease, and there are few cases of third portion. If pancreatic invasion and lymph node metastasis are not observed as in this case, it is necessary to examine the indication of partial duodenectomy.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report.

BACKGROUND: Therapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined. CASE PRESENTATION: A 66-year-old man was initially diagnosed with NSCLC with multiple intrapulmonary metastases and abdominal lymph node metastasis in the tail of the pancreas, and bronchial biopsy and diagnostic imaging were performed. Pathologic examination of the lung showed poorly differentiated adenocarcinoma cells expressing epithelial marker and PD-L1. Therefore, pembrolizumab monotherapy for NSCLC was given. The pulmonary lesions shrank markedly and were in complete remission after 8 months of anti-PD-1 therapy, though no therapeutic effect was observed in the pancreatic site. Distal pancreatectomy was then performed, and histopathological examination showed that the tumor was UCOGC originating from the pancreas. The histologic findings of the resected specimen mimicked those of the lung biopsy specimen, leading to the final assessment that the lung tumors were metastatic foci that migrated from the UCOGC, and only the metastatic lesions benefited from pembrolizumab therapy. CONCLUSION: Immune checkpoint inhibitors have limited therapeutic effects on primary lesions of pancreatic cancer, but they may exert antitumor effects on pulmonary metastases of UCOGC.

[A Case of Intraductal Papillary Mucinous Carcinoma of the Pancreas Extending Widely within the Pancreas Resected by Total Pancreatectomy].

A 78-year-old woman visiting our hospital with the chief complaint of abdominal pain was diagnosed with ischemic colitis. CT pointed out pancreatic enlargement, so detailed pancreatic examination was conducted in parallel with treatment. In enhanced CT and MRI, the main pancreatic duct significantly extended over the entire length, and mural nodules scattered in the main pancreatic duct were observed. It was diagnosed with main duct intraductal papillary mucinous neoplasm (IPMN), which is likely to be intraductal papillary mucinous carcinoma(IPMC), and total pancreatectomy was performed. Pathological findings showed diffuse dilation of the main pancreatic duct, non-invasive IPMC progressed over approximately the entire length of the main pancreatic duct, mucinous carcinoma-tubular adenocarcinoma was widely infiltrated in pancreatic tissues around mural nodules. The cancer remained in the pancreas and was eventually diagnosed with IPMC, invasive, pT2, pN0, and pStage ⅠB. This case was an IPMN with high-risk stigmata, and it was an adaptive case of total pancreatectomy because mural nodules extended to the entire pancreas. In recent years, total pancreatectomy has come to be expected good results by the progress of diabetes treatment and the development of pancreatic enzyme agents, it is necessary to carefully judge each case for adaptation.

[Multimodal Therapy for Stage â £ Gallbladder Carcinoma Achieved Long-Term Survival-A Case Report].

A 75-year-old man with a chief complaint of abdominal pain visited our hospital and was diagnosed with Stage Ⅳ gallbladder carcinoma that infiltrated the transverse colon with distant lymph node metastases. He received gemcitabine plus cisplatin chemotherapy, which led the primary lesion to shrink. However, transverse colon obstruction occurred, and semi- urgent right hemicolectomy and extended cholecystectomy were performed. A year and 2 months after first diagnosis, an inferior pancreatic head lymph node swelling was detected. Chemoradiotherapy was performed using S-1, and the lymph node swelling was reduced. Despite continuous S-1 therapy, the lymph node gradually started to swell again, which led to duodenum obstruction by compression. He underwent gastrojejunal bypass; however, his general condition gradually worsened, and he died 2 years and 6 months after the first diagnosis. Even in cases of unresectable gallbladder carcinoma, multimodal therapy, such as surgery, chemoradiotherapy, and palliative gastrointestinal bypass, may archive a long prognosis of 2 years and 6 months.

Body weight loss after surgery affects the continuity of adjuvant chemotherapy for pancreatic cancer.

BACKGROUND: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy. METHODS: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis. RESULTS: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%. CONCLUSIONS: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.

[A Case of Resection of Intraductal Papillary Mucinous Carcinoma Detected Due to Acute Pancreatitis].

A 67-year-old man visiting our hospital with the chief complaint of sudden upper abdominal pain was diagnosed with acute pancreatitis. Based on computed tomography findings, intraductal papillary mucinous neoplasm(IPMN)was suspected as the cause of the pancreatitis and detailed examination was conducted following its alleviation. Endoscopic retrograde and magnetic resonance cholangiopancreatography showed marked dilation of the main pancreatic duct, with a mural nodule inside the main pancreatic duct at the pancreatic head. Main duct IPMN was diagnosed and pancreaticoduodenectomy was performed 3 months after the onset of acute pancreatitis. The histopathological findings showed a tumor proliferating in a mold pattern in the lumen of the dilated main pancreatic duct, resulting in a diagnosis of intraductal papillary mucinous carcinoma(IPMC). The presence of IPMN should be considered as a cause of acute pancreatitis; if findings suggestive of IPMN are found on imaging, detailed examinations and treatment are needed in consideration of the potential for malignancy following alleviation of pancreatitis.

[Short-Term and Long-Term Outcomes of Colonic Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer].

We examined the short-term and long-term outcomes in 50 patients who underwent stenting as a bridge to surgery(BTS) for obstructive colorectal cancer. The patients comprised 30 men and 20 women, with a mean age of 74.0 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.4 days. No serious complications related to stenting occurred. Colonoscopy after stenting was important for the preoperative diagnosis of coexisting lesions and planning of the extent of resection. Elective and one-stage surgeries could be performed in all patients after stenting. Regarding long-term outcomes, the 5-year overall survival rate and disease-free survival rate in the BTS patients with Stage Ⅱ plus Ⅲ cancer were 73.1% and 55.7%, respectively. The results of this study suggest that BTS for obstructive colorectal cancer is an effective treatment strategy for not only short-term but also long-term outcomes.

Lethal Bleeding from a Duodenal Cancerous Ulcer Communicating with the Superior Mesenteric Artery in a Patient with Pancreatic Head Cancer.

Pancreatic cancer often invades the duodenum and causes obstruction, but rarely causes massive duodenal bleeding. A 68-year-old male was admitted to our hospital because of vomiting. Enhanced abdominal CT showed a hypovascular tumor with air bubbles in the uncinate process of the pancreas. The tumor invaded the duodenum and metastasized to the liver and peritoneum. The main trunk of the superior mesenteric artery (SMA) was circumferentially involved. After admission, he had hematemesis and melena. Emergency gastroduodenoscopy revealed pulsating vessels in the third portion of the duodenum and he eventually experienced hemorrhagic shock. Severe bleeding occurred from his mouth and anus like a catastrophic flood. It was difficult to sustain blood pressure even with massive blood transfusion with pumping. After insertion of an intra-aortic balloon occlusion catheter, the massive bleeding was eventually stopped. Although we attempted interventional radiography, aortography revealed direct communication between the main SMA trunk and the duodenal lumen. The tumor was considered anatomically and oncologically unresectable. Thus, we did not perform further intervention. The patient died 2 h after angiography. Herein, we report the case of pancreatic head cancer causing lethal bleeding associated with tumor-involved SMA. Duodenal bleeding associated with pancreatic cancer invasion should be considered as an oncogenic emergency.

Role of caveolin-1 in hepatocellular carcinoma arising from non-alcoholic fatty liver disease.

The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1. HLE cells treated with oleic acid (OA) showed robust proliferation, whereas CAV-null HepG2 cells showed reduced proliferation and increased apoptosis. CAV-1 knockdown in HLE cells attenuated the OA-induced increase in proliferation and enhanced apoptosis. Liquid chromatography-tandem mass spectrometry analysis revealed that the levels of OA-containing ceramide, a pro-apoptotic factor, were higher in HepG2 and CAV-1-deficient HLE cells than in HLE cells, suggesting that CAV-1 inhibits apoptosis by decreasing the level of OA-containing ceramide. These results indicate that CAV-1 is important for NAFLD-HCC survival in fatty acid-rich environments and is a potential therapeutic target.

Usefulness of four-dimensional flow-sensitive magnetic resonance imaging to evaluate hemodynamics in the pancreaticoduodenal artery.

Pancreaticoduodenal artery (PDA) aneurysm associated with celiac axis compression by the median arcuate ligament (MAL) is a rare disorder, but may be lethal if ruptured. Therefore, prophylactic surgical treatments need to be considered when MAL compresses the celiac axis. We herein report the usefulness of an arterial flow analysis for objectively evaluating this pathophysiology under four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI). Celiac artery stenosis was incidentally found under contrast-enhanced CT in a 50-year-old woman with symptomatic solitary pancreatic insulinoma. Under 4D-flow MRI, retrograde blood flow and aberrant wall shear stress were detected in the pancreaticoduodenal artery arcade. After obtaining informed consent, enucleation for insulinoma concomitant with MAL dissection was performed. Hypoglycemic attack completely resolved immediately after surgery. One month after surgery, 4D-flow MRI revealed normalized vectorial flow and wall shear stress in the PDA arcade without hypoglycemic attack. 4D-flow MRI is a very useful and non-invasive modality for objectively evaluating visceral artery hemodynamics.

Stearate-to-palmitate ratio modulates endoplasmic reticulum stress and cell apoptosis in non-B non-C hepatoma cells.

The increased prevalence of hepatocellular carcinoma (HCC) without viral infection, namely, NHCC, is a major public health issue worldwide. NHCC is frequently derived from non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis, which exhibit dysregulated fatty acid (FA) metabolism. This raises the possibility that NHCC evolves intracellular machineries to adapt to dysregulated FA metabolism. We herein aim to identify NHCC-specifically altered FA and key molecules to achieve the adaptation. To analyze FA, imaging mass spectrometry (IMS) was performed on 15 HCC specimens. The composition of saturated FA (SFA) in NHCC was altered from that in typical HCC. The stearate-to-palmitate ratio (SPR) was significantly increased in NHCC. Associated with the SPR increase, the ELOVL6 protein level was upregulated in NHCC. The knockdown of ELOVL6 reduced SPR, and enhanced endoplasmic reticulum stress, inducing apoptosis of Huh7 and HepG2 cells. In conclusion, NHCC appears to adapt to an FA-rich environment by modulating SPR through ELOVL6.

[A Case of Advanced Gallbladder Cancer with Paraaortic Lymph Node Metastases Successfully Treated by Chemotherapy and Conversion Surgery].

The patient was a 76-year-old man who was admitted to our hospital with a diagnosis of ileus. A gallbladder tumor was found incidentally on CT, and it was diagnosed as gallbladder cancer. Enlargement of multiple lymph nodes, including the paraaortic lymph nodes, was observed, and PET-CT further showed FDG uptake in the lymph nodes. Based on these findings, the patient was diagnosed with Stage ⅣB gallbladder cancer with paraaortic lymph node metastases. Since surgical resection was not possible, chemotherapy with gemcitabine and cisplatin(GEM plus CDDP)was started. After completion of 4 courses of GEM plus CDDP, the enlarged lymph nodes were decreased in size on CT, and there was no FDG uptake on PET-CT. These findings indicated downstaging to Stage Ⅱ; thus, conversion surgery with extended cholecystectomy and lymph node dissection was performed. The pathological diagnosis confirmed that the patient had Stage Ⅱ cancer(pT2N0M0). A case of unresectable gallbladder cancer that was treated with GEM plus CDDP and subsequent conversion surgery is reported, along with a literature review.

[Four Cases of Ileocolic Intussusception Associated with Malignant Lymphoma of the Ileum].

We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy. Thus, ileocecal resection or right hemicolectomy was performed. Macroscopically, all tumors were polypoid type and were present within 25 cm from the valve of Bauhin. Histological diagnoses were diffuse large B-cell lymphoma(DLBCL)in 2 patients, T-cell lymphoma in one, and follicular lymphoma in one. Postoperative chemotherapy was performed in patients with DLBCL and T-cell lymphoma. Tumors are commonly the cause of intussusception in adults; therefore, emergent surgery is imperative. When malignant lymphoma is diagnosed, a multidisciplinary approach that includes postoperative chemotherapy is necessary.

Duodenal adenocarcinoma successfully diagnosed with transabdominal ultrasonography.

Adenocarcinoma arising from the duodenum is relatively rare. Diagnosis of this disease at an early stage is difficult because its symptoms are usually nonspecific. We herein present a case in which duodenal adenocarcinoma was successfully found by transabdominal ultrasonography. Under ultrasonography, the tumor was located in the proximal duodenum apart from the papilla of Vater, and the serosa was intact. Other diagnostic modalities showed no evidence of adjacent organ invasion or distant metastasis. Therefore, pancreatoduodenectomy was performed and the postoperative course was uneventful. The ultrasonographic findings corresponded well with the pathological diagnosis. The following three procedures were essential in this case: systematic scanning of the digestive tract to determine the location of the lesion, graded compression ultrasound to remove air bubbles from the region of interest, and precise observation of the intestinal walls using proper transducers. The precise and skillful performance of transabdominal ultrasonography using a suitable device can help to diagnose duodenal adenocarcinoma, a rare malignancy.

Accumulation of arachidonic acid-containing phosphatidylinositol at the outer edge of colorectal cancer.

Accumulating evidence indicates that cancer cells show specific alterations in phospholipid metabolism that contribute to tumour progression in several types of cancer, including colorectal cancer. Questions still remain as to what lipids characterize the outer edge of cancer tissues and whether those cancer outer edge-specific lipid compositions emerge autonomously in cancer cells. Cancer tissue-originated spheroids (CTOSs) that are composed of pure primary cancer cells have been developed. In this study, we aimed to seek out the cancer cell-autonomous acquisition of cancer outer edge-characterizing lipids in colorectal cancer by analysing phospholipids in CTOSs derived from colorectal cancer patients with matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS). A signal at m/z 885.5 in negative ion mode was detected specifically at the surface regions. The signal was identified as an arachidonic acid (AA)-containing phosphatidylinositol (PI), PI(18:0/20:4), by tandem mass spectrometry analysis. Quantitative analysis revealed that the amount of PI(18:0/20:4) in the surface region of CTOSs was two-fold higher than that in the medial region. Finally, PI(18:0/20:4) was enriched at the cancer cells/stromal interface in colorectal cancer patients. These data imply a possible importance of AA-containing PI for colorectal cancer progression, and suggest cells expressing AA-containing PI as potential targets for anti-cancer therapy.

Expression of indocyanine green-related transporters in hepatocellular carcinoma.

BACKGROUND: Indocyanine green (ICG), an organic anion used in liver function tests, is known to accumulate in hepatocellular carcinoma (HCC) tissues after an intravenous injection. Because the intratumoral expression of transporters for chemical agents influences the behaviors of some malignant tumors, we investigated whether the expression of ICG-related transporters influenced the clinicopathologic features of HCC. MATERIALS AND METHODS: ICG accumulation patterns were examined using near-infrared spectroscopy and the protein expression of ICG-related transporters was assessed using immunohistochemistry and immunoblotting in 40 resected HCC specimens. We also determined whether the intratumor expression of these transporters affected intratumor lipid composition by imaging mass spectrometry. RESULTS: Immunoblot analysis revealed that the expression of organic anion transporting polypeptide 1B3 (OATP1B3) and multidrug resistance p-glycoprotein (MDR)-3, as influx and efflux transporters, respectively, were significantly higher in ICG-accumulated HCC (ICG-high HCC) than in ICG-low HCC. ICG was fluorescently observed in the pseudoglands and bile canaliculi abundantly expressing MDR3. An immunohistochemical examination revealed significantly worse disease-free and overall survival rates in patients with MDR3-negative HCC, in which the intratumoral accumulation of some phosphatidylcholine species was observed under imaging mass spectrometry. CONCLUSIONS: The intratumoral expression of MDR3, a key efflux transporter of ICG, affected the prognosis of patients with HCC, presumably by altering the lipid composition of the lipid bilayers.

Pancreatoduodenal artery aneurysm resulting from median arcuate ligament compression successfully treated with laparoscopic ligament section.

True aneurysms of the pancreatoduodenal arteries are frequently associated with stenosis or occlusion of the celiac trunk caused by median arcuate ligament compression. Celiac stenosis cannot be cured, even by transarterial embolization, which has recently become a good alternative to open surgical repair. To prevent recurrence, management of median arcuate ligament compression to correct hemodynamics in vascular networks should also be performed. Herein we report a case of pancreatoduodenal arterial aneurysm with median arcuate ligament compression that was successfully treated with minimally invasive laparoscopic median arcuate ligament section. The patient was discharged 4 days after surgery with no complications. Enhanced CT 1 month after surgery revealed no residual celiac trunk stenosis or aneurysm. Normalization of blood flow by laparoscopic median arcuate ligament section is a good option for some patients with a pancreatoduodenal arterial aneurysm.

Detection of intrahepatic veno-venous shunts by three-dimensional venography using multidetector-row computed tomography during angiography.

PURPOSE: The hepatic vein (HV) can be removed during hepatectomy if there is an effective intrahepatic veno-venous shunt (vv-shunt). We evaluated the efficacy of vv-shunt detection by three-dimensional (3D) venography reconstructed from multidetector-row computed tomography (MDCT) during angiography. METHODS: 3D venography was reconstructed using computer software in 88 patients with intrahepatic tumors. RESULTS: We found that 12 patients had one shunt [4 right hepatic vein (RHV)-middle hepatic vein (MHV) and 12 RHV- inferior right hepatic vein (IRHV)] and 1 patient had 2 shunts (RHV-MHV and -IRHV), confirming a clinically efficient vv-shunt in 14.8% of the patients. In one patient with an RHV-IRHV shunt, the preserved RHV-IRHV shunt worked well and prevented congestion of the postero-caudal subsegment after central bisegmentectomy with partial resection of the RHV ventral trunk for huge hepatocellular carcinoma (HCC). CONCLUSIONS: Although the vv-shunt detection rate by 3D venography is low, a visualized vv-shunt proved to be efficient. Thus, invasive occlusion venography is avoidable if a vv-shunt is seen on 3D venography.

Pancreatic metastases of cerebellar hemangiopericytoma occurring 24 years after initial presentation: report of a case.

Hemangiopericytoma (HPC) preferentially developing in soft tissues and the meninges has been gradually recognized to be an aggressive, highly metastatic tumor. We herein report the case of a 65-year-old male with pancreatic metastases of cerebellar HPC that developed following two resections of intracranial local recurrent foci, 24 years after the initial craniotomy and 7 years after resection of metastases to the lungs and kidneys. Follow-up abdominal computed tomography scanning and magnetic resonance imaging revealed a solitary tumor in the pancreatic body. Since no other recurrent foci were detectable, distal pancreatectomy was performed. Another metastasis was incidentally found in the resected pancreas. Both foci were pathologically proven to be metastases of HPC. Among the 12 reported cases of pancreatic metastases of HPC, including ours, this case showed the longest duration between initial onset and the development of pancreatic metastases, suggesting that providing long-term follow-up is necessary for HPC patients.