Significance of in vitro photodynamic cytodiagnosis using 5-aminolevulinic acid in solid pancreatic tumors extracted by endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND: Recently, photodynamic diagnosis using 5-aminolevulinic acid (5-ALA) has gained attention for the diagnosis of neoplastic diseases. In the present study, an in vitro method of photodynamic cytodiagnosis (PDCD) performed using the reagent 5-ALA in the cytodiagnosis of solid pancreatic tumors was developed. Here, we assess the accuracy of PDCD for malignancy. MATERIALS AND METHODS: EUS-FNA was performed from September 2015 to March 2018 in patients with solid pancreatic tumors at Osaka Rosai Hospital. Samples were diagnosed independently by an expert pathologist and a medical doctor with conventional cytology and PDCD. RESULTS: A total of 53 patients (35 males, average age: 70.2 years old) were enrolled. The definitive diagnoses were 7 benign lesions and 46 malignant lesions. Using the in vitro PDCD method, the detection of reddish fluorescence in cell samples indicated cancer cells. PDCD had a sensitivity of 91.3% (42/46) and a specificity of 100% (7/7), while conventional cytology had a sensitivity of 93.5% (43/46) and a specificity of 85.7% (6/7). Two patients were successfully diagnosed with malignancy only by the PDCD method. CONCLUSIONS: In vitro PDCD performed using the 5-ALA method can effectively and safely identify a diagnosis of pancreatic cancer without requiring an expert pathologist. The sensitivity of this technique could be increased in the diagnosis of pancreatic malignancy by combining it with the conventional method.

[Usefulness of Fluorescent Urine Cytology in the Diagnosis of Urothelial Carcinoma].

Five-aminolevulinic acid, an amino acid that is metabolized in the cytoplasm to become protoporphyrin IX, is used in photodynamic diagnosis in various carcinomas because it accumulates in higher concentrations in tumor tissue than in normal tissue. 5-Aminolevulinic acid-induced fluorescent urine cytology is more sensitive than conventional urine cytology only in low grade urothelial carcinoma (UC), but it showed a tendency for higher sensitivity in high grade UC. To increase the number of patients and reconsider our previous findings, we compared the sensitivity and specificity of preoperative urine cytology and fluorescent urine cytology in 343 patients diagnosed as having UCs pathologically (215 bladder cancers, 128 upper tract UCs) and 197 non-cancer patients at Osaka Rosai Hospital from March 2013 to December 2019. The sensitivities of fluorescent urine cytology and conventional urine cytology were 81.1% and 63.3% (p<0.001), respectively, and specificities were 92.9% and 93.9% (p=0.84), respectively. The sensitivity of fluorescent urine cytology was superior to that of conventional urine cytology in both low grade UC (76.8% vs 41.1%, p<0.001) and high grade UC (83.1% vs 74.0%, p=0.023).

[pCR Achievement in Two Cases Treated with XELOXIRI as Neoadjuvant Chemotherapy for Locally Advanced Rectal Cancer].

BACKGROUND: Neoadjuvant chemotherapy is designed to prevent disease recurrence, particularly distant recurrence, and to improve overall patient survival. We present 2 cases where pathological complete response(pCR)was obtained after administering XELOXIRI as neoadjuvant chemotherapy for locally advanced rectal cancer. Case 1: The patient was a 63-year-old man diagnosed with rectal cancer(Ra, cT4aN1M0, cStage Ⅲa)and treated with 6 courses of XELOXIRI as neoadjuvant chemotherapy. After systemic chemotherapy, he underwent laparoscopy-assisted low anterior resection and showed a pCR. Case 2: The patient was a 56-year-old man diagnosed with rectal cancer(Rb, cT3N3M0, cStage Ⅲb)and treated with 6 couses of XELOXIRI as neoadjuvant chemotherapy. After systemic chemotherapy, he underwent low anterior resection and showed a pCR. CONCLUSION: We present 2 cases treated with XELOXIRI as neoadjuvant chemotherapy for locally advanced rectal cancer where pCRwas achieved.

[A Case of Colon Cancer with Peritoneal Dissemination and Liver Metastasis That Responded to Comprehensive Treatment by Perioperative Chemotherapy and Cytoreductive Surgery].

A 64-year-old man was referred to our hospital to determine the cause of fecal occult blood. Colonoscopy revealed a type Ⅱtumor located in the ascending colon. Histopathologic analysis of the tumor biopsy specimen revealed moderately differen- tiated, tubular adenocarcinoma with KRAS exon 2(G12V)mutation. FDG-PET/CT revealed high trace accumulation in the S4 of the liver and in multiple sites spread across the abdominal cavity(cT4aN1M1c2[H1, P3], cStage Ⅳc). Chemotherapy using S-1 plus oxaliplatin(SOX)with bevacizumab(Bmab)was administered. After 8 courses of SOX with Bmab, the volume of the ascending colon cancer and liver metastasis reduced, and peritoneal disseminations disappeared. We, therefore, considered that curability B resection was suitable, and performed right hemicolectomy, total omentectomy, and resection of the rectovesical peritoneum. Histopathological examination of surgical specimens revealed extensive fibrosis from the submucosa to subserosal tissue with some tubular adenocarcinoma cells(histological effect: Grade 2). For maintenance therapy, trifluri- dine/tipiracil plus Bmab was administered after cytoreduction. The patient is in remission for 26 months without recurrence. Perioperative chemotherapy and cytoreductive surgery are useful for the treatment of colon cancer with diffuse peritoneal dissemination.

High performance of 5-aminolevulinic acid-induced fluorescent selective upper tract urinary cytology.

OBJECTIVES: To investigate the efficacy of selective upper tract urinary cytology using extracorporeal 5-aminolevulinic acid for the diagnosis of upper urinary tract urothelial carcinoma. METHODS: We evaluated 104 patients who underwent radical nephroureterectomy and were diagnosed pathologically as having upper urinary tract urothelial carcinoma between March 2013 and May 2019 in Osaka Rosai Hospital. Preoperatively, we collected upper tract urinary cytology from both sides, and compared the sensitivity and specificity between conventional urine cytology and 5-aminolevulinic acid-induced fluorescent urine cytology. RESULTS: The sensitivity of 5-aminolevulinic acid-induced fluorescent selective upper tract urinary cytology was significantly higher than conventional cytology (90.4% vs 66.3%, P < 0.001), whereas the specificity was equally high (100% vs 98.2%, P = 1.0). In more detailed analysis, the sensitivity of 5-aminolevulinic acid-induced fluorescent selective upper tract urinary cytology was significantly higher than that of conventional cytology unrelated to patients' age (<76 years: 90.2% vs 68.6%, P = 0.013; ≥76 years: 90.6% vs 64.2%, P = 0.021), sex (male: 89.2% vs 67.5%, P = 0.001; female: 95.2% vs 61.9%, P = 0.02) or pT stage (pT1 or less: 91.4% vs 69.0%, P = 0.005; pT2 or more: 89.1% vs 63.0%, P = 0.006), tumor grade (high grade: 91.0% vs 70.5%, P = 0.002; low grade: 88.5% vs 53.8%, P = 0.013), and tended to be more efficacious for tumors that could not be detected by imaging techniques (83.3% vs 50.0%, P = 0.075). CONCLUSIONS: 5-Aminolevulinic acid-induced fluorescent selective upper tract urinary cytology is more sensitive than conventional cytology for the diagnosis of upper urinary tract urothelial carcinoma, regardless of pT stage and tumor grade.

High diagnostic efficacy of 5-aminolevulinic acid-induced fluorescent urine cytology for urothelial carcinoma.

BACKGROUND: In general, urine cytology is often problematic because of its low sensitivity, especially for low-grade urothelial carcinoma (UC) in clinical practice. To improve the sensitivity, we focused on 5-aminolevulinic acid (5-ALA), because recent studies suggested that 5-ALA-induced urine cytology can be used for photodynamic diagnosis. In this study, we evaluated the diagnostic efficacy of 5-ALA-induced fluorescent urine cytology for UC. METHODS: We included in this study 318 patients comprising 158 non-cancer patients, 84 bladder tumor patients, and 76 upper urinary tract urothelial carcinoma (UUT-UC) patients treated in our institution from March 2013 to September 2018. Using the same voided urine sample, we compared sensitivity and specificity between conventional urine cytology and 5-ALA-induced fluorescent urine cytology. RESULTS: Overall, the sensitivity of 5-ALA-induced fluorescent urine cytology was significantly higher than that of conventional urine cytology (86.9% vs. 69.4%; p = 0.0002), and the specificity was equivalently high (96.2% vs. 95.6%; p = 1.0). In subgroup analysis, the high sensitivity of 5-ALA-induced fluorescent urine cytology was also detected regardless of age, sex, and tumor type. However, in terms of stage and grade, differences were only detected in patients with less than pTa stage (89.2% vs. 52.1%; p = 0.0001) and low-grade tumor (91.5% vs. 51.1%; p < 0.0001). CONCLUSIONS: 5-ALA-induced fluorescent urine cytology was significantly more effective for UC diagnosis when compared with the conventional cytology, especially in patients with low-stage and low-grade tumors. These findings indicate that 5-ALA-induced fluorescent urine cytology may potentially be a very useful tool for clinical use.

[A Case of Scirrhous Gastric Carcinoma Diagnosed by Staging Laparoscopy].

We report a case of scirrhous gastric carcinoma diagnosed by staging laparoscopy and discuss some literature reviews. A 60-year-old man was referred because of a choking sensation and weight loss, and gastroendoscopy revealed thickening of the entire circumference of the wall at the gastric cardia. Scirrhous gastric carcinoma was suspected, and biopsy was performed at many points and times by endoscopic examination, but the histologic findings revealed no malignant features. We performed staging laparoscopy, peritoneal washing cytology, and biopsy of the nodules in the abdominal wall. He was diagnosed with advanced gastric cancer with peritoneal dissemination and has received chemotherapy. Staging laparoscopy is a useful method for diagnosis and determination of the management of scirrhous gastric carcinoma.

[A Case of Liver Metastasis of Intrahepatic Cholangiocarcinoma That Achieved Clinical Complete Response after Gemcitabine and Cisplatin Combination Chemotherapy].

We report a case of liver metastasis of intrahepatic cholangiocarcinoma that achieved clinical complete response after gemcitabine(GEM)and cisplatin(CDDP)combination chemotherapy. The patient was a 69-year-old man who was diagnosed with intrahepatic cholangiocarcinoma with hilar invasion and intrahepatic metastasis(cT4N0M0, Stage ⅣA)and was initially treated with right trisegmentectomy with left portal vein resection, lymph node dissection, and reconstruction of the left portal vein and biliary tract after transhepatic portal vein embolization(PTPE). S-1 was administered continuously as postoperative adjuvant chemotherapy, and the patient showed no signs of recurrence. Three years after the surgery, a CT scan showed LDA 10mm in diameter in the middle area of the remnant liver. We suspected liver metastasis when both serum CA19-9 and DUPAN-2 levels were elevated with the increasing size of LDA; liver biopsy was then performed, and he was diagnosed with liver metastasis of intrahepatic cholangiocarcinoma. After 3 courses of combination chemotherapy containing GEM and CDDP, a CT scan revealed that the liver metastasis reduced in size, and PR was achieved based on the RECIST standard. After 12 courses, the liver metastasis disappeared, and the patient had achieved CR based on the RECIST standard. The patient has received S-1 following the combination chemotherapy and survived for 6 years since initial treatment without any other metastatic lesions.

Anti-mitochondria antibody-related tubulointerstitial nephritis accompanied by severe hypokalemic paralysis.

A 47-year-old man presented with severe hypokalemic paralysis and respiratory failure. A large amount of potassium was administered along with providing intensive care, and his condition improved. Hypokalemia was attributed to increased urinary potassium excretion. A kidney biopsy was performed to make a definitive histological diagnosis. It revealed acute tubulointerstitial nephritis (TIN). After the diagnosis, prednisolone was administered, and the TIN gradually improved. From the clinical course and laboratory findings, the TIN was presumed to be an autoimmune disorder. Further specific autoantibody tests were positive for anti-mitochondrial antibody (AMA), which has been gaining increasing attention in regard to TIN. In addition, all previous cases of TIN associated with AMA have affected females. The detailed pathogenetic mechanisms are as yet unclear and require further investigation.

[Renal Pelvic Cancer with Delayed Diagnosis Due to Left Renal Injury : A Case Report].

We report a case of renal pelvic cancer found after left renal trauma. A 63-year-old man was admitted to our hospital because of gross hematuria after he had fallen down the stairs two days earlier. He had asymptomatic severe anemia (Hb : 3. 6 g/dl). Abdominal computed tomography (CT) scan revealed bilateral ureteropelvic stones, bilateral severe hydronephrosis and hematoma of the left upper renal pelvis. We diagnosed him with left renal pelvic hemorrhage by trauma, and transcatheter arterial embolization (TAE) was performed. After TAE, gross hematuria improved, but some hematuria continued to be noted. We suspected malignancy, and examined the patient with contrast-enhanced CT, transurethral resection and retrograde pyelography combined with urine cytology in the upper urinary tract, all with no evidence of malignancy. However, four months after the left renal injury, follow-up CT revealed multiple metastatic lesions. We performed a left nephrectomy, and the resulting pathological diagnosis was invasive urothelial carcinoma with squamous differentiation of the renal pelvis. We performed 7 courses of chemotherapy, but the multiple metastatic lesions progressed, and he died of the disease 19 months after the operation.

A Rare Case of Vascular Leiomyosarcoma Originating from a Branch Vessel of the External Iliac Vein.

Leiomyosarcoma arising from the external iliac vein is uncommon. This is a report of a 51-year-old Japanese man with venous leiomyosarcoma originating from a branch vessel of the left external iliac vein. The tumor was found during a medical examination, and the patient had no symptoms. Computed tomography showed a 72 × 49 mm mass adjacent to the left external iliac vein. The tumor was resected en-block along with ligation of the external iliac vein due to strong adhesion with the tumor. Histological examination showed venous leiomyosarcoma, and its origin was thought to be a branch vessel of the left external iliac vein. The patient has remained free from recurrence at 30 months after surgery.

Laparoscopic Resection of a Jejunal Inflammatory Fibroid Polyp that Caused Occult Gastrointestinal Bleeding, Diagnosed via Capsule Endoscopy and Double-Balloon Enteroscopy: A Case Report.

An inflammatory fibroid polyp (IFP) is a mesenchymal tumor of the gastrointestinal tract. IFPs in the small intestine are the most frequently detected with symptoms, such as abdominal pain and tarry stool due to intussusception. Accordingly, few studies have reported jejunal IFP as a cause of occult gastrointestinal bleeding (OGIB) diagnosed via both of capsule endoscopy (CE) and double-balloon enteroscopy (DBE). A 68-year-old woman presented with a progression of anemia and a positive fecal occult blood test result. Esophagogastroduodenoscopy and total colonoscopy findings were unremarkable. CE revealed a tumor with bleeding in the jejunum. DBE also revealed a jejunal polypoid tumor. Bleeding from the tumor seemed to have caused anemia. The patient underwent partial laparoscopic resection of the jejunum, including resection of the tumor. The tumor was histopathologically diagnosed as IFP. To our knowledge, this is the first reported case of laparoscopic resection of jejunal IFP with OGIB diagnosed via CE and DBE preoperatively.

[A Patient Underwent Pancreaticoduodenectomy with Reconstruction of Replaced Right Hepatic Artery].

A 78 year-old man was diagnosed as a pancreatic cancer in department of gastroenterology in our hospital. Enhanced computed tomography demonstrated an aberrant right hepatic artery(ARHA)arising from superior mesenteric artery(SMA). We conducted sub-stomach preserving pancreaticoduodenectomy(SSPPD- II A-1). As the preoperative diagnosis, right hepatic artery(RHA)was arising from SMA and running through the tumor, and we resected the ARHA with the tumor and reconstructed RHA to gastroduodenal artery(GDA). Pathological diagnosis was non invasive tumor with neither lymph node metastasis nor invasion of the vasculature. We report a case of the patient underwent pancreaticoduodenectomy with reconstruction of aberrant right hepatic artery.

Spontaneous complete regression of a brain stem glioma pathologically diagnosed as a high-grade glioma.

BACKGROUND: Spontaneous regressions of brain stem gliomas are extremely rare. Only six cases have been reported in the literature. CASE PRESENTATION: We describe the case of a patient who was diagnosed with a pontomedullary dorsal brain stem glioma at the age of 15 years. An open biopsy showed the presence of an anaplastic glioma. Because the patient and her parents refused conventional therapies, including radiation and chemotherapy, we followed up the patient by performing magnetic resonance imaging scans on her every 3 months. At 3 months after biopsy, we observed the radiological disappearance of her tumor. One year after biopsy, the tumor retained the spontaneous complete regression observed earlier. CONCLUSION: In this case report, we present the first report of the spontaneous complete regression of a brain stem glioma that was histologically proven to be a high-grade glioma and we believe that this regression was the natural progression of this case, as may be the scenario in a few other cases of brain stem gliomas.

Production of insulin-like growth factor-II in hepatocellular carcinoma with recurrent hypoglycemia: a case report.

A 35-year-old woman, who was an HBV carrier, complained of fever for 2 weeks, and thus, she was admitted in our hospital. Both serum AFP and PIVKA-II levels were abnormally high, and an abdominal enhanced CT revealed the presence of multiple masses in both lobes of the liver. She was diagnosed with hepatocellular carcinoma (T4, N0, M0, and Vp4) and was treated with transcatheter arterial infusion chemotherapy. On the 4th day of her illness, her serum glucose level was 26mg/dl. Glucose infusion and intravenous hyperalimentation were not effective, and she experienced repeated hypoglycemic attacks. Based on the low levels of both insulin (0.4µU/ml) and insulin-like growth factor (IGF)-I (14ng/ml), we made a diagnosis of non-islet cell tumor hypoglycemia associated with hepatocellular carcinoma. The patient was orally administered prednisolone at a dose of 20mg/day. On the 49th day of illness, the hepatocellular carcinoma ruptured, and 2 days later, she died because of hemorrhage shock. Postmortem immunohistochemical staining for IGF-II was positive in the tumor cells of the liver. Furthermore, Western immunoblotting revealed the presence of high-molecular-weight form of IGF-II in the serum of the patient.

[A Case Report of Inguinal Malignant Lymphoma after Surgery for Hepatocellular Carcinoma].

An 81-year-old woman was followed up for hepatitis C from 1994. Sheh ad a previous history of hypertension and appendicitis. In October 2014, the patient underwent subsegmentectomy(S8)and cholecystectomy for hepatocellular carcinoma (HCC)(T2N0M0, Stage II ). From December 2015, the patient had taken ledipasvir-sofosbuvir orally for hepatitis C virus (HCV). In January 2016, we confirmed HCV-RNA shade transformation. In September 2016, enhanced CT showed a mass in theright lower quadrant of her abdomen. Shehad a hard 3 cm mass in thesameplaceon physical exam. PET-CT showed no significant abnormality except for the mass in the right lower quadrant of her abdomen. Therefore, we identified the differential diagnosis as a lymph node metastasis of HCC, an abdominal wall primary tumor, or a malignant lymphoma. We resected theinguinal malignant lymphoma to confirm thediagnosis. Examination of tissuefrom theinguinal malignant lymphoma indicated diffuselargeB -cell lymphoma. We report an interesting case of an inguinal malignant lymphoma in a patient with chronic HCV who had experienced hepatectomy.

[A Colorectal Cancer with Invasive Micropapillary Carcinoma].

A 76-year-old woman with bloody stool visited a nearby hospital. Colonoscopy showed a type 1 tumor in the rectum, and the biopsy indicated moderately differentiated adenocarcinoma. She was referred to our hospital. Abdominal contrast-enhanced CT did not show swollen lymph nodes in the regional nodes or distant metastases. Laparoscopic lower anterior resection was performed. Histopathological examination indicated pT1b, pN3, ly3, and v1, fStage III b, which had a partial invasive micropapillary carcinoma(IMPC)component of papillary adenocarcinoma. Although she received postoperative adjuvant chemotherapy, she died of a thromboembolism with paraneoplastic syndrome 20 months after the operation. IMPC has a high incidence of lymphatic invasion and lymph node metastases. IMPC is rare in cases of colorectal cancer and it is important to accumulate and investigate colorectal cancer patients with IMPC.

[Anorectal Malignant Melanoma Is a Very Rare Disease and Has a Poor Prognosis].

We performed abdomino-perineal-resection(APR)on 2 cases of anorectal malignant melanoma. The first case was a 70- year-old woman suffering from bloody stool. Colonoscopy showed a black tumor in the rectum. Biopsy revealed a malignant melanoma. A CT scan showed multiple lung metastases and liver metastasis. She underwent surgery for the purpose of bleeding control, but died shortly thereafter because her liver and lung metastases had worsened. The second case was a 43- years-old man suffering from bloody stool. He had a black type 3 tumor in the rectum. A biopsy revealed malignant melanoma. A CT scan showed lateral lymph node swelling. He underwent APR with right side-lateral dissection. An established treatment for anorectal malignant melanoma has not been agreed upon and it is controversial. We experienced 2 cases that underwent surgery and we report them along with relevant information from the literature.

[A Subcutaneous Metastasis from Renal Pelvic Carcinoma Growing Rapidly after radical Nephrectomy : A Case Report].

A 78-year-old man was admitted to our department for a right renal mass detected by computed tomography which was accompanied by right hypochondriac pain. Dynamic computed tomography demonstrated a 7cm hypovascular right renal mass invading the liver. No metastatic disease was evident. Transabdominal nephrectomy and partial hepatectomy were performed under the diagnosis of right renal cell carcinoma in July 2014. Pathological examination revealed right renal pelvic carcinoma with liver invasion. After the operation, a subcutaneous nodule in the right forearm rapidly grew in one week. A needle biopsy revealed that it was a metastasis of the urothelial carcinoma. Additionally, lung metastases and lymph node swelling were detected. The patient received two courses of combination chemotherapy (gemcitabine, carboplatin) in August 2014. The subcutaneous metastasis was decreased, but it was not effective for other metastases. Two courses of another combination chemotherapy (methotrexate, vinblastine, epirubicin, calboplatin) were performed. It was effective for all metastatic lesions. During the third course, the patient developed melancholia and rejected additional therapy. He died in March 2015 due to disease progression.