Discovery of lipid profiles in plasma-derived extracellular vesicles as biomarkers for breast cancer diagnosis.

Lipids are a major component of extracellular vesicles; however, their significance in tumorigenesis and progression has not been well elucidated. As we previously found that lipid profiles drastically changed in breast tumors upon progression, we hypothesized that lipid profiles of plasma-derived extracellular vesicles could be utilized as breast cancer biomarkers. Here, we adopted modified sucrose cushion ultracentrifugation to isolate plasma-derived extracellular vesicles from breast cancer (n = 105), benign (n = 11), and healthy individuals (n = 43) in two independent cohorts (n = 126 and n = 33) and conducted targeted lipidomic analysis. We established a breast cancer diagnostic model comprising three lipids that showed favorable performance with the area under the receiver operating characteristic curve of 0.759, 0.743, and 0.804 in the training, internal validation, and external test sets, respectively. Moreover, we identified several lipids that could effectively discriminate breast cancer progression and subtypes: phosphatidylethanolamines and phosphatidylserines were relatively higher in Stage III, whereas phosphatidylcholines and sphingomyelins were higher in Stage IV; phosphatidylcholines and ceramides were correspondingly concentrated in HER2-positive patients, while lysophosphatidylcholines and polyunsaturated triglycerides were concentrated in the triple-negative breast cancer subtype. Lipid profiling of plasma-derived extracellular vesicles is a non-invasive and promising approach for diagnosing, staging, and subtyping breast cancer.

Mediastinal and Hilar Lymph Node Metastases from Renal Cell Carcinoma with Concomitant Lung Carcinoma: A Rare Case with Unique Diagnostic Challenges.

A 75-year-old man presented to our hospital 1 year after partial renal resection for clear cell carcinoma. A right lower lobe lung nodule noted at the time of surgery had increased to 3.0 cm in diameter and was confirmed as squamous cell lung carcinoma by bronchoscopic cytology. Computed tomography had also revealed paratracheal lymph node swelling. He underwent right lower lobectomy with lymph node dissection by video-assisted thoracic surgery. Pathological examination confirmed squamous cell carcinoma of the lung but diagnosed the right hilar and mediastinal lymph node metastases as clear cell carcinoma.

[A Case of Sigmoid Colon Cancer with Bladder Fistula Treated by Laparoscopic Radical Resection].

The patient was a woman in her 70 s. Computed tomography(CT)showed a sigmoid colon tumor invading the uterus and ovaries, and a fistula to the bladder. The patient was scheduled to receive neoadjuvant chemotherapy(NAC), but while waiting for treatment, generalized peritonitis due to perforation of the tumor was observed, and a laparoscopic transverse colostomy was performed. After NAC with CAPOX and FOLFIRI plus panitumumab, the tumor was found to have shrunk, and a laparoscopic posterior pelvic exenteration was performed. The bladder including the fistula was partially resected, and the tumor, uterus, and right ovary were resected in combination as R0, besides the ureter and remaining bladder could be preserved. The postoperative course was uneventful, and the patient is alive without recurrence to date. In this article, we report a case of a patient with sigmoid colon cancer with a bladder fistula who underwent laparoscopic surgery after NAC, and bladder function could be preserved, with some discussion of the literature.

Detection of von Hippel-Lindau gene mutation in circulating cell-free DNA for clear cell renal cell carcinoma.

The therapeutic landscape of metastatic clear cell renal cell carcinoma (ccRCC) has rapidly expanded, and there is an urgent need to develop noninvasive biomarkers that can select an optimal therapy or evaluate the response in real time. To evaluate the clinical utility of circulating tumor DNA (ctDNA) analysis in ccRCC, we established a highly sensitive assay to detect mutations in von Hippel-Lindau gene (VHL) using a combination of digital PCR and multiplex PCR-based targeted sequencing. The unique assay could detect VHL mutations with a variant allele frequency (VAF) <1.0%. Further, we profiled the mutation status of VHL in 76 cell-free DNA (cfDNA) and 50 tumor tissues from 56 patients with ccRCC using the assay. Thirteen VHL mutations were identified in cfDNA from 12 (21.4%) patients with a median VAF of 0.78% (range, 0.13%-4.20%). Of the 28 patients with VHL mutations in matched tumor tissues, eight (28.6%) also had VHL mutation in cfDNA with a median VAF of 0.47% (range, 0.13%-2.88%). In serial ctDNA analysis from one patient, we confirmed that the VAF of VHL mutation changed consistent with tumor size by radiographic imaging during systemic treatment. In conclusion, VHL mutation in cfDNA was detected only in a small number of patients even using the highly sensitive assay; nevertheless, we showed the potential of ctDNA analysis as a novel biomarker in ccRCC.

[Postoperative Gastric Metastasis from Needle Tract Seeding after Using of EUS-FNA for Pancreatic Body Cancer-A Case Report].

A 67-year-old woman with a pancreatic cancer diagnosed by endoscopic ultrasound with fine needle aspiration(EUS- FNA)was underwent distal pancreatectomy. Two years and 10 months after the operation, a computed tomography scan revealed a tumor in the posterior wall of the lower body of the stomach. Upper gastrointestinal endoscopy showed a 15 mm-sized submucosal tumor on the posterior wall of the angular region, and its biopsy showed tubular adenocarcinoma that it was resembling the resected pancreatic cancer. Needle tract seeding(NTS)of the pancreatic cancer to the gastric wall was suspected. After 5 courses of chemotherapy with gemcitabine and nab-paclitaxel, the tumor shrank and there were no other signs of metastasis, we performed distal gastrectomy. The pathological findings of the resected specimen showed a tubular adenocarcinoma, consistent with the primary pancreatic tumor. We finally diagnosed as the NTS of the pancreatic cancer to the gastric wall. In the case of EUS-FNA for the body or tail tumor of pancreas, it should be paid attention to the recurrence due to NTS because the surgical resection does not include the needle tract site.

[A Case of Giant Gastrointestinal Stromal Tumor of the Jejunum in the Kingdom of Cambodia].

A 60-year-old Khmer woman visited a hospital established by a Japanese non-profit organization in the Kingdom of Cambodia with complaints of swelling in the left abdomen and appetite loss for 2 months. Abdominal computed tomography scan showed a mass measuring 14.6×13.4×19.3 cm with internal necrosis in the left abdomen. On laparotomy, a large tumor involving the jejunum had adhered to the transverse and descending colons. The tumor, measuring 25×20×10 cm and weighing 2,994 g, was excised along with 65 cm of the jejunum. Histopathological examination revealed a gastrointestinal stromal tumor(GIST). Postoperative course was uneventful. Thanks to the cooperation with the Japanese and the Cambodian people, the surgery was successful in spite of a shortage of medical personnel and medical resources in Cambodia.

[Surgery for Anal Canal Squamous Cell Carcinoma after Prostate Brachytherapy-A Case Report].

Generally, the first treatment plan for anal canal squamous cell carcinoma(SCC)is chemo-radiation therapy(CRT). We experienced an extremely rare surgery case of anal canal SCC after prostate brachytherapy. A man in his 70s who had undergone brachytherapy for prostate cancer 8 years before visited our hospital because of blood in feces. A tumor prolapsed from the anal verge, and biopsy revealed SCC. Contrast-enhanced computed tomography showed front-wall thickness in the lower rectum, but we could not evaluate it in detail because of the halation by brachytherapy seeds. We performed laparoscopic abdominoperineal resection to avoid an overdose of radiation for the rectum. Pathological staging was pT2N1aM0, pStage ⅢA. These findings might suggest radiation-induced cancer after brachytherapy.

[A Case of Neuroendocrine Carcinoma of Ascending Colon with Early Recurrence after Surgery].

A 65-year-old male received the positive result of fecal occult blood. Colonoscopy was performed to reveal a tumor in the ascending colon. The result of biopsy was neuroendocrine carcinoma. Under the preoperative diagnosis of neuroendocrine carcinoma in the ascending colon, cT3N0M0, cStage Ⅱ, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological result was neuroendocrine carcinoma in the ascending colon, pT4aN2M0, pStage Ⅲc. The R0 resection was achieved. As adjuvant chemotherapy, the regimen of cisplatin plus irinotecan was administered for 4 courses. No recurrence was seen until 9 months after the operation, when multiple peritoneal and hepatic metastasis were detected on CT scan. The chemotherapy regimen of etoposide plus carboplatin was started and is now ongoing. The patient is now alive 13 months after the operation.

[Surgical Resection of the Lymph Node Metastasis after Liver Resection for Hepatocellular Carcinoma].

A 76-year-old man had undergone right lobectomy after transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)in segment 5/6 of the liver. He had undergone TACE for intrahepatic recurrence in segment 1 eight months after the operation. Abdominal CT revealed intrahepatic recurrence in segment 2 and segment 3 and a hepatic portal lymph node swelling 13 months after the operation, he underwent TACE and radiofrequency ablation for intrahepatic lesions. There was neither intrahepatic recurrences nor new extrahepatic lesions, and the hepatic portal lymph node resection was performed. He was discharged on postoperative day 8, and there has been no subsequent recurrence over 42 months after initial treatment. The lymph node metastasis of HCC is rare and systemic chemotherapy such as molecular targeted argent is the standard treatment, but its prognosis is poor. When a patient has a resectable metastasis with controlled intrahepatic lesions, lymph node resection appears to be an effective option.

[Advanced Colon Cancer Resected after a Neoadjuvant Chemotherapy of CAPOXIRI-A Case Report].

We report a case ofadvanced colon cancer, stage cT4bN0M0 in the descending colon with formation ofabscesses in the retroperitoneal space ofa 66-year-old woman. After constructing a transverse colostomy and percutaneous abscess drainage, chemotherapy was initiated with CAPOX. After 4 courses of CAPOX, the tumor had significantly regressed; therefore, the regimen was switched to a triplet combination called CAPOXIRI. After 3 courses of CAPOXIRI, the tumor had become smaller and had separated from the iliopsoas muscle, which led us to perform surgical resection. Left hemicolectomy was performed with R0 resection, and the tumor was pathologically diagnosed as ypT3N0M0. The patient is alive 12 months after the surgery, with no signs of recurrence.

[A Case of Late-Onset Recurrent Rectal Cancer Associated with Anal Fistulas].

A 71-year-old man underwent laparoscopic lower anterior resection(D3 dissection)for rectal cancer and bilateral lung metastases. Histopathological findings indicated Ra, type 2, tub2, ly0, v2, pN0, pM1(PUL1), pStage Ⅳ. The lung metastases had disappeared after postoperative chemotherapy and the patient entered cCR. Two years after the surgery, the patient's anal fistulas appeared sclerotic. Biopsy revealed recurrent rectal cancer. We performed an abdominoperineal resection and rectus abdominis muscle flap. Currently, the patient is alive at 9 months after surgery with no re-recurrence.

Trans-tract electrocoagulation can decrease the need for postoperative nephrostomy tube after endoscopic combined intrarenal surgery.

AIM: To assess the efficacy and safety of trans-tract electrocoagulation at the end of endoscopic combined intrarenal surgery for renal or ureteral stones. METHODS: The present study included patients who underwent endoscopic combined intrarenal surgery from May 2010 to March 2018. After June 2013, the trans-tract electrocoagulation procedure, to coagulate bleeding from the access tract using a resectscope was carried out at the end of the operation. We compared the patients' background and surgical outcomes between patients with and without trans-tract electrocoagulation. RESULTS: Between the trans-tract electrocoagulation (n = 225) and non-trans-tract electrocoagulation (n = 72) groups, the stone number was significantly smaller (1:2:3 or more, 126:72:27 vs 59:10:3, P = 0.001) and the initial stone-free rates were significantly higher (80% vs 72%, P = 0.006) in the trans-tract electrocoagulation group than in the non-trans-tract electrocoagulation group. Patients experienced a higher nephrostomy tube-free rate (67% vs 26%, P < 0.0001), shorter postoperative catheterization time (2.8 ± 3.8 vs 5.4 ± 5.0 days, P = 0.002) and shorter hospital stay (6.5 ± 3.6 vs 8.8 ± 5.0 days, P = 0.0001) in the trans-tract electrocoagulation group than in the non-trans-tract electrocoagulation group. CONCLUSIONS: Trans-tract electrocoagulation in endoscopic combined intrarenal surgery is a safe and efficient procedure that decreases the need for nephrostomy tube placement after surgery.

[A Case of Pulmonary Metastases of Colon Cancer with Submucosal Invasion].

In general, distant metastasis is uncommon in colorectal submucosal(SM)invasion without lymph node metastasis. We experienced an extremely rare case of synchronous pulmonary metastases for colon cancer in SM invasion. A man in his 70s was seen at the hospital for a positive fecal occult blood test. Colonoscopy revealed 3 lesions in the sigmoid colon and endoscopic mucosalresection revealed 2,000 mm SM invasion in all 3 lesions. Computed tomography showed no signs of distant lymph node or liver metastasis but showed small nodules in both lungs. Radical treatment included laparoscopic anterior resection with lymph node dissection. Histological examination showed no residual tumor in the colon and no lymph node metastasis. Two years after surgery, the number of lung nodules gradually increased and we performed partial resection of the left lung, which was diagnosed as pulmonary metastasis from colon cancer by histological examination. Therefore, we resected the opposite-side pulmonary metastases. The patient has exhibited no other signs of recurrence in the 2 years since the last operation.

[A Case of Long-Term Survival of Liver Metastasis from Biliary Carcinoma after Pancreaticoduodenectomy Treated by Multimodal Therapy].

A 73-year-old man underwent a subtotal stomach preserving pancreaticoduodenectomy(SSPPD)for biliary carcinoma without regional lymph node metastasis. Although S-1 was administrated as adjuvant chemotherapy after the operation, the serum CA19-9 level was gradually elevated, and a liver metastasis of 27mm in diameter was detected in Couinaud's segment 8 during chemotherapy. We administrated gemcitabine(GEM)and cisplatin(CDDP)combination therapy(GC therapy). The liver tumor was immediately shrunk to 6mm and kept up the PR state after 15 courses of GC therapy. A stereotactic body radiation therapy(SBRT)was performed 1 year 8 months after the operation. The patient has been alive without recurrence for 4 years since the SBRT. Although systemic chemotherapy is the standard treatment for the recurrence of biliary carcinoma, a loco-regional therapy such as SBRT may be an effective alternative when a patient has a solitary metastasis to the liver with no other evidence of recurrence.

[A Case of Recurrence in the Lateral Pelvic Lymph Node after Local Excision of Lower Rectal pT1a Cancer].

The patient was a man in his 70s who visited our hospital to undergo an examination for fecal occult blood, which detected a 20 mm, Ⅱa lesion in the lower rectum on colonoscopy. He was diagnosed with SM-invasive cancer and was planned to undergo trans-anal local excision. After the surgery, he had a good postoperative course without complications. The pathological findings were Ⅱa, tub1, 22×16 mm, pT1a(950 mm), int, INF a, ly0, v0, pHM0, pVM0(300 mm). He was followed up after the surgery, but was diagnosed with lateral lymph node recurrence 4 years after a local surgery. The surgery involved right-sided lateral lymphadenectomy with resection of the ureter, spermatic duct, seminal vesicle, and piriformis muscle. He was diagnosed with lymph node metastasis with invasion of the spermatic duct based on pathology. Eight courses of adjuvant chemotherapy containing CapeOX was administered. Unfortunately, primary squamous cell lung cancer was detected, and he died after surgery for recurrence in the second year. It is suggested that it is necessary to note lateral lymph node recurrence on postoperative follow-up for lower rectal cancer at any stage.

[A Case of Anastomotic Recurrence of Rectal Cancer 22 Years after Surgery].

In general, anastomotic recurrence of colorectal cancer occurs within 3 years after surgery. We encountered an extremely rare case of anastomotic recurrence over 20 years after surgery. A 70-year-old woman who had undergone low anterior resection for rectal cancer 22 years previously was admitted to the hospital because of anal bleeding. Colonoscopy revealed a 1.5 cm sized, elevated lesion on the anastomotic site, and a biopsy revealed an adenocarcinoma(tub2). EUS demonstrated that the tumor was located on the staples, and the depth of the tumor was expected to be within the muscle layer of the rectum. Computed tomography showed no signs of distant metastasis. Given the diagnosis of anastomotic recurrence of rectalcancer 22 years after surgery, laparoscopic abdominoperinealresection was performed. Histologicalassessment showed that the tumor was on the staples, and did not exhibit vascular and lymphatic invasion. Finally, she was diagnosed with anastomotic recurrence due to implantation. The patient has exhibited no other signs of recurrence in the 3 years since the last surgery.

[Hepatocellular Carcinoma with Bile Duct Thrombosis - A Case Report].

Hepatocellular carcinoma(HCC)is not commonly observed with bile duct thrombosis.Here, we report a case of HCC with bile thrombi that extended to the liver hilum.The patient was a 61-year-old man who visited us due to untreated type B hepatitis.He underwent screening with a CT scan that revealed LDA on the right posterior lobe of his liver with infiltration of the bile duct.Generally, bile resection and reconstruction should be considered for curative resection for bile thrombi; however, we attempted to conserve the common bile duct to preserve the options of percutaneous therapy in case of tumor recurrence.We performed right lobectomy of the liver.The bile duct thrombus was extracted without bile duct resection or reconstruction.The patient is alive 6 months after the surgery without any development.

[Gallbladder Carcinoma That Occurred 50 Years after Cholecystojejunostomy].

Creation of a cholecystojejunostomy has been recommended as one option in the palliation of biliary obstruction due to pancreatic carcinoma.However, it was a technique used for biliary drainage for acute cholecystitis a long time ago.We describe a patient who underwent a cholecystojejunostomy for acute cholecystitis 50 years prior to presentation, and then revealed a gallbladder carcinoma.

Impact of biomarker changes during neoadjuvant chemotherapy for clinical response in patients with residual breast cancers.

BACKGROUND: Residual cancer burden or Ki67 expression levels in residual tumors reportedly provided significant prognostic information for a non-pathological complete response subset after neoadjuvant chemotherapy (NAC). However, the significance of Ki67 reduction for clinical response during chemotherapy in each subtype or menopausal status is yet to be determined. METHODS: A total of 183 breast cancers surgically removed after chemotherapy were recruited for this study. Expression levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki67 were determined immunohistochemically for semiquantitative measurement and these biomarkers were compared in pre- and post-NAC samples from pathological non-responders (n = 125). Responses to chemotherapy were evaluated both clinically and pathologically. RESULTS: Ki67 expression levels after NAC (median 5 %, range 0-70 %) were significantly reduced compared with before NAC (25, 1-80 %, P < 0.0001), but only in patients who attained clinical response. This significant suppression of Ki67 in clinical responders was consistently observed in breast cancers from the ER-positive subset, but not the ER-negative subset in the total test set (n = 120). These observations were also made in the validation set (n = 63). Among premenopausal, but not postmenopausal patients, a significant decrease in PgR expression levels was detected in breast cancers of patients who attained clinical response (pre-NAC 50, 0-100 %, post-NAC 5, 0-20 %; P = 0.0003). CONCLUSION: The impact of Ki67 suppression on clinical response seems to be restricted to ER-positive breast cancers. Since PgR expression levels of premenopausal ER-positive cancers were significantly reduced in clinical responders, inhibition of estrogen signaling due to chemotherapy-induced amenorrhea may be involved in this association.

[A Case of Synchronous Double Cancers of the Liver and Pancreas Treated Using Pancreaticoduodenectomy and Liver Resection].

A 50-year-old woman had a 12mm liver tumor at segment 4 and was diagnosed with hemangioma. Two years later, the liver tumor had grown to 27mm in diameter, and a new pancreatic tumor was detected using CT examination. The pancreatic tumor was suspected of being pancreatic carcinoma, based on the results of endoscopic-ultrasound-guided fine-needlebiopsy( EUS-FNA)of the pancreas. The liver tumor was diagnosed as adenocarcinoma using liver biopsy. Because of its slow growth and the solitary liver tumor, synchronous pancreatic cancer and intrahepatic cancer were suspected. We therefore performed pancreaticoduodenectomy with portal vein resection and partial liver resection of segment 4. Upon histological analysis, carcinoma in situ was detected in the liver tumor and the patient was diagnosed with synchronous double cancers of the liver(cholangiocellular carcinoma)and pancreas(invasive ductal carcinoma). Our case indicated that it is very difficult to distinguish cholangiocellular carcinoma from metastatic liver tumor using diagnostic images. We should therefore consider the possibility of cholangiocellular carcinoma when a solitary tumor in the liver is detected at the same time as pancreatic cancer.