E2F target score is associated with cell proliferation and survival of patients with hepatocellular carcinoma.

BACKGROUND: E2F target genes are essential for the cell cycle. A score that quantifies its activity is expected to reflect the aggressiveness and prognosis of hepatocellular carcinoma. METHODS: Cohorts of hepatocellular carcinoma patients (total n = 655) from The Cancer Genome Atlas, GSE89377, GSE76427, and GSE6764 were analyzed. The cohorts were divided into high versus low by the median. RESULTS: All the Hallmark cell proliferation-related gene sets were consistently enriched in hepatocellular carcinoma with high E2F targets score, and E2F score was associated with grade, tumor size, American Joint Committee on Cancer staging, proliferation score, and MKI67 expression, as well as with less abundance of hepatocytes and stromal cells. E2F targets enriched DNA repair, mTORC1 signaling, glycolysis, and unfolded protein response gene sets and were significantly associated with the higher intratumoral genomic heterogeneity, homologous recombination deficiency, and progression of hepatocellular carcinoma. On the other hand, there was no relationship between E2F targets and mutation rates or neoantigens. High E2F hepatocellular carcinoma did not enrich any of the immune-response-related gene sets but was associated with high infiltration of Th1, Th2 cells, and M2 macrophage; however, there was no difference in cytolytic activity. In both early (I and II) and late (III and IV) stages of hepatocellular carcinoma, a high E2F score was associated with worse survival and was an independent prognostic factor for overall and disease-specific survival in patients with hepatocellular carcinoma. CONCLUSION: The E2F target score, associated with cancer aggressiveness and worse survival, could be used as a prognostic biomarker in patients with hepatocellular carcinoma.

18F­fluorodeoxyglucose positron emission tomography predicts recurrence and histological grade of extrahepatic bile duct cancer.

Malignant tumors in cholangiocarcinoma are diagnosed and staged using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and clinical analysis. However, comprehensive analysis, including pathological analysis, has not yet been sufficiently performed. In the present study, the maximum standardized uptake value (SUVmax) was calculated using FDG-PET and its relationship with clinicopathological factors was analyzed. The present study included 86 patients who underwent preoperative FDG-PET/computed tomography (CT) and did not receive chemotherapy among 331 patients with hilar and distal cholangiocarcinoma. Receiver operating characteristic analysis with recurrence events was used to determine the SUVmax cutoff of 4.9. Immunohistochemical staining of glucose transporter 1 (Glut1), hypoxia-inducible factor-1α and Ki-67 was performed for pathological analysis. The standardized uptake value (SUV)-high group (SUVmax ≥4.9) had a higher postoperative recurrence rate (P<0.046) and higher Glut1 and Ki-67 expression rates (P<0.05 and P<0.0001, respectively). Furthermore, SUVmax and Glut1 expression (r=0.298; P<0.01) and SUVmax and Ki-67 expression rates (r=0.527; P<0.0001) were positively correlated. The preoperative measurement of SUVmax by PET-CT is useful in predicting recurrence as well as cancer malignancy.

[A Case of Myocardial Metastasis of Esophageal Squamous Cell Carcinoma].

Myocardial metastasis for esophageal squamous cell carcinoma(ESCC)is relatively rare and it is diagnosed as a part of widespread metastasis in the terminal stage. We experienced a case of myocardial metastasis of ESCC treated effectively with chemoradiotherapy. A 56-year-old man was diagnosed ESCC(clinical T3N2M0, Stage III). He received neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of the 3 regional lymph nodes. The pathological diagnosis was moderate differentiated squamous cell carcinoma, CT-pT3(T3), pN1, sM0, fStage III. Four months after surgery, he had no clinical symptom, however myocardial metastasis located in the apex was detected on the follow up positron emission tomography(PET). Chemoradiotherapy was performed for the myocardial metastasis. Myocardial metastasis treated effectively with chemoradiotherapy almost disappeared on the PET and computed tomography taken 3 months after chemoradiotherapy. He died, however, of multiple liver and bone metastases 15 months after the initial surgery.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

[A Case of Remnant Pancreatic Cancer after Conversion Surgery for Advanced Distal Bile Duct Cancer Treated with Chemotherapy].

The patient was an 82-year-old man who received a total of 25 courses of GEM/CDDP therapy for unresectable distal bile duct cancer with multiple liver metastases. After the chemotherapy, no liver metastasis was detected on computed tomography. Then, he underwent pancreaticoduodenectomy(ⅡA-1, D2)as a conversion surgery(T2N0M0, fStageⅠB)at 2 years and 11 months after the initial diagnosis. Postoperatively, the patient received GEM therapy for 2 years and had no recurrence. Three years and 10 months after the surgery, computed tomography revealed a tumorous lesion with a poor contrasting effect on the remaining pancreas and a positive accumulation of SUVmax 8.6 was detected at the same site through the FDG-PET examination. We diagnosed the lesion as residual pancreatic cancer and performed remnant total pancreatectomy and splenectomy. The histopathological findings showed tumors arising from the residual pancreatic epithelium; therefore, we diagnosed his lesion as residual pancreatic cancer(T3N1aM0, fStage ⅡB). After the second surgery, he is being treated with adjuvant therapy with S-1 and is alive without recurrence. In this case, long-term survival was possible for 7 years and 4 months from the initial diagnosis of unresectable distal bile duct cancer. Metachronous double cancer of unresectable bile duct and pancreatic cancer is presumed to have a poor prognosis. However, long-term survival is suggested to be possible if multidisciplinary therapies are successful.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

[A Case of Long-Term Survival of a Patient with Cholangiocarcinoma and Liver Metastatic Recurrence Who Responded to Gemcitabine plus Cisplatin Therapy].

A 65-year-old woman was diagnosed with cholangiocarcinoma and underwent hepato-pancreatoduodenectomy. The pathological diagnosis was Bpd, circ, papillary-infiltrating type, 51×47×7mm, tub2>tub1>por1, T2, ly1, v1, ne1, pN0, pDM0, pHM0, pEM0, pPV0, pA0, R0, pStageⅠ. She received adjuvant chemotherapy with S-1, which was changed to gemcitabine plus cisplatin therapy(GC therapy)when hepatic recurrence and lymph node metastasis were identified 3 months postoperatively. The hepatic recurrence disappeared, and the lymph node metastasis was reduced after the patient completed 27 courses of GC therapy. We discontinued GC therapy as no recurrence had been observed for a long time. The patient remains well without any evidence of cancer recurrence for more than 48 months postoperatively.

[The Impact of Neutrophil-Lymphocyte Ratio on the Prognosis in Patients Who Underwent Esophagectomy for Esophageal Cancer].

BACKGROUND: Thene utrophil-lymphocyteratio (NLR)reflects a patient's systemic inflammatory response. Several studies have revealed that the NLR is associated with a poor prognosis in several types of malignant tumors such as colorectal and lung cancer. The aim of this study was to evaluate the impact of preoperative NLR on the prognosis of patients with esophageal cancer. METHODS: The NLR was calculated for 93 consecutive patients with clinical Stage II or III esophageal cancer, who underwent curative esophagectomy following neoadjuvant chemotherapy between 2011 and 2013. The impact of preoperativeNLR on overall survival(OS)after esophagectomy was evaluated. The NLR cut off value was set to 2. RESULTS: The 3-year OS of patients with NLR≥2 was significantly shorter than patients with NLR<2(40.5% vs 67.9%, p=0.005). In a multivariateCox model, NLR≥2(HR: 2.342, 95%CI: 1.095-5.007, p=0.028), pathological depth of tumor(HR: 3.207, 95%CI: 1.114- 9.233, p=0.031), and an ageove r 60(HR: 2.342, 95%CI: 1.117-6.501, p=0.027)were identified as independent prognostic factors for OS after esophagectomy. CONCLUSIONS: The preoperative NLR was significantly associated with a poor prognosis in esophageal cancer patients who underwent curative esophagectomy following neoadjuvant chemotherapy.

[A Case of Duodenal Cancer with Familial Adenomatous Polyposis].

A 34-year-old man was diagnosed with familial adenomatous polyposis(FAP)in September 2011, and he underwent endoscopic mucosal resection(EMR)due to multiple polyps in the duodenum and small intestine. Three months later, duodenal cancer was found, and he underwent a subsequent EMR. The pathological findings showed residual cancer cells in the lateral margin; therefore, EMR was performed again. Total colectomy and partial resection of the small intestine was performed in December 2012. Esophagogastroduodenoscopy(EGD)was then performed every 3-6 months, and EMR was performed 4 times. We followed up the patient annually, starting 2014. In January 2016, recurrence of the duodenal cancer was found; therefore, he underwent a pancreatoduodenectomy. The pathological diagnosis was adenocarcinoma, tub2> tub1, pT1a, N0, M0, fStage I A. There were many adenomas ranging from low-grade to high-grade in the duodenal mucosa. The patient remains well without any evidence of cancer recurrence more than 18 months after the last operation. When treating patients with duodenal adenoma complicated by FAP, regardless of age, strict follow-up is important.

[A Case of Neuroendocrine Carcinoma of the Esophagus Treated with Neoadjuvant Chemotherapy Comprising 5-Fluorouracil plus Cisplatin].

Esophageal neuroendocrine carcinoma is relatively rare and the prognosis is poor owing to its aggressive malignancy. We experienced a case of neuroendocrine carcinoma of the esophagus treated with neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin. A 71-year-old man was diagnosed with esophageal carcinoma(clinical T3N1M0, Stage III ). He received neoadjuvant chemotherapy comprising 5-fluorouracil plus cisplatin, followed by subtotal esophagectomy with dissection of 3 regional lymph nodes. Immunohistochemical findings were synaptophysin-positive, CD56-positive, Ki-67(labeling index) B90%. The final diagnosis was neuroendocrine carcinoma, categorized as CT-pT1a-MM, pN0, Stage 0. The pathological response to neoadjuvant chemotherapy was Grade 2. The patient is alive 8 months after esophagectomy without metastasis.

[A Case of Curatively Resected Ascending Colon Cancer Invading the Duodenum after Neoadjuvant Chemotherapy].

A 64-year-old woman with anorexia and anemia was diagnosed with ascending colon cancer invading the duodenum. Considering the difficulty of curative resection, we first performed gastrojejunostomy and ileostomy. After surgery, the patient received FOLFIRI with cetuximab as neoadjuvant chemotherapy. After 9 courses of the regimen, enhanced computed tomography revealed shrinkage of the lesion, with the efficacy evaluated as a partial response. The patient underwent right hemico- lectomy and partial resection of the duodenum. The pathological diagnosis was pT3(SS), pN0(0/30), ly1, v1, pPM0, pDM0, pRM0, fStage II . On histopathological examination, the efficacy of chemotherapy was evaluated as Grade 1a. The patient received adjuvant chemotherapy with FOLFIRI and remains well without any evidence of recurrence more than 6 months after surgery.

[A Case of Extranodal Nasal Type, NK／T Cell Lymphoma in the Ileum with Perforated Peritonitis during Chemotherapy].

A 65-year-old woman complaining of melena and a high fever was admitted to our hospital. Colonoscopy revealed a large tumor with a wide ulcer in the terminal ileum, and nasal type, extranodal NK/T cell lymphoma was suspected via biopsy. Owing to rapid progression of hepatocellular damage with hepatomegaly and splenomegaly, chemotherapy with CHOP was initiated immediately. Two days later, the patient developed panperitonitis, and emergency laparotomy was performed. The tumor in the terminal ileum widely adhered to the bladder, where a deep perforated ulcer was found, for which palliative ileocecal resection was performed. Enlargement of the residual tumor caused an abdominal abscess, intestinal obstruction, and hepatic failure, and the patient died 75 days after surgery. In summary, we initiated chemotherapy to control the deteriorating systemic condition of the patient. However, nasal type, extranodal NK/T cell lymphoma is a rapidly progressing lymphoma occasionally accompanied by perforation of the tumor. Surgery preceding chemotherapy should be considered an alternative treatment.

[A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

[A Case of Pseudo-Meigs Syndrome Associated with Metachronous Ovarian Metastasis from Ascending Colon Cancer].

We experienced a case of pseudo-Meigs syndrome associated with metachronous metastasis to the ovary from ascending colon cancer. A 65-year-old woman underwent curative surgery for ascending colon cancer at another hospital. A follow-up CT carried out 3 months after the surgery revealed a right ovarian tumor and a large amount of ascites. The patient was diagnosed with ovarian metastasis from ascending colon cancer with carcinomatous peritonitis. Palliative care was recommended, and she presented at our department for a second opinion. In spite of a large amount of ascites and pleural effusion, no disseminating tumor was detected on contrast-enhanced CT at our hospital, and we recommended that she undergo a diagnostic laparotomy. The laparotomy was negative for carcinomatous peritonitis and a right oophorectomy was performed. The histopathological findings indicated that the ovarian tumor was consistent with metastasis from ascending colon cancer. After the surgery, we initiated chemotherapy with mFOLFOX6+bevacizumab and the symptoms were well controlled. A follow-up CT carried out 11 months after the surgery revealed a left ovarian tumor and increased ascites, and the patient underwent a left oophorectomy. Then, chemotherapy with the same regimen was administered for 12 months, and she did not develop any signs of recurrence for 27 months after the surgery. Ovarian metastasis from colon cancer may occasionally cause pseudo-Meigs syndrome, and it is important to be aware of the usefulness of oophorectomy for the control of ascites and pleural effusion.

Computed tomographic lymphography for sentinel lymph node biopsy in male breast cancer: report of two cases.

Male breast cancer is rare, accounting for less than 1% of breast cancers. Because of its rarity evidence of the usefulness sentinel lymph node biopsy (SLNB) for male breast cancer has not been established. Moreover, a navigation system which can easily determine the incision site of SLNB is needed because a second incision for SLNB is necessary in most cases. We report successful computed tomographic lymphography (CTLG)-guided SLNB in two male breast cancer cases: the first patient was a 79-year-old man and the second was a 64-year-old man. Both had presented with a lump behind the nipple. Clinical diagnoses were early breast carcinoma in both cases. The second patient took tamoxifen 20 mg daily as neoadjuvant endocrine therapy. SLNs were clearly visualized by CTLG, allowing mastectomies with SLNB to be performed. Both SLNB were negative, such that axillary lymph node dissection was not needed. Preoperative CTLG is useful for visualizing lymph flow and detecting SLN in male breast cancer.

[A case of advanced rectal cancer treated effectively with intersphincteric resection and preoperative chemotherapy].

An approximately 50-year-old man with rectal cancer(RbP)[ cT3(cA), cN3, cM0, and cStage IIIb] who desired anus preservation was administered mFOLFOX6 therapy. This treatment decreased the size of both the tumor and the lymph node, and intersphincteric resection (ISR) was performed. Histopathology demonstrated tumor invasion beyond the muscularis propria, and the histological effectiveness was Grade 2. Because computed tomography showed an abscess in the dissection area, we performed postoperative drainage and the patient recovered. Therapy with mFOLFOX6 was repeated after the patient was discharged from hospital. Increased adoption of anus-preserving surgery is expected via successful control of local recurrence and distant metastasis by neoadjuvant chemotherapy.