Induction chemotherapy and hepatic artery embolization followed by extended resection for locally advanced gallbladder cancer: a case report.

BACKGROUND: Surgical resection plays a critical role in the curative therapy of patients with gallbladder cancer. However, extended resection for locally advanced gallbladder cancer is a controversial procedure because of the high operative morbidity, mortality, and poor prognosis after surgery, without consensus of its suitability. Several reports have described preoperative treatment modalities to reduce the risk of mortality and morbidity and improve the curability of surgery for locally advanced GBCA. However, only a few well-designed studies have verified the benefits of these preoperative strategies. CASE PRESENTATION: A 62-year-old male patient presented to our department with a gallbladder tumor detected on abdominal ultrasound during an annual medical checkup. Multi-phase enhanced CT revealed a gallbladder tumor with a maximum diameter of 34 mm, invading the right hepatic artery, pancreatic head, hepatic flexure of the colon, and first portion of the duodenum. We diagnosed gallbladder carcinoma as cT4 cN0 cM0 cStage IVA in the Union for International Cancer Control (UICC) classification 8th edition. After administration of 12 cycles of gemcitabine and cisplatin plus S-1 regimen, tumor shrinkage was observed on computed tomography, and elevated serum CA19-9 levels were reduced to normal limits. After preoperative hepatic artery embolization, we performed gallbladder bed resection with pancreaticoduodenectomy (minor hepatopancreatoduodenectomy) and combined resection of the right hepatic artery and hepatic flexure of the colon. Histological examination revealed no evidence of lymph node metastasis (ypT4 ypN0 ycM0 yp Stage IVA in the 8th edition of the UICC). The proximal bile duct and dissected margins were negative. CONCLUSIONS: The combination of induction chemotherapy and preoperative hepatic artery embolization, followed by minor hepatopancreatoduodenectomy and combined resection of the involved arteries and partial colon, could be a feasible treatment strategy for patients with locally advanced gallbladder cancer invading neighboring organs.

[A Case of Colorectal Cancer with Asymptomatic Idiopathic Pneumatosis Intestinalis during Bevacizumab Administration].

We present the case of a 75-year-old woman who received CapeOX plus Bmab therapy(capecitabine, oxaliplatin, and bevacizumab)after primary excision for an unresectable advanced sigmoid colon cancer with remote metastasis. Pneumatosis intestinalis(i.e., the presence of isolated gas in the abdominal cavity)was revealed accidentally during a periodical imaging examination in the small intestine and transverse colon, albeit no subjective symptoms were reported. Owing to the absence of definitive evidence of pneumatosis intestinalis and gastrointestinal perforation, the patient was diagnosed with idiopathic pneumatosis intestinalis. Bmab was discontinued, and CapeOX therapy alone was continued after follow-up. Approximately 4 months later, pneumatosis intestinalis had completely disappeared. Bmab is a vascular endothelial growth factor antibody with well-known side effect of gastrointestinal-perforation. However, there have been few reports on pneumatosis intestinalis; to our knowledge, there have been no reports on pneumatosis intestinalis associated with colorectal cancer in Japan. Further, the report suggests the need for appropriate and immediate management of pneumatosis intestinalis following diagnosis.

Epidermoid cyst within an intrapancreatic accessory spleen exhibiting abrupt changes in serum carbohydrate antigen 19-9 level: a case report.

BACKGROUND: Epidermoid cyst within an intrapancreatic accessory spleen (ECIAS) is a rare disease. While the detection of solid components relevant to an accessory spleen is a key diagnostic finding, the differential diagnosis between ECIAS and malignant tumors is difficult without resection in patients with no other findings of an accessory spleen. CASE PRESENTATION: A 73-year-old male was found to have an elevated carbohydrate antigen (CA) 19-9 level (95 U/mL) at an annual checkup, and a cystic lesion in the pancreatic tail was located by abdominal ultrasound. Abdominal magnetic resonance imaging (MRI) revealed a multicystic mass, 24 mm in diameter, which exhibited varying intensities on T2-weighted images. There were no findings suggesting solid components on contrast-enhanced computed tomography and magnetic resonance imaging. Re-evaluation of serum CA 19-9 level revealed a rapid increase to 901 U/mL, which declined to 213 U/mL 3 weeks later. Ruling out the lesion's malignant potential was difficult, and the patient underwent distal pancreatectomy with splenectomy. Histological findings revealed an ECIAS including multiple cysts, with the mucinous component of each cyst exhibiting different stages of biological reaction; one ruptured cyst exhibited inflammatory changes. CONCLUSIONS: Careful observation for changes in serum CA 19-9 level and MRI findings might facilitate the diagnosis of ECIAS without a solid component by imaging studies.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

AIM: In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). PATIENTS AND METHODS: A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. RESULTS: Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the log-rank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. CONCLUSION: Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report.

INTRODUCTION: von Hippel-Lindau disease (vHL disease) is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A) associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET), and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. CASE PRESENTATION: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography-computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A) was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10-15%) pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. CONCLUSION: A two-staged resection is a safe and effective treatment option for bilateral pheochromocytoma and PNET associated with vHL disease.

Simultaneously Diagnosed and Successfully Treated Rectovaginal and Vesicovaginal Fistulae after Low Anterior Resection with Concomitant Resection of Female Genitalia.

Rectovaginal fistula (RVF) and vesicovaginal fistula (VVF) are infrequent but distressing complications after pelvic surgery. However, their adequate treatment is not well described. Here, we simultaneously encountered and successfully treated RVF and VVF after radical surgery for rectal cancer. A 70-year-old woman underwent low anterior resection (LAR) combined with resection of the uterus, the bilateral adnexa, and the upper side of the vagina, as well as diverted ileostomy for rectal cancer. A month after the surgery, she developed urinary incontinence and underwent medical treatment, but her symptoms did not improve. Evaluation with contrast enema before stoma closure revealed the presence of RVF and VVF. We repaired the VVF and RVF via transabdominal and transperineal approaches. After 6 months, ileostomy was closed and the patient had no recurrence of cancer and fistula. In LAR with hysterectomy and resection of the vaginal wall, there is a risk of RVF and VVF. The excision and closure of the fistula tract and omental flap can be effective to treat both fistulae.

A case of diffuse cavernous hemangioma of the appendix: laparoscopic surgery can facilitate diagnosis and treatment.

BACKGROUND: A cavenous hemangioma of the appendix (CHA) is rare. The clinical pathophysiology and adequate management of a CHA have not been sufficiently explained since reports on CHA are scarce. CASE PRESENTATION: A 56-year-old woman presented with chronic right lower quadrant pain. Abdominal contrast-enhanced computed tomography revealed a thickened appendix (1.5 cm in diameter) and some focal calcifications in the appendiceal wall. No acute inflammatory signs were visible around the appendix. For diagnosis and treatment, we performed a laparoscopic surgery. Intraoperative findings included purple granular lesions that were spread diffusely along the surface of the appendix. Since these lesions were spread to the terminal ileum, laparoscopic ileocecal resection was performed. Upon macroscopic inspection, purple-colored, raspberry-like lesions were found diffusely on the serosal surface of the appendix. No lesions were found on the mucosal surface. Hematoxylin and eosin staining indicated the presence of blood-filled sinus-like spaces largely in the subserosal layer. Immunohistochemistry analysis indicated that CD34-positive cells lined these spaces. Given these findings, we diagnosed the patient with a diffuse cavernous vascular malformation of the appendix. CONCLUSIONS: CHA is difficult to diagnose. A laparoscopic approach may be useful for both the diagnosis and treatment of the disease.

Mesenchymal Stem Cells Contribute to Hepatic Maturation of Human Induced Pluripotent Stem Cells.

BACKGROUND: Induced pluripotent stem cells (iPSCs) are human somatic cells that have been reprogrammed to a pluripotent state. Several methods have been used to generate hepatocyte-like cells from iPSCs. However, these hepatic cells have limited clinical application because of their immature function compared to primary hepatocytes. Mesenchymal stem cells (MSCs) have been reported to inhibit apoptosis of hepatic cells and to improve hepatic regeneration in acute liver injury. Therefore, we expected that MSCs had the potential to positively contribute to the maturation of hepatic cells. Here we demonstrate the effect of MSCs on the maturation of hepatoblasts derived from human iPSCs. METHODS: MSCs were isolated from human bone marrow and cultured to 70-80% confluence. MSC-conditioned medium (MSC-CM) was collected 48 h after culture in hepatic maturation medium. Human iPSC-derived hepatoblasts were then cultured for 6 days with MSC-CM. Hepatic functions were analyzed and compared to those from cells cultured in general maturation medium. RESULTS: Cells in both groups had a cuboidal morphology typical of hepatocytes. The proportion of Oct4-positive cells was decreased and those of albumin- and alpha-fetoprotein-positive cells were increased in the MSC-CM group. Albumin secretion and urea synthesis as well as cytochrome P450 (CYP) 3A4 activity were enhanced in the MSC-CM group. The gene expressions of some CYP enzymes were upregulated as demonstrated by RT-PCR. CONCLUSION: Secreted molecules from human MSCs could enhance the hepatic function of human iPSC-derived hepatocyte-like cells. Although more technological innovations are needed, MSC-CM will be useful as a novel efficient strategy for clinically relevant hepatic cell maturation.

Successful Resection of Isolated Para-Aortic Lymph Node Recurrence from Advanced Sigmoid Colon Cancer following 156 Courses of FOLFIRI Regimen.

Isolated para-aortic lymph node (PLN) recurrence from colorectal cancer (CRC) is rare, with no currently validated treatments. Few reports have described the successful resection of isolated PLN involvement from CRC following chemotherapy. We report the case of a 63-year-old man who underwent sigmoidectomy for sigmoid colon cancer at our hospital. Pathological examination demonstrated advanced sigmoid colon cancer with metastatic involvement in both of the tested PLNs. Palliative chemotherapy was initiated four weeks after surgical resection, with administration of the FOLFIRI regimen. Four years after the operation, computed tomography (CT) revealed an enlarged PLN below the left renal vein. As PLN enlarged to 15 mm in the minor axis on a CT scan in 2014 after receiving a total of 156 courses of the FOLFIRI regimen, we considered the enlarged PLN to represent an isolated metastasis. Accordingly, lymph node resection was performed with microscopically negative margins. The patient maintained a good quality of life without any side effects throughout the whole course of his treatment and remains disease-free at 24 months without chemotherapy after resection of the isolated PLN. Curative resection following chemotherapy may improve survival of carefully selected advanced CRC patients with locoregional recurrence, such as isolated PLN involvement.

A novel difficulty scoring system for laparoscopic liver resection.

Early on, laparoscopic liver resection (LLR) was limited to partial resection, but major LLR is no longer rare. A difficulty scoring system is required to guide surgeons in advancing from simple to highly technical laparoscopic resections. Subjects were 90 patients who had undergone pure LLR at three medical institutions (30 patients/institution) from January 2011 to April 2014. Surgical difficulty was assessed by the operator using an index of 1-10 with the following divisions: 1-3 low difficulty, 4-6 intermediate difficulty, and 7-10 high difficulty. Weighted kappa statistic was used to calculate the concordance between the operators' and reviewers' (expert surgeon) difficulty index. Inter-rater agreement (weighted kappa statistic) between the operators' and reviewers' assessments was 0.89 with the three-level difficulty index and 0.80 with the 10-level difficulty index. A 10-level difficulty index by linear modeling based on clinical information revealed a weighted kappa statistic of 0.72 and that scored by the extent of liver resection, tumor location, tumor size, liver function, and tumor proximity to major vessels revealed a weighted kappa statistic of 0.68. We proposed a new scoring system to predict difficulty of various LLRs preoperatively. The calculated score well reflected difficulty.