A Case of Primary Aldosteronism Turned Out to Be Adrenocortical Carcinoma With Disorganized Steroidogenesis.

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis, which essentially needs an early diagnosis because surgery is the only hope of a cure. On the other hand, primary aldosteronism (PA) is an overproduction of aldosterone from the adrenal glands and is known as one of the most common causes of secondary hypertension and hypokalemia. It is mostly a benign disease. ACC accompanied by PA is extremely rare, which can result in delayed diagnosis and clinical pitfalls. A 56-year-old woman was diagnosed with PA. Mild, symptomatic PA was clinically diagnosed as a right-sided aldosterone-producing adenoma (APA) with adrenal tumor using adrenal vein sampling (AVS). The tumor imaging findings showed abnormalities on computed tomography (CT) in terms of size and attenuation value compared with typical benign adenomas. Twelve months later, the tumor was confirmed to be an ACC with cortisol hypersecretion. The resected ACC specimen did not clearly show positive findings for CYP11B1 or CYP11B2, and disorganized steroid production was suspected. However, the prevalence and clinical characteristics of adrenocortical carcinomas with disorganized steroid production remain unclear. Steroidogenic enzyme immunostaining analysis is important not only for the diagnosis of adrenal adenoma but also for a better understanding of the clinical course of hormone-producing ACC.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

[Curative Resection of Sigmoid Colon Cancer with Multiple Liver Metastases by Long-Term Multidisciplinary Treatment].

A male patient in his 80s underwent colonic stenting for obstructive sigmoid colon cancer with multiple liver metastases. With systemic chemotherapy for approximately 1 year, the liver metastasis disappeared, so laparoscopic sigmoid colectomy was performed for the primary lesion. No recurrence was observed for a while, although CT revealed liver metastasis in the liver S4, and radiofrequency ablation was performed. Radiation therapy was performed for the liver metastasis of liver S2 that subsequently appeared. After a recurrence-free period of approximately 2 years, a rapid regrowth of liver metastasis in liver S2 was observed. Thus, 4 years and 3 months after the initial diagnosis, lateral segmentectomy of the liver was performed. Five years have passed since the first visit, and he is alive without recurrence. The patient had obstructive colorectal cancer with unresectable liver metastasis, and as the obstruction was released by a colonic stent, systemic chemotherapy was prioritized. Hence, liver metastasis was controlled, and the primary lesion was resected. Furthermore, for the liver metastasis that appeared later, various loco-regional cancer therapies were provided to achieve a cancer-free state.

Extra-endocrine phenotypes at infancy in multiple endocrine neoplasia type 2B: A case series of six Japanese patients.

Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare disease, most often caused by a de novo p.Met918Thr RET mutation. Medullary thyroid carcinoma of MEN2B has a good prognosis if diagnosed by one year of age. However, diagnosis of MEN2B within the first year of life is markedly challenging owing to its high de novo occurrence and lack of clarity in terms of extra-endocrine symptoms that could aid early diagnosis. Herein, we present six cases of Japanese children with MEN2B harboring the p.Met918Thr RET variant. Exploratory data extraction was conducted using a questionnaire. The patients underwent thyroidectomy at a median age of 11 yr (range, 6-19 yr). Four of the six patients underwent neonatal hospitalization at birth without complications, and three tested positive for neuroblastoma screening at infancy. The patients presented at least one MEN2B-associated symptom before one year of age, including ganglioneuromas, pseudo-Hirschsprung disease, alacrima, bumpy lips, sucking disability, or decreased muscle tone, along with other suspected comorbidities, such as Williams or Prader-Willi syndrome. This case series demonstrates that MEN2B manifests through several extra-endocrine symptoms by the age of one year.

[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.

[A Case of Unresectable Recurrent Colorectal Cancer with Regorafenib Treatment and Long-Term Survival].

This paper reports a case in which the patient has survived for 5 years and 6 months after recurrence of colorectal cancer by chemotherapy, and especially in regorafenib as fourth-line therapy has obtained stable disease(SD)for 2 years and 6 months. A man in his 70s underwent left hemicolectomy in the diagnosis of descending colon cancer. Four years and 4 months after the operation, abdominal CT revealed paraaortic lymph node metastasis. When SOX plus bevacizumab was performed as first-line therapy, partial response(PR)was obtained, and PR was maintained for a long time. After progressive disease(PD), IRIS was performed as second-line therapy, but the effect was not obtained. Panitumumab was started as third-line therapy, and PR was temporarily recognized, but since it became PD again, regorafenib was introduced as fourth- line therapy. After regorafenib administration, reduction of paraaortic lymph nodes and lowering of CEA are recognized, and long SD can be maintained. This case can be said to be 1 case in which the usefulness of regorafenib was shown as a salvage- line for unresectable colorectal cancer.

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.

[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.

Implications of thyroid autoimmunity in infertile women with subclinical hypothyroidism in the absence of both goiter and anti-thyroid antibodies: lessons from three cases.

There is a great deal of research interest regarding the underlying causes of slightly elevated TSH values in patients with subclinical hypothyroidism (SH) without abnormal findings on ultrasonography or anti-thyroid antibodies. Twelve infertile women with thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb)-negative nongoitrous SH were referred to our department of endocrinology between September 2007 and September 2015. None had been diagnosed with autoimmune thyroid disease or had any possible causes of SH. In all cases, LT4 was prescribed to bring TSH value below 2.5 mIU/L. Among those with infertility treatments, six (50%) became pregnant and gave birth to infants. Here, we report three of these six women who successfully became pregnant with infertility treatments and were found to have thyroid autoimmunity on data obtained during the postpartum period. Two developed postpartum thyroiditis, and the remaining one woman was temporarily weakly positive for TPOAb at 9 months postpartum. We describe three infertile subclinically hypothyroid women without goiter or anti-thyroid antibodies with potential thyroid autoimmunity. Thyroid autoimmunity is one of the most important issues for management of pregnant women, and thus, our findings are noteworthy for the care of infertile women with SH. This report provides valuable insights into the presence of autoimmunity in nongoitrous thyroid-associated antibody-negative SH patients.

[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.

[A Case of Retroperitoneal Liposarcoma That Required Three Times Surgical Resections during Four Years].

The patient was a 64-year-old man, who had undergone surgical resection for a right retroperitoneal giant tumor. The histopathological diagnosis was a well-differentiated liposarcoma. Two years and 4 months after the initial surgery, 3 recurrent lesions were found on the dorsal side of the colon hepatic flexure, and resection was performed. One year and 1 month after the secondary surgery, the tumor recurred again, and invaded the right abdominal wall and right transverse colon. Tumor was completely resected macroscopically. All resected tumors were well-differentiated liposarcoma. There have not been any signs of recurrence until 1 year and 6 months after the last operation. For retroperitoneal liposarcoma, complete surgical resection is the only established treatment, but the tumor often recurs. Aggressive resection against recurrent cases is known to contribute to life prognosis, but there is a possibility of the degeneration to a highly malignant dedifferentiated tumor while recurrence is repeated. Therefore, sufficient follow-up observation is needed.

[Results of Preoperative Colon Stent Placement for Obstructive Colorectal Cancer].

We examined short-term outcomes in 34 patients who had stenting as a bridge to surgery(BTS)for obstructive colorectal cancer during the 5-year period between April 2012 and March 2017.T he patients were 22 men and 12 women with a mean age of 72.6 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.5 days.No serious complications related to stenting occurred.Elective surgery could be performed in all patients after stenting.The mean number of days to surgery was 24.7 days.Laparoscopic surgery was performed in 14 patients.Postoperative complications included minor leakage in 1 patient, an abdominal wall abscess due to tumor invasion of the abdominal wall in 1 patient, and heart failure and pneumonia, as serious complications, in 1 patient each.Colorectal stenting in patients with obstructive colorectal cancer is a safe and relatively simple procedure.This is an effective treatment strategy in which preoperative colorectal decompression enables a one-stage resection.

[Findings from Total Colonoscopy in Obstructive Colorectal Cancer Patients Who Underwent Stent Placement as a Bridge to Surgery(BTS)].

We clinically investigated 34 patients with obstructive colorectal cancer who underwent placement of a colonic stent as a bridge to surgery(BTS), focusing on endoscopic findings after stent placement.Twenty -nine patients(85.3%)underwent colonoscopy after stent placement, and the entire large intestine could be observed in 28(96.6%).Coexisting lesions were observed in 22(78.6%)of these 28 patients.The lesions comprised adenomatous polyps in 17 patients(60.7%), synchronous colon cancers in 5 patients(17.9%), and obstructive colitis in 3 patients(10.7%), with some overlapping cases.All patients with multiple cancers underwent one-stage surgery, and all lesions were excised at the same time.Colonoscopy after colonic stent placement is important for preoperative diagnosis of coexisting lesions and planning the extent of resection. These considerations support the utility of colonic stenting for BTS.

[Long-Term Complete Response by S-1 Chemotherapy for Gastric Cancer with Para-Aortic Lymph Node Metastases].

We describe a 67-year-old man with long-term CR by S-1 chemotherapy for gastric cancer with para-aortic lymph node metastases after reduction surgery. The patient presented at our hospital with epigastric pain. He was diagnosed with gastric cancer with para-aortic lymph node metastases. We performed gastrectomy and D1 lymphadenectomy without any resection of the para-aortic lymph node metastases. We treated the patient with oral S-1 chemotherapy. The initial treatment schedule was 100mg/body/day, twice daily for 4weeks with 2weeks of rest. Grade 1 neutropenia developed at the end of the second course of treatment. The regimen was changed to 2 weeks of administration, with 1 week of rest. The para-aortic lymph node metastases immediately responded to the chemotherapy. Abdominal CT showed almost complete regression of the lymph node metastases 10 months postoperatively. The patient has received S-1 chemotherapy and remained in remission for more than 5 years 6 months.

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is essential because it is associated with increased risk of parathyroid cancer. A 30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was surgically removed and was histologically confirmed to be an adenoma. However, PHPT due to another parathyroid tumor reoccurred two years after the surgery. Although no HPT-JT-associated manifestations other than PHPT were detected, HPT-JT was strongly suspected based on the exclusion of multiple endocrine neoplasia (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73, which encodes the tumor suppressor protein parafibromin. The residual parathyroid glands were all removed without autotransplantation of parathyroid gland taking into consideration prospective parathyroid carcinogenesis. The resected parathyroid tumor was also an adenoma. The present case highlights that HPT-JT should be considered and CDC73 mutation analysis should be performed, especially in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid involvement, and PHPT presenting with severe hypercalcemia even if there is no positive family history.

Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-κB signalling.

CARMA1-mediated NF-κB activation controls lymphocyte activation through antigen receptors and survival of some malignant lymphomas. CARMA1 clusters are formed on physiological receptor-mediated activation or by its oncogenic mutation in activated B-cell-diffuse large B-cell lymphomas (ABC-DLBCLs) with constitutive NF-κB activation. However, regulatory mechanisms and relevance of CARMA1 clusters in the NF-κB pathway are unclear. Here we show that SH3 and GUK domain interactions of CARMA1 link CARMA1 clustering to signal activation. SH3 and GUK domains of CARMA1 interact by either intra- or intermolecular mechanisms, which are required for activation-induced assembly of CARMA1. Disruption of these interactions abolishes the formation of CARMA1 microclusters at the immunological synapse, CARMA-regulated signal activation following antigen receptor stimulation as well as spontaneous CARMA1 clustering and NF-κB activation by the oncogenic CARMA1 mutation in ABC-DLBCLs. Thus, the SH3-GUK interactions that regulate CARMA1 cluster formations are promising therapeutic targets for ABC-DLBCLs.