Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors.

OBJECTIVE: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). BACKGROUND: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. METHODS: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. RESULTS: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs. CONCLUSIONS: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Laparoscopy-Assisted Proximal Gastrectomy with the Hinged Double Flap Method.

BACKGROUND: No standard proximal gastrectomy method for gastric cancer of the upper third of the stomach (UGC) has been established because few of the current methods prevent gastro-esophageal reflux and allow easy postoperative endoscopic surveillance. In the present study, we describe laparoscopic proximal gastrectomy with the hinged double flap method (Kamikawa's method) in detail and examine the short- to medium-term outcomes of this approach, which resulted in excellent postoperative function. METHODS: Between 2011 and 2015, 24 patients with early-stage primary UGC underwent laparoscopic proximal gastrectomy with the above-mentioned method. The celiac and hepatic nerves were preserved without pyloroplasty. A hand-sewn esophagogastric anastomosis was produced intracorporeally. RESULTS: There were no in-hospital deaths, and none of the patients were converted to open surgery. Complications occurred in two patients in the early part of this study (minor anastomotic leakage in one case and an abdominal abscess in the other). None of the patients exhibited symptoms of reflux. Regarding the patients' postoperative endoscopic classifications, 17, 2, and 1 patient were considered to have grade N or M, grade A, and grade B esophagitis, respectively. All of the patients remain alive, and no cases of postoperative bowel obstruction or recurrent cancer have been observed. CONCLUSIONS: This method can be performed safely and achieves excellent outcomes in terms of preventing gastro-esophageal reflux. It deserves further evaluation in a multi-center clinical study.

[A case of pathologically complete response of esophageal carcinoma treated with low-dose 5-FU/CDDP as neoadjuvant chemotherapy].

The patient was a 75-year-old woman with advanced esophageal cancer and lymph-node swelling in the mediastinum(cStage RR). We administered preoperative chemotherapy(5-FU 500mg/body×10, CDDP 10mg/body×10). She received the two courses without showing any serious side effects. The primary tumor revealed remarkable improvement, but the rigidity of the esophagus wall and swelling of the lymph nodes were not resolved, and images showed that the patient exhibited a partial response to the treatment. Radical resection of the esophageal carcinoma was performed. Pathological examination of the resected specimens revealed no malignant cells in the esophagus, no metastasis of the lymph node, and the response evaluation was grade 3. The patient showed no recurrence 4 years and eleven months after the operation. In lonclusion, this rare case of esophageal carcinoma showed a pathologically complete response when treated with low-dose 5-FU/CDDP as neoadjuvant chemotherapy.

[A case of gastric cancer with rhabdoid features showing better prognosis through S-1/CDDP chemotherapy].

Although gastric cancers(GCs)with rhabdoid features are rare, they are known to show a poorer prognosis compared with conventional GCs. Indeed, more than half of reported GCs with rhabdoid features died within 6 months after receiving any kind of initial treatment. Obviously, no effective chemotherapy has been reported. In this study, we present a case of GC with rhabdoid features which showed a better response to a chemotherapy, S-1/CDDP, and lived for over 12 months after the initial chemotherapy. A 75-year-old man was seen in our hospital for epigastralgia. Detailed examinations revealed that he had GC at Stage IV. Consequently, he underwent S-1/CDDP treatment. This treatment produced a good response for 6 months, minimizing the size of the primary tumor and eradicating distant metastases. Re-growth of the primary tumor without uprising distant metastasis was confirmed 8 months after the initialS -1/CDDP treatment, and the patient went through a gastrectomy for curative care. After surgery, a precise pathological examination revealed that the primary tumor possessed a poorly differentiated adenocarcinoma that contained tumor cells with typical rhabdoid features. In the end, the patient died of liver metastasis 13 months after the initial S-1/CDDP chemotherapy.

Effectiveness of gallium scintigraphy in diagnosing a spontaneous giant chronic expanding hematoma of the adrenal gland: A case report.

INTRODUCTION: A chronic expanding hematoma in the retroperitoneal space is a rare disease with poorly understood pathology, and preoperative diagnosis of such hematomas using conventional methods is sometimes difficult. PRESENTATION OF CASE: A 68-year-old man with a history of slowly progressive abdominal distention was referred to our department for further evaluation. Contrast-enhanced CT revealed a large retroperitoneal tumor of the adrenal gland. MRI revealed that the tumor was iso-intense to hyperintense on T2-weighted imaging, with heterogeneous signal intensity on T1-weighted imaging without fat components. Angiography of the left adrenal artery confirmed many extravasations into the tumor. However, gallium scintigraphy showed no accumulation in the tumor. These findings were suggestive of a chronic expanding hematoma of left adrenal gland. This patient underwent complete tumor resection. Postoperative histopathological findings revealed a chronic expanding hematoma. DISCUSSION: Chronic expanding hematomas are slowly expanding, space-occupying masses as a result of trauma, surgery, or bleeding disorders. Chronic expanding hematomas mimic malignant tumors such as sarcomatous lesions. Although CT and MRI are used to obtain the diagnosis, the diagnosis is sometimes difficult. Gallium scintigraphs play a pivotal role in the differential diagnosis between them. CONCLUSION: Gallium scintigraphs, magnetic resonance imaging and computed tomography, are useful tools to differentiate chronic expanding hematomas from sarcomatous lesions.

Ureteral metastasis from appendiceal cancer: report of a case.

We report a case of primary appendiceal cancer that metastasized to the ureter. The patient was a 51-year-old woman who complained of persistent left back pain and right lower abdominal pain. After a detailed examination she was diagnosed to have cancer of the appendix, multiple liver metastases, and left hydronephrosis. Since an obstruction of the ileocecum was obvious, she underwent an ileocecal resection and a resection of the spindle-shaped tumor invading the left ureter. Lymph node metastases were found at the root of the superior mesenteric artery. The spindle-shaped tumor was considered to be due to invasion of the appendiceal cancer to the left ureter. The patient died 5 months postoperatively.

Ciliated foregut cyst of the gallbladder: report of a case.

We report the rare case of a gallbladder cyst arising from the foregut remnants. A 36-year-old woman was referred to our hospital after screening ultrasonography (US) detected a tumor in the gallbladder. On admission, she was well and her blood analyses were all normal. US showed a cystic mass with internal high-echoic lesions, and computed tomography (CT) demonstrated a protruding tumor with slight enhancement in the gallbladder. Angiography provided no additional information; however, sequential CT-arteriography (CTA) clearly demonstrated that this tumor was a cystic lesion. Surgical exploration was performed, first because of the difficulty in establishing a definite diagnosis, and also because the patient wanted the tumor removed. The resected specimen contained a unilocular cystic tumor that looked like a submucosal tumor. Histologically, the wall of the cyst was lined by ciliated stratified columnar epithelium with interspersed goblet cells and underlying smooth muscle fibers. The mass was finally diagnosed as a congenital ciliated foregut cyst of the gallbladder. Cysts of the gallbladder are uncommon and the majority are acquired. To our knowledge, this represents only the fourth report of a ciliated foregut cyst of the gallbladder in the literature. Although rare, an awareness of this entity could allow a preoperative diagnosis to be made, whereby surgical exploration may be avoided. CT-A is a very useful diagnostic tool, especially when the nature of the tumor presents a difficult differential diagnosis.

A gastric duplication cyst with an aberrant pancreatic ductal system: report of a case.

We report an extremely rare case of a gastric duplication cyst together with an aberrant pancreatic ductal system, which communicated with the stomach rather than the pancreatic ductal system with no evidence of pancreatitis. A 46-year-old woman developed severe abdominal pain after a 10-year history of occasional mild abdominal pain. Upper gastrointestinal barium radiography showed a rigidity of the stomach wall, and gastroscopy revealed a fistula orifice at a greater curvature of the gastric body. Subsequent endoscopic suction of mucous secretion from within the fistula provided immediate pain relief. Abdominal computed tomography and ultrasonography showed a cystic mass contiguous with the stomach wall. Surgical exploration revealed an uncommon anomaly of a gastric duplication cyst with the aberrant pancreatic lobe. The patient made an uneventful recovery and remains well 4 years after surgery. We also herein review ten other similar cases of this uncommon congenital anomaly reported in the literature.