Clinical Significance of Adjuvant Surgical Resection for Initially Unresectable Pancreatic Cancer Responsive to Arterial Infusion Chemotherapy.

BACKGROUND/AIMS: We have reported a clinically meaningful local-control effect and a hepatic metastatic tumor-regression effect of transcatheter peripancreatic arterial embolization-hepatic and splenic arterial infusion chemotherapy (TPPAE-HSAIC) for unresectable advanced pancreatic cancer. The aim of this study was to evaluate the clinical significance, of adjuvant surgical resection after TPPAE-HSAIC. METHODOLOGY: We assessed histopathological findings and outcomes of 6 patients who underwent surgical resection of tumors judged to be radically resectable after attaining tumor down-staging or long-term tumor control following TPPAE-HSAIC for pancreatic cancer initially diagnosed as unresectable. RESULTS: Clinical stage at the initial diagnosis was T4N0M0 Stage III in 4 patients and T4N0M1 Stage IV in 2 patients. The durations of TPPAE-HSAIC ranged from 5 to 46 months with a median of 19 months. An R0 resection was performed in 5 of the 6 patients (83%) and pathological down-staging, from the viewpoint of clinical stage, was observed in 4 patients. Of the 5 patients with R0 resection, one died from a postoperative complication at 7 months and another from pulmonary metastasis at 30 months post-operatively, while the other 3 patients have survived for 45 to 83 months to date. CONCLUSIONS: If surgical resection of pancreatic cancer initially diagnosed as unresectable can be carried out in patients responding favorably to TPPAE-HSAIC, the likelihood of long-term survival might be increased.

[Loss of CD23 expression after bortezomib plus dexamethasone therapy in CCND1/IGH-positive multiple myeloma].

A 69-year-old male was referred to our hospital because of anemia, renal insufficiency, and a positive urine test for Bence-Jones protein. A bone marrow examination showed 73.7% of myeloma cells with lymphoplasmacytic morphology, the strong expressions of CD20 and CD23 by flow cytometry, and the chromosomal aberration of CCND1/IGH by FISH analysis. He was diagnosed with multiple myeloma, IgG-λ type. The initial treatment with bortezomib plus dexamethasone (BD) provided a rapid decrease in the level of IgG; however, he developed bortezomib-induced recurrent paralytic ileus accompanied by aspiration pneumonia during the second course. Interestingly, CD23 expression on myeloma cells decreased from 87.7% to 2.2% after 2 courses of BD. Negative CD23 expression was maintained following lenalidomide plus dexamethasone therapy. There are extremely few reports on CD23 expression on myeloma cells, and this is the first case report of multiple myeloma in which CD23 expression was lost after BD therapy.

[Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia].

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab.

[Primary diffuse large B-cell lymphoma of the uterine cervix successfully treated with rituximabplus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy-a case report].

Primary malignant lymphoma of the uterine cervix is a rare disease, and the therapeutic strategy has not been clearly established. A 45-year old woman presented with vaginal bleeding and hypermenorrhea in January 2012. Physical examination revealed a mass in the pelvic cavity approximately the size of a neonate's head. Pelvic magnetic resonance imaging(MRI) showed a solid mass 11 cm in size in the uterine cervix with homogeneous low intensity on T1-weighted images, iso-high intensity on T2-weighted images, and heterogeneous iso-high intensity on gadolinium-diethylenetriaminepentaacetate(Gd- DTPA)-enhanced images. Multiple lymphadenopathy were also detected in the pelvis. The Papanicolaou smear indicated class 5 cervical cytology, and a subsequent histological examination by a punch biopsy of the cervix showed diffuse infiltration of medium- to large-sized mononuclear cells that stained positive for CD20 and CD79a and negative for CD3, CD5, and EBER. Bone marrow biopsy revealed no abnormality. Positron emission tomography-computed tomography(PET-CT)showed strong fluorodeoxyglucose(FDG)accumulation in the uterine cervix mass, and in the pelvic and right inguinal lymphadenopathy. The patient was diagnosed with diffuse large B-cell lymphoma of the uterine cervix, Ann Arbor stage II AE. She was successfully treated with 8 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP) chemotherapy, and maintains a complete remission.

[A case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy].

We report a case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy (EIS). A 64-year-old man with alcoholic liver cirrhosis was hospitalized because of repeated anal bleeding. Colonoscopy revealed external anal varices connecting with rectal varices. Three days after admission, external anal variceal bleeding was observed. Angiography revealed that the anorectal varices formed by hepatofugal inferior mesenteric vein drained into the internal iliac vein. On angiography, the variceal blood flow rate was extremely low, therefore we performed EIS. Seven days after therapy, thrombosis of anorectal varices was observed.

Pulsatile tinnitus as a first symptom of essential thrombocythemia.

Tinnitus is the sensation of sound inside the head and is a common symptom encountered daily by otorhinolaryngologists. Pulsatile tinnitus sufferers hear rhythmical noise at the same rate as a heartbeat and can present a diagnostic challenge. In this report, we present a 32-year-old patient with pulsatile tinnitus that led to the diagnosis of essential thrombocythemia. The symptom of pulsatile tinnitus allowed an early diagnosis of essential thrombocythemia and a more favorable prognosis. The case demonstrates the importance of blood tests for all patients who present with pulsatile tinnitus of unknown origin.

[A case of early esophageal adenocarcinoma arising from esophageal cardiac glands].

A 54-year-old man was referred to our hospital with an esophageal lesion. On esophagogastroduodenoscopy a pedunculated elevated lesion about 15mm in diameter was identified in the abdominal esophagus. The surface of the lesion had irregular nodules with white coating. We found no Barrett's mucosa around the lesion. A biopsy specimen of this tumor showed well-differentiated adenocarcinoma. A lower esophagus-proximal gastrectomy was performed because this tumor was suspected to invade the submucosal layer. Eventually, the histological diagnosis after resection was esophageal adenocarcinoma arising from cardiac glands, limited to the mucosal layer (M2). This origin of the esophageal adenocarcinoma is rare. Furthermore, this form of the tumor is especially unusual, and there have been few reports of similar cases.

Hearing results for ossicular reconstruction using a cartilage-connecting hydroxyapatite prosthesis with a spearhead.

OBJECTIVE: Assessment of the efficacy of ossicular reconstruction using a cartilage-connecting hydroxyapatite prosthesis designed with a spearhead to reduce extrusion and dislocation of the implant. PATIENTS: All patients undergoing ossicular reconstruction after chronic ear surgery, connecting the cartilage to the prosthesis, with a minimum of 1 year of postoperative follow-up. MAIN OUTCOME MEASURES: Postoperative change in pure-tone averages. Air-bone gap closures, and implant extrusion rates. RESULTS: Overall mean pure-tone averages improved by 12.2 dB (ranged between -40 and 60 dB). In total, 68.4% of the patients achieved an air-bone gap less than 20 dB. Gains in the mean air conduction thresholds were 9.5 dB in cases of partial ossicular reconstruction and 14.9 dB in cases with total ossicular reconstruction (p < 0.05). The overall extrusion rate was 4.21%. CONCLUSION: The cartilage-connecting hydroxyapatite prosthesis with a spearhead was found to restore hearing to a satisfactory level. The extrusion rate was relatively low. The cartilage-connecting hydroxyapatite prosthesis with a spearhead is an effective ossicular implant and offers an attractive alternative for ossicular reconstruction, particularly for total ossicular reconstructions.

[A case of unresectable advanced pancreatic cancer with peritoneal dissemination responding to continuous dose S-1 monotherapy after chemo-radiation therapy].

A 57-year-old woman with a pancreatic body tumor was admitted to our hospital. She was diagnosed with unresectable advanced pancreatic cancer (stage IVb) due to portal vein invasion, arterial invasion, retro peritoneal invasion and lymphnode metastases, so radiation therapy (50 Gy/25 Fr) with concurrent arterial infusion of gemcitabine (GEM) was carried out. After the chemo-radiation therapy, her arterial infusion treatment of GEM was continued in our outpatient clinic for 3 months until she was complicated with ascites due to peritoneal dissemination. Peritonitis carcinomatosa was controlled by S-1 oral administration with intraperitoneal infusion of MMC and CDDP. For 18 months after discharge, she has maintained good quality of life without any adverse effects by a continuous dose of S-1 at our outpatient clinic.

[Transcatheter embolization of an inferior mesenteric arteriovenous fistula with frequent mucous diarrhea].

We report a case of inferior mesenteric arteriovenous fistula without portal hypertension or mesenteric ischemia. A 64-year-old man had developed frequent mucous diarrhea during the previous month. Colonoscopy showed highly edematous mucosa of the rectum. Barium enema demonstrated localized stricture of the same part but no evidence of malignancy. Finally we established a diagnosis by 3D-CT and selective abdominal angiography. Transcatheter arterial embolization was successfully performed. After that, his symptoms gradually improved as all abnormal findings on colonoscopy, barium enema and abdominal CT disappeared.

Optical imaging of glycinergic inhibition in the vestibular and cochlear nuclei.

Using multiple-site optical recording techniques, the spatiotemporal activity was observed in both the cochlear and vestibular nucleus in newborn mice. The optical responses were obviously enhanced by bath-applied strychnine. A quantitative analysis showed higher enhancements to occur in the cochlear nucleus than in the vestibular nucleus. Optical imaging enables us to visualize the spatiotemporal extent of the inhibitory receptive field after the application of strychnine.

Mechanisms for increment of platelet associated IgG and platelet surface IgG and their implications in immune thrombocytopenia associated with chronic viral liver disease.

In addition to hypersplenism, immunological destruction of platelets by elevated platelet associated IgG (PAIgG) and platelet surface IgG (PSIgG) has been proposed as a causative factor for thrombocytopenia in chronic liver disease (CLD), although the implication of PAIgG may be debatable since recent investigations on idiopathic thrombocytopenic purpura disclosed the fact that PAIgG largely relates to the intra-platelet IgG in alpha-granules and not to PSIgG. Further, with regard to the elevated PSIgG of CLD, characterization as to whether it mainly represents anti-platelet glycoprotein (GP) antibodies or IgG contained in the immune complex has not been elucidated. Thirty-seven patients with chronic viral liver disease (CVLD); 31 hepatitis C and 6 hepatitis B were included in this study. First we monitored the changes in levels of PAIgG, alpha-granule IgG, PSIgG and mean platelet volume (MPV) during the course of partial splenic arterial embolization (PSE). The elevated level of PAIgG decreased after PSE, paralleling that of alpha-granule IgG, while PSIgG showed no change; MPV decreased reciprocally with the increase of platelet count. These results indicate that the increment of PAIgG in CVLD may be caused by accelerated destruction of platelets; this generally evokes hyperproduction of large-sized thrombocytes, which have an increased capability to uptake circulating IgG. To characterize PSIgG, we then tested CVLD patients for antiplatelet GP antibodies and found only a 5.4% positivity. It was also found that circulating immune complex levels in CVLD patients were clearly elevated, correlating with the levels of PSIgG. Thus, it was surmised that immune complexes bound to the platelet surface, and not platelet specific GP antibodies, may be playing a crucial role in platelet destruction of CVLD, possibly through phagocytosis by macrophages.

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig.

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig.

This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.

A comparative randomized trial of intermittent intrahepatic arterial carboplatin- versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage IV).

BACKGROUND/AIMS: The study was performed to investigate the anti-tumor effect, survival rate, and toxicity of intermittent intrahepatic infusion chemotherapy with carboplatin suspended in lipiodol. METHODOLOGY: We conducted a randomized controlled study containing either doxorubicin or carboplatin in 65 patients with advanced hepatocellular carcinoma. RESULTS: The results observed in the carboplatin- and doxorubicin-lipiodol groups included: response rates, 29.0 and 20.6% respectively, 1-year survival rates of, 60.4% and 40.4%, respectively, and the difference achieved statistical significance (p=0.025). The median survival of 31 patients who received carboplatin emulsified with lipiodol was 16.9 months, 34 patients who received doxorubicin was 12.1 months. The difference achieved statistical significance. CONCLUSIONS: Compared with doxorubicin, carboplatin caused neither cardiotoxicity nor nephrotoxicity, and side effects of nausea and vomiting were less severe. Therefore, carboplatin is effective and preferable for repeated intrahepatic arterial administration to treat advanced hepatocellular carcinoma over a relatively long period.

Superselective transcatheter embolization for acute lower gastrointestinal hemorrhage after endoscopic mucosal resection: a report of 3 cases.

One of the most common complications related to endoscopic mucosal resection is hemorrhage; in almost every case, the bleeding is endoscopically managed, but some cases are unresponsive to the treatment. We have encountered three cases of endoscopically uncontrollable lower gastrointestinal hemorrhage after endoscopic mucosal resection in the colon which we successfully treated by urgent superselective transcatheter embolization. In our three cases, massive hemorrhage occurred immediately after endoscopic mucosal resection of a sessile polyp 25-40 mm in diameter, two cases in the ascending colon and one in the rectum. Although hemoclip placement was attempted in every case, hemostasis was not achieved. Emergency angiography disclosed massive extravasation of the contrast material in the colon. Hemostasis was achieved immediately after superselective transcatheter arterial embolizations with microcoils, with no observable ischemic complications and without the need of transfusions. In conclusion, superselective transcatheter embolization with microcoils should be considered a safe and efficient treatment option for endoscopically uncontrollable lower gastrointestinal hemorrhage occurring after endoscopic mucosal resection.

[Usefulness of CT arteriography for transcatheter peripancreatic arterial embolization to patients with advanced pancreatic cancer].

We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.

[Three cases of multiple liver metastases of carcinoid tumor responding to hepatic arterial infusion chemotherapy using degradable starch microspheres].

We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.

[A case of gastric carcinoma with multiple skin, bone, and bilateral ovary metastasis; effective treatment by chemotherapy].

A 40-year-old female visited our hospital with general malaise. She was diagnosed with gastric carcinoma with multiple skin, bone, and bilateral ovary metastases. Chemotherapy with 5-FU (1,000 mg/w) and cisplatin (10 mg/w) was performed in the outpatient clinic. Two years after the initial diagnosis, CEA was elevated. She then was given chemotherapy of CPT-11 (40 mg/w) in the outpatient clinic after 1 cycle of combined chemotherapy of CPT-11 and cisplatin. She died 38 months after the initial diagnosis. Weekly 5-FU/CDDP or low-dose CPT-11 appear to be effective for such a gastric carcinoma with systemic metastases without impairing quality of life.

A novel treatment for early gastrointestinal carcinoma by ultrasonic endoscopic mucosal stripping.

PURPOSE: The aim of this study was to clarify the indications for a new endoscopic mucosal resection (EMR) technique that employs a cavitational ultrasonic surgical aspirator (CUSA). Endoscopic mucosal resection has proved an effective technique for treating early mucosal gastrointestinal cancer. However, resecting a lesion larger than 2 cm en bloc requires special devices and a long processing time; and it engenders the risk of bleeding, perforation, and other complications. METHODS: We investigated application of the CUSA for detaching the mucosa from the muscularis propria of extracted porcine stomachs and then clarified the specification of an endoscopic ultrasonic scalpel for endoscopic mucosal resection by investigating characteristics of two original, handmade prototype cavitational ultrasonic surgical aspirators. RESULTS: Use of a cavitational ultrasonic surgical aspirator should improve the ease and safety of detaching the mucosa. A small, high-power ultrasonic cylindrical vibrator should be developed to make possible a probe-type scalpel with a piezoelectric vibrator mounted in the tip of a catheter. An ultrasonic transmission-type scalpel could lead to the development of a new endoscopic mucosal resection device for clinical use. CONCLUSIONS: The CUSA should enable us to develop a safer, simpler, time-saving scalpel for endoscopic mucosal resection, although some resolvable technical problems remain. The CUSA might enable us to diagnose carcinoma invasion into the submucosa in aspirated specimens and then aspirate out the entire invading submucosal carcinoma.