[Laparoscopic Splenectomy for Metachronous Splenic Metastasis of Fallopian Tube Cancer with Synchronous Rectal Metastasis-A Case Report].

A 59-year-old woman underwent simple abdominal total hysterectomy with bilateral salpingo-oophorectomy, partial omentectomy, and extirpation of intrapelvic disseminated nodules for right fallopian tube cancer with rectal metastasis and peritoneal dissemination as primary debulking surgery(PDS). The histopathological diagnosis was high grade serous carcinoma( HGSC)of the right fallopian tube. After adjuvant chemotherapy with 4 courses of paclitaxel-carboplatin(TC), low anterior resection of the rectum for rectal metastasis and pelvic and para-aortic lymph node dissection were performed as interval debulking surgery(IDS). Histopathologically, lymph node metastasis was detected only in the right obturator lymph node. After adjuvant chemotherapy with 4 courses of TC, bevacizumab maintenance monotherapy was administered. Three years after PDS, laparoscopic splenectomy for splenic metastasis and extirpation of the solitary peritoneal metastases were performed as secondary debulking surgery(SDS). After adjuvant chemotherapy with 4 courses of TC, olaparib maintenance monotherapy was administered. The patient has remained alive without recurrence for 4 years after SDS and for 7 years after PDS. No case of metachronous splenic metastasis from fallopian tube cancer with synchronous rectal metastasis has been reported; however, long-term prognosis may be expected with PDS, IDS and SDS for platinum-sensitive HGSC.

[Neuroendocrine Carcinoma of the Non-Ampullary Duodenum-A Case Report].

A 69-year-old woman was admitted to a territory hospital because of severe right hypochondoralgia after 2 weeks of internal medicine for persistent epigastralgia. Gastroduodenal endoscopy revealed a large tumor with a fistula in the duodenal bulb that expanded to the stomach. Histopathologically, the biopsy specimen indicated a poorly differentiated adenocarcinoma and HER2 negative. Computed tomography revealed that the tumor invaded the left lobe of the liver. The patient was referred to our hospital for cancer treatment. After 1 course of chemotherapy with S-1 and CDDP, laparoscopic gastroenterostomy bypass was performed because of tumor hemorrhage and poor food intake. However, the tumor hemorrhage and poor food intake continued, and the tumor enlarged. Therefore, left hemihepatectomy and distal gastrectomy with resection of the duodenal bulb were performed 1 month after bypass surgery. Histological testing confirmed the diagnosis of duodenal large-cell neuroendocrine carcinoma invading the liver without lymph node metastasis. Adjuvant chemotherapy was not administered, and the patient has been alive without recurrence for 7 years and 3 months. Neuroendocrine carcinoma of the non-ampullary duodenum is very rare; however, a large cell type without lymph node metastasis may be a factor in the long-term prognosis.

[A Case of Gastric Neuroendocrine Carcinoma with Bulky Lymph Node Metastases, Solitary Liver Metastasis, and Left Adrenal Metastasis Curatively Resected after Chemotherapy].

A 68-year-old man presented with generalfatigue due to anemia. Gastrointestinalendoscopy showed a tumor approximately 60mm in diameter in the lesser curvature of the angle of the stomach. Large cell neuroendocrine carcinoma was diagnosed by biopsy of a tumor specimen. Computed tomography revealed bulky regional lymph node metastases, solitary liver metastasis, and left adrenal metastasis. After three courses of combined chemotherapy with S-1 and CDDP, the gastric lesion and lymph node metastases shrunk, but the liver metastasis and left adrenal metastasis enlarged. After three courses of combined chemotherapy with ramucirumab and paclitaxel, the liver metastasis and left adrenal metastasis also shrunk, and no other new metastatic lesions appeared. Accordingly, total gastrectomy with lymph nodes dissection, partial resection of the liver and left adrenalectomy were performed for a curative resection. The histological findings revealed neuroendocrine carcinoma and adenocarcinoma of the stomach. The lesions of the liver and lymph nodes were all burned out, and a tiny metastatic lesion of neuroendocrine carcinoma was left in the left adrenal gland. S-1 was administrated for 3 months after surgery. The patient has been alive for 16months without recurrence after surgery.

Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow.

Leg immersion in carbonated water improves endothelial-mediated vasodilator function and decreases arterial stiffness but the mechanism underlying this effect remains poorly defined. We hypothesized that carbonated water immersion increases muscle blood flow. To test this hypothesis, 10 men (age 21 ± 0 years; mean ± SD) underwent lower leg immersion in tap or carbonated water at 38°C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and tissue oxygenation index using near-infrared spectroscopy, skin blood flow by laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 ± 14 to 83 ± 31 mL/min; P < 0.001) and skin blood flow (by 779 ± 312%, P < 0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495). In addition, the change in PA blood flow in response to immersion in carbonated water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no relations was found for tap water immersion. These findings indicate that water carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow increases in response to lower leg immersion in carbonated water likely due to a large increase in skin blood flow.

[A Case of Recurrent Ascending Colon Cancer with Concomitant Dementia Successfully Treated with Chemotherapy].

A 72-year-old man with advanced dementia presented with a right lower abdominal painful mass, and on detailed examination and investigation, was diagnosed to have moderately differentiated circumferential tubular adenocarcinoma infiltrating the abdominal wall in the middle of the ascendingcolon. It was extremely painful, and there was also a risk of ileus if left untreated. Therefore, laparoscopic right hemicolectomy was performed. One year after surgery, examination revealed local recurrence. After consultation with family members, we started with chemotherapy, usingcapecitabine and bevacizumab. It is our policy to administer chemotherapy under adequate surveillance. Thus, outpatient chemotherapy was safely administered in a dementia patient with shrinkage of local recurrent lesions.

[A Case of Uterine Body Metastasis from Sigmoid Colon Adenocarcinoma].

We report a case of metastatic carcinoma to the uterine body from a colorectal adenocarcinoma. A 73-year-old woman underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma 2 years before. In the following study, her serum carcinoembryonic antigen level was elevated, and a uterine body tumor invading the rectal wall was detected via enhanced computed tomography. Colonoscopic examination revealed an elevated lesion at the rectum, which was diagnosed as an adenocarcinoma. Based on these results, we diagnosed the uterine tumor as metastatic tumor from the colon carcinoma. Immunostaining was negative for CK7, but positive for CK20. Thus, we confirmed metastasis of the sigmoid colon cancer to the uterus. Metastasis to the female genital tract from extragenital malignancies are rare, and the prognosis is extremely poor. However, some patients attain long-term survival by surgical intervention even in such cases.

[Long-Term Survival after Multidisciplinary Treatment for Resected Pancreatic Adenocarcinoma with Recurrence of Pulmonary Metastases - A Case Report].

Recent studies indicated that isolated pulmonary metastases could define a favorable subgroup in metastatic pancreatic cancer. We report a case of isolated pulmonary metastases after curative resection of pancreas head cancer treated with chemotherapy and pulmonary metastasectomy survived for 79 months after recurrence. A 72-year-old male underwent pancreatoduodenectomy for pancreas head cancer. Adjuvant chemotherapy was done with gemcitabine hydrochloride (GEM)for 6 months and then S-1 for 2 months. Twenty-seven months after surgery, 2 small metastatic nodules in the left lung was detected. Chemotherapy with GEM was performed but the lesions grew larger very slowly. A new metastatic nodule was detected in the right lung 40 months after surgery and pleural effusion was detected 52 months after surgery. Then combination chemotherapy with GEM and S-1 was performed for 3 months followed chemotherapy with S-1 alone. Seventytwo months after surgery, chemotherapy with GEM was performed again because of patient's intolerance to S-1. Ninety months after initial surgery, pulmonary metastasectomy of the right lung was performed because of its resistance to chemotherapy. Chemotherapy with GEM was started again 4 months after pulmonary metastasectomy but serum levels of tumor markers remained increase. Combination chemotherapy with GEM and nab-paclitaxel was started 8 months after pulmonary metastasectomy but the patient died 16 months after pulmonary metastasectomy.

Direct observation of structural properties and fluorescent trapping sites in macrocyclic porphyrin arrays at the single-molecule level.

By utilizing single-molecule defocused wide-field fluorescence microscopy, we have investigated the molecular structural properties such as transition dipole moment orientations and the angular relationship among chromophores, as well as structural distortions and flexibilities depending on the ring size, in a series of cyclic porphyrin arrays bearing close likeness in overall architectures to the LH2 complexes in purple bacterial photosynthetic systems. Furthermore, comparing the experimental results with molecular dynamics simulations, we ascertained site selection for fluorescent trapping sites. Collectively, these experimental and computational results provide the basis for structure-property relationships and energy hopping/emitting processes in an important class of artificial light-harvesting molecular systems widely used in molecular electronics technology.

[A case report of metastatic anal fistula cancer treated with neoadjuvant chemotherapy].

A 69-year-old man with perianal pain was diagnosed with an anal fistula and a rectal tumor by magnetic resonance imaging and pulmonary tuberculosis by computed tomography. A colonoscopy confirmed the presence of a circular mass in the rectum 6 cm from the anal verge. Histological examination revealed a moderately differentiated adenocarcinoma. Initially, seton drainage was used to improve the perianal pain. After 2 months of anti-tuberculosis therapy, the patient underwent low anterior resection for the rectal cancer. Six months after surgery, a perianal tumor was detected at the postoperative site of the anal fistula. Biopsy of the tumor revealed adenocarcinoma. Because the histological appearance of the second tumor was identical to the rectal cancer, it was diagnosed as a metastatic anal fistula cancer. The tumor shrunk after 3 courses of neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) plus bevacizumab and there was no evidence of distant metastasis. Local resection of the anal fistula cancer was performed. Six months postoperatively, the patient is doing well and shows no sign of recurrence.

[Successful treatment of a patient using mFOLFOX6 after laparoscopic surgery for rectal cancer with peritoneal dissemination].

A 58-year-old man underwent laparoscopic surgery for rectal cancer(rectal sigmoid)complicated by intestinal obstruction. He had no liver metastasis. Although many nodules suspected to have arisen from peritoneal dissemination were observed in the pelvic cavity, we performed anterior resection assuming that the primary lesion was resectable. The surgical findings were sSE, sN2, sP3, sStage IV, and histopathological findings were signet-ring cell carcinoma, pSE, pN2, pP+, pStage IV. After 8 courses of adjuvant chemotherapy with modified 5-fluorouracil/Leucovorin/oxaliplatin(mFOLFOX6), carcinoembryonic antigen( CEA)decreased to a normal level, and positron emission tomography-computed tomography(PET-CT)showed no abnormal accumulation that suggested metastasis. To evaluate the effectiveness of this procedure, laparoscopic peritoneal biopsy was performed 5 months after surgery, revealing histopathological disappearance of the peritoneal dissemination lesion. The patient has been followed up and has been receiving S-1 for 1 year after the first surgery. No evidence of recurrence has been observed.

Clinical outcomes and prognosis after thoracoscopic esophagectomy with two-field lymph node dissection for lower thoracic esophageal cancer.

AIM: The aim of this study was to evaluate the clinical outcomes and prognostic factors of thoracoscopic esophagectomy with two-field lymph node dissection for lower thoracic esophageal cancer. PATIENTS AND METHODS: From January 2003 to December 2011, 84 patients with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy with two-field lymph node dissection. Clinicopathological information, postoperative complications, mortality, type of recurrent diseases and factors predictive of survival were analyzed. RESULTS: Postoperative complications were diagnosed in 37 patients and the mortality was 1.2%. Lymph node metastases were found in 43 patients (51.2%). The 5-year survival rate of all patients was 60.5%. Pathological T factor, lymph node metastasis, pathological staging, and venous invasion were independent prognostic factors. Among the patients with lymph node metastasis, the survival rate of those with upper mediastinal and/or celiac area involvement was significantly worse than that of those without involvement of these areas. CONCLUSION: Thoracoscopic esophagectomy with two-field lymph node dissection is a safe and appropriate surgical intervention for patients with lower thoracic esophageal cancer without complication of lymph node metastases to the upper mediastinum and/or celiac area.

[Clinical outcomes of thoracoscopic esophagectomy after neoadjuvant chemotherapy].

AIM: With recent advances in multimodal therapy for esophageal cancer, neoadjuvant chemotherapy (NAC) followed by surgery has become the standard treatment for advanced resectable esophageal cancer. This study analyzed the feasibility and clinical outcomes of thoracoscopic esophagectomy (TE) after NAC. PATIENTS AND METHODS: We retrospectively analyzed 129 patients who underwent TE with radical mediastinal lymph node dissection between January 2005 and December 2012. Of these patients, 54 received NAC( NAC+group) and 75 did not( NAC-group).The perioperative clinical outcomes, number of dissected nodes, and postoperative mortality were compared between the 2 groups. RESULTS: The operation time in the NAC+group was significantly longer than that in the NAC-group( p<0.01).However, the estimated blood loss was significantly less in the NAC+group( p<0.01).There was no significant difference in the number of dissected nodes and the frequency of postoperative complications between the 2 groups. CONCLUSION: TE can be safely adopted for the treatment of patients with advanced esophageal cancer after NAC.

[A case of repeated postoperative recurrence of gastric cancer treated via laparoscopic approach].

A 74-year-old man who had undergone distal gastrectomy was diagnosed with metastasis to the spleen and transverse colon 27 months after the operation, and 6 courses of combination therapy with S-1 and cisplatin (CDDP) were administered. However, both lesions showed progressive disease (PD) after chemotherapy. Massive gastrointestinal hemorrhage from colon metastases was observed following the administration of irinotecan(CPT-11). Therefore, total remnant gastrectomy, splenectomy, and partial transverse colectomy were performed via the laparoscopic approach. Chemotherapy using paclitaxe(l PTX) was initiated after surgery. However, bowel obstruction due to intestinal metastatic lesions developed after 4 courses of PTX therapy, and right hemicolectomy and partial resection of the small intestine were performed laparoscopically. Although combination therapy of capecitabine and CDDP were administered, the patient died 28 months after the diagnosis of recurrent disease. Typically, surgical intervention is rarely effective in cases of recurrent disease from gastric cancer. However, a favorable quality of life was obtained in the case of our patient with aggressive multimodal therapy that included laparoscopic surgery.

[Present state and prospects of adjuvant chemotherapy for gastric cancer].

In Japan, a one-year administration of S-1 is the standard adjuvant treatment for stage II/III gastric cancer after curative gastrectomy with a D2 lymph-node dissection.The treatment is recommended in the Japanese Guidelines for Treatment of Gastric Cancer(3rd Edition).Using data from results of a 5-year follow-up of the ACTS-GC trial, it was confirmed that using S-1 significantly improves the 5-year overall survival over surgery alone.However, the recurrence rate of stage III gastric cancer is still too high.More powerful treatment using multiple drugs is needed for this disease.This paper presents a new perspective for the development of post-operative adjuvant chemotherapy in the future, based on clinical trials recently reported.

A novel liver retraction technique for lateral lobe of the liver during laparoscopic surgery using silicone disk.

For safe and effective laparoscopic surgery it is important to maintain a favorable view of the operative field. However, the use of a conventional liver retractor needs an additional wound and carries a risk for liver injury during surgery. We developed a novel retraction technique for the lateral lobe of the liver using a silicone disk (Hakko Co. Ltd.) during laparoscopic surgery. We used a silicone disk that consists of a silicone rubber membrane inside a flexible ring and four monofilament threads. The disk can be inserted into the abdomen under the pneumoperitoneum through a 12-mm port and is located at the dorsal side of the lateral lobe of the liver. The threads are withdrawn through the abdominal wall, two threads close to the infraxiphoid space and the other two threads bilaterally below the costal arch. Thus, the lateral lobe of the liver is safely raised to the ventral side and covered with a silicone membrane. We introduced this technique for various laparoscopic operations, such as gastrectomy, gastroplasty, and fundoplication. There were no complications related to the procedure. This retraction technique is easy, results in less liver damage, and provides an excellent operative view around the esophageal hiatus. The silicone membrane covering the lateral lobe reduces the risk of liver injury during surgery using laparoscopic forceps to a low level.

Rapid intramolecular hole hopping in meso-meso and meta-phenylene linked linear and cyclic multiporphyrin arrays.

A series of zinc porphyrin arrays comprised of a meso-meso linked porphyrin dimer, a meta-phenylene linked dimer, gable-like tetramers consisting of the meso-meso linked dimers bridged via a meta-phenylene linker, and a dodecameric ring composed of this alternating dimeric pattern were singly oxidized, and intramolecular hole hopping between the porphyrin moieties was probed using electron paramagnetic resonance (EPR) spectroscopy. Electron nuclear double resonance (ENDOR) spectroscopy was also used to probe hole hopping within the dimers. Rapid hole hopping occurs between both porphyrins within both dimers and among three porphyrins of the tetramers with rates >10(7) s(-1) at 290 K. Additionally, the hole hops among 8-12 porphyrins in the dodecameric ring with a rate that is >10(7) s(-1) at 290 K, but hopping is slow at 180 K. These results show that hole hopping is rapid even though the meta-phenyl bridges and direct meso-meso linkages do not provide optimal electronic coupling between the porphyrins within these multiporphyrin arrays. This greatly expands the scope of possible structures that can be employed to tailor the design of long distance charge transport systems.

Structural dependence on excitation energy migration processes in artificial light harvesting cyclic zinc(II) porphyrin arrays.

A series of covalently linked cyclic porphyrin arrays CNZ that consist of N/2 of meso-meso directly linked zinc(II) porphyrin dimer subunits Z2 bridged by 1,3-phenylene spacers have been prepared by Ag(I)-promoted oxidative coupling reaction. We have investigated the excitation energy migration processes of CNZ in toluene by using femtosecond transient absorption anisotropy decay measurements by taking 2Z2 composed of two Z2 units linked by 1,3-phenylene as a reference molecule. On the basis of the excitation energy transfer rate determined for 2Z2, we have revealed the excitation energy hopping rates in the cyclic arrays CNZ by using a regular polygon model. The number of excitation energy hopping sites N(flat) calculated by using a regular polygon model is close to the observed N(expt) value obtained from the transient absorption anisotropy decays for C12Z-C18Z with circular and well-ordered structures. On the other hand, a large discrepancy between N(flat) and N(expt) was found for smaller or larger arrays (C10Z, C24Z, and C32Z). In the case of C10Z, m-phenylene linked 2Z2 motif with the interchromophoric angle of 120 degrees is not well suited to make a cyclic pentagonal array C10Z based on planar pentagonal structure. This geometrical factor inevitably causes a structural distortion in C10Z, leading to a discrepancy between N(expt) and N(flat) values. On the contrary, the presence of highly distorted conformers such as figure-eight structures reduces the number of effective hopping sites N(expt) in large cyclic arrays C24Z and C32Z. Thus, our study demonstrates that not only the large number of porphyrin chromophores in the cyclic arrays CNZ but the overall rigidity and three-dimensional orientation in molecular architectures is a key factor to be considered in the preparation of artificial light harvesting porphyrin arrays.

Excitation energy migration processes in cyclic porphyrin arrays probed by single molecule spectroscopy.

By using single molecule fluorescence spectroscopy we have investigated the excitation energy migration processes occurring in a series of cyclic porphyrin arrays bearing a close proximity in overall architectures to the LH2 complexes in purple bacterial photosynthetic systems. We have revealed that the conformational heterogeneity induced by the structural flexibility in large cyclic porphyrin arrays, which provides the nonradiative deactivation channels as an energy sink or trap, reduces significantly the energy migration efficiency. Our study provides detailed information on the energy migration efficiency of the artificial light-harvesting arrays at the single molecule level, which will be a guideline for future applications in single molecular photonic devices in the solid state.

Synthesis of nanometer-scale porphyrin wheels of variable size.

Starting from 1,3-phenylene linked diporphyrin zinc(II) complex 2ZA, repeated stepwise Ag I-promoted coupling reactions provided linear oligomers from 2nZA up to 128ZA. Of these zigzag shaped porphyrin arrays, the Ag I-promoted intramolecular cyclization reaction of 2 nZA (n=5, 6, 8, 9, 12, and 16) under dilute conditions gave the corresponding cyclic porphyrin wheels C2nZA (n=5, 6, 8, 9, 12, and 16), whereas large arrays 2nZA (n=24, 32, and 48) did not provide cyclic porphyrin products. These large discrete porphyrin arrays and wheels were fully characterized by means of 1H NMR spectroscopy, MALDI-TOF mass spectrometry, UV/Vis absorption spectroscopy, GPC-HPLC analysis, and the scanning tunneling microscopy (STM) technique. The STM images of C12ZA and C18ZA reveal their large circular structures. In the cyclic structures of C2nZA in solution, however, the gradual decrease in fluorescence quantum yields and fluorescence lifetimes are observed, reflecting some conformational heterogeneities. Collectively, the present work provides an important contribution to the construction of fully covalently linked large cyclic arranged porphyrin arrays with ample electronic interactions as a model of light-harvesting antenna.

A hexagonal prismatic porphyrin array: synthesis, STM detection, and efficient energy hopping in near-infrared region.

A belt-shaped hexagonal cyclic porphyrin array 2 that comprises of six meso-meso, beta-beta, beta-beta triply linked diporphyrins 3 bridged by 1,3-phenylene spacers is prepared by oxidation from cyclic dodecameric array 1 consisting of six meso-meso directly linked diporphyrins 4 with DDQ and Sc(OTf)3. The absorption spectrum of 2 is similar to that of the constituent subunit 3 but shows a slight red-shift for the Q-bands in near-infrared (NIR) region, indicating the exciton coupling between the neighboring diporphyrin chromophores. Observed total exciton coupling energies in the absorption spectra were largely matched with the calculated values based on point-dipole exciton coupling approximation. It was found that the experimental exciton coupling strength (292 cm(-1)) of the Q-band in 2 is slightly larger than the calculated one (99 cm(-1)), indicating that the electronic communications are enhanced through 1,3-phenylene linkers in hexameric macromolecule. A rate of the excitation energy hopping (EEH) that occurs in 2 at the lowest excited singlet state in the near-infrared region has been determined to be (1.8 ps)(-1) on the basis of the pump-power dependent femtosecond transient absorption (TA) and the transient absorption anisotropy (TAA) decay measurements. The 2 times faster EEH rate of 2 than that of 1 (4.0 ps)(-1) mainly comes from involving through-bond energy transfer among diporphyrin subunits via 1,3-phenylene bridges as well as Förster-type through-space EEH processes. STM measurement of 2 in the Cu(100) surface revealed that it takes several discrete conformations with respect to the relative orientation of neighboring diporphyrins. Collectively, an effective EEH in the NIR region is realized in 2 due largely to the intensified oscillator strength in the S(1) state (Q-band) and the close proximity held by 1,3-phenylene spacers.