Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

BACKGROUND: We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). METHODS: A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. RESULTS: Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). CONCLUSIONS: Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

Extent of regional lymphadenectomy and number-based nodal classification for non-ampullary duodenal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the adequate extent of regional lymphadenectomy according to tumor location and the impact of number-based nodal classification on survival in patients with non-ampullary duodenal adenocarcinoma (NADAC). METHODS: A total of 85 patients with NADAC who underwent surgery were enrolled. The frequency of metastasis was calculated for each node group in the respective tumor locations for 63 patients who underwent lymphadenectomy for pT2-pT4 tumor. RESULTS: The frequency of metastasis in the pancreaticoduodenal (nos. 13 and 17) and superior mesenteric artery (no. 14) nodes was high (16.7 %-52.3 %) regardless of tumor location. Metastasis in the perigastric (nos. 3 and 4d) and right celiac artery (no. 9) nodes was not uncommon (14.3 %-22.2 %) for tumors in the first portion. The frequency of metastasis in the pyloric (nos. 5 and 6) and the other peripancreaticoduodenal (nos. 8 and 12) nodes varied depending on tumor location but could not be ignored for staging. When these nodes were classified as regional nodes, the 5-year survival in patients with pN0, pN1 (1-2 positive nodes), and pN2 (≥3 positive nodes) were 82.9 %, 51.7 %, and 19.2 %, respectively (p < 0.001). pN classification independently predicted survival (pN1, p = 0.022; pN2, p < 0.001). CONCLUSIONS: Nos. 5, 6, 8, 12, 13, 14, and 17 nodes in all advanced NADAC and nos. 3, 4d, and 9 nodes in advanced NADAC in the first portion should be considered as regional nodes for accurate staging. The number-based nodal classification allows good patients' prognostic stratification.

Solitary choroidal metastasis of distal cholangiocarcinoma: A case report.

Metastatic choroidal carcinoma is rare and generally has a poor prognosis. The present case report describes a case of choroidal metastasis from distal cholangiocarcinoma, which was successfully managed using stereotactic radiotherapy (SRT). A 67-year-old Japanese man underwent pancreaticoduodenectomy for distal cholangiocarcinoma. The pathological stage was T2N0M0 stage IIA, according to the Union for International Cancer Control 8th edition. After surgery, the patient received adjuvant chemotherapy with oral TS-1® for 1 month. A total of 2 months after surgery, the patient was readmitted to hospital due to decreased visual acuity. Fundoscopy revealed a macular hole in the right eye that accounted for the decreased visual acuity. Additionally, Goldmann three-mirror contact lens examination revealed a 4-mm choroidal mass with a yellowish color situated at a considerable distance from the optic nerve. Magnetic resonance imaging revealed an enhanced choroidal mass. Based on the findings of ophthalmologic examinations and the patient's history of cholangiocarcinoma, they were diagnosed with choroidal metastasis from distal cholangiocarcinoma. SRT was administered at a total dose of 40 Gy divided into 8 Gy fractions. A total of 1 year after SRT, the patient achieved complete remission without decreased visual acuity. The patient remains alive and in good health without recurrence, 4 years after the diagnosis of choroidal metastasis. To the best of our knowledge, this is the second reported case of intraocular metastasis from cholangiocarcinoma. In conclusion, SRT may provide an opportunity to control metastatic choroidal carcinoma without decreasing visual acuity.

Initial Impact of the COVID-19 Outbreak on ADHD Symptoms Among University Students in Japan.

Objectives: The coronavirus disease 2019 pandemic and its associated societal responses are anticipated to have wide-ranging effects on youth development and mental health. Depression, anxiety, and attention deficit hyperactivity disorder (ADHD) are the three most common mental health problems among university students. Many factors that can threaten mental health during the outbreak affect these three conditions, as well as sleep conditions, in undergraduate students. Thus, determining how these abrupt changes in students' circumstances impact their mental health is very important from a public health perspective. Methods: We investigated the usual conditions and changes in ADHD symptoms during the outbreak, in relation to depressive and sleep-related symptoms among undergraduate students. A total of 252 students, primarily juniors, completed the online survey. Results: The results showed that 12% of the students exceeded the cut-off score of the ADHD questionnaire before the pandemic. Approximately 6%-21% of the university students, especially those with ADHD traits, rated their ADHD behaviors as worse during the outbreak than that before the outbreak. Conclusion: Female students and undergraduates with ADHD traits are more susceptible to experiencing further deterioration of ADHD (inattention) symptoms during the pandemic. In cases where it is difficult to intervene with ADHD symptoms, approaching circadian rhythm or depression will be of considerable clinical use.

[A Case of Pathological Complete Response after Neoadjuvant Therapy for Resectable Pancreatic Cancer].

We report a case of resectable pancreas tail cancer treated with 2 courses of neoadjuvant therapy which is gemcitabine and S-1 therapy, and pathological diagnosis of the resected specimen revealed pathological complete response. A 56-year- old woman was referred to our hospital because she had back pain after eating for 5 months and her previous abdominal ultrasonography revealed an enlarged pancreatic tail. The tumor size was reduced from 30 mm to 12 mm, and the chemotherapy response was judged to be partial response. The patient underwent distal pancreatectomy, splenectomy, and D2 lymph node dissection. Intraoperative findings showed a pancreatic tail with a depression and surface erythema, thus we also diagnosed the patient as having pancreatic capsular invasion(S1). Postoperative histopathological examination revealed a 10×10 mm area of pancreatic parenchyma, which was replaced by fibrous tissue, with no evidence of active cancer cells. The patient was discharged from the hospital on the 14th after surgery.

[Intra-abdominal recurrence with bleeding 7 years after curative resection of primary synovial sarcoma of the spermatic cord with localized dissemination:a case report].

Primary synovial sarcoma of the spermatic cord is quite rare and has not been reported in Japanese literature. We report a case of primary synovial sarcoma of the spermatic cord and localized dissemination of the tumor in a patient who experienced recurrence of intra-abdominal bleeding 7 years after curative resection of the primary lesion. A 70-year-old man was admitted with disturbance on urination and lower abdominal pain. Computed tomography (CT) of the abdomen revealed two lesions:a 10-cm intrapelvic tumor with hemorrhage and a 4-cm tumor adjacent to the bladder. Curative excision of the tumors was performed. Histological examination revealed that the larger lesion was a primary tumor of the spermatic cord with proliferation of spindle cells in cellular fascicles in a monotonous pattern, which was compatible with histologic findings of monophasic fibrous synovial sarcoma. The smaller lesion was a disseminated tumor. The diagnosis of synovial sarcoma was confirmed by the detection of a SS18 (SYT) -SSX1 fusion gene. After discharge, the patient received adjuvant chemotherapy, including ifosfamide and doxorubicin. No recurrence was evident thereafter. Seven years after the operation, the patient experienced sudden abdominal pain and swelling and was transferred to our hospital. CT showed a 17-cm tumor with massive hemorrhage in the omental bursa. Through catheterization of the superior mesenteric artery, bleeding from a branch of the dorsal pancreatic artery was identified. Because of the difficulty of catheterizing the bleeding branch, he underwent emergency resection of the tumor and partial resection of the colon. Histologic examination and genetic testing revealed that the tumor was a recurrence of the synovial sarcoma. After discharge, the patient received treatment with gemcitabine and docetaxel. However, 7 months after the second surgery, intraperitoneal manifestations recurred. The patient died 14 months after the second resection. This case suggests that curative surgical resection of the primary synovial sarcoma of the spermatic cord contributes to prolonged survival. However, because the recurrence rate of synovial sarcoma is high, multidisciplinary treatment, including chemotherapy and radiotherapy, might be necessary.

Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer.

PURPOSE: This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS: Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS: Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION: The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

Oncological outcomes of surgery for recurrent biliary tract cancer: who are the best candidates?

BACKGROUND: This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease. METHODS: A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%). RESULTS: In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p < 0.001). Surgery was an independently prognostic factor (p < 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%). CONCLUSION: Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.

Efficacy and safety of ramucirumab plus paclitaxel therapy for advanced gastric cancer patients treated previously with docetaxel-containing chemotherapy.

BACKGROUND: Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear. METHODS: This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen. RESULTS: In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043). CONCLUSIONS: RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

Clinicopathological Characteristics and Surgical Outcomes of Primary Cystic Duct Carcinoma: A Multi-institutional Study.

BACKGROUND: The role of surgery in the management of primary cystic duct carcinoma (CDC) remains unclear especially in advanced disease. This study aimed to evaluate long-term outcomes in patients undergoing surgery for primary CDC. METHODS: From a multi-institutional database, we identified 41 patients who underwent surgery for primary CDC, defined as a part of gallbladder carcinoma with the tumor centre located in the cystic duct. RESULTS: Of the 41 patients, 31 (75.6%) underwent preoperative biliary drainage for jaundice. Twenty-eight (68.3%) patients underwent extensive resection including major hepatectomy (n = 21), pancreaticoduodenectomy (n = 4), or both procedures (n = 3). Thirty-four (82.9%) patients had ≥ pT3 tumor, while 31 (75.6%) patients had involvement of contiguous organs/structures. Nodal and distant metastasis was found in 26 (63.4%) and 7 (17.1%) patients, respectively. Most patients (90.2%) had perineural invasion. Median overall survival was 23.7 months in all 41 patients. Factors independently associated with both overall and disease-specific survival were pN (P = 0.003 and P = 0.007, respectively) and pM (P = 0.003 and P = 0.013, respectively) classification. Median survival was 75.3, 17.7, and 5.2 months for patients with pN0M0 (n = 14), pN1/2pM0 or pN0pM1 (n = 21), and pN1/2pM1 (n = 6) disease, respectively (P < 0.001). CONCLUSIONS: Primary CDC is characterized by locally advanced disease with aggressive histopathological characteristics at surgery, leading to extensive resection during treatment. Surgery provides potential benefits for patients with pN0pM0 disease, whereas pN1/2 and/or pM1 status appear to have strong adverse effects on survival.

Hepatitis B surface antigen incorporated in dissolvable microneedle array patch is antigenic and thermostable.

Alternatives to syringe-based administration are considered for vaccines. Intradermal vaccination with dissolvable microneedle arrays (MNA) appears promising in this respect, as an easy-to-use and painless method. In this work, we have developed an MNA patch (MNAP) made of hydroxyethyl starch (HES) and chondroitin sulphate (CS). In swines, hepatitis B surface antigen (HBsAg) formulated with the saponin QS-21 as adjuvant, both incorporated in HES-based MNAP, demonstrated the same level of immunogenicity as a commercially available aluminum-adjuvanted HBsAg vaccine, after two immunizations 28 days apart. MNAP application was associated with transient skin reactions (erythema, lump, scab), particularly evident when the antigen was delivered with the adjuvant. The thermostability of the adjuvanted antigen when incorporated in the HES-based matrix was also assessed by storing MNAP at 37, 45 or 50 °C for up to 6 months. We could demonstrate that antigenicity was retained at 37 and 45 °C and only a 10% loss was observed after 6 months at 50 °C. Our results are supportive of MNAP as an attractive alternative to classical syringe-based vaccination.

[Two cases of pancreatic cancer with multiple liver metastases treated with radical treatment after successful treatment with gemcitabine plus S-1 therapy].

UNLABELLED: We report two cases of pancreatic cancer with multiple liver metastases for which successful gemcitabine (GEM) +S-1 therapy facilitated radical resection. Case 1: A 40-year-old man with jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, he was administered GEM +S-1 (GEM 1,000 mg/m² on days 1 and 8; S-1, 100mg/day for 14 days). Administration of seven courses of therapy achieved complete remission (CR) of the metastatic lesions. Considering the possibility of residual tumors, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Although pathological examination revealed a residual tumor in the primary lesion, R0 resection was achieved. GEM+S-1 therapy was resumed, and the patient is currently relapse-free. Case 2: A 65-year-old man with obstructive jaundice was diagnosed with pancreatic head cancer and multiple metastases. Radical treatment was not possible. Therefore, GEM +S-1 therapy was initiated. After 11 therapy courses, only one metastatic lesion remained. Radical treatment was then deemed possible, and a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination revealed residual tumors in the primary lesion and the peripancreatic lymph nodes. However, the liver nodules were only fibrotic, and their surgical radicality was R0. GEM +S-1 therapy was resumed, and the patient is currently relapse-free. CONCLUSION: The high response rate of GEM+S-1 therapy suggests its usefulness in facilitating radical resection after treatment with (GEM) +S-1.

Significant change of spin transport property in Cu/Nb bilayer due to superconducting transition.

The combination between the spin-dependent and super-conducting (SC) transports is expected to provide intriguing properties such as crossed Andreev reflection and spin-triplet superconductivity. This may be able to open a new avenue in the field of spintronics, namely superconducting spintronics because a superconductor itself has great potential for future nanoelectronic applications. To observe such SC spin transports, the suppression of the extrinsic effects originating from the heating and Oersted field due to the electric current is a crucial role. Pure spin current without accompanying the charge current is known as a powerful mean for preventing such extrinsic effects. However, non-negligible heat flow is found to exist even in a conventional pure spin current device based on laterally-configured spin valve because of the heating around the spin injector. Here, we develop a nanopillar-based lateral spin valve, which significantly reduces the heat generation, on a superconducting Nb film. By using this ideal platform, we found that the spin absorption is strongly suppressed by the SC transition of Nb. This demonstration is the clear evidence that the super-conducting Nb is an insulator for the pure spin current.

Giant hepatic cyst with septal structure: diagnosis and management.

The hepatic cyst is a common benign liver tumor, and no surgical treatment is necessary. However, it is difficult to correctly diagnose the giant hepatic cyst containing the solid septal structures inside, from the malignant cystadenocarcinomas. The various imaging modalities such as computed tomography, magnetic resonance imaging, and ultrasonography, have been developed and are useful for the diagnosis of these liver tumors. Reviewing the other reports in this paper, the combination of more than 2 modalities will help to diagnose these tumors; however, the malignant potential is unable to be excluded if the tumor is huge. Therefore, the surgical resection should be considered for the huge hepatic cysts with septal structures if the correct diagnosis is unable to be made. For example, when the hemorrhages cause the granulation in the septa which often shows neovascularization, the imaging modalities are unable to define this situation from the malignant tissue with hypervascularity. Therefore, with the careful review of other reports, we conclude that if the imaging studies show the possible malignant potential or the sizing-up is marked, the surgical treatment should be considered with the consent from the patients.

[An 84-year-old man with highly advanced gastric cancer showing good response after chemotherapy with docetaxel, cisplatin and S-1 combination therapy].

An 84-year-old man had the wall thickness of his stomach accidentally detected by CT scan, and was diagnosed as type 2 advanced gastric cancer with liver and lung metastasis. Chemotherapy with docetaxel, cisplatin and S-1 combination therapy was adopted. Grade 4 neutropenia was revealed, but the treatment could be continued by G-CSF or by down dosing the anticancer agents. By maintaining CR of the primary lesion and PR of the liver and lung metastases, he has been kept at a PS 0 state and has been receiving regular outpatient treatment for 28 months now since the beginning of treatment.

Portal vein infusion chemotherapy with gemcitabine after surgery for pancreatic cancer.

PURPOSES: Pancreatic cancer still has a poor prognosis even after curative resection because of the high incidence of postoperative liver metastasis. This study prospectively evaluated the feasibility and tolerability of portal vein infusion chemotherapy of gemcitabine (PVIG) as an adjuvant setting after pancreatic resection. METHODS: Thirteen patients enrolled in this study received postoperative chemotherapy with PVIG. The patients received intermittent administration of gemcitabine (800 mg/m(2)) via the portal vein on days 1, 8, and 15 after surgery. The tolerability and the toxicity of PVIG were closely monitored. RESULTS: The PVIG was started on an average of 3.1 days after surgery. Complete doses of chemotherapy (three sessions of portal infusion) were accomplished in 11 of the 13 patients. Grade 3 or 4 leukocytopenia was observed in three patients (23 %), and liver dysfunction was found in one patient (7.7 %). Grade 2 sepsis developed in two cases due to bloodstream infection. Liver metastasis was the first site of recurrence in only two patients. CONCLUSIONS: PVIG can be administered to the liver with acceptable toxicity, but myelosuppression is similar to the systemic use of gemcitabine. Careful observation is required even for locoregional chemotherapy.

Surgical outcomes of minor hepatectomy for locally advanced gallbladder carcinoma.

BACKGROUND/AIMS: This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. METHODOLOGY: A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. RESULTS: Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p<0.001), pM classification (p=0.001) and resection of the extrahepatic bile duct (p=0.048) were independently significant factors associated with survival after resection. CONCLUSIONS: Hepatectomy procedure may not significantly affect surgical outcomes in patients with gallbladder carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to possible tumor cells.