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Background Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment. Methods As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board‐certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated. Results Sixty‐four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0). Conclusions Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics., Highlight Ando and colleagues analyzed data from 163 patients with pancreatic trauma in a nationwide multicenter study. They found that serum amylase and C‐reactive protein levels were significantly higher in patients with main pancreatic duct injuries, indicating that endoscopic retrograde pancreatography was the most accurate imaging modality for assessing pancreatic duct injury.

Aim Early operative outcomes of enhanced-view totally extraperitoneal repair (eTEP) for ventral hernias Material and Methods We have retrospectively analysed the date of 41 patients who underwent an eTEP procedure on between November 2018 and April 2021 by a single surgeon and monitored until May 2021. Results During the study period, 29 endoscopic transversus abdominis muscle release and 12 endoscopic Rives-Stoppa techniques were performed to repair incisional (30), umbilical (6), epigastric (3), and spigelian, and parastomal hernias occurred in 1 patient each. The mean age was 68.0 years, mean BMI was 26.4 kg/m2. The hernial orifice centers were as follows: M2 in 7, M3 in 23, M4 in 5, L2 in 4, L4 in 1, and M2 and L2 (2 orifices) in 1 patient. Nine cases of large incisional hernia (width ≥10cm) were included. An average mesh area of 624cm2 was used for an average defect area of 57cm2. Mean operative time, blood loss, and length of hospital stay were 278 min, 5 ml, 6 days, respectively. Only one case was converted to an open operation due to presence of severe adhesions. Postoperative complication consisted of hematoma (n = 1) and a small bowel obstruction due to a tear of the posterior sheath (n = 1). There was no hernia recurrence at mean follow-up of 448 days. No patient reported significant pain at the surgical site at the first postoperative follow up. Conclusions Judging from our short-term results, eTEP approach for ventral hernias can be an attractive option for selected cases.

A 69-year-old woman was referred to our department with complaints of abdominal discomfort in the standing position. She had undergone robot-assisted radical cystectomy and ileal conduit urinary diversion for bladder cancer 10 months earlier. Abdominal CT revealed a parastomal hernia. Laparoscopic parastomal hernia repair using the Pauli technique was performed successfully with no recurrence after a 4-month follow-up. Although there are concerns about potential mesh-related complications and long-term results, this novel approach can be a successful option for parastomal hernia repair. As far as we know, this is the first English-language report on the application of Pauli parastomal hernia repair combined with a pure laparoscopic approach.

Aim This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer. Patients and methods Each patient received four cycles of 260 mg/m2 nab-paclitaxel with 6 mg/kg trastuzumab (8 mg/kg as the loading dose) every 3 weeks (q3w) followed by four cycles of FEC (500/100/500 mg/m2) q3w. The primary endpoint was pathological complete response (pCR) rate. Results Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%. Conclusion Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

Introduction Necrotizing soft tissue infection (NSTI) of the chest wall is a rare, rapidly spreading, highly lethal surgical disease. Radical debridement interferes with the important anatomical function of the chest wall. We report a case of chest wall NSTI that was successfully managed with early diagnosis and serial debridement. Presentation of case A 43-year-old, previously healthy woman presented with severe malaise and worsening right axillary pain. She was severely lethargic and had a painful, large, pale lesion with surrounding erythema of the right chest and trunk. Computed tomography revealed NSTI, with diffuse soft tissue inflammation extending from the axilla to the lower abdomen. There was no obvious entry portal. Prompt surgical drainage was established. Group A streptococcus infection was diagnosed. During her 3-month postoperative course, she underwent four more surgeries, including two debridements. This treatment proved successful and avoided the need for complicated muscle flap reconstruction. She was discharged on postoperative day 109. Discussion Group A streptococcus can cause NSTI even in immunocompetent patients without an entry portal. Radical debridement is recommended for infection control. Preserving anatomical chest wall function, however, is also important. Serial debridement with close follow-up solved the problem in this patient. Conclusions Serial debridement with close follow-up enabled to avoid large tissue deficits and complicated reconstruction in the case of NSTI of the chest wall., Highlights • Necrotizing soft tissue infection of the chest wall is rare and lethal. • Radical debridement could interfere with the anatomical function of the chest wall. • Adequate drainage with minimum skin incision avoids large tissue defects. • Serial debridement with close follow-up enabled to avoid complicated reconstruction

We herein report a rare case of a patient who developed a spindle cell tumor at the inferior mesenteric artery clipping site. A 58-year-old man underwent laparoscopy-assisted sigmoid colectomy for sigmoid colon cancer. As follow-up, CT scans were performed every 6 months after the primary surgery. At the 1-year CT, an nodular soft tissue density mass measuring 54 mm in diameter was found in the mesentery. Although we initially suspected locoregional recurrence of the colon cancer resected 1 year earlier, PET-CT showed that the tumor was unrelated to the previous cancer. During the subsequent laparotomy, the mass appeared to originate from the inferior mesenteric artery clipping site, and it adhered to the jejunum and the left ureter. We completely resected the tumor and part of the jejunum, which we separated from the abdominal aorta and left ureter. The tumor was histologically diagnosed of a spindle cell tumor. The patient has been free from recurrence since the surgery more than 4.5 years ago. Preoperative PET-CT was helpful in ruling out local recurrence of colon cancer, which might have made palliative care a better option than surgical resection.

Right-sided blunt traumatic diaphragmatic injury (TDI) is a rare injury that is rarely repaired by the minimally invasive approach in the acute setting. Laparoscopic repair of right-sided TDI is challenging because the liver often obstructs access to the injury site. Herein, we report a case wherein acute right-sided blunt TDI was successfully repaired using a combined laparoscopic and thoracoscopic approach. A 30-year-old man presented with shortness of breath after falling on his back while jumping on a snowboard. CT revealed a right-sided TDI. As the patient was haemodynamically stable, laparoscopic repair was planned. Laparoscopy revealed a right-sided diaphragmatic rupture. As the posterior portion was covered by the liver and difficult to access, we added trocars in the chest cavity and closed the diaphragmatic defect with a thoracic approach. A combined laparoscopic and thoracoscopic approach can repair right-sided diaphragmatic injury by a minimally invasive approach even in the acute setting.

Background/aim In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. Patients and methods HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. Results Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. Conclusion In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

Background The oncological effectiveness of preoperative radiotherapy for locally advanced colon cancer is unclear. We report a case of pathological complete response in a patient with locally advanced ascending colon cancer after preoperative radiotherapy following failure of chemotherapy. Case presentation A 65-year-old Japanese woman presented with malaise and hematochezia. A computed tomography (CT) revealed a tumor in the ascending colon which seemed to infiltrate the adjacent structures. She was diagnosed with locally advanced ascending colon cancer stages T4b, N2a, M0, and IIIC. We selected modified FOLFOX6 with panitumumab as neoadjuvant chemotherapy. However, we discontinued the chemotherapy after the 8th cycle because of disease progression and severe adverse effects. The patient then underwent radiotherapy of 60 Gy in 30 fractions, resulting in significant tumor size reduction. One month after the radiotherapy, we performed a right hemicolectomy with multivisceral resection without complications. Histopathologically, we found no residual cancer cells in the resected specimen. The patient remains alive and has not required additional therapies for 24 months, as there are no signs of recurrence. Conclusions The present case suggests that preoperative radiotherapy might be an effective treatment options for locally advanced colon cancer.

Background/aim Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m2/3weeks regimen. Patients and methods Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. Results Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. Conclusion Nab-PTX 175 mg/m2/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

Objective:Little is known about the associations between family satisfaction with end-of-life care and caregiver burden. We conducted a researcher-assisted questionnaire survey to clarify the impact of caregiver burden on family satisfaction and to determine the types of burden that decrease family satisfaction.Method:Bereaved family caregivers of patients with advanced cancer who received our outreach palliative care service were retrospectively identified. Family satisfaction with the end-of-life care provided by the palliative care service and caregiver burden were quantified using the Japanese versions of the FAMCARE Scale and the Zarit Burden Interview (ZBI), respectively.Results:Our study subjects included 23 family caregivers. The mean scores on the FAMCARE Scale and the ZBI for the total population were 72.8 ± 11.2 and 22.8 ± 17.3, respectively, indicating moderate-to-high satisfaction and low-to-moderate burden. Caregiver burden had a strong negative correlation to family satisfaction with end-of-life care (Spearman's rho [ρ] = −0.560, p = 0.005), which remained after adjustment for potential confounders (standardized beta [β] = −0.563, p = 0.01). Several burden items—including loss of control, personal time, social engagement with others, feeling angry with the patient, feeling that the patient wants more help than he/she needs, and a wish to leave the care to someone else—were associated with decreased satisfaction. The major cause of dissatisfaction for family members included the information provided regarding prognosis, family conferences with medical professionals, and the method of involvement of family members in care decisions.Significance of results:Caregiver burden can be a barrier to family satisfaction with end-of-life care at home. A home care model focused on caregiver burden could improve end-of-life experiences for patients and family caregivers.

Early prediction of therapeutic outcome is important in determining whether the ongoing therapy is beneficial. In addition to anatomical response determined using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, recent studies have indicated that change in tumor glucose use on or after treatment correlates with histopathologic tumor regression and patient outcomes. This Perspective discusses the use of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for pharmacodynamic evaluation in a very early phase of treatment to predict clinical outcomes in patients with advanced non–small-cell lung cancer. We conducted a study to assess whether early metabolic response determined using FDG-PET correlated with clinical outcomes in patients treated with gefitinib or those treated with carboplatin plus paclitaxel (CP). Early metabolic response to gefitinib, but not CP, correlated with the late metabolic response, anatomical response, progression-free survival, and even overall survival. A rapid effect of molecular targeted agents might not be aptly evaluated using the conventional criteria, eg, RECIST, in a very early phase of treatment before volumetric shrinkage of the tumor. Based on the findings of several studies, and on the findings from our study, use of FDG-PET might enable prediction of clinical outcomes at a very early stage of treatment, especially in patients treated with molecular targeted agents with rapid clinical efficacy.

A 9-year-old boy, who had a blunt blow to the epigastric abdomen by a bicycle handle, was transferred to our hospital. Enhanced computed tomography (CT) demonstrated the complete transection of the pancreas with the large hematoma between the pancreatic head and body. Pancreatic parenchyma preserving Letton-Wilson procedure composed of proximal stump closure and distal pancreaticojejunostomy was performed. The patient recovered without significant complications and was discharged on postoperative day 15. He had no abnormalities in the follow-up CT and endocrine function as well 1 year following surgery. We herein have reported this successful case in which Letton-Wilson procedure was successfully committed for blunt traumatic pancreatic transection in 9-year-old child.

Women undergoing surgery for primary breast cancer routinely have suction drains inserted deep to the wounds. A lack of data exists in relating how long suction drains should stay in situ after major breast surgery.This study evaluates the appropriate timing of drain removal by comparing the 5-day-long postoperative drainage or drain removal when less than 50 mL/24 h to conventional drain removal.This controlled clinical trial was undertaken between February 1997 and May 2012 with a total of 214 consecutive patients who underwent elective total or partial mastectomy with level II axillary lymph node dissection. The main outcome measures included the length of hospital stay, and surgical morbidity, especially seroma formation.In the study group, the age and operation time were significantly increased compared to the conventional group whereas the median hospital stay was significantly shorter in the study group than the control group (7 days vs. 9 days; p0.05). The incidence of seroma was 42.8 % in the study group and 31.6 % in the control group (p = 0.14). The mean number of outpatient visits for seroma was 3.6 in the study group and 1.5 in the control group (p0.05). Drainage volume of more than 150 mL/24 h all resulted in seroma formation.The new criteria for early drain removal are safe and acceptable despite the slightly increased chance of seroma formation.

International audience; BackgroundChemotherapy combined with radiotherapy is the standard treatment of “limited-stage” small-cell lung cancer. However, controversy persists over the optimal timing of thoracic radiotherapy and chemotherapy.Material and methodsWe performed a meta-analysis of individual patient data in randomised trials comparing earlier versus later radiotherapy, or shorter vs. longer radiotherapy duration, as defined in each trial. We combined the results from trials using the stratified log-rank test to calculate pooled hazard ratios (HRs). The primary outcome was overall survival.ResultsTwelve trials with 2,668 patients were eligible. Data from nine trials comprising 2,305 patients were available for analysis. The median follow-up was 10 years. When all trials were analysed together, “earlier or shorter” vs. “later or longer” thoracic radiotherapy did not affect overall survival. However, the HR for overall survival was significantly in favour of “earlier or shorter” radiotherapy among trials with a similar proportion of patients who were compliant with chemotherapy (defined as having received 100% or more of the planned chemotherapy cycles) in both arms (HR 0.79, 95% CI 0.69–0.91) and in favour of “later or longer” radiotherapy among trials with different chemotherapy compliance (HR 1.19, 1.05–1.34, interaction test p

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

The epidermal growth factor receptor (EGFR) gene is highly polymorphic and its expression and activity may be affected by various polymorphisms. There have been several studies examining associations between EGFR polymorphisms and clinical outcome of lung cancer therapy; however, the underlying mechanism is largely unknown. The present study investigated EGFR polymorphism status and its correlation with clinicopathological features in Japanese non-small cell lung cancer (NSCLC) patients. We investigated 5 polymorphisms in the EGFR gene (-216G/T, -191C/A, 8227G/A, D994D and R497K) in 274 surgically-treated NSCLC patients. TaqMan single nucleotide polymorphism (SNP) genotyping assays and a PCR-based assay were used to analyze these polymorphisms. In our cohort of patients we did not find any evidence of the -191C/A polymorphism. Our results showed that the patients with the 8227GA or AA type in intron 1 had a significantly better prognosis with the anti-EGFR therapy than the patients with the GG type (p=0.0448) in terms of recurrence of lung cancer. No significant association was observed between 3 other SNPs (-216G/T, D994D and R497K) and clinicopathological features. The EGFR 8227G/A polymorphism in intron 1 may be associated with clinical outcome in NSCLC patients treated with EGFR tyrosine kinase inhibitors.

IntroductionThere are a large number of global clinical trials ongoing for patients with non-small cell lung cancer (NSCLC). Ethnic difference in toxicity has not been adequately studied.MethodsWe performed a systematic search in PubMed for randomized phase II and III trials of NSCLC from January 2000 to December 2009, examining ethnic difference in hematological toxicity due to cytotoxic chemotherapy. Ethnicity was classified into Asian and non-Asian. We chose three treatment regimens used for NSCLC globally: cisplatin plus gemcitabine (CG), cisplatin plus vinorelbine (CV), and carboplatin plus paclitaxel (CP). We applied sensitivity analysis to examine unreported ethnic differences in hematological toxicities by changing the percentage of Asian patients from 0 to 18% in trials reported from the United States and Europe.ResultsWe identified 12 phase II trials and 38 phase III trials of NSCLC with a total of 11,271 patients. Among these, 14 trials had reported ethnic origins. Grade 3/4 toxicities were more frequently observed in the Asian studies. On the basis of sensitivity analysis, odds ratio of grade 3/4 neutropenia was significantly higher in Asian patients than non-Asian, when treated with CG (OR = 1.55–3.45, p < 0.001), CV (OR = 2.99–4.43, p < 0.001), and CP (OR = 4.79–6.22, p < 0.001). Grade 3/4 anemia was also significantly higher in Asians with CG (OR = 3.10–3.27, p < 0.001), CV (OR = 1.99–2.43, p < 0.001), and CP (OR = 1.34–1.52, p < 0.001–0.004). However, no significant difference was observed in thrombocytopenia with CG (OR = 0.66–2.04, p < 0.001–1.000), CV (OR = 0.42–0.57, p = 0.097–0.323), or CP (OR = 1.21–1.39, p = 0.114–0.152).ConclusionsSevere hematological toxicity was frequently observed in Asian patients compared with non-Asian (mostly whites) in the treatment of chemotherapy for NSCLC.

OBJECTIVE Elderly patients prefer to receive less-toxic therapy. Monotherapy using drugs such as vinorelbine, gemcitabine or docetaxel is a preferable chemotherapy in elderly patients with advanced non-small-cell lung cancer. Gefitinib shows remarkable efficacy in patients with advanced non-small-cell lung cancer, who have activating epidermal growth factor receptor mutations. Adenocarcinoma histology is related to these mutations. Therefore, we conducted a phase II study of gefitinib as a first-line therapy in elderly patients with pulmonary adenocarcinoma. METHODS Eligible patients were 70 years or older, had pulmonary adenocarcinoma, stage IIIB or IV disease, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions. Patients were treated with oral gefitinib 250 mg daily until disease progression or unacceptable toxicity. RESULTS Thirty-one patients were enrolled, of whom 30 were eligible. The median age was 78.5 years. The response rate was 20%, the disease control rate was 47%, the median progression-free survival was 2.7 months and the median overall survival was 11.9 months. Narrowing it down to those who had never smoked, the response rate increased to 43%, the disease control rate increased to 57%, the median progression-free survival prolonged to 7.1 months and the median overall survival prolonged to 13.0 months. The most frequent toxicity was rash. Other major toxicities were diarrhea, anorexia, liver dysfunction and anemia. These toxicities were mild and easily managed. CONCLUSIONS Gefitinib as a first-line therapy is active and well tolerated in elderly patients with pulmonary adenocarcinoma, especially in those who have never smoked.

Small molecule inhibitors targeting epidermal growth factor receptor (EGFR) are known to be active against non-small cell lung cancer (NSCLC) although the pharmacodynamics of these agents on malignant pleural effusion (MPE) remains unclear. Here we describe a case of lung adenocarcinoma with massive MPE treated successfully by gefitinib and chest drainage. Using sequential MPE samples before and during gefitinib therapy, the morphological changes and apoptosis of cancer cells were analyzed. Apoptosis of cancer cells was detected as early as 4 hours on, but not before, gefitinib therapy, suggesting that the pharmacodynamic assessment of such molecular targeting agents might be feasible for MPE.

Purpose We conducted a phase I trial of the topoisomerase I inhibitor topotecan for the purpose of determining the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of topotecan when administered weekly to patients with advanced non–small-cell lung cancer. Patients and Methods Twelve patients with stage IIIB or IV disease were treated with topotecan by 30-minute intravenous infusion on days 1, 8, and 15 every 4 weeks. The dose was escalated in 2-mg/m 2 increments from the starting dose of 4 mg/m 2 until the MTD was reached. After the MTD had been reached in previously treated patients, chemotherapy-naive patients were enrolled for treatment at that dose, and the dose was escalated to estimate the MTD in the treatment-naive group. Results The MTD of topotecan was determined to be 6 mg/m 2 in the previously treated group and 8 mg/m 2 in the chemotherapy-naive group. All 3 previously treated patients experienced DLT at the 6-mg/m 2 dose level. Although only 1 of the 3 previously treated patients experienced DLT (grade 4 neutropenia for ≥ 3 days) at the 8-mg/m 2 dose level, skipping the topotecan dose on day 15 because of neutropenia was reported in 2 patients. Anorexia and general fatigue were the common nonhematologic toxicities. Conclusion The recommended dose of topotecan for phase II studies in previously untreated patients is 6 mg/m 2 on days 1, 8, and 15, every 28 days, and 4 mg/m 2 appears to be a suitable dose for use in previously treated patients with this schedule.

遺伝性球状赤血球症は赤血球の膜異常に起因する疾患で，溶血性貧血，黄疸および脾腫を呈する．治療として中等度～重症例に対し脾臓摘出術が施行されるが，脾組織の散布による異所性脾や残存副脾による再燃がまれに問題となる．今回，我々は脾臓摘出17年後に骨盤内副脾腫大にて再燃し，腹腔鏡下副脾摘出術を施行した遺伝性球状赤血球症の1例を経験したため報告する．症例は21歳の女性で，4歳時に遺伝性球状赤血球症および胆石症に対し脾臓摘出，胆嚢摘出術を受けている．術後17年目に黄疸の再燃にて当院血液内科を受診し，腹部骨盤CTにて骨盤内に8 cm大の腫瘤を指摘され，脾シンチグラムにて同部位に集積を認めた．骨盤内副脾腫大による遺伝性球状赤血球症の再燃と診断され，腹腔鏡下副脾摘出術が施行された．患者は術後6日目に軽快退院した．本疾患は副脾の存在にて，術後数年以上経過してからも再燃の可能性があることを念頭においたフォローアップが必要である．

Objective: The aim of this study was to investigate the safety, pharmacokinetic and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte colony-stimulating factor, in lung cancer patients with chemotherapy-induced neutropenia. Methods: Eighteen Japanese lung cancer patients who had experienced severe neutropenia (absolute neutrophil counts ,0.5 � 10 9 cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 mg/kg). Patients received the same chemotherapy regimen as in their previous cycle and pegfilgrastim was injected subcutaneously the day after chemotherapy ended in each treatment cycle. Pharmacokinetic, pharmacodynamic and safety analyses were performed. Results: Dose-limiting toxicity and serious adverse events related to pegfilgrastim were not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum serum concentrations and area under the serum concentration‐time curves of pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1 patient (5.5%) required rescue treatment by filgrastim. Conclusions: A single dose of pegfilgrastim increases the serum concentration of pegfilgrastim for several days in a dose-dependent manner and is not associated with significant toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia was observed at all dose levels. Based on these data, further studies are warranted to determine the recommended dose of pegfilgrastim for Japanese patients with chemotherapy-induced neutropenia.

Introduction The aim of this study was to determine and evaluate the recommended dose of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 and evaluate the efficacy and safety in patients with previously treated non-small cell lung cancer. Methods In phase I, patients with previously treated non-small cell lung cancer were treated with docetaxel (starting dose 40 mg/m 2 ) intravenously on day 1 and oral administration of S-1 at a fixed dose of 80 mg/m 2 on days 1 to14 every 3 weeks. The recommended dose was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II. Results The recommended dose of docetaxel was 40 mg/m 2 in combination with S-1 80 mg/m 2 /d. Of 30 patients enrolled in phase II part, 29 patients were eligible and analyzed. No complete response and 7 (24.1%) partial responses were observed, for an overall response rate of 24.1% (95% confidence interval, 10.3-43.5%). Median overall survival was 11.8 months. The 1-year survival rate was 42%. The grade 3 to 4 hematologic toxicities were neutropenia (34.5%), leukopenia (20.6%), and anemia (10.3%). The grade 3 to 4 nonhematological toxicities included fever 2 (6.9%), diarrhea 1 (3.4%), stomatitis 1 (3.4%), cerebral infarction 1 (3.4%), and pneumonitis 1 (3.4%). There was one treatment-related death due to relapse of drug induced pneumonitis. Conclusions This combination chemotherapy is highly active and well tolerated in previously treated patients with non-small cell lung cancer. These results are encouraging and warrant additional investigation.

It has been reported that the R497K polymorphism of the epidermal growth factor receptor (EGFR) gene has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. On other hand, EGFR gene mutations at kinase domain in non-small cell lung cancer (NSCLC) have been examined for their ability to predict sensitivity to gefitinib or erlotinib.We investigated the EGFR mutations and/or R497K polymorphism statuses in 225 surgically treated NSCLC cases. 192 adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of exon 13 was analyzed by PCR-RFLP method.EGFR mutations at kinase domain were found from 95 of 225 lung cancer patients. In 86.2% of patients, homo- or heterozygous Lys497 allele was present. No correlation existed between R497K EGFR genotype and clinico-pathological features, such as gender, smoking status, and pathological subtypes.EGFR mutation status was not correlated with R497KEGFR genotype of lung cancers. In node-negative patients, R497KEGFR genotype was not correlated with disease outcome. In node-positive patients, however, R497K EGFR was significantly associated with better overall survival. This association was attributable to neo-adjuvant or adjuvant chemotherapy. In 46 total gefitinib treated NSCLC patients, the prognosis was not different between the EGFR wild type (GG) patients and AG+AA patients. R497KEGFR polymorphism might be associated with favorable prognosis of advanced lung cancers and correlated with chemosensitivity.

Background Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC), and some common somatic mutations in EGFR have been examined for their ability to predict sensitivity to gefitinib or erlotinib. However, EGFR mutations at exon 20 have been reported to predict resistance to gefitinib therapy. Materials and methods We investigated the EGFR mutations and/or polymorphism statuses at kinase domain in 303 surgically treated non-small cell lung cancer (NSCLC) cases. One hundred ninety-four adenocarcinoma cases were included. The presence or absence of EGFR polymorphism of kinase domains was analyzed by direct sequences. We have also investigated EGFR polymorphism status at exon 20 for 23 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. Results EGFR mutations at kinase domain were found in 75 of 303 lung cancer patients. During sequencing of EGFR tyrosine kinase domain in tumors, 86 EGFR polymorphism (G2607A) cases were identified at exon 20. G2067A polymorphism was significantly higher in nonadenocarcinomas (37.4%) than in adenocarcinoma (25.3%, P = 0.0415). The polymorphism status did not correlate with gender, smoking (never smoker versus smoker), and EGFR mutations. In 46 total gefitinib treated NSCLC patients, there was a tendency toward better prognosis in EGFR wild type (GG) patients than AG + AA patients. EGFR polymorphism in Japanese lung cancers seemed to be less frequent than Caucasian lung cancers. Conclusions EGFR-tyrosine kinase polymorphism might be associated with clinicopathological background of lung cancers.

von Recklinghausen病 (VRD) に小腸GISTおよび褐色細胞腫を合併した症例を経験した. 症例は30歳時にVRDと診断された33歳, 女性. 顔色不良および腹痛を訴え産婦人科受診. CT上, 骨盤内に石灰化を伴う13cm大の腫瘍, 左副腎に3cm大の腫瘍を認めた. 精査にて骨盤内腫瘍はGISTの疑い, 左副腎腫瘍は褐色細胞腫と診断され, 当科へ転科後手術が施行された. 骨盤内の腫瘍は空腸が起始部であり, 小腸部分切除, さらに左副腎摘出術を施行した. 小腸腫瘍は病理学的に悪性GISTの診断, また副腎の褐色細胞腫にも悪性を示唆する所見を認めた. 術後1年現在再発を認めていない. VRDに合併した複数の悪性腫瘍の報告が散見され, 予後に関与する可能性があるため, 早期発見のための全身検索が重要であると考える.

症例は21歳, 男性. 労災事故にて左前胸部と右背部に鈍的外傷を受傷し他院に救急搬送. CTにて外傷性肝腎損傷があったため当院に救急搬送された. CT上, 受傷数時間での肝被膜下血腫の増大はあったものの, 全身状態, 血液検査データに著変なく経過観察とした. 受傷3日目に肝被膜下血腫の急速な増大を認め肝腎不全となったが, ヨード造影剤を用いた血管造影でAP shunt (arterioportal shunt) の存在は示唆されたものの出血部位の同定がされなかったためTAE (transcatheter arterial embolization) は施行せず輸血やCHDF (continuous hemodiafiltration) などの保存的治療を行い, その後徐々に軽快をみせた. 外傷性肝損傷において, 被膜下血腫増大による肝不全例, また被膜下血腫症例に対するTAEの報告は非常に稀であるが, 本症例の場合, 炭酸ガスDSA (digital subtraction angiography) も含めた早期の血管造影・IVR (interventional radiology) により被膜下血腫増大を防げた可能性もあったのではないかと考えられた.

Background. Univariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS). Methods. A literature-based meta-analysis of PFS outcomes as measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, and EGFR TKI were obtained. Comparison of the pooled HR was performed by metaregression analysis. Results. Among the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HR for PFS was 0.29 (95% confidence interval [CI]: 0.21–0.39) for never-smokers and 0.54 (95% CI: 0.38–0.76) for ever-smokers (p < .007 by metaregression). The pooled PFS HR for exon 19 deletion was 0.25 (95% CI: 0.19–0.31) and 0.44 for exon 21 substitution (95% CI: 0.34–0.57) (p < .001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24–0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28–0.84) (p = .261 by metaregression analysis). Conclusion. EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis.

One of the most common morbidities of pancreaticoduodenectomies is delayed gastric emptying (DGE). The recent advent of subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) attempts to lessen this troublesome complication; however, the incidence of DGE still remains to be 4.5–20 %. This study aims to evaluate whether the incidence of DGE can be reduced by the side-to-side gastric greater curvature-to-jejunal anastomosis in comparison with the gastric stump-to-jejunal end-to-side anastomosis in SSPPD. Between October 2007 and September 2012, a total of 160 consecutive patients who had undergone SSPPD were analyzed retrospectively. In the first period (October 2007–March 2010), gastrojejunostomy was performed with end-to-side anastomosis in 80 patients (SSPPD-ETS group). In the second period (April 2010–September 2012), gastrojejunostomy was performed with the greater curvature side-to-jejunal side anastomosis in 80 patients (SSPPD-STS group). The postoperative data were collected prospectively in a database and reviewed retrospectively. The incidence of DGE was 21.3 % in the SSPPD-ETS group and 2.5 % in the SSPPD-STS group (P = 0.0002). According to the classification of the International Study Group of Pancreatic Surgery (ISGPS), the incidence of DGE of grades A, B, and C were 5, 5, and 7 in the SSPPD-ETS group and 0, 2, and 0 in the SSPPD-STS group, respectively. The overall morbidity and postoperative hospital stay of the two groups were not significantly different. The greater curvature side-to-side anastomosis of gastrojejunostomy is associated with a reduced incidence of DGE after SSPPD.

Purpose We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE. Patients and Methods Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle. Results Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%). Conclusion EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.

Objectives: The combination of irinotecan and cisplatin given every 4 weeks is one of the standard treatments for advanced nonsmall-cell lung cancer (NSCLC) in Japan. The purpose of this study is to evaluate the efficacy, safety and dose-intensity as a measure of the feasibility of 3-week scheduling of irinotecan and cisplatin in patients with advanced NSCLC in phase II study. Methods: Previously untreated patients with stage IIIB and IV NSCLC were treated intravenously with irinotecan (60 mg/m2) on days 1 and 8 and cisplatin (60 mg/m2) on day 1 of a 3-week cycle. Results: Of the 28 patients enrolled, 27 were evaluable for response and toxicity. The response rate was 30% (95% confidence interval, 14–50%). The median duration of response was 16 weeks (range, 10–26 weeks). The median survival time for all patients was 52 weeks and the 1-year and 2-year survival rates were 48% and 29%, respectively. The dose-intensity of irinotecan was 34 mg/m2/wk (range, 19–40). The major toxicities observed were neutropenia (grade 3, 30%; 4, 30%), leukopenia (grade 3, 30%), and diarrhea (grade 3, 22%). Other toxicities were generally mild. Conclusions: Three-week scheduling of irinotecan and cisplatin is effective and feasible in advanced NSCLC.

Purpose Docetaxel has shown activity in elderly patients with advanced non–small-cell lung cancer (NSCLC). This randomized phase III trial evaluated the efficacy and safety of docetaxel versus vinorelbine (the current standard treatment) in elderly patients. Patients and Methods Chemotherapy-naïve patients age 70 years or older with stage IIIB/IV NSCLC and performance status 2 or lower were eligible. Patients randomly received docetaxel 60 mg/m2 (day 1) or vinorelbine 25 mg/m2 (days 1 and 8) every 21 days for four cycles. The primary end point was overall survival. Overall disease-related symptom improvement was assessed using an eight-item questionnaire. Results In total, 182 patients were enrolled. Median age was 76 years (range, 70 years to 86 years). There was no statistical difference in median overall survival with docetaxel versus vinorelbine (14.3 months v 9.9 months; hazard ratio, 0.780; 95% CI, 0.561 to 1.085; P = .138). There was a significant difference in median progression-free survival (5.5 months v 3.1 months; P < .001). Response rates were also significantly improved with docetaxel versus vinorelbine (22.7% v 9.9%; P = .019). The most common grade 3 to 4 toxicities were neutropenia (82.9% for docetaxel; 69.2% for vinorelbine; P = .031) and leukopenia (58.0% for docetaxel; 51.7% for vinorelbine). Other toxicities were mild and generally well tolerated. Docetaxel improved overall disease-related symptoms over vinorelbine (odds ratio, 1.86; 95% CI, 1.09 to 3.20). Conclusion Docetaxel improved progression-free survival, response rate, and disease-related symptoms versus vinorelbine. Overall survival was not statistically significantly improved at this time. Docetaxel monotherapy may be considered as an option in the standard treatment of elderly patients with advanced NSCLC.

The benefits established in efficacy trials, usually randomized, controlled trials conducted under highly controlled circumstances with maximized internal validity, can frequently not be demonstrated in clinical practice at the community level. Effectiveness trials are tools to evaluate the applicability of a treatment in a wider setting with maximized external validity, to observe uncommon adverse events, and to identify factors influencing the main outcomes and risks. Important areas in relation to lung cancer treatment that will benefit from effectiveness trials include gefitinib monotherapy and bevacizumab therapy combined with cytotoxic chemotherapy for advanced non-small cell lung cancer. These therapies were found to produce life-threatening nonhematologic toxicity at a high incidence of up to 5%; however, the risk factors for these toxicities have not yet been fully established. Effectiveness trials of adjuvant chemotherapy after surgery with long-term follow-up are also important to obtain reliable information as to secondary malignancy and noncancer-related deaths. Development of an infrastructure for effectiveness trials is crucial because of the necessity to deal with large numbers of patients, sometimes as many as 10,000 patients, from many hospitals. The extensive research time involved and the considerable cost of these trials may be reduced with the use of Internet resources. Effectiveness trials are a fundamental step toward bridging the gap between clinical research and clinical practice and effectively implementing new therapies in clinical practice.

BACKGROUND. Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS. One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS. Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS. Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study. Cancer 2006. © 2006 American Cancer Society.

患者は36歳,女性. 2002年より潰瘍性大腸炎の診断に至り内科的治療をしていた. 2004年に入り潰瘍性大腸炎の再燃と自己免疫性溶血性貧血を合併し,内科的治療では悪化し,大量下血を伴い外科的治療となった.準緊急的に潰瘍性大腸炎と自己免疫性溶血性貧血に対して1期目に用手補助腹腔鏡下(HALS)脾摘・大腸亜全摘,回腸瘻造設, S状結腸瘻増設術を施行し, 2期目に腹腔鏡補助下に残存大腸全摘術,回腸嚢肛門管吻合術を施行した.若年の重症型の潰瘍性大腸炎症例に対して準緊急手術であったがHALSにて安全に施行でき, 2期目の腹腔鏡手術につなげることができたので整容的にも優れた方法と思われたので報告する.

Much evidence has accumulated that the epidermal growth factor receptor (EGFR) and its family members are strongly implicated in the development and progression of lung cancers. Somatic mutations of the EGFR gene were found in about 25–40% of Japanese lung cancer patients. More recently, erbB2 mutations are found in about 4% of European-derived lung cancer patients. We have investigated EGFR and erbB2 mutation status in 95 surgically treated nonsmall cell lung cancer (NSCLC) cases from Nagoya City University Hospital. Seventy-five adenocarcinoma cases were included. The presence or absence of EGFR and ernB2 mutations of kinase domains were analyzed by reverse transcription polymerase chain reaction (RT-PCR) amplifications and direct sequences. We have also investigated erbB2 mutation status in 27 surgically treated NSCLC cases followed by treatment with gefitinib from Kinki-chuo Chest Medical Center. EGFR mutations (CTGfiCGG; L858R) were found from 14 of 95 lung cancer patients. We also detected the deletion 1a-type mutations from 9 patients and deletion 4-type mutations from 6 patients in exon 19. In exon 20, 4 mutations including 2 novel mutations were found. Total EGFR mutations were present in 35 patients (36.8%). These mutation statuses were significantly correlated with gender (women 73.3% vs. men 20%, p < 0.0001), smoking status (never smoker 69.4% vs. smoker 16.9%, p < 0.0001), pathologic subtypes (adenocarcinoma 45.1% vs. nonadenocarcinoma 12.5%, p 5 0.0089) and differentiation status of the lung cancers (well 51% vs. moderately or poorly 18.4%, p 5 0.0021). On the other hand, erbB2 mutation was only found from 1 of 95 patients, at exon 20. This patient was female and a never smoker with adenocarcinoma. This 12 nucleotide insertion mutation (2324–2325 ins ATACGTGATGGC) was located in the exon 20 at kinase domain (775–776 ins YVMA). There was no erbB2 mutation in 27 gefitinib-treated NSCLC patients. In total, we have found only 1 erbB2 mutation from 122 (0.8%) Japanese NSCLC patients. There was a significantly higher erbB2 positive (21/31) ratio in EGFR mutant patients (13/25, 52.0%) compared to EGFR wild-type patients (10/ 62, 16.1%; p 5 0.0247). The NSCLC specimen with erbB2 mutation showed 11 immunoreactivity. The EGFR mutation status might correlate with the clinicopathologic features related to good response to gefitinib, such as gender, smoking history and pathologic subtypes of lung cancers. However, erbB2 mutation is rare from Japanese lung cancer and is of limited value for molecular target therapy. ' 2005 Wiley-Liss, Inc.