A single-center retrospective analysis of the efficacy and safety of a modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting agents as second-line chemotherapy in Japanese patients with recurrent or nonresectable colorectal cancer.

Background: As the second-line chemotherapy for stage IV recurrent or nonresectable colorectal cancer, our hospital started a modified treatment regimen comprising of irinotecan plus S-1 (IRIS) [tegafur/gimeracil/oteracil (S-1)] plus molecular targeting agents (MTAs), i.e., an epidermal growth factor receptor (EGFR) inhibitor such as panitumumab (P-mab) or cetuximab (C-mab) or vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab (B-mab) since October 2012. The purpose of this study is to evaluate the efficacy and safety of this modified regimen. Methods: This retrospective study included 41 patients with advanced recurrent colorectal cancer at our hospital whom at least 3 courses of chemotherapy were conducted from January 2015 to December 2021. Based on the location of the primary tumor, patients were classified into two group (right-sided group, proximal to the splenic curve, and left-sided, distal to the splenic curve). We assessed archived data on RAS and BRAF status and UGT1A1 polymorphisms and use of the VEGF inhibitor bevacizumab (B-mab) and the EGFR inhibitors panitumumab (P-mab) and cetuximab (C-mab). In addition, progression-free survival rate (36M-PFS) and the overall survival rate (36M-OS) were calculated. Furthermore, the respective median survival time (MST), the median number of treatment courses; the objective response rate (ORR) and clinical benefit rate (CBR) and the incidence of adverse events (AEs) were assessed as well. Results: There were 11 patients (26.8%) in the right-sided group, and 30 patients (73.2%) in the left-sided group. There were 19 patients with RAS wild type (46.3%) (1 in the right sided group and 18 in the left sided group). P-mab was used for 16 of these patients (84.2%), C-mab for 2 (10.5%), and B-mab for 1 (5.3%); the remaining 22 patients (53.7%). Ten patients in the right group and 12 patients in the left group were a mutated type and received B-mab. BRAF testing was performed in 17 patients (41.5%); as more than 50% of patients (58.5%) were included before the assay's introduction. Five patients in the right-sided group and 12 patients in the left-sided group had wild type. There was no mutated type. UGT1A1 polymorphism was tested in 16/41 patients: Eight were wild type (8/41 patients, 19.5%) and 8, mutated type. Regarding the *6/*28 double heterozygous type, there was only 1 patient in the right-sided group and the remaining 7 patients were in the left-sided group. The total number of chemotherapy courses was 299, and the median number, 6.0 (range, 3-20). PFS, OS, and MST were as follows: 36M-PFS (total/Rt/Lt), 6.2%/0.0%/8.5% (MST; 7.6/6.3/8.9 months); and 36M-OS (total/Rt/Lt), 32.1%/0.0%/44.0% (MST; 22.1/18.8/28.6 months). The ORR and CBR were 24.4% and 75.6%, respectively. The majority of AEs were grades 1 or 2 and were improved with conservative treatment. Grade 3 leukopenia was observed in 2 cases (4.9%), neutropenia in 4 cases (9.8%), and malaise/nausea/diarrhea/perforation in 1 case each (2.4%). Grade 3 leukopenia (2 patients) and neutropenia (3 patients) were more commonly observed in the left-sided group. Diarrhea and perforation were also common in the left-sided group. Conclusions: This second-line modified IRIS regimen with MTAs is safe and effective and results in good PFS and OS.

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer.

Background: From 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients). Methods: Data were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared. Results: Baseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80-92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80-88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027). Conclusions: Approximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.

Severe Sacral Region Pressure Ulcer Infection Treated in Negative Pressure Wound Therapy with Instillation and Dwelling: A Case Report.

We report a case of severe sacral osteomyelitis and sepsis with pressure ulcer infection treated with negative pressure wound therapy with instillation and dwelling (NPWTi-d) V.A.C.ULTA® from an early stage. Case: A 76-year-old man, bedridden because of dementia and an old cerebral infarction, was treated in a nursing facility for a sacral region pressure ulcer. He had a fever for three days and was transferred to the emergency department. The quick SOFA (sequential organ failure assessment) score at the hospital visit was three points. A coccyx and black mud-formed necrotic tissue attached to the sacral region pressure ulcer with a strong putrid odor sloughed off. Sacral region pressure ulcer infection, sepsis, disseminated intravascular coagulation, and purulent sacral osteomyelitis were diagnosed, and urgent debridement was performed. We treated the patient with meropenem, clindamycin, and vancomycin, and we performed irrigation debridement every day and transduced the V.A.C.ULTA® care system from AOD9, that led to good granulation at the infection site. The wound area underwent simple closure on AOD35 and the patient was transferred to the medical treatment hospital. Since dressing change is relatively easy in the emergency department of a secondary medical care institution with little man power, V.A.C.ULTA® therapy may be useful in treating severe cases of pressure ulcer infections.

Characteristic of the acute drug intoxication conveyed by Kanagawa helicopter emergency medical service.

Aim: Various critical cases have been transported since the use of the Kanagawa Helicopter Emergency Medical Service (HEMS) started at Tokai University Hospital (Isehara, Japan) in 2002, including cases of acute poisoning. We analyzed the characteristics of acute poisoning cases conveyed by the HEMS. Methods: Kanagawa HEMS conveyed 3,814 cases from July 2002 to March 2013, and acute drug and poison intoxication was diagnosed in 131 of these cases. We undertook a descriptive statistical study of these cases. Results: The causative agent was found to be psychiatric prescription drugs in 39.7% of cases, pesticides in 29.7%, alcohol in 8.4%, analgesics in 5.3%, detergent or bleach in 6.1%, oil, natural gas, or thinner in 4.6%, and others in 6.1%. At HEMS contact, systolic blood pressure was less than 90 mmHg in 18.3% of cases, and 40.2% were in coma. Endotracheal intubation was carried out in 44.5% of cases, and 6.9% died within 24 h of hospital admission. The cases of poisoning that we transported in the HEMS were often in shock and/or coma on arrival at the field, and rapid endotracheal intubation was required in nearly half of them, as many were in a serious condition. Conclusion: We believe that outcomes were more likely to be improved by appropriate early treatment by the HEMS. It will be necessary to further compare the ambulance service with the HEMS to evaluate their efficacy in the future.

Comparison of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy in patients with colorectal cancer: Final results from a single center.

In recent years, the use of laparoscopic surgery has been expanded to include radical curative resection. In a previous study, 212 patients with primary colorectal cancer (stages I-III) underwent radical curative resection by hand-assisted laparoscopic surgery (HALS) (n=98) or conventional laparotomy (CL) (n=114) and were compared with respect to 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS). The study included 210/212 patients who were followed up to 5 years, including 96 patients who underwent HALS and 114 treated with CL. The two groups were matched for stage, clinical background, and postoperative management. Patient characteristics were compared and the 5Y-RFS and 5Y-OS were determined. The 5-year follow-up rate was 97.6%. In stage I-III patients, 5Y-RFS and 5Y-OS showed no significant differences between HALS and CL. The patients with stage I disease accounted for 41.7% (40/96) of the patients undergoing HALS, while stage I patients only accounted for 23.7% (27/114) of the patients undergoing CL, and the difference was significant (P=0.005). Stage II patients undergoing CL were older than those treated with HALS (P=0.017). However, there were no differences in the characteristics of stage III patients undergoing HALS or CL. In conclusion, HALS achieved a similar survival to CL in patients with stage I to III colorectal cancer. Compared with CL, HALS was performed more safely and achieved superior cosmetic results.

A Prospective, Single-Arm, Single-Center, Case Series to Determine the Feasibility of Safe Skill Transfer for Transabdominal Preperitoneal (TAPP) Repair Utilizing a Hands-On Mentorship Model.

OBJECTIVES: It is difficult to introduce laparoscopic surgery in institutions with a small number of patients, and surgical training relies heavily on mentors to produce well-trained surgeons. The aim of this study was to determine whether implementation of a hands-on mentorship model could provide safe skill transfer for transabdominal preperitoneal (TAPP) repair. METHODS: A trainee who had no experience with TAPP repair underwent operative tutorials until the mentor judged that the trainee could carry out the operation independently. Ten patients who underwent an elective TAPP repair were prospectively enrolled in this study. RESULTS: No cases had over 5 mL of bleeding, intraoperative/postoperative complications, or recurrence. There were significant differences in operation times between the first 4 cases and the later 5 cases, except for a bilateral inguinal hernia case. CONCLUSION: A prospective, single-arm, single-center, case series showed the feasibility of safe skill transfer for TAPP repair using a hands-on mentorship model.

The first case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis.

We report a rare case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis. This appears to represent the first report of amebic intra-abdominal tumor. A 31-year-old woman presented to a local doctor with only a sensation of abdominal fullness. Abdominal computed tomography (CT) showed a huge intra-abdominal tumor in the left abdominal cavity, and she was referred to our hospital. Colonofiberscopy for detailed examination showed multiple slight, discrete ulcers in the cecum. Ameboid trophozoites were identified from biopsy specimens, and asymptomatic amebic colitis was diagnosed. Oral metronidazole (MTZ) was administered at 1500 mg/day for 10 days. CT 14 days after starting MTZ showed no change in the intra-abdominal tumor, and resection of the tumor was therefore performed. Pathological examination revealed Entamoeba histolytica with engulfed erythrocytes complicated by hemorrhagic cyst. If an intra-abdominal tumor is present and colitis is observed, amebic intra-abdominal tumor should be considered among the differential diagnoses.

Comparison of hand-assisted laparoscopic surgery and conventional laparotomy for rectal cancer: Interim results from a single center.

Minimally invasive laparoscopic surgery has become widespread and the indications for such surgery have recently been extended to various conditions, including rectal cancer. The objective of this study was to compare the clinical outcome of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy (CL) in patients with rectal cancer. Patients who underwent radical resection of stage I-III primary rectal cancer (n=111) were classified into those receiving HALS (n=57) and those receiving CL (n=54); the two groups were matched for stage and postoperative treatment. The 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS) were calculated and compared between the two groups. Intraoperative blood loss, operating time, postoperative hospital stay and complications were also compared between the two groups. There were no significant differenceS in 3Y-RFS or 3Y-OS between the HALS and CL groups for patients with all-stage (I, II and III) rectal cancer. The mean (median) intraoperative blood loss was 344.0 (247.0) ML in the HALS group vs. 807.5 (555.5) ML in the CL group (P<0.001). The mean (median) postoperative hospital stay was 19.8 (17) and 25.5 (18.3) days, respectively (P=0.039). There were no significant differences in the operating time or the incidence of complications between the two groups. Based on these results, HALS was found to be comparable to CL regarding survival, while achieving less blood loss and a superior cosmetic outcome. However, longer follow-up is required to confirm these findings.

Comparison of hand-assisted laparoscopic surgery and conventional laparotomy for colorectal cancer: Interim results from a single institution.

The present study aimed to compare the results of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy (CL) at a single institution in Japan. Of the 212 patients with stage I/II/III colorectal cancer who received a curative resection, 98 patients underwent HALS and 114 patients underwent CL. The clinical background and post-operative management did not differ between the two groups. There were no significant differences in the 3-year relapse-free and 3-year overall survival rates between the HALS and CL groups for the patients in any stage. Blood loss during surgery was 250.1 and 135.5 ml (mean and median; the same hereafter) in stage I patients receiving HALS versus 608.2 and 315.5 ml in stage I CL patients (P=0.006), while it was 277.6 and 146 ml in stage II patients receiving HALS versus 548.6 and 347 ml in stage II CL patients (P=0.004). Post-operative hospital stay was recorded at 16.8 and 15 days in stage III patients receiving HALS versus 23.1 and 21 days in stage III CL patients (P=0.001). There were no significant differences in the operating time or complications between the two groups. These results indicate that the survival rate was comparable for HALS and CL, while HALS caused less surgical stress and achieved a better cosmetic outcome. The results of the final analysis of this cohort are awaited.

Characteristics of elderly Japanese patients with severe burns.

In this study, we report the clinical characteristics of elderly Japanese patients with severe burns. We studied the clinical features of 76 adult patients with severe burns, 35 of whom (46.1%) were ≥65 years old. We evaluated the characteristics of patients with respect to each type of burn. In addition, we studied the rate of death and survival in the elderly and also between the elderly and non-elderly patients. The following parameters were either assessed or compared between the elderly and non-elderly: gender, average age, vital signs (Glasgow Coma Scale, systolic blood pressure, heart rate and respiratory rate) and PaO(2)/FiO(2) (P/F) ratio at admission, cause of burn and a history of physical or psychiatric disease. Further, we investigated whether the burn was caused by attempting suicide and determined the percent total body surface area (%TBSA), second- and third-degree burn area, burn index (BI), prognostic burn index (PBI), presence of tracheal burns, presence of alcohol intoxication and overdose poisoning, presence of tracheal intubation, outcome and cause of death. The male:female ratio of the elderly patients was 17:18 (average age, 78.1 (8.2) years). Burns were mostly caused by flame (26/35), followed by scalding (8/35). Ten patients had attempted suicide. The %TBSA, second-degree burn area, third-degree burn area, BI and PBI, respectively were 46.6% (26.7%), 15.3% (19.0%), 35.6% (26.0%), 41.1 (25.2) and 119.2 (25.9). Of the 35 patients, 23 died. The notable characteristics of the elderly patients who died were flame as the cause of the burns: high %TBSA, BI and PBI, and a high rate of tracheal intubation. Elderly patients constituted approximately 45% of our study population. Most burns were caused by flames. The incidence of accidental bathtub-related burns was higher and that of suicide attempts was lower in the elderly patients, as compared with the non-elderly patients. Severe burns were fatal for elderly patients. Therefore, elderly Japanese people should be educated on how to prevent non-intentional burns.

A 92-year-old man with retropharyngeal hematoma caused by an injury of the anterior longitudinal ligament.

Traumatic retropharyngeal hematoma is a rare condition and may be lethal in some cases. In patients with this condition, the absence of a vertebral fracture or a major vascular injury is extremely rare. We present the case of a 92-year-old man who hit his forehead by slipping on the floor in his house. He had no symptoms at the time; however, he experienced throat pain and dyspnea at 6 hours after the injury. On arrival, he complained of severe dyspnea; therefore, an emergency endotracheal intubation was performed. A lateral neck roentgenogram after intubation showed dilatation of the retropharyngeal and retrotracheal space and no evidence of a cervical vertebral fracture. Cervical computed tomography (CT) with contrast medium revealed a massive hematoma extending from the retropharyngeal to the superior mediastinal space but no evidence of contrast medium extravasation or a vertebral fracture. However, sagittal magnetic resonance imaging (MRI) revealed an anterior longitudinal ligament (C4-5 levels) injury. We determined that the cause of the hematoma was an anterior longitudinal ligament injury and a minor vascular injury around the injured ligament. Therefore, we recommend that patients with retropharyngeal hematoma undergo sagittal cervical MRI when roentgenography and CT reveal no evidence of injury.

Arterial embolization in patients with grade-4 blunt renal trauma: evaluation of the glomerular filtration rates by dynamic scintigraphy with 99mTechnetium-diethylene triamine pentacetic acid.

BACKGROUND: High-grade blunt renal trauma has been treated by arterial embolization (AE). However, it is unknown whether AE preserves renal function, because conventional renal function tests reflect total renal function and not the function of the injured kidney alone. Dynamic scintigraphy can assess differential renal function. METHODS: We performed AE in 17 patients with grade-4 blunt renal trauma and determined their serum creatinine (sCr) level and glomerular filtration rate (GFR; estimated by dynamic scintigraphy) after 3 months. In 4 patients with low GFR of the injured kidney (<20 ml.min-1.1.73 m-2), the GFR and sCr were measured again at 6 months. Data are presented as median and interquartile range (25th, 75th percentile). RESULTS: The median GFR of the injured kidney, total GFR, and median sCr at 3 months were 29.3 (23.7, 35.3) and 96.8 (79.1, 102.6) ml.min-1.1.73 m-2 and 0.6 (0.5, 0.7) mg/dl, respectively. In the patients with low GFR (ml.min-1.1.73 m-2), the median GFR of the injured kidney, total GFR, and median sCr (mg/dl) were 16.2 (15.7, 16.3), 68.7 (61.1, 71.6), and 0.7 (0.7, 0.9), respectively, at 3 months and 34.5 (29.2, 37.0), 90.9 (79.1, 98.8), and 0.7 (0.7, 0.8), respectively, at 6 months. CONCLUSIONS: The function of the injured kidney was preserved in all patients, indicating the efficacy of AE for the treatment of grade-4 blunt renal trauma.

Comparative study of nifekalant versus amiodarone for shock-resistant ventricular fibrillation in out-of-hospital cardiopulmonary arrest patients.

BACKGROUND: In Japan, intravenous nifekalant (NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation. METHODS AND RESULTS: Between August 2007 and April 2009, 403 consecutive out-of-hospital patients with cardiopulmonary arrest were transferred to the Emergency Medical Service of Tokai University. Of these, 30 patients with first defibrillation failure or VF recurrence were enrolled for this NIF/AMD study. The final defibrillation success (and hospital survival rate) was 67% (10/15) in the AMD and 47% (7/15) in the NIF group. The discharge survival rate was 53% (8/15) in the AMD and 21% (4/15) in the NIF group (P = 0.06). Notably, all 4 survivors in the NIF group could take up normal daily life again, whereas this was restricted to only 2 patients from the 11 survivors in the AMD group. The difference is probably partly attributable to longer time from AMD administration to defibrillation success compared with NIF. In the cases of defibrillation failure, VF continued in 4/8 by NIF, however, asystole or pulseless electrical activity occurred in 4/5 patients by AMD. CONCLUSIONS: AMD may be borderline superior over NIF to facilitate defibrillation in out-of-hospital patients with cardiopulmonary arrest. However, from the view point of preservation of brain function, NIF is not inferior to AMD for CPR.