Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well defined as a therapy for preventing diabetic polyneuropathies, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. Sodium zinc histidine dithiooctanamide (DHL-HisZn_Na) is a water-soluble substance, with strong antioxidant and anti-inflammatory properties, similar to α-lipoic acid with histidine bound to α-lipoic acid and zinc chelated with sulfur atoms. DHL-HisZn_Na slowly loses its stability under dry conditions in the dark and under refrigeration. Purification is essential for use after long-term storage. In this study, ethanol crystallization and suspension methods were utilized in development for the first time as purification methods for DHL-HisZn_Na.

Objective: This study evaluated the short-and long-term outcomes of laparoscopic colectomy versus open surgery in obese patients (body mass index >= 25 kg/m2) with locally advanced colon cancer to ascertain the non-inferiority of laparoscopic surgery to open surgery. Methods: In this large cohort study (UMIN-ID: UMIN000033529), we retrospectively reviewed prospectively collected data from consecutive patients who underwent laparoscopic or open surgery for pathological stage II-III colon cancer between 2009 and 2013. A comparative analysis was performed after propensity score matching between the laparoscopic and open surgery groups. The primary endpoint was the 3-year relapse-free survival (RFS). Results: We identified 1575 eligible patients from 46 institutions. Each group comprised 526 propensity score-matched patients. Comparing the laparoscopic versus open surgery group, laparoscopic surgery was significantly associated with increased median operating time (225 vs. 192.5 min; P < .0001) and decreased median estimated blood loss (20 vs. 140 ml; P < .0001). Lymph node retrieval (20 vs. 19; P = 0.4392) and postoperative complications (4.6% vs. 5.7%; P = 0.4851) were similar, postoperative hospital stay was shorter (10 vs. 12 days; P < .0001), and the 3-year RFS rates were similar (82.8 vs. 81.2%). The hazard ratio (HR) for relapse-free survival for laparoscopic versus open surgery was 0.927 (90% confidence interval [CI], 0.747-1.150, one-sided P for non-inferiority = .001), indicating that for obese patients with colon cancer, laparoscopic surgery was non-inferior to open surgery. Conclusion: Laparoscopic surgery in obese patients with colon cancer offers advantages in terms of short-term outcomes and no disadvantages in terms of long-term outcomes.

Postoperative pancreatic fistula (POPF) is a critical complication of laparoscopic gastrectomy (LG). However, there are no widely recognized anatomical landmarks to prevent POPF during LG. This study aimed to identify anatomical landmarks related to POPF occurrence during LG for gastric cancer and to develop an artificial intelligence (AI) navigation system for indicating these landmarks. Dimpling lines (DLs)—depressions formed between the pancreas and surrounding organs—were defined as anatomical landmarks related to POPF. The DLs for the mesogastrium, intestine, and transverse mesocolon were named DMP, DIP, and DTP, respectively. We included 50 LG cases to develop the AI system (45/50 were used for training and 5/50 for adjusting the hyperparameters of the employed system). Regarding the validation of the AI system, DLs were assessed by an external evaluation committee using a Likert scale, and the pancreas was assessed using the Dice coefficient, with 10 prospectively registered cases. Six expert surgeons confirmed the efficacy of DLs as anatomical landmarks related to POPF in LG. An AI system was developed using a semantic segmentation model that indicated DLs in real-time when this system was synchronized during surgery. Additionally, the distribution of scores for DMP was significantly higher than that of the other DLs (p < 0.001), indicating the relatively high accuracy of this landmark. In addition, the Dice coefficient of the pancreas was 0.70. The DLs may be used as anatomical landmarks related to POPF occurrence. The developed AI navigation system can help visualize the DLs in real-time during LG.

Although the short-term outcomes of bridge-to-surgery (BTS) procedures using self-expandable metal stents are favorable, concerns remain regarding worsened prognosis due to tissue injury in the tumor area. Herein, we describe a newly developed covered stent, the Kawasumi Jabara colonic stent™, designed to reduce tissue damage/injury associated with stent-related complications in BTS procedures. This study aimed to evaluate the efficacy and safety of the Kawasumi Jabara colonic stent as a BTS for obstructive colorectal cancer (OCC). This multicenter retrospective observational study included 44 OCC patients who underwent BTS with stents at four facilities between September 2020 and November 2022. The groups of patients receiving the Kawasumi Jabara and non-covered colonic stents were designated Groups C and NC, respectively. Treatment outcomes related to stent placement and surgery were compared using propensity score matching (PSM) analysis. Groups NC and C (n = 34 and 10, respectively) showed no significant differences in sex, age, tumor location, histological type, Colorectal Obstruction Scoring System (CROSS) score, or cStage; however, the stent placement duration was shorter in Group C. No significant differences were found in terms of the technical and clinical success rates for stent placement. Stent dislocation was observed in 0 and 2 cases in Groups C and NC, respectively. PSM analysis between eight cases, each from Groups C and NC, revealed no significant differences in stent-related or surgical outcomes between the groups. However, regarding the gross injury score in the resected specimens, Group C had a lower score than Group NC (1.8 vs. 5.5), and the proportion of pathological tissue injury involving deeper layers was also lower in Group C (37.5

Background:Laparoscopic surgery is reported to be useful in obese or elderly patients with colon cancer, who are at increased risk of postoperative complications because of comorbidities and physical decline. However, its usefulness is less clear in patients who are both elderly and obese and may be at high risk of complications. Methods:Data for obese patients (body mass index ≥25) who underwent laparoscopic or open surgery for stage II or III colon cancer between January 2009 and December 2013 were collected by the Japan Society of Laparoscopic Colorectal Surgery. Surgical outcomes, postoperative complications, and relapse-free survival (RFS) were compared between patients who underwent open surgery and those who underwent laparoscopic surgery according to whether they were elderly (≥70 y) or nonelderly (<70 y). Results:Data of 1549 patients (elderly, n = 598; nonelderly, n = 951) satisfied the selection criteria for analysis. Length of stay was shorter and surgical wound infection was less common in elderly obese patients who underwent laparoscopic surgery than in those underwent open surgery. There were no significant between-group differences in overall complications, anastomotic leakage, ileus/small bowel obstruction, or RFS. There were also no significant differences in RFS after laparoscopic surgery according to patient age. Conclusion:Laparoscopic surgery is safe in elderly obese patients with colon cancer and does not worsen their prognosis. There was no significant difference in the effectiveness of laparoscopic surgery between obese patients who were elderly and those who were nonelderly.

Constipation in children can be classified as transient or chronic and as functional or organic. Although most pediatric constipation is functional, organic constipation may be masked by a chronic course. We encountered a case of chronic constipation refractory to treatment with rectal fixation and subsequently diagnosed it as organic constipation. A 14-year-old boy experienced chronic constipation since 8 years of age, and used to attempt defecation for more than 1 h at a time. The symptoms did not improve with conservative treatment such as medications. Rectal contrast revealed that the rectum was flexed ventrally and separated from the sacrum, with dilatation of the intestine on the oral side. He was diagnosed with organic constipation due to insufficient fixation of the rectum to the sacrum, and underwent laparoscopic rectal fixation. Postoperative rectal contrast revealed that the rectum had traveled along the curved surface of the sacrum. Defecation remarkably improved after the surgery. In this case, chronic organic constipation occurred due to insufficient fixation of the rectum to the sacrum, and could be resolved by rectal fixation. We should recognize insufficient fixation of the rectum to the sacrum as one of the causes of chronic constipation, and treat childhood chronic constipation accordingly.

Introduction: 8K ultra-high-definition (UHD) images enabling clearer recognition of anatomical structures could contribute to further development of surgical techniques and advanced applications in endoscopic surgery fields. This study aimed to clarify effects and challenges of endoscopic surgery with 8K UHD endoscopy compared to existing endoscopy systems. Methods: In this multicenter, cross-sectional, questionnaire survey, data were collected from surgical participants who newly used and observed 8K UHD endoscopy in patients undergoing surgery from February 2020 to February 2021. Survey items included sense of presence, reality, depth perception, visibility of tissue, eyestrain, and degree of satisfaction for operators and observers, and weight, operability, focus adjustment, physical fatigue, eyestrain, and satisfaction for camera assistants. Participants rated each 8K UHD endoscopic surgery on a one-to-five scale (definitively inferior, relatively inferior, equivalent, relatively superior, definitively superior) compared to the existing endoscopy system of each facility. Results: Overall, questionnaire responses from 139 participants assessing 8K UHD endoscopic surgery were collected from surgeries performed in 46 patients. Respective ratings of operators and observers included sense of presence: "superior or relatively superior", 97.8% and 91.5%; reality: "superior or relatively superior", 76.1% and 72.3%; and visibility of tissue: "superior or relatively superior", 93.5% and 87.2%. Weight was rated as "inferior or relatively inferior" by 73.9% of camera assistants and focus adjustment as "inferior" by 60.9% of them. Conclusions: 8K UHD endoscopic surgery enabled identification of surgical anatomies more clearly, provided a sense of presence and reality, and might improve educational effect. Technological development is expected to reduce the burden of camera assistants.

BACKGROUND:Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC.METHODS:A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires.RESULTS:In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients' preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization.CONCLUSIONS:The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Chemotherapy-induced alopecia is frequently induced by various regimens of chemotherapy and has a significant impact on mental health and quality of life. However, the effect of available current treatment for chemotherapy-induced alopecia is not sufficient. This study aimed to clarify the therapeutic effects and mechanism of skin cooling and the antioxidant α-lipoic acid derivative on chemotherapy-induced alopecia. We developed a chemotherapy-induced alopecia model of cyclophosphamide (120 μg/g) using Institute of Cancer Research mice. We used cooling therapy and α-lipoic acid derivative application as the treatments. We compared the alopecia score, hair bulb diameter, insulin-like growth factor-1 level, vascular permeability, and apoptosis between the control and treatment groups. The alopecia score significantly improved in each treatment group compared with that in the cyclophosphamide group. Hair bulb diameter significantly improved in the cyclophosphamide + cooling group compared with that in the cyclophosphamide group. The insulin-like growth factor-1 level and vascular permeability level was significantly retained and suppressed, respectively, in each treatment group compared with that in the cyclophosphamide group. The number of apoptotic cells in the vascular endothelium significantly decreased in the cyclophosphamide + α-lipoic acid derivative group compared with that in the cyclophosphamide group. In conclusion, cooling therapy and α-lipoic acid derivative facilitated recovery from chemotherapy-induced alopecia caused by cyclophosphamide through decreasing vascular permeability.

Although intussusception in adults generally results from malignant tumors and polyps, intussusception caused by chronic diverticulitis is extremely rare. We present the case of a 59-year-old man treated with steroids and biopharmaceuticals at the Department of Dermatology for psoriasis vulgaris. Cecal diverticulitis frequently recurred, for which he was treated during follow-up. This time, endoscopy showed a circumferential stenosis in the ascending colon, and computed tomography showed the appearance of a target sign in the right colon. As a result, the patient was preoperatively diagnosed as having intussusception of the ascending colon triggered by diverticulitis of the cecum and underwent laparoscopic right colectomy. Pathological findings of the specimen revealed multiple diverticulitis of the cecum. Therefore, we thought that the intussusception was caused by chronic inflammation of the diverticula and surrounding fibrosis. Among intussusception in adults, chronic diverticulitis should be considered as a target of surgical treatment on rare occasions.

AbstractAimWhether a laparoscopic procedure can contribute to the improvement of clinical outcomes in obese patients with stage II/III rectal cancer compared to an open procedure remains unclear.ObjectiveThis study evaluated the technical and oncological safety of laparoscopic surgery versus open surgery in obese patients (body mass index [BMI] ≥25 kg/m2) with rectal cancer.Patients and MethodsData were collected from patients with pathological stage II/III rectal cancer and analyzed. Operations were performed via laparoscopic or open surgery from 2009 to 2013. A comparative analysis was performed after applying propensity score matching to the two cohorts (laparoscopic group and open group). The primary endpoint was 3‐y relapse‐free survival (RFS).ResultsOverall, 524 eligible cases were collected from 51 institutions. Equal numbers of propensity score‐matched patients were included in the laparoscopic (n = 193) group and open (n = 193) group. Although the rate of D3 lymph node dissection did not differ between the laparoscopic group (87.0%) and the open group (88.6%), the median number of harvested lymph nodes was significantly lower in the laparoscopic group versus open group (17.5 vs 21, P = 0.0047). The median postoperative hospital stay was also significantly shorter in the laparoscopic group (14 d) vs the open group (17 d) (P = 0.0014). Three‐y RFS was not significantly different between the two groups (hazard ratio 1.2454, 95% confidence interval 0.9201–1.6884, P = 0.4689).ConclusionThe short‐ and long‐term results of this large cohort study (UMIN ID: UMIN000033529) indicated that laparoscopic surgery in obese rectal cancer patients has advantageous short‐term outcomes and no disadvantageous long‐term outcomes.

BACKGROUND:Standard treatment for diffuse peritonitis due to colorectal perforation may be insufficient to suppress inflammatory reaction in sepsis. Thus, developing new treatments is important. This study aimed to examine whether intraperitoneal irradiation by artificial sunlight suppresses inflammatory reaction in a lipopolysaccharide (LPS)-induced peritonitis model after surgical treatments.MATERIALS AND METHODS:Mice were divided into naive, nontreatment (NT), and phototherapy (PT) groups. In the latter two groups, LPS was intraperitoneally administered to induce peritonitis and removed by intraperitoneal lavage after laparotomy. The PT group was irradiated with artificial sunlight intraperitoneally. We evaluated the local and systemic inflammatory reactions. Murine macrophages were irradiated with artificial sunlight after stimulation by LPS, and cell viability and expression of tumor necrotizing factor-α (TNF-α) were evaluated.RESULTS:As a local inflammatory reaction, the whole cell count, the expression of interleukin-6 and TNF-α in the intra-abdominal fluid, and the peritoneal thickness were significantly lower in the PT group than in the NT group. As a systematic inflammatory reaction, the expression of serum TNF-α, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β were significantly lower in the PT group than in the NT group. Irradiation by artificial sunlight suppressed the expression of TNF-α in murine macrophages without affecting cell viability.CONCLUSIONS:Intraperitoneal irradiation by artificial sunlight could suppress local and systemic inflammatory reactions in the LPS-induced peritonitis murine model. These effects may be associated with macrophage immune responses.

Chemotherapy-induced alopecia is one of the most difficult adverse events of cancer treatment for patients. However, it is still unknown why anticancer drugs cause hair loss. We aimed to clarify the mechanism of chemotherapy-induced alopecia in mice using an in vivo imaging technique with a two-photon microscope, which enables observation of the deep reaction in the living body in real time. In this study, ICR mice were injected intraperitoneally with cyclophosphamide (120 µg/g). Changes in the hair bulb morphology, subcutaneous vessel permeability, and vessel density were evaluated by two-photon microscopy and conventional methods. In order to determine whether there is a causal relationship between vascular permeability and hair loss, we combined cyclophosphamide (50 µg/g) with subcutaneous histamine. Using two‐photon microscopy and conventional examination, we confirmed that the hair bulbs became smaller, blood vessels around the hair follicle decreased, and vascular permeability increased at 24 hours after cyclophosphamide injection [corrected]. Apoptosis occurred in vascular endothelial cells around the hair follicle. Additionally, hair loss was exacerbated by temporarily enhancing vascular permeability with histamine. In conclusion, cyclophosphamide caused a decrease in vascular density and an increase in vascular permeability, therefore increased vascular permeability might be one of the causes of chemotherapy-induced alopecia.

Background Although obstructive colitis with colon cancer is not a rare disease, most cases can be improved with conservative therapy. We report a case of a patient who underwent a laparoscopic two-stage operation for rectal cancer with refractory obstructive colitis after kidney transplantation. Case presentation The patient was a 71-year-old man taking immunosuppressants who had previously undergone right living kidney transplantation for chronic nephritis. He presented to hospital complaining of abdominal pain and was diagnosed as having rectal cancer with obstructive colitis. Although conservative therapy by fasting was continued for 5 weeks, his obstructive colitis did not improve. Therefore, we decided to perform a two-stage operation. First, we performed a laparoscopic Hartmann's operation. It took 6 months for his obstructive colitis to improve after this operation, and then we performed a laparoscopic colorectal anastomosis. There were no postoperative complications in either operation. Conclusion A laparoscopic two-stage operation could be one of the operative options to reduce postoperative complications in patients with comorbidities such as taking immunosuppressants.

Background An esophageal diverticulum is rare and is frequently associated with esophageal motility disorders. Jackhammer esophagus is also rare, is characterized by esophageal hypercontraction, and comprises 4.1% of esophageal motility disorders. Here, we report a case of a patient successfully treated by laparoscopic transhiatal surgery for an epiphrenic esophageal diverticulum derived from a jackhammer esophagus diagnosed with high-resolution manometry (HRM). Case presentation The patient was a 78-year-old man who presented to the hospital with dysphagia. A diverticulum was detected in the lower part of his esophagus by upper gastrointestinal endoscopy. HRM was performed to investigate esophageal motility disorders. His integrated relaxation pressure was normal at 25.9 (< 26) mmHg, but his distal contractile integral (DCI) was very high at 21,464 (1500–13,000) mmHg s cm. Esophageal peristalsis was preserved. Therefore, the patient was diagnosed as having an epiphrenic esophageal diverticulum derived from a jackhammer esophagus for which laparoscopic transhiatal diverticulectomy and Heller-Dor procedure were performed. The postoperative course was uneventful. His symptoms improved, and the level of DCI also returned to a normal level of 3867 mmHg s cm at 2 months after the operation. Conclusion Laparoscopic transhiatal diverticulectomy and esophagomyotomy can be useful procedures for an epiphrenic esophageal diverticulum derived from a jackhammer esophagus due to their lower invasiveness.

Among synchronous colorectal cancers (SCRCs) reported previously, the incidence of quadruple advanced SCRCs is very rare. We present the case who underwent laparoscopic two-segment resection of the colon requiring two anastomoses that was performed for quadruple advanced cancers, and four tumors were curatively removed. There were no signs of recurrence at 64 months after surgery. Laparoscopic surgery provided less invasiveness even for quadruple advanced SCRCs in terms of early recovery with an acceptable long-term outcome.

Insufficient coverage of the area of a possible groin hernia is an important risk factor in hernia recurrence. To prevent recurrence, it is important to use the appropriate mesh size based on the size of the myopectineal orifice (MPO), which is the weak area of the abdominal wall where inguinal hernias occur. We aimed to estimate the appropriate mesh size for groin hernias by investigating MPO size. Four hundred and six patients underwent groin hernia repair using a totally extraperitoneal (TEP) approach at the Zeze Hospital between July 2009 and December 2017. We investigated patients’ backgrounds, MPO components dimensions, and hernia recurrence, and evaluated the appropriate mesh size. The 359 male and 47 female patients had an average age of 63 ± 15 years. In 171, 147, and 88 cases, hernias were localized to the right, left, and bilaterally, respectively. The number of lateral, medial, femoral, and combined hernias was 317, 124, 11, and 42, respectively. The 95th percentile for the horizontal and vertical lengths in cases of hernia orifice ≥ 3 cm were 9.6 cm and 7.0 cm, respectively, while it was 9.2 cm and 6.4 cm in cases of hernia orifice < 3 cm. We added 2 cm and 3 cm to the 95th percentile for the length and width of the MPO, resulting in 13.2 × 10.4 cm and 15.6 × 13.0 cm in cases with hernia orifice < 3 cm and ≥ 3 cm, respectively. Relapse after TEP occurred in 1 patient (0.2%). The appropriate mesh size for TEP repair, derived from intraoperative MPO measurements, was estimated as 13.2 × 10.4 cm and 15.6 × 13.0 cm when the hernia orifice was < 3 cm and ≥ 3 cm, respectively. Using appropriate mesh sizes based on MPO measurement may reduce groin hernia recurrence after TEP.

PURPOSE:Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of anticancer drugs; however, there are currently no mechanisms to completely prevent CIA. In this study, we performed a clinical trial to examine whether sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), an alpha-lipoic acid derivative, prevents CIA in patients with breast cancer.METHODS:Between July 2014 and May 2015, we performed a multi-center, single arm, clinical trial involving 103 breast cancer patients who received adjuvant chemotherapy at three medical institutions in Japan. During chemotherapy, a lotion containing 1% DHL-HisZnNa was applied daily to the patients' scalps. The primary endpoint was the incidence of grade 2 alopecia; the secondary endpoints were the duration of grade 2 alopecia, alopecia-related symptoms, and drug-related adverse events. Alopecia was evaluated by three independent reviewers using head photographs taken from four angles.RESULTS:Safety analysis was performed for 101 patients who started the protocol therapy. After excluding one patient who experienced disease progression during treatment, 100 patients who received at least two courses of chemotherapy underwent efficacy analysis. All original 101 patients developed grade 2 alopecia, the median durations of which were 119 days (112-133 days) and 203 days (196-212 days) in the groups treated with four and eight courses of chemotherapy, respectively. Mild or moderate adverse events potentially related to DHL-HisZnNa were observed in 11 patients. Alopecia-related symptoms were observed in 53 patients (52%).CONCLUSIONS:The application of 1% DHL-HisZnNa to the scalp did not prevent CIA. However, this drug may promote recovery from CIA.TRIAL REGISTRATION NUMBER:UMIN000014840.

Background: Recently, laparoscopic (Lap) intersphincteric resection (ISR) for low-lying rectal cancer is gradually permeating worldwide. However, the usefulness of Lap-ISR after neoadjuvant chemoradiotherapy (NCRT) has not been clarified. This retrospective study aimed to evaluate the feasibility of Lap-ISR after NCRT for locally advanced low-lying rectal cancer. Methods: Fourteen patients with primary locally low-lying rectal cancer were enrolled in this study and underwent curative Lap-ISR between January 2008 and December 2011. Seven patients underwent Lap-ISR after NCRT (NCRT group) and seven patients underwent Lap-ISR without NCRT (non-NCRT group). Patient characteristics, short-term outcomes, postoperative anal function, and long-term oncological outcomes were evaluated and compared between the groups. Results: The tumor diameter was significantly larger in the NCRT group than the non-NCRT group (38±7 and 28±9 mm, respectively; P=0.04) and cStage was significantly more advanced in the NCRT group than the non-NCRT group (P=0.02). There were no significant differences in operative data or postoperative course between the groups. The Wexner score measured 5 years after initial surgery was significantly higher the NCRT group than the non-NCRT group (8.8±4.1 and 4.6±1.9, respectively; P=0.04). There were no significant differences in local recurrence rate, distant recurrence rate, or cancer-specific death rate between the two groups (median follow-up period was 60 months). Conclusions: Lap-ISR after NCRT is a feasible treatment option based on short-term outcomes, long-term oncological outcomes, and postoperative anal function. These data suggest that Lap-ISR after NCRT may be an appropriate treatment option for locally advanced low-lying rectal cancer.