Current status and future perspectives of the managements of metastatic hormone-sensitive prostate cancer.

PURPOSE: The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically. Here, we provide the current status and future prospective of the management of mHSPC. METHODS: We reviewed recent literature of landmark studies on the managements of mHSPC. RESULTS: Upfront docetaxel or androgen receptor signaling inhibitor (ARSi) in addition to ADT has improved survival in mHSPC patients and has become the new standard of care. Triplet therapy with docetaxel, ARSi and ADT also improved survival. In the future, triplet therapy may become the standard of care. Oligometastatic mHSPC patients could benefit from local therapy. The inclusion of risk factors or the genetic biomarkers will provide the best treatment for individual mHSPC patients. CONCLUSION: Strong systemic therapy in the first-line treatment of mHSPC has been shown to improve survival and quality of life. Currently, several clinical trials are evaluating novel compounds such as PARP inhibitor, AKT inhibitor, and immune checkpoint inhibitor. The therapeutic landscape of mHSPC management will change dramatically.

The quality of life after laparoscopic ventral and incisional hernia repair with closure and non-closure of fascial defect.

PURPOSE: In this retrospective, non-randomized study, we compared the quality of life (QOL) of patients who underwent laparoscopic ventral and incisional hernia repair (LVIHR) with fascial defect closure or non-defect closure and examined the factors associated with the QOL after LVIHR. METHODS: Between February 2013 and 2016, we conducted a single-center, follow-up study of 33 consecutive midline hernia patients who underwent LVIHR. Overall, 14 cases underwent intraperitoneal onlay mesh repair (IPOM), and 19 underwent IPOM with fascial defect closure (IPOM-plus). Patients were interviewed using the 36-item Short Form Health Survey (SF-36) to assess their pre- and postoperative QOL (at 1, 3, 6, and 12 months after surgery). The QOL, as assessed by the SF-36, was compared before and at 1 year after surgery, and the risk factors associated with the QOL were examined. RESULTS: Overall, scores for 5 of the 8 domains and 1 of the 3 components of SF-36 had improved by 1 year after surgery compared with before surgery. The scores for the SF-36 domains and components at 1 year post-surgery were comparable in patients undergoing IPOM or IPOM-plus. Obesity, operative time, hernia size, and mesh size were factors correlated with the QOL. CONCLUSIONS: LVIHR improved the QOL, regardless of defect closure.

Strategy of laparoscopic surgery for colon cancer of the splenic flexure: a novel approach.

BACKGROUND: The splenic flexure (SF) anatomy is complex due to multiple vessels, surrounding organs, layers, and irregular adhesions [1-3]. METHODS: Our laparoscopic approach involves a lateral-to-medial approach to the left-sided transverse mesocolon (TM), a medial-to-lateral approach to the left mesocolon (LM), and take-down of the remnant SF. First, the omental bursa is opened and its posterior wall and the anterior layer of the TM are dissected along the pancreas, where a gauze is placed. The TM is spread cephalad. A window in the TM is opened in the gauze seen through the TM. If necessary, the middle colic vessels are divided with lymph node (LN) dissection. Then the left colic artery is divided with LN dissection using a medial approach. The LM is widely dissected from the retroperitoneum to reach the TM window. While observing the pancreas through the window, the LM and TM are divided from the pancreas close to the SF. The descending colon is mobilized from its lateral attachment. Finally, the SF is taken down from the spleen by separating remnant structures, including adhesions. Subsequently, functional end-to-end anastomosis was performed extracorporeally. RESULTS: During March 2012-December 2016, 39 patients with left-sided transverse or descending colon cancer underwent this treatment. The mean operative time, blood loss, number of harvested LNs, and hospital stay duration were 283 min, 45 ml, 15, and 9 days, respectively. No patient needed conversion to open surgery or had organ injury, anastomotic leakage, or Clavien-Dindo III-V complications. There were 7/13/18/1 patients with Stage I/II/III/IV colon cancer, respectively. Nineteen cases had positive LNs. All patients were alive with one local and two distant recurrences at a mean 24-month follow-up. CONCLUSIONS: This is a safe and effective surgical strategy for treating colon cancer of the SF, strategically designed to resect the SF after dissecting the surrounding structures.

The Change in Neutrophil Lymphocyte Ratio from the First to the Last Repeat Prostate Biopsy Proposed as a Marker of Carcinogenesis.

INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.

[A Resected Case of Cancer in the Ileum of the Blind Loop after an Ileotransverse Colostomy].

We report a resected case of cancer at the ileum of the blind loop. An 81-year-old male underwent an appendectomy for acute appendicitis and an ileotransverse colostomy for postoperative obstruction when he was 14 years old. He underwent radiation therapy for prostate cancer when he was 75 years old. Six years later, enhanced computed tomography revealed a 7 cm mass in the ileum of the blind loop. Colonoscopy showed wall thickening at the ileum of the blind loop, and biopsy revealed an adenocarcinoma. We performed partial resection of the ileum. The patient was discharged 17 days after surgery. Cancer at the ileum of the blind loop after an ileotransverse colostomy has rarely been reported.

Tumescent TAPP: laparoscopic inguinal hernia repair after the preperitoneal tumescent injection of diluted lidocaine and epinephrine saline solution and carbon dioxide gas.

PURPOSE: Laparoscopic transabdominal preperitoneal inguinal hernia repair (TAPP) is technically difficult and not infrequently followed by postoperative complications and pain, especially when performed by inexperienced surgeons. To simplify TAPP and reduce postoperative pain, we devised a novel procedure whereby TAPP is carried out after the inguinal preperitoneal infiltration of diluted lidocaine and epinephrine saline solution and carbon dioxide gas (tumescent TAPP). This report introduces the concept of tumescent TAPP and summarizes its operative results. METHODS: About 120 ml of diluted lidocaine and epinephrine solution and 60 ml of CO2 gas were infiltrated into the inguinal preperitoneal space through a transabdominal needle before TAPP. Tumescent TAPP was performed for 400 patients (355 men, 45 women; mean age, 63.2 years). RESULTS: Using tumescent TAPP, we found it easier to confirm the inguinal anatomy and dissect the preperitoneal layer and inguinal floor, with less bleeding. The mean operation time was 101.9 min and there were few perioperative complications and minimal pain. CONCLUSIONS: Tumescent TAPP makes conventional TAPP easier and safer; however, this procedure should be verified by a comparative study with conventional TAPP.

[Cyst of the tunica albuginea testis : a case report].

This report concerns a case of cyst of the tunica albuginea testis in a 74-year-old man, who presented with a painful swelling of right scrotal contents. Magnetic resonance imaging (MRI) and ultrasonography revealed a cystic mass on the surface of the right testicle. We performed resection of the cystic wall. The histological findings indicated cyst of the tunica albuginea testis. In this series, we collected 30 cases in the Japanese literature.

[Three cases of proliferative cystitis causing hydronephrosis].

We report three cases of proliferative cystitis causing hydronephrosis. Three patients presented with a complaint of miction pain, gross hematuria or pollikisuria. Cystoscopic findings revealed papillary sessile tumor from neck to orifice. Transurethral resection of the bladder tumor (TURBT) was performed because the tumor was not responsive to medical treatment. The pathological diagnosis was intestinal type or typical type of cystitis glandularis and no malignant cells were observed. After the operation, although hydronephrosis improved in two cases, the left hydronephrosis did not improve in one case and ureteralileostomy was performed. Five year after the last operation, there is no evidence of recurrence of the tumor. Tumor formation arising from proliferative cystitis is relatively rare. Pathogenesis and management of this rare condition are discussed.

[Metastatic tumor of the spermatic cord from gastric cancer: a case report].

A 66-year-old man presented with a painless swelling of left scrotal contents. We performed left inguinal orchiectomy and left inguinal lymphnode dissection. Histopathological examination revealed spermatic cord metastases from gastric carcinoma. We collected 44 cases of metastatic tumor of the spermatic cord from gastric cancer in the Japanese literature.

Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

Polyoxazoline-conjugated porcine serum albumin as an artificial plasma expander for dogs.

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs. The aqueous POx-PSA solution showed moderately high colloid osmotic pressure and good blood cell compatibility. Actually, lyophilized powder stored for 1 year can regenerate into a homogeneous solution. The circulation half-life of POx-PSA in rats was 2.1-fold longer than that of naked PSA. Rats produced neither anti-PSA IgG antibody nor anti-POx IgG antibody, which suggests excellent immunological stealth properties of POx-PSA. Complete resuscitation of hemorrhagic shock in rats was achieved soon after injection of POx-PSA solution. Serum biochemistry tests and histopathological observations indicated no abnormality in the related organs. When POx-PSA was administered to dogs intravenously, (i) no serum biochemical or hematological alteration was observed, also (ii) no overt deterioration of animal health was observed. These results indicate that POx-PSA has potential as an artificial plasma expander for dogs.

Evaluation of Machine Learning Interatomic Potentials for the Properties of Gold Nanoparticles.

We have investigated Machine Learning Interatomic Potentials in application to the properties of gold nanoparticles through the DeePMD package, using data generated with the ab-initio VASP program. Benchmarking was carried out on Au20 nanoclusters against ab-initio molecular dynamics simulations and show we can achieve similar accuracy with the machine learned potential at far reduced cost using LAMMPS. We have been able to reproduce structures and heat capacities of several isomeric forms. Comparison of our workflow with similar ML-IP studies is discussed and has identified areas for future improvement.

Successful Treatment of Pancreatic Fistula Following Surgery for Congenital Biliary Dilatation with Endoscopic Ultrasound-Guided Transduodenal Drainage.

Despite improvements in surgical techniques and perioperative management, postoperative pancreatic fistula (PF) is often difficult to treat and can be fatal due to various complications without effective drainage. Here, we report a case of PF following surgery for congenital biliary dilatation (CBD) successfully managed by endoscopic ultrasound (EUS)-guided transduodenal drainage. A 55-year-old woman underwent extrahepatic bile duct resection, including the gallbladder, and biliary tract reconstruction for CBD. On the 10th postoperative day (POD), computed tomography (CT) showed fluid retention observed from the upper edge of the pancreatic head to the surface of the right lobe of the liver. First, percutaneous fine-needle aspiration was performed on the fluid retention in the lateral part of the liver on the 11th POD. The amylase level in the drainage was high (30,156 U/L), and we diagnosed it as PF. Percutaneous drainage was difficult for fluid retention on the cut surface of the pancreas; thus, drainage under EUS guidance was decided. On the 13th POD, EUS was performed, a scan of the duodenal bulb revealed fluid retention with debris inside, and approximately 20-mL fluid was aspirated (amylase: 139,200 U/L). Although the inflammatory response temporarily improved, it recurred, so we decided to perform continuous drainage. On the 21st POD, EUS was performed again; a 19-G needle was used; a 0.025-in angle-type Jagwire was advanced into the fluid retention and expanded using a 7-Fr dilator; and then, a 6-Fr endoscopic nasoabscess drain (ENAD) tube was placed. On the 29th POD, CT showed that the fluid retention on the upper edge of the head of the pancreas had shrunk to a thickness of approximately 20 mm. On the 30th POD, the patient started eating. The ENAD tube was removed on the 38th POD. The patient was discharged from the hospital on the 45th POD without any symptoms. EUS-guided transduodenal drainage is an effective treatment option for postoperative PF following surgery for CBD.

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

[Prostate cancer in a young adult : a case report].

We report a case of prostate cancer in a 41-year-old male. The patient initially visited another institution with a chief complaint of left breech pain. He was referred to our hospital for further investigation. Serum level of PSA was 267ng/ml and multiple bone metastases were found on bone scintigram. Digital rectal examination revealed a stony-hard prostate. Computed tomography showed multiple lung and lymph node metastases. Transperineal needle biopsy of the prostate revealed moderately differentiated adenocarcinoma (Gleason score 4＋5) frombilateral lobes (the 3th Edition). The patient was diagnosed with cT4N1M1c prostate cancer and maximal androgen blockade therapy was commenced.

A retrospective investigation of minor risk factors as prognostic predictors and treatment indications in oral squamous cell carcinoma.

Abstract. BACKGROUND/PURPOSE: The clinical significance of minor risk factors remins uncertain in oral squamous cell carcinoma (OSCC) patients. The purpose of this study was to investigate the clinical impact of minor risk factors in OSCC patients. MATERIALS AND METHODS: The cases of OSCC patients that underwent surgery were retrospectively analyzed. Patients with major risk factors for recurrence, such as positive surgical margins or extracapsular spread, were excluded. The impact of possible minor risk factors on treatment outcomes was analyzed. One hundred and seventy-five patients with primary OSCC that underwent surgery were included in this study. RESULTS: The 5-year overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) rates were 81.2%, 91.0%, and 72.4%, respectively. In multivariate analyses, RFS exhibited a significant association with the pattern of invasion (grade 4 vs. grades 1-3: hazard ratio: 3.096, 95% confidence interval: 1.367-6.884, p < 0.01), OS exhibited a tendency towards associations with the pattern of invasion and perineural invasion, and CSS displayed a tendency towards an association with perineural invasion. The prognosis of the patients with ≥2 minor risk factors was significantly worse than that of the patients with 0 or 1 minor risk factor(s) (OS: 91.6% vs. 64.5%, respectively, p < 0.01; CSS: 98.9% vs. 78.9%, respectively, p < 0.001; and RFS: 81.2% vs. 58.5%, respectively p < 0.05). CONCLUSION: Grade 4 invasion and perineural invasion might be significant minor risk factors in OSCC patients. The presence of ≥2 minor risk factors might be a predictor of a poor prognosis in OSCC patients.

Comparison of Abiraterone and Combined Androgen Blockade Therapy for High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Propensity Score-Matched Analysis.

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

Assembling a library of typical surgery video clips to construct a system for assessing the surgical difficulty of laparoscopic cholecystectomy.

BACKGROUND: To explore best practices for acute cholecystitis, it is necessary to construct a system to assess the difficulty of laparoscopic cholecystectomy (LC) based on intraoperative findings. In this study, multiple evaluators assessed videos of LC to assemble a library of typical video clips for 25 intraoperative findings. METHODS: We have previously identified 25 items that contribute to surgical difficulty in LC. For each item, roughly 30-second video clips were submitted from videos of LC performed at member institutions. We then selected one typical video from the collected clips based on simple tabulation of the instances of agreement. Inter-rater agreement was assessed with Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except in the case of two assessment items ("edematous change" and "easy bleeding"), κ or AC significantly exceeded 0.5 and the typical videos were judged to be applicable. For the two remaining items, the evaluation was repeated after clarifying the definitions of positive and negative findings. Eventually, they were recognized as typical. The completed video clip library contains 31 clips and is divided into five categories (http://www.jshbps.jp/modules/project/index.php?content_id=13). CONCLUSIONS: This clip library may be highly useful in clinical settings as a more objective standard for assessing surgical difficulty in LC.

[The usefulness and adverse events of bevacizumab combined with chemotherapy against advanced or recurrent colorectal cancer].

We examined clinical results of 35 patients on bevacizumab(BV)combined with chemotherapy at our hospital. The subjects were 35 patients with advanced or recurrent colorectal cancer who received BV combined with chemotherapy for approximately 2 years. Their median age was 66 years(41 to 86 years), PS was 2 or less for all; it was first-line therapy in 21 patients, second-line in 12 patients and thirdline in 2 patients. The concomitant chemotherapy was mFOLFOX 6 in 24 / patients, 5-FU/LV in 8 patients and FOLFIRI in 3 patients. Therapeutic efficacy was CR in 2 patients, PR in 10 patients, and the overall response rate was 35%. There were 7 adverse events of Grade 3 or higher, among which 4 events were leucopenia. Neither overall survival nor any concomitant chemotherapy reached the median periods. Moreover, the median periods of / progression-free survival in mFOLFOX6/FOLFIRI were 191 days. BV combined with chemotherapy should be actively introduced as first-line therapy against advanced or recurrent colorectal cancer because of its high therapeutic efficacy.