BRAF-mutant microsatellite-stable rectal cancer with acquired KRAS mutation leading to drug resistance in liver metastasis.

BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.

Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy.

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

Laparoscopic Resection Combined with a Transsacral Approach for a Recurrent Tailgut Cyst with a Refractory Fistula.

Tailgut cyst is a rare cystic disease of the anterior sacral surface and the remains of an embryonic tail gut. Tailgut cysts have a potential for malignancy, and complete resection with an adequate surgical margin is necessary. Even if incomplete resection does not result in recurrence of malignant disease, there is a risk of local infection leading to refractory fistulas. The optimal treatment for such refractory recurrent lesions has not been reported. We describe a case in which the combination of laparoscopic and transsacral approaches was effective for resecting a recurrent refractory fistula after incomplete resection of a tail gut cyst.

Perineal Squamous Cell Carcinoma Arising in an Epidermal Cyst.

A 90-year-old Japanese woman who had been aware of a subcutaneous mass on the right perineal region for 5 years was referred to our hospital for further examination and treatment because of the rapid growth of the mass and bleeding that began 3 months earlier. A biopsy of the mass revealed a diagnosis of well-differentiated squamous cell carcinoma. On preoperative examination, the tumor was 90×40 mm in size and was suspected to have partially invaded the levator ani muscle and external sphincter. Since a preoperative cardiac evaluation indicated severe aortic stenosis, we performed transcatheter aortic valve implantation. A radical resection was then performed with general anesthesia. The skin and subcutaneous tissue defects were reconstructed with a posterior gluteal-thigh propeller flap, and a sigmoid colostomy was created. The patient had a good postoperative course and was transferred to a rehabilitation facility 28 days after the surgery. Epidermal cysts are a common benign tumor, and clinicians should keep in mind that these cysts can become malignant.

Robot-assisted laparoscopic surgery for rectal cancer in a patient with a horseshoe kidney: A case report.

A 52-year-old, Japanese man presented to the hospital with a complaint of anal bleeding, and detailed examination resulted in a diagnosis of locally advanced rectal cancer. The patient underwent total neoadjuvant therapy followed by short-course radiation therapy and consolidation chemotherapy, which provided a partial response. After preoperative contrast-enhanced computed tomography showed a horseshoe kidney, robot-assisted, precise, laparoscopic, low anterior resection with D3 dissection and ileostomy construction was performed. The horseshoe renal isthmus was elevated surrounding the inferior mesenteric artery, and the left ureter and seminal vessels ran in front of the kidney. The hypogastric nerve traveled ventral to the horseshoe kidney. With robotic surgery, it was possible to perform more precise surgery while recognizing vascular and nerve anatomy in a rectal cancer patient with a horseshoe kidney due to good three-dimensional visibility and articulated forceps manipulation.

Precision laparoscopic sentinel node navigation surgery for femoral skin cancer.

Navigation surgery using indocyanine green (ICG) fluorescence imaging has been used in thoracoabdominal surgery, and its usefulness has been reported in many cases. In this study, laparoscopic lateral lymph node dissection was performed using ICG fluorescence imaging in a patient with left femoral spinous cell carcinoma with inguinal and external iliac lymph node metastases. Spinous cell carcinoma is classified as a rare cancer in Japan, and there is a scarcity of evidence for pelvic lymph node dissection, as well as a lack of studies that mention the dissection area. We hypothesized that visualization of lymph nodes and lymph flow using intraoperative ICG fluorescence imaging would indicate the area of dissection and lead to more efficient dissection. In conclusion, intraoperative ICG fluorescence imaging may be useful in this area where there is limited evidence, although there are some limitations.

Use of ileal bypass in the surgical management of two rare cases of ileal-neobladder fistula in patients who underwent radical cystectomy.

PURPOSE: An entero-neovesical fistula (ENF) is a rare troublesome complication of an orthotopic ileal bladder substitution. We report on a novel, safe technique to close ileal neovesical fistulas without extensive adhesiolysis using an NK-stapler (ENDOPATH® ENDOCUTTER ETS; Johnson & Johnson, Cincinnati, OH, USA). PATIENTS: We treated two cases of postoperative ENF after orthotopic ileal bladder substitution for radical cystectomy. Case 1 was a 63-year-old male with occasional fecaluria, and Case 2 was a 73-year-old male who experienced continuous fecaluria.Surgical procedureAfter laparotomy, we mobilized the ascending colon to bypass the anastomosis of the primary surgery by an ileo-ileal, ileo-ascending colon anastomosis. The distance between the fistula and bypass was about 10 cm. We made tunnels in the mesentery between the bypass and fistula, without damaging blood vessels, to insert the jaw of the NK-stapler. We closed the afferent and efferent loops using NK-staplers (45 mm ×2), followed by a Lembert anastomosis covering the stapler's suture lines. RESULTS: They were discharged on the ninth and seventh postoperative days, respectively. In Case 1, we experienced recanalization of the fistula after three postoperative months and required second closure with the same procedure was needed. They have not experienced any symptoms of ENF since. CONCLUSIONS: This technique is worth considering for the surgical treatment of ENF because it does not require unnecessary dissection and can ultimately achieve fistula closure.

Curative resection of ureteral metastasis of rectal cancer: a case report and review of literature.

The metastasis to the ureter in colorectal cancer had been recognized at the stage of an autopsy. These days, according to the progression of diagnostic modalities, a few cases of long-time survival after curative surgery of metastatic ureteral tumor of colorectal cancer were reported. We present a case of a metastatic ureteral tumor of rectal cancer who had 32 months of recurrence-free survival after extirpation. After preoperative chemoradiotherapy, a 47-year-old man underwent laparoscopic low anterior resection and left unilateral pelvic node dissection for lower rectal cancer. He underwent several metastasectomies for recurrent tumors in the liver and lung. At the 42nd postoperative month, a contrast-enhanced CT scan showed thickening of the ureteral wall and left hydronephrosis. Transureteroscopic biopsy revealed metastatic adenocarcinoma of rectal cancer. At the 52nd postoperative month, partial ureteral resection and vesicoureteral neo-anastomosis were performed after confirming negative resection margin with rapid intraoperative pathology. He has 32 months of recurrence-free survival after metastasectomy of the left ureter. We review the literature presenting surgery of the metastatic ureteral tumor of colorectal cancer. Although it is a rare recurrence pattern, curative resection of ureteral metastasis might provide a possibility of long-time recurrence-free survival in such patients.

Image Navigation Surgery With the Fluorescent Ureteral Catheter of Recurrent Tumors in the Pelvic Cavity.

INTRODUCTION: Ureteral injury during pelvic surgery is a serious complication that requires special attention. The fluorescent ureteral catheter near-infrared ray catheter sets are 6.0F catheters containing fluorescent substances along their length that can be recognized by a laparoscopic indocyanine green camera. We present our experience using a near-infrared ray catheter in 6 consecutive patients who underwent surgery for recurrent pelvic tumors. TECHNIQUE: The near-infrared ray catheters were inserted into the bilateral ureters in all patients, with the exception of patient 5 (left unilateral), by urologists using a cystoscope with the same technique as that commonly used in placing ureteral stents under general anesthesia. A laparoscopic indocyanine green camera was adapted to identify the ureters. From February 2020 to July 2020, 6 consecutive patients with recurrent pelvic tumors underwent surgery using a near-infrared ray catheter. In 3 patients, recurrent tumors were detected in the pelvic cavity after surgery for colon cancer (1 patient each of peritoneal recurrence behind the seminal vesicles, lymph node metastasis on the residual superior rectal artery, and peritoneal recurrence at the peritoneal reflection). Two patients had postoperative local recurrences of rectal cancer. The last patient had a recurrence of cervical carcinoma invading the rectum. RESULTS: All patients underwent surgery under ureteral image navigation using near-infrared ray catheter not only for ureter preservation during the operation (4 patients) but also for the combined resection of the ureter with recurrent tumors (2 patients). One patient experienced postoperative ureteral stenosis on postoperative day 21 that required a ureteral double J-stent placement in the left ureter. CONCLUSION: Near-infrared ray catheter has the potential to reduce inadvertent periureteral dissection because the ureter can be identified before approaching it.

[Diagnosis of Serous Adenocarcinoma following Pneumatosis Intestinalis Development during Bevacizumab Therapy for Cancer of Unknown Primary-A Case Report].

A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.

Immuno-hyperthermia effected by antibody-conjugated nanoparticles selectively targets and eradicates individual cancer cells.

Hyperthermia has been used for cancer therapy for a long period of time, but has shown limited clinical efficacy. Induction-heating hyperthermia using the combination of magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF), termed magnetic hyperthermia (MHT), has previously shown efficacy in an orthotopic mouse model of disseminated gastric cancer. In the present study, superparamagnetic iron oxide nanoparticles (SPIONs), a type of MNP, were conjugated with an anti-HER2 antibody, trastuzumab and termed anti-HER2-antibody-linked SPION nanoparticles (anti-HER2 SPIONs). Anti-HER2 SPIONs selectively targeted HER2-expressing cancer cells co-cultured along with normal fibroblasts and HER2-negative cancer cells and caused apoptosis only in the HER2-expressing individual cancer cells. The results of the present study show proof-of-concept of a novel hyperthermia technology, immuno-MHT for selective cancer therapy, that targets individual cancer cells.Abbreviations: AMF: alternating magnetic field; DDW: double distilled water; DMEM: Dulbecco's Modified Eagle's; Medium; f: frequency; FBS: fetal bovine serum; FITC: Fluorescein isothiocyanate; GFP: green fluorescent protein; H: amplitude; Hsp: heat shock protein; MHT: magnetic hyperthermia; MNPs: magnetic nanoparticles; PI: propidium iodide; RFP: red fluorescent protein; SPION: superparamagnetic iron oxide (Fe3O4) nanoparticle.

Hyperthermia generated by magnetic nanoparticles for effective treatment of disseminated peritoneal cancer in an orthotopic nude-mouse model.

Magnetic hyperthermia (MHT), which combines magnetic nanoparticles (MNPs) with an alternating magnetic field (AMF), holds promise as a cancer therapy. There have been many studies about hyperthermia, most of which have been performed by direct injection of MNPs into tumor tissues. However, there have been no reports of treating peritoneal disseminated disease with MHT to date. In the present study, we treated peritoneal metastasis of gastric cancer with MHT using superparamagnetic iron oxide (Fe3O4) nanoparticle (SPION) coated with carboxydextran as an MNP, in an orthotopic mouse model mimicking early peritoneal disseminated disease of gastric cancer. SPIONs of an optimal size were intraperitoneally administered, and an AMF (390 kHz, 28 kAm-1) was applied for 10 minutes, four times every three days. Three weeks after the first MHT treatment, the peritoneal metastases were significantly inhibited compared with the AMF-alone group or the untreated-control group. The results of the present study show that MHT can be applied as a new treatment option for disseminated peritoneal gastric cancer.Abbreviations: AMF: alternating magnetic field; Cy1: cytology-positive; DMEM: Dulbecco's Modified Eagle's Medium; FBS: fetal bovine serum; H&E: hematoxylin and eosin; HIPEC: hyperthermic intraperitoneal chemotherapy; MEM: Minimum Essential Medium; MHT: magnetic hyperthermia; MNPs: magnetic nanoparticles; P0: macroscopic peritoneal dissemination; RFP: red fluorescent protein; SPION: superparamagnetic iron oxide (Fe3O4) nanoparticle.

Para-sacral approach followed by laparoscopic low anterior resection of a gastrointestinal stromal tumour at the anterior wall of the lower rectum.

AIM: We present a para-sacral approach followed by a laparoscopic low anterior resection of gastrointestinal stromal tumours located between the urethra and the low rectum. METHOD: Case 1 is a 56-year-old male patient whose tumour (37 × 28 mm) was located 3.0 cm above the anal verge between the anterior wall of the rectum and the urethra; he underwent surgery after 14 months' administration of imatinib mesylate (400 mg/day). Case 2 is a 68-year-old male patient who presented with dysuria; a tumour (89 × 84 mm) was detected between the urethra and the anterior wall of the low rectum by MRI. He underwent surgery after 5 months' administration of imatinib mesylate (400 mg/day). In order to perform sphincter-preserving surgery and avoid injury not only to the tumour capsule but also to the urethra, a para-sacral approach followed by laparoscopic low anterior resection was adopted in these patients. Restoration of bowel continuity was done by coloanal anastomosis in case 1 and the double stapling technique in case 2. The postoperative course of the patients was uneventful. In case 2, tumour dissection from the urethra caused injury to the posterior wall of the urethra, which could be repaired easily under direct vision. The urethral catheter was removed after 117 postoperative days, and the diverting stoma was closed after 143 postoperative days. CONCLUSION: The para-sacral approach followed by a laparoscopic low anterior resection of an extraluminal gastrointestinal stromal tumour located between the urethra and anterior wall of the low rectum enables R0 resection of the tumour and an appropriate reconstruction of the rectum.

p62 is a useful predictive marker for tumour regression after chemoradiation therapy in patients with advanced rectal cancer: an immunohistochemical study.

AIM: This study aimed to evaluate the relationship between p62 expression status and tumour regression grade in advanced rectal cancer. METHODS: We enrolled 47 consecutive patients with advanced rectal cancer who underwent chemoradiation therapy (CRT) before surgery. p62 expression in the biopsy specimens was immunohistochemically evaluated, and p62 expression score (staining intensity × positive tumour cells, %) was calculated (range 0-300). The relationship between p62 expression score and CRT effect was analysed. RESULTS: The staining intensity was +2 and +3 in 29 and 18 patients, respectively. The median proportion of positive neoplastic cells was 87.8%, and that of the p62 expression score was 200. Stronger staining intensity and a higher proportion of p62-positive neoplastic cells were significantly associated with CRT non-effectiveness (P = 0.0002 and P = 0.0116, respectively), and a higher p62 expression score was significantly associated with CRT non-effectiveness (P < 0.0001). The optimal cut-off value for predicting the CRT effect was 240. CONCLUSIONS: A higher p62 expression score was significantly associated with less CRT effectiveness in patients with advanced rectal cancer. Analysis of p62 expression score using biopsy specimens is a useful and easily assessable prediction marker for CRT effect and might help select patients who can undergo a 'watch-and-wait' strategy after CRT.

Two cases of primary solitary fibrous tumor in the pelvis resected using laparoscopic surgery.

BACKGROUND: We report two resected cases of solitary fibrous tumors (SFT) that were accidentally found in the pelvic cavity. CASE PRESENTATION: Case 1 was a 54-year-old male. A colonoscopy for the examination of intestinal polyps revealed an extramural tumor in the right anterior wall of the low rectum. A preoperative MRI showed a well-demarcated T1 low and T2 mixed intensity extramural tumor (53 × 36 mm) located right lateral to the low rectum and behind the seminal vesicle. Laparoscopic surgery was successful for tumor extirpation. Immunohistochemical examination of the specimen revealed STAT6 (+) and CD34 (+) cells, a Ki67 positivity of 7-8%, a mitotic index of 4-5/50 HPF, and a diagnosis of SFT. There was no recurrence 29 months after surgery. Using RT-PCR and sequencing, we detected the NAB2-STAT6 fusion gene but the locus of genomic inversion was not detected. Case 2 was a 43-year-old male that received conservative treatment for appendicitis. A CT scan accidentally revealed a tumor of 40 mm of length in the left obturator area. A MRI revealed a well-demarcated T1 and T2 high intensity tumor. The patient underwent surgical biopsy. Immunohistochemical examination of the biopsy revealed STAT6 (+) and CD34 (+) cells, Ki67 positive cells < 1%, and a diagnosis of SFT. We could not detect the NAB2-STAT6 fusion gene in the extirpated tumor. CONCLUSIONS: Two cases of pelvic SFT were diagnosed by immunohistochemical examination, RT-PCR and sequencing and successfully resected by laparoscopic surgery.

Inhibitory effect of a mouth rinse formulated with chlorhexidine gluconate, ethanol, and green tea extract against major oral bacterial species.

Mouth rinses are a useful supplementary tool for the prevention of oral infectious diseases. Although the antimicrobial effects of mouth rinses have been investigated, there are few studies focusing on the comparison of the effects among various oral bacterial species. In the present study, the inhibitory effect of a commercial mouth rinse, "ConCoolF," and each of its major components, chlorhexidine gluconate, ethanol, and green tea extract, on multiple species of oral bacteria were investigated. Inhibition of bacterial growth was observed in all cariogenic streptococcal species with different genera, serotypes, and strains isolated from different countries when either the complete mouth rinse or chlorhexidine gluconate were used. However, no growth inhibition was observed when the bacteria were exposed to ethanol or green tea extract. Interestingly, growth inhibition was greatly reduced in non-cariogenic streptococci compared with cariogenic streptococci. In addition, both the mouth rinse and chlorhexidine gluconate inhibited the biofilms formed by both Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis), among which the inhibitory effect against S. mutans was higher than that against P. gingivalis. These results suggest that a mouth rinse containing chlorhexidine gluconate, ethanol, and green tea extract, or chlorhexidine gluconate alone, exhibits antimicrobial activity against several oral bacteria species, having greater activity against pathogenic bacteria.

[Successful Multimodality Treatment Including Three-Stage Operation for Esophageal Cancer with Esophagorespiratory Fistula - A Case Report].

The esophagorespiratory fistula(ERF)is a fatal complication ofesophageal cancer, because ofadvanced oncological status and poor conditions due to pneumonia and/or malnutrition.We report here a case of patient who was successfully treated for esophageal cancer with ERF with multimodality therapy including three-stage operation. A 65-year-old woman ofesophageal cancer received preoperative chemotherapy, and developed EFR before operation. Prolonged conservative therapies for ERF let her general condition get worse. Therefore, the patient underwent esophagostomy and gastrostomy to recover her condition. She received chemo-radiotherapy followed by esophagectomy. And she was performed the reconstruction next month. She is still alive without recurrence at 20 months after resection. In previous reports, a total of 6 cases have been performed esophagectomy for esophageal cancer with ERF in Japan. Only one case was reported that had survived longer than 12 months. This multimodality therapy can be one ofthe best strategies for the patients ofesophageal cancer with ERF, even ifthey have poor condition.

[Radical Thoracoscopic Esophagectomy for Elderly Patients with Advanced Esophageal Cancer].

We report a case of an elderly patient with advanced esophageal cancer who underwent multidisciplinary treatment. An 86-year-old male consulted our hospital with complaints of pharynx discomfort and difficulty in swallowing. He was preoperatively diagnosed with esophageal cancer, T3N2M0, Stage III . We performed 2 courses of cisplatin plus 5-FU therapy as neoadjuvant chemotherapy. The primary tumor and metastatic lymph nodes reduced in size, and thoracoscopic esophagectomy in the prone position was performed. Pathological findings were esophageal cancer, pT3-Ad, INF b, ly2, v1, IM0, pPM0, pDM0, pRM1, pN3, pStage III . As the radical margin was positive, chemoradiotherapy was performed. We continued postoperative chemotherapy for approximately 1 year, and the patient has survived without relapse for 4 years from esophagectomy. Even in patients over 80 years old, long-term prognosis can be expected by performing radical surgery and chemoradiotherapy.