Comparison of short-term outcomes between robot-assisted and laparoscopic rectal surgery for rectal cancer: A propensity score-matched analysis using the Japanese Nationwide diagnosis procedure combination database.

Background: The use of robot-assisted surgery for rectal cancer is increasing, but its short-term results remain unclear. We compared the short-term outcomes of robot-assisted and laparoscopic surgery for rectal cancer using a nationwide inpatient database. Methods: We analyzed patients registered in the Japanese Diagnosis Procedure Combination database who underwent robot-assisted or laparoscopic surgery for rectal cancer from April 2018 to March 2020. Postoperative complication rates, anesthesia time, length of hospital stay, and cost were compared using propensity score matching for low anterior resection (LAR), high anterior resection (HAR), and abdominoperineal resection (APR). Results: Among 38 090 rectal cancer cases, 1992 LAR, 357 HAR, and 310 APR pairs were generated by propensity score matching and analyzed. Anesthesia time was longer for robot-assisted surgery compared with laparoscopic surgery (LAR: 388.6 vs. 452.8 min, p < 0.001; HAR: 300.9 vs. 393.5 min, p < 0.001; APR: 4478.5 vs. 533.5 min, p < 0.001). Robot-assisted surgery was associated with significantly shorter hospital stay for LAR (22.3 vs. 20.0 days, p < 0.001) and APR (29.2 vs. 25.9 days, p = 0.029). Total costs for LAR were significantly lower for robot-assisted surgery (2031511.6 vs. 1955216.6 JPY, p < 0.001). The complication rates for robot-assisted surgery tended to be fewer than laparoscopic surgery for all procedures, but the differences were not significant. Conclusions: Although the anesthesia time was longer for robot-assisted surgery, the procedure resulted in shorter hospital stay for LAR and APR, and lower costs for LAR compared with laparoscopic surgery. Robot-assisted surgery can thus help to reduce costs and can be performed safely.

Advantages of preoperative counseling with video for robotic rectal cancer surgery compared with conventional counseling: A randomized controlled trial.

PURPOSE: Surgeons should provide patients with appropriate explanations before surgery and obtain informed consent. However, this process requires time and effort and can be a great burden. The purpose of this study was to compare preoperative counseling with video (VC) and conventional counseling (CC) for rectal cancer patients. METHODS: Rectal cancer patients indicated for surgery were included between April 2021 and March 2022, and eligible patients were randomly assigned to the CC and VC groups. The primary outcomes were the comprehension, satisfaction, and anxiety levels, and the secondary outcome was the preoperative counseling time. This exploratory study protocol was registered with the UMIN Clinical Trials Registry (UMIN000038133). RESULTS: We included 13 patients in the CC group and 17 in the VC group. All eligible patients were scheduled for robotic rectal cancer surgery. There were no significant differences between the two groups, including patients' general condition, preoperative diagnosis, and planned procedures. Although the comprehension, satisfaction, and anxiety test scores were not significantly different between the groups, the preoperative counseling time was significantly shorter in the VC group than in the CC group (20 vs. 35 minutes, P = .002). A 4-year college degree significantly increased the counseling time, whereas VC significantly decreased it. CONCLUSION: Using videos in preoperative counseling for rectal cancer patients is useful. This novel method could reduce the burden on surgeons during preoperative counseling in the era of robotic surgery and work style reforms.

Robotic-assisted Surgery: Expanding Indication to Colon Cancer in Japan.

In recent years, robotic-assisted surgery has demonstrated remarkable progress as a minimally invasive procedure for colorectal cancer. While there have been fewer studies investigating robotic-assisted surgery for the treatment of colon cancer than rectal cancer, evidence regarding robotic-assisted colectomy has been accumulating due to increasing use of the procedure. Robotic-assisted colectomy generally requires a long operative time and involves high costs. However, as evidence is increasingly supportive of its higher accuracy and less invasive nature compared to laparoscopic colectomy, the procedure is anticipated to improve the ratio of conversion to laparotomy and accelerate postoperative recovery. Robotic-assisted surgery has also been suggested for a specific level of effectiveness in manipulative procedures, such as intracorporeal anastomosis, and is increasingly indicated as a less problematic procedure compared to conventional laparoscopy and open surgery in terms of long-term oncological outcomes. Although robotic-assisted colectomy has been widely adopted abroad, only a limited number of institutions have been using this procedure in Japan. Further accumulation of experience and studies investigating surgical outcomes using this approach are required in Japan.

Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis.

PURPOSE: To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM). METHODS: The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence. RESULTS: Recurrence was detected during the median follow-up time of 52 months in 445 (73.7%) of the total 604 patients analyzed. A postoperative CEA level >5 ng/ml was an independent predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29-3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2% and a positive predictive value of 84.2% for recurrence. Patients with a high postoperative CEA level had a significantly higher recurrence rate, with a shorter time until recurrence and a higher frequency of multiple metastatic sites than those with a low postoperative CEA level. Among the patients with recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was detected. CONCLUSIONS: A postoperative CEA level >5 ng/ml was an independent predictor of recurrence; however, CEA testing was not a reliable surveillance tool to identity recurrence after liver resection.

Clinical Significance of Methylation and Reduced Expression of the Quaking Gene in Colorectal Cancer.

BACKGROUND: This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis. MATERIALS AND METHODS: Oligonucleotide microarray expression profiling was carried out on a panel of primary CRC specimens (n=17) and CRC cell lines (n=5), followed by methylation analysis using methylation-specific polymerase chain reaction. QKI expression levels were assessed in 156 primary CRCs by qRT-PCR and immunohistochemistry. RESULTS: Low QKI expression was observed in 47.7% in CRCs. QKI promoter methylation was detected in 32.1% of patients with CRC, and in these patients mRNA expression in tumor tissue was significantly down-regulated compared to matched normal tissues (p=0.049). There was a significant relationship between low QKI expression and recurrence after surgery (p=0.004). Low QKI expression was an independent risk factor for recurrence after surgery in 153 patients with CRC without distant metastases (p=0.036). CONCLUSION: Patients with tumors expressing low levels of QKI experienced significantly higher rates of tumor recurrence after curative surgery and worse prognoses. Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. Loew QKI expression may be a useful clinical biomarker for predicting recurrence and prognosis.

[A case of postoperative colon cancer with peritoneal dissemination in which a long-term response was achieved using panitumumab maintenance therapy].

A 66-year-old man underwent a sigmoidectomy for advanced sigmoid colon cancer. The pathological examination revealed that the tumor was T3, N0, M0, and KRAS wild type. Fifteen months after surgery, the patient was hospitalized with stenosis of the anastomosis due to recurrent disease that had disseminated to the peritoneum, and which was unresectable. After transverse colostomy, the patient received 8 courses of mFOLFOX6+panitumumab (Pmab), and 39 courses of infusional 5-fluorouracil (5-FU) + Leucovorin (LV)+ Pmab. A partial remission (PR) was maintained for 27 months. The utility of maintenance therapy with an anti-epidermal growth factor receptor (EGFR) antibody-based regime has not previously been demonstrated. In this case, a long PR was achieved using infusional 5-FU+LV+Pmab, suggesting that this is a useful maintenance therapy following mFOLFOX6 + Pmab. However, the side effects resulting from Pmab treatment reduced the patient's quality of life (QOL). We suggest that Pmab maintenance therapy can be established by controlling the side effects of the anti-EGFR antibody.

[Three cases of anal squamous cell carcinoma treated with chemoradiotherapy].

We reviewed the clinical records of 3 patients with anal squamous cell carcinoma treated with chemoradiotherapy (CRT). Case 1: The patient was diagnosed with StageI (T1N0M0) and treated with cisplatin (CDDP)+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. She achieved partial response(PR), and underwent a salvage surgery. Seven months after the surgery, she died from other comorbidities. Case 2: The patient was diagnosed with Stage I (T1N0M0) and treated with CDDP+5-FU+radiation. Chemotherapy was discontinued after the second course because of adverse effects. He achieved PR, and underwent a salvage surgery. Three years and 7 months after the surgery, he died from other comorbidities. Case 3: The patient was diagnosed with Stage IIIB (T4N1M0) and treated with MMC+S-1+radiation. Chemotherapy was discontinued after the first course because of adverse effects. She achieved complete response (CR) and is still surviving without cancer recurrence. We conclude that CRT is an effective treatment for anal squamous cell carcinoma.

[A case of poorly differentiated adenocarcinoma of the uterine cervix treated with paclitaxel and carboplatin after positive PAX 8 immunostaining].

PAX 8 is a paired-box gene that plays an important role in the embryogenesis of the thyroid gland, Müllerian ducts, and renal/upper urinary tract. PAX 8 expression is observed in carcinomas from each of these sites. Accordingly, PAX 8 immunostaining has been reported to be useful for the diagnosis of these carcinomas. Here, we report a case in which PAX 8 was useful for the diagnosis of a patient with cervical adenocarcinoma and multiple metastases. A 55-year-old female patient complained of cough and genital bleeding. Examination revealed a uterine cervical mass, masses in both breasts, and enlargement of the lymph nodes and subcutaneous nodules. Histology of the uterine cervical mass biopsy revealed a poorly differentiated adenocarcinoma. Cytology of the aspiration biopsy specimens of the breast masses indicated scirrhous cancer. PAX 8 immunostaining of the uterine cervical mass and breast mass biopsies was positive. We determined that the breast masses were metastases of the cervical adenocarcinoma and decided to treat the patient with chemotherapy consisting of paclitaxel and carboplatin. A partial response was observed. A hysterectomy was performed 5 months after chemotherapy because corpus cancer was newly diagnosed. The cervical adenocarcinoma was undetectable in the surgical specimen. Fifteen months have passed since the completion of chemotherapy and the metastases has been under control.

[Resection for the treatment of bleeding caused by ovarian metastasis after hepatectomy for metachronous liver metastasis from sigmoid colon cancer].

We describe the case of a 75-year-old woman who underwent bilateral oophorectomy for bleeding due to right ovarian metastasis after hepatectomy for metachronous liver metastasis from sigmoid colon cancer. She underwent curative resection for sigmoid colon cancer( T4a, N2, M0, Stage IIIC). She received adjuvant chemotherapy of tegafur/uracil(UFT) plus leucovorin for 6 months. The patient underwent hepatectomy for liver metastasis 13 months after the primary resection for sigmoid colon cancer. One year after liver resection, the patient underwent emergency surgery for the treatment of bleeding due to ovarian metastasis. She received adjuvant capecitabine chemotherapy for 6 months after oophorectomy. The patient was alive with no evidence of disease 36 months after her oophorectomy. In the present report, we describe the case of a patient who underwent repeated resection for distant metastases after sigmoidectomy. These findings suggest that therapeutic strategies including surgical resection will be very important in the future.

[A case of advanced rectal cancer treated with leucovorin, fluorouracil, and oxaliplatin plus panitumumab preoperative chemotherapy].

A 58-year-old woman had a very large advanced rectal cancer( with wild-type K-RAS expression). Abdominal computed tomography( CT) revealed a space-occupying lesion in the pelvis and an enlarged lymph node. We established a diagnosis of unresectable rectal cancer and subsequently performed transverse colostomy. The patient received 6 courses of Leucovorin, fluorouracil, and oxaliplatin( mFOLFOX6) plus panitumumab( Pmab), 2 courses of simplified Leucovorin plus 5-fluorouraci(l sLV5-FU) plus Pmab, and 1 course of Pmab. The size of the primary tumor decreased remarkably after chemotherapy. Low anterior resection was performed. The pathological stage was T4a, N0, M1, Stage IVa. The results from this case suggest that mFOLFOX6 plus Pmab preoperative chemotherapy is a useful regimen for the treatment of locally advanced K-RAS wild-type rectal cancer.

[A case of advanced rectal cancer with bone metastasis successfully treated with chemo-radiation therapy].

A 62-year-old man presented to a hospital with left buttock pain, and sacral neoplasia was suspected. He was referred to our hospital. Colonoscopy( CS) and bone biopsy showed rectal cancer with metastasis to the sacrum. There was no bleeding or ileus associated with the primary lesion, and the sacral metastasis was unresectable; therefore, we decided to provide palliative care for pain relief. Radiation therapy( 40 Gy) was performed on the sacral metastasis and included the primary lesion, and zoledronate was administered concomitantly. Both CS and computed tomography (CT) showed tumor regression of both the primary and metastatic lesions, and the patient's carcinomatous pain was alleviated. Irinotecan, 5- fluorouracil, and Leucovorin (FOLFIRI)+cetuximab was administered to reduce the progression of the primary lesion. After 3 months, CT showed significant tumor regression of both the primary and metastatic lesions. The sacral metastasis was no longer evident on the CT images, and positron emission tomography( PET)-CT did not show fluorodeoxyglucose (FDG) accumulation. The primary lesion had shrunk and become flat, but biopsy indicated residual lesion. Although clinically the frequency of bone metastasis of colon cancer has been reported to be 8.6 to 10.7%, single metastasis is not often seen. In this report, we present a case of advanced rectal cancer with bone metastasis, which was successfully treated with chemo-radiation therapy.

[A case of recurrent rectal cancer successfully treated for a long period with capecitabine plus oxaliplatin and bevacizumab therapy].

A 62-year-old woman was diagnosed as having rectal cancer and underwent low anterior resection. The final pathological diagnosis was RS, type 3, circ, mod>muc>por>,pSE, ly1, v1, pN2, sH0, sP0, cM0, fStage IIIb, with KRAS mutation. Adjuvant chemotherapy with tegafur-uracil( UFT) plus Leucovorin( LV) was administered for 6 months. Ten months after surgery, right internal iliac and common iliac lymph node metastasis and peritoneal dissemination were diagnosed. In October 2009, capecitabine plus oxaliplatin (CapeOX) plus bevacizumab (Bmab) therapy was initiated. In May 2010, diagnostic imaging revealed a complete response after 42 months. In the present report, we describe the case of a patient with rectal cancer who experienced postoperative recurrence and achieved long-term complete response with CapeOX plus Bmab therapy. We also include a brief review of the literature.

[A case of neuroendocrine carcinoma of the anal canal with multiple bone metastases successfully treated with combined modality therapy].

Neuroendocrine carcinoma (NEC) of the anal canal is a comparatively rare tumor with a poor prognosis. We report herein a case of NEC of the anal canal with multiple bone metastases that was successfully treated with combined therapy. A 63-year-old man was referred to our hospital with the chief complaint of anal and back pain. A tumor was found in the anal canal, and pathologic examination revealed it to be NEC( Ki-67 expression>50%); fluorodeoxyglucose( FDG) positron emission tomography (PET)-computed tomography (CT) showed multiple bone metastases. Initially, a l-leucovorin/5- fluorouraci(l 5-FU)/oxaliplatin( L-OHP)(: mFOLFOX6)/bevacizumab( Bmab) regimen and octreotide were administered to treat the unresectable and advanced NEC. Strontium-89 and zoledronate were used to treat pain related to the bone metastases. After 3 months, the tumor and bone metastases became difficult to identify. The patient experienced grade 2 neurotoxicity after 5 months, and thus, we stopped L-OHP administration. After 10 months, we reintroduced L-OHP because of additional progression of the bone metastases.

[Long-surviving patient with hilar cholangiocarcinoma by gemcitabine monotherapy].

An 80-year-old woman visited our department with the complaint of icterus and brown urine. After detailed examination, she was diagnosed with cT4N0M (-), cStage IVa, hilar cholangiocarcinoma. We believed that she could be cured with surgery, but she and her family did not agree to the surgical procedure. Chemotherapy was scheduled, and gemcitabine (GEM) therapy was started in April 2011. GEM therapy reduced significantly the level of the CA 19-9 tumor marker, and diagnostic imaging allowed a judgment of partial response or stable disease after 18 months. In the present report, we describe a case of a patient with hilar cholangiocarcinoma who achieved long-term survival with GEM therapy. We also include a brief literature review.

[A patient with sigmoid colon cancer( cStage IV) who responded to preoperative chemotherapy with mFOLFOX6 plus bevacizumab and was subsequently able to undergo a radical operation].

There are a growing number of reports of unresectable, advanced colorectal cancer and multiorgan invasive colorectal cancer for which extended surgery was avoided or a radical operation was performed after down-staging, or tumor size reduction, was achieved by chemotherapy. Here we describe a case of sigmoid colon cancer (cStage IV) for which preoperative chemotherapy improved the outcome of surgery. The patient was a 57-year-old man with sigmoid colon cancer of sufficient size to block the passage of the endoscope. The cancer was found to be widely infiltrated and adherent to the peritoneum over the bladder, with effusion around the tumor that made peritoneal disseminated metastasis a strong possibility. Moreover, many regional and periaortic lymph nodes were swollen. Sigmoid colon cancer at Stage IV was diagnosed. After preoperative chemotherapy [mFOLFOX6+bevacizumab (Bev)] was administered, tumor size decreased sufficiently to allow the endoscope to pass through. The effusion around the tumor disappeared, and lymph node swellings were reduced. The surgical findings revealed no evidence of peritoneal metastasis, and tumor adhesion to the peritoneum over the bladder was small, which limited the extent of combined peritonectomy. Ultimately, the histopathological diagnosis was Stage II,and histological evaluation of the drug therapy effects was that the tumor was then Grade 1b. Although clinical studies are currently conducted on preoperative chemotherapy for locally advanced colorectal cancer, preoperative chemotherapy is not established as standard treatment due to lack of clear evidence. The evaluation of the usefulness of preoperative chemotherapy is warrants future clinical studies.

[A case of recurrent gastric cancer responding to CPT-11].

A 68-year-old man underwent total gastrectomy for gastric cancer(Stage II). Adjuvant chemotherapy with S-1 was administered. At 21 months after the operation, he received a nephron catheter because of hydronephrosis caused by para-aortic lymph node metastases. Then, weekly paclitaxel was given as a second-line treatment. However, his tumor marker level increased and he therefore received CPT-11 (160 mg/m2) as a third-line treatment at 28 months after the operation. At 7 days after the first CPT-11 administration, he was hospitalized because of a severe adverse event involving nausea and general fatigue, which caused a continuous fever of 39°C and renal failure at 14 days after administration. However, hydration enabled him to recover several days later. Computed tomography scan revealed the lymph node metastases to be partial remission.

Cardiomyogenesis in the developing heart is regulated by c-kit-positive cardiac stem cells.

RATIONALE: Embryonic and fetal myocardial growth is characterized by a dramatic increase in myocyte number, but whether the expansion of the myocyte compartment is dictated by activation and commitment of resident cardiac stem cells (CSCs), division of immature myocytes or both is currently unknown. OBJECTIVE: In this study, we tested whether prenatal cardiac development is controlled by activation and differentiation of CSCs and whether division of c-kit-positive CSCs in the mouse heart is triggered by spontaneous Ca(2+) oscillations. METHODS AND RESULTS: We report that embryonic-fetal c-kit-positive CSCs are self-renewing, clonogenic and multipotent in vitro and in vivo. The growth and commitment of c-kit-positive CSCs is responsible for the generation of the myocyte progeny of the developing heart. The close correspondence between values computed by mathematical modeling and direct measurements of myocyte number at E9, E14, E19 and 1 day after birth strongly suggests that the organogenesis of the embryonic heart is dependent on a hierarchical model of cell differentiation regulated by resident CSCs. The growth promoting effects of c-kit-positive CSCs are triggered by spontaneous oscillations in intracellular Ca(2+), mediated by IP3 receptor activation, which condition asymmetrical stem cell division and myocyte lineage specification. CONCLUSIONS: Myocyte formation derived from CSC differentiation is the major determinant of cardiac growth during development. Division of c-kit-positive CSCs in the mouse is promoted by spontaneous Ca(2+) spikes, which dictate the pattern of stem cell replication and the generation of a myocyte progeny at all phases of prenatal life and up to one day after birth.

[A case of primary malignant lymphoma of the spleen which was difficult to be diagnosed].

A 55-year-old woman who had a chief complaint of left abdominal and back pain. She was diagnosed with pancreatic cancer associated with splenic metastasis (Stage IVb) by CT and MRI study and was treated with chemotherapy of gemcitabine (GEM). Chemotherapy was discontinued due to adverse event (grade 3). CT study at this point reveals the effectiveness of GEM. The tumor was localized, and an operation was performed. The tumor was diagnosed as primary malignant lymphoma (diffuse large B-cell lymphoma) of the spleen. The splentic tumor is extremely rare, so a surgical treatment was indicated for making a correct diagnosis. This was an interesting case of malignant lymphoma that GEM revealed a cytoreductive result.

[A case of locally advanced pancreas cancer effectively treated by multidisciplinary strategy].

A 64-year-old female with a primary complaint of abdominal and back pain was diagnosed as locoregionally advanced pancreas cancer. She underwent distal pancreatectomy and received postoperative adjuvant chemotherapy of gemcitabine (GEM). Abdominal CT after 14 months showed a local recurrence without far organ metastasis. She was treated with radiation and the chemotherapy of S-1, which resulted in a stable control by a follow up CT. Then she is undergoing the combination chemotherapy of GEM and S-1. The patient is alive for 26 months after the operation.