[Re-Administration of Anti-EGFR Antibody Drugs for Unresectable Colorectal Cancer-Focusing on Tumor Markers].

The 2022 edition of the Guidelines for the Treatment of Colorectal Cancer described rechallenge therapy as a backward treatment for unresectable colorectal cancer, but currently, there is no evidence to support its benefit. We reviewed 6 cases of rechallenge therapy in which tumor marker trends could be followed in our department. Two cases had a rapid decline in tumor markers that was maintained for 7-8 months. In 3 cases, PR was also confirmed on imaging. In contrast, there was 1 case with no decrease in tumor markers at all. Our findings suggest that cases of wild-type RAS prior to rechallenge therapy and cases that are responsive to initial anti-EGFR antibody drugs may have been involved in the effect of rechallenge therapy.

A Case Report of Primary Unresectable Hilar Cholangiocarcinoma Causing Colonic Obstruction Due to Peritoneal Dissemination.

Although surgical resection is the only available treatment to achieve long-term survival in biliary tract cancer, many cases are often identified at an advanced stage at the time of diagnosis. Radiotherapy may be an alternative option to prolong survival in cases with locally advanced unresectable disease. While there are some reports of long-term survival after radiotherapy for unresectable biliary tract cancer, it is rare that clinical symptoms are exhibited by peritoneal dissemination more than 8 years after radiotherapy and that resection can be performed. Our case was a 55-year-old female who had visited with a complaint of jaundice and was diagnosed with primary unresectable hilar cholangiocarcinoma. She received definitve chemoradiotherapy, and repeated receiving maintenance chemotherapy thereafter until clinical manifestation. During follow-up, she was diagnosed with stenosis of the sigmoid colon, which was attributed to peritoneal dissemination of cholangiocarcinoma. We herein report a rare case of primary unresectable hilar cholangiocarcinoma after chemoradiotherapy which was followed by chemotherapy that was controlled for more than 8 years but eventually caused colonic obstruction attributed to peritoneal dissemination.

[A Case of Ascending Colon Cancer with Skull Metastasis].

A 55-year-old woman became aware of a tumor on the left side of the head in July, 2020 and was referred to our hospital in September because of its rapid growth. A head CT showed a neoplastic lesion of the skull. A CT from the neck to the pelvis revealed an ascending colon tumor and multiple lesions in the liver, which was suspected as metastasis. A colonoscopy also showed a type 2 like lesion in the ascending colon, and a biopsy showed adenocarcinoma. A pedunculated polyp had been pointed out in the ascending colon at another hospital four years previously, and the pathological result was an adenoma, but endoscopic mucosal resection was not performed. It is considered that the adenoma became advanced colon cancer with metastasis through the mechanism of multistage carcinogenesis. Metastatic lesions of the ascending colon cancer was suspected with regard to the skull lesion. In addition to the rapid growth, surgical removal was desirable from the viewpoint of cosmetology, and surgery was performed in November. The postoperative pathological diagnosis was a metastatic skull tumor derived from ascending colon cancer. The diagnosis was Stage IVb according to the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (9th Edition). Although chemotherapy was started after surgery, the metastatic liver cancer increased rapidly and the patient passed away in April, 2021.

[Two Cases of Synchronous Double Primary Prostate Cancer Accompanying Bone Metastasis and Colon Cancer].

We report two cases of synchronous double primary cancers, which were composed of prostate cancer accompanied by bone metastasis and colon cancer, within only five months of each other. The first was a 77-year-old man whose ECOG PS was 0. He was referred to our hospital in March 2020 because abdominal CT scan, which was performed at a clinic for the purpose of close examination of poor control of diabetes, showed wall thickening of the sigmoid colon. A further examination revealed prostate cancer accompanied by metastatic bone cancer and sigmoid colon cancer. Laparoscopic sigmoid colectomy was performed in April. Currently, six months after the surgery, both the prostate cancer and its accompanying metastatic bone cancer are well controlled by hormonal therapy. The second case was an 86-year-old man with an ECOG PS of 3 who was brought to our hospital by ambulance in August, 2020 because of fever and abdominal pain. A close examination revealed cecal cancer accompanying acute appendicitis. Prostate cancer accompanied by metastatic bone cancer was also diagnosed. Laparoscopic ileocecal resection was performed in the same month, but, unfortunately, the patient had repeated aspiration pneumonia and he finally passed away 43 days after surgery. We discuss the treatment strategy for colorectal cancer with synchronous or metachronous prostate cancer, which has been increasing in recent years, and include epidemiological considerations.

The prognostic significance of the expression of monocarboxylate transporter 4 in patients with right- or left-sided colorectal cancer.

AIM: Monocarboxylate transporter 4 (MCT4) is a proton pump that exchanges lactate through the plasma membrane. The present study investigated the clinical significance of the expression of MCT4 in patients with right- or left-sided colorectal cancer (CRC). METHODS: Surgical specimens from 237 CRC patients were immunohistochemically stained with polyclonal anti-MCT4 antibodies. The relationships among the MCT4 expression, the clinicopathological factors, and the prognosis were evaluated. RESULTS: Thirty-six (62.1%) of 58 patients with right-sided CRC and 95 (53.1%) of 179 patients with left-sided CRC showed the high expression of MCT4. The MCT4 expression was significantly correlated with gender and lymph node metastasis in patients with right-sided CRC, and size, depth of invasion, distant metastasis, and tumor-node-metastasis stage in patients with left-sided CRC. A univariate analysis demonstrated that the expression of MCT4 was a significant prognostic factor in both right- and left-sided CRC patients. A multivariate analysis demonstrated the expression of MCT4 was a significantly independent prognostic factor in patients with left-sided CRC, but not in those with right-sided CRC. CONCLUSIONS: Our results suggest that the high expression of MCT4 is a useful marker for tumor progression and a poor prognosis in CRC patients, especially those with left-sided CRC.

A Review of 7 Cases of Laparoscopic Cholecystectomy for Pediatric Cholecystolithiasis.

Pediatric cholecystolithiasis is a relatively rare disease, but it is recently increasing in Japan. Laparoscopic cholecystectomy (LC) is a standard procedure for cholecystolithiasis not only in adults but also in children, and we are aggressively introducing single-incision laparoscopic cholecystectomy (SILC) at our hospital. We reviewed the patient characteristics, operation procedures and outcomes of 7 children (15 years old and under) with cholecystolithiasis who underwent LC in our hospital between August 1995 and December 2015. The 7 patients included 5 males and 2 females, with a mean age of 8 years 6 months. Underlying diseases were found in 5 patients (cerebral palsy in 2 patients, pancreaticobiliary maljunction with common bile duct stones in 1, acute lymphocytic leukemia in 1, hereditary stomatocytosis in 1), and none were found in the other 2. LC (3 conventional LC and 2 SILC) was performed in 5 of the patients. Laparoscopic choledocholithotomy was performed in 1 patient and laparoscopic splenectomy (LS) was performed in 1 patient at the same time. The mean operative time in all the cases of LC was 108 (70-140) minutes (conventional LC 113 (70-140) min, SILC 100 (90-100) min). Intraoperative cholangiography was performed in 4 cases and omitted in 3 cases. The only postoperative complication was a wound infection in 1 patient. The umbilical skin incision length in the SILC was 2.0 cm. We conclude that LC can be safely performed for children with cholecsytolithiasis, and that SILC is feasible and advantageous in terms of its improved cosmesis.

A Case of Retroperitoneal Paraganglioma.

We report a surgical case of retroperitoneal paraganglioma. A paraganglioma is a catecholamine-producing tumor originating in the chromaffin cells of the sympathetic ganglion. It is a kind of pheochromocytoma which occurs on the outside of the adrenal gland. The patient was a 72 year old male with a history of hypertension and a pacemaker implantation. A mass in the ventral side of the right iliopsoas muscle was detected during a routine contrasting computed tomography (CT) examination for checking his pacemaker. The mass was considered to be malignant, and a laparotomy and mass enucleation was performed. It was diagnosed as phaeochromocytoma, based on the pathology and immunestology of the excised specimen. The hypertension was cured soon after the surgery. Nine months after surgery, there is no evidence of any abnormality or recurrence. There is a previous report of a recurrence 25 years after surgery, so a careful follow-up of this patient will be necessary in the future.

A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma enriched with hyaluronan (HA), a major component of extracellular matrix known to play a critical role in tumor progression. The mechanisms that regulate HA synthesis in PDAC are poorly understood. To investigate whether DNA methylation and HA production from PDAC cells are associated, we studied the effect of 5-aza-2'-deoxycitidine (5-aza-dC), an inhibitor of DNA methylation, or DNA methyltransferase 1 (DNMT1) knockdown by small interfering RNA, on the HA production from PDAC cells. HA production into the conditioned medium was evaluated in PDAC cells treated with 5-aza-dC or DNMT1 knockdown. mRNA expression of HA synthase (HAS) genes was investigated by real-time RT-PCR. Treatment of PDAC cells with 5-aza-dC led to a significant increase in the HA production (up to 2.5-fold increase) in all 4 cell lines tested. This enhanced HA production by 5-aza-dC treatment was accompanied by increased mRNA expression of HAS2 and HAS3. Furthermore, increased HA production and HAS2/HAS3 mRNA expression was also observed in PDAC cells by knockdown of DNMT1. These findings provide evidence, for the first time, that epigenetic mechanism is involved in the regulation of HA synthesis in PDAC cells.

Reduced Port Distal Gastrectomy With a Multichannel Port Plus One Puncture (POP).

BACKGROUND: This report describes the techniques and outcomes of reduced port distal gastrectomy (RPDG) with a multichannel port plus one puncture (POP) for gastric cancer patients. PATIENTS AND METHODS: A total of eight patients underwent a RPDG using the Eï½¥Z Access™/LAPPROTECTOR™ (Hakko Co. Ltd., Tokyo, Japan) oval type devices with POP by a single surgeon. The median age of the patients was 66 years (range 48-75 years), and their median BMI was 22.3 kg/m2 (range 17.7-26.8 kg/m2). One (12.5 %) of eight patients was female. A thin caliber trocar MiniPort™ (Covidien, New Haven, CT) was inserted at the left upper quadrant by puncture without incision. An assistant used Endo Relief™ (Hope Denshi Co. Ltd., Chiba, Japan) needlescopic forceps. In three cases, the pre-bent forceps (KTY-I, Adachi Industry Co. Ltd., Gifu, Japan) was introduced for surgeon's left hand. After the liver was retracted with a 2-0 Prolene suture, a distal subtotal resection of the stomach with D1+ or D2 lymph node dissection was performed. The Roux-en-Y method or Billroth-I anastomosis was used for reconstruction. The short-term patient outcomes were investigated to evaluate the feasibility of RPDG with POP. RESULTS: We employed this technique without the use of additional trocars in every patient except one. No conversion to laparotomy was observed. Both the Endo Relief™ forceps and prebent forceps were useful to maintain countertraction and keep triangulation. The median length of the operation was 374 (range, 268-420) minutes, and the median estimated blood loss was 45 (range, 5-180) ml. The median number of dissected lymph nodes was 32 (range 22-46). Neither major postoperative complications, such as anastomotic leakage and stricture, nor postoperative mortality were observed. The mean length of the hospital stay was 1,5 days. The umbilical wound was indistinct. CONCLUSION: RPDG with POP using a needlescopic device procedure is feasible in terms of patient safety and curability.

Single-incision laparoscopic cholecystectomy for acute cholecystitis: A retrospective cohort study of 52 consecutive patients.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) has become increasingly popular but its role in acute cholecystitis remains controversial. METHODS: We compared the clinical features and outcomes of SILC procedures between 52 patients with acute cholecystitis (the AC group) and 308 patients without acute cholecystitis (the NAC group). We also analyzed clinical variables to identify factors affecting difficulties associated with SILC for acute cholecystitis. RESULTS: The patients in the AC group were significantly older than those in the NAC group (72 vs. 61 years, median, P = 0.0005). The preoperative levels of white blood cell counts were significantly higher in the AC group than in the NAC group (6600 vs. 5500/µL, P = 0.0004). The operative time was significantly longer in the AC group than in the NAC group (188 vs. 135 min, P < 0.0001). The volume of intraoperative blood loss was significantly larger in the AC group than in the NAC group (20 vs. 5 mL, P < 0.001). Furthermore, additional trocar insertion was required in 12% in the NAC group, whereas it was required in 60% in the AC group (P < 0.0001). Regarding the difficulties of SILC for acute cholecystitis, delayed operation (after 72 h from the onset) was significantly associated with a prolonged operative time, while a higher grade of acute cholecystitis (grade II or III) was significantly associated with an increased blood loss during surgery. CONCLUSIONS: These findings suggest that when compared to SILC for gallbladder diseases without acute inflammation, SILC for acute cholecystitis was associated with a longer operative time, increased blood loss, higher rate of additional trocar requirement, higher rate of postoperative complications, and longer hospital stay. The difficulties associated with SILC for acute cholecystitis were affected by the timing of surgery and the grade of inflammation.

A new oval multichannel port to facilitate reduced port distal gastrectomy.

BACKGROUND: This report describes the techniques and outcomes of reduced port distal gastrectomy (RPDG) using a new oval multichannel port. MATERIAL AND METHODS: We performed reduced port distal gastrectomy through the E·Z Access™ oval type device with three trocars in the umbilical incision, plus the use of additional 5 mm and 2 mm ports. All routine procedures performed in conventional laparoscopic distal gastrectomy (CLDG) were achieved in RPDG. RESULTS: We employed this technique without the use of additional trocars or conversion to laparotomy in all 25 patients. The median length of the operation was 340 (range, 220-487) minutes, and the median estimated blood loss was 30 (range, 5-440) ml. Neither major postoperative complications, such as anastomotic leakage and stricture, nor postoperative mortality were observed. The mean length of the hospital stay was 11 days. The umbilical wound was indistinct. The patients were also highly satisfied with the cosmetic outcome. CONCLUSION: Reduced port surgery using the E · Z Access™ oval type device was successfully applied for gastric cancer. This method is technically feasible, produces superior cosmetic results and thus could be an attractive surgical option for gastric cancer patients.

Postoperative complications following single-incision laparoscopic cholecystectomy: a retrospective analysis in 360 consecutive patients.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is being increasingly performed based on recent evidence showing its cosmetic advantages. However, there is limited information on outcome data for SILC with respect to postoperative complications. METHODS: We retrospectively reviewed a consecutive series of 360 patients undergoing SILC to evaluate the rate, features, and risk factors of postoperative complications. RESULTS: During a median follow-up period of 671 days, 17 patients (4.7 %) developed postoperative complications, including bile duct injuries, intraabdominal abscess, wound infection, incisional hernia, paralytic ileus, and pneumonia. Reoperation was required in five patients (1.4 %). Overall inpatient mortality occurred in one patient (0.3 %) who developed aspiration pneumonia. In multivariate stepwise regression analyses, poor physical status (American Society of Anesthesiologists score of ≥3) and preoperative diagnosis of acute cholecystitis were identified as significant risk factors for the development of postoperative complications (P = 0.0009 and P = 0.04, respectively). CONCLUSIONS: These findings suggest that SILC is a relatively safe procedure with an acceptable postoperative complication rate but requires careful attention especially in patients with poor physical status and/or acute cholecystitis.

Rare combination of familial adenomatous polyposis and gallbladder polyps.

Familial adenomatous polyposis is associated with a high incidence of malignancies in the upper gastrointestinal tract (particularly ampullary adenocarcinomas). However, few reports have described a correlation between familial adenomatous polyposis and gallbladder neoplasms. We present a case of a 60-year-old woman with familial adenomatous polyposis who presented with an elevated mass in the neck of the gallbladder (measuring 16 mm × 8 mm in diameter) and multiple small cholecystic polyps. She had undergone a total colectomy for ascending colon cancer associated with familial adenomatous polyposis 22 years previously. The patient underwent laparoscopic cholecystectomy under a preoperative diagnosis of multifocal gallbladder polyps. Pathologic examination of the resected gallbladder revealed more than 70 adenomatous lesions, a feature consistent with adenoma of the gallbladder. This case suggests a requirement for long-term surveillance of the biliary system in addition to the gastrointestinal tract in patients with familial adenomatous polyposis.

Rapid postoperative reduction in prognostic nutrition index is associated with the development of pancreatic fistula following distal pancreatectomy.

BACKGROUNDS: Despite recent advances in surgical techniques and devices for pancreatic remnant closure, postoperative pancreatic fistula (POPF) still remains one of the common complications after distal pancreatectomy (DP). Identification of risk factors for POPF may lead to the development of new strategies to prevent this ominous complication. METHODS: We retrospectively reviewed data on 44 patients undergoing DP with the use of a stapler to identify risk factors for POPF. Study variables included preoperative prognostic nutritional index (PNI) and reduction rate of PNI on postoperative day (POD) 7. RESULTS: POPF occurred in 23 patients (52%), of which 13 (56%) were grade B or C. Univariate analyses comparing patients with POPF and those without POPF showed significant differences in body mass index (P = 0.0102), pancreatic thickness (P = 0.0134), white blood cell count on POD7 (P = 0.0432), C-reactive protein level on POD7 (P = 0.0123), and PNI reduction rate (P = 0.0471). A multivariate analysis revealed pancreatic thickness (P = 0.0121) and PNI reduction rate (P = 0.0165) to be significant factors for POPF. Furthermore, the PNI reduction rate was significantly higher in patients with clinically relevant (grade B/C) POPF than in those with no or grade A POPF (P = 0.0257). In most patients, the massive postoperative PNI reduction preceded the diagnosis of clinically relevant POPF. CONCLUSIONS: These findings suggest that rapid postoperative reduction in PNI is associated with the development of POPF.

Pancreatic somatostatinoma diagnosed preoperatively: report of a case.

CONTEXT: Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. CASE REPORT: We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymph nodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum. Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of the pancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed histopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells were positive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwent pylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively after surgery. CONCLUSIONS: A rare case of pancreatic somatostatinoma with lymph node metastases was presented. Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

Risk factors for a prolonged operative time in a single-incision laparoscopic cholecystectomy.

BACKGROUND: A prolonged operative time is associated with adverse post-operative outcomes in laparoscopic surgery. Although a single-incision laparoscopic cholecystectomy (SILC) requires a longer operative time as compared with a conventional laparoscopic cholecystectomy, risk factors for a prolonged operative time in SILC remain unknown. METHODS: A total of 20 clinical variables were retrospectively reviewed to identify factors for a prolonged operative time (longer than 3 h) in a total of 220 consecutive patients undergoing SILC. RESULTS: The median operative time was 145 min (range, 55-435) and a prolonged operative time was required in 62 patients (28%). Independent factors that predict a prolonged operative time as identified through multivariate analysis were body mass index (BMI) (P = 0.009), acute cholecystitis (P < 0.001) and operator (resident or staff surgeon) (P < 0.001). Furthermore, a prolonged operative time was significantly associated with an increased amount of intra-operative blood loss (P < 0.001) and a prolonged stay after surgery (P < 0.001). CONCLUSIONS: These findings suggest that a higher BMI, acute cholecystitis and a resident as an operator significantly increase the duration of SILC procedures.

[A review of 13 cases of obturator hernia].

We reviewed clinical features of patients who we treated for obturator hernia. The subjects were 13 patients who underwent an operation for obturator hernia in our hospital between April 2002 and December 2012. The mean age was 78.5 years, and all patients were female. The mean body mass index was 16.8 kg/m(2). The Howship-Romberg sign was present in only 3 patients. All patients were correctly diagnosed by preoperative pelvic computed tomography. All patients underwent operation. Operative procedures included the laparoscopic approach in 8 patients, the open approach in 3 patients and the inguinal approach in 2 patients. The hernia hilus was repaired with a simple closure in 5 patients, and with a mesh in 8 patients. The hernia contents were small intestine in all the patients. Three patients underwent partial resection of the small intestine because of necrosis of the intestine wall. Three patients had a recurrence of the obturator hernia. In our present series, the patients with obturator hernia were slender females at an advanced age. Plevic CT was useful for the diagnosis of obturator hernia.

A newly developed oval-shaped port device (E•Z ACCESS Oval type) for use in reduced port surgery: initial clinical experiences with cholecystectomy.

We recently developed an oval-shaped E•Z Access device designed exclusively for use with the LAP PROTECTOR™ Oval type device (Hakko Co. Ltd., Tokyo, Japan). The transverse abdominal opening diameter made by round-shaped (Alexis® Wound Retractor, Applied Medical, Rancho Santa Margarita, CA; and LAP PROTECTOR™ Round type) and oval-shaped (LAP PROTECTOR™ Oval type) wound retractors was measured and compared in 5 patients with cholecystolithiasis. Each device was placed through a single 25-mm longitudinal umbilical incision, and the length of trocar separation was compared. LESS cholecystectomy was then performed using the oval-shaped E•Z ACCESS/LAP PROTECTOR™. The transverse abdominal opening diameter was maximized with the LAP PROTECTOR™ Oval type device. The average distance between the working-ports for the glove method, round-shaped, and oval-shaped E•Z ACCESS/LAP PROTECTOR™ devices in the 25-mm umbilical incisions were 20 ± 0.8 mm, 24 ± 1.5 mm, and 35 ± 0.8 mm, respectively. Wider trocar separation was achieved using the oval-shaped device, making the surgical procedures easier to perform. No perioperative port-related or surgical complications were observed. LESS cholecystectomy using the E•Z ACCESS Oval type device was found to be technically feasible. The Oval type device appears to allow for wider trocar separation, thereby reducing stress on the surgeon, ensuring patient safety, and providing cosmetic benefits.

Laparoendoscopic single-site common bile duct exploration using the manual manipulator.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery has developed as a new surgical modality that has increased cosmetic benefits over conventional endoscopic surgery. However, there are no reports about LESS surgery in common bile duct exploration. This report presents a LESS surgery to manage CBD stones by laparoscopic choledochotomy and C-tube placement with favorable outcomes. METHODS: This retrospective review analyzes 13 patients who underwent LESS CBD exploration with C-tube drainage for choledocholithiasis. The technique is herein described and the outcomes measured. The Radius Surgical System (Tübingen Scientific Medical, Tübingen, Germany) is a flexible manual manipulator that was applied for suturing and ligation to overcome the difficulties associated with LESS surgery. RESULTS: The diameters of the CBDs ranged from 12 to 20 mm, the median number of stones was 5.8, and the median diameter of stones was 9 mm. All of the routine procedures including choledochotomy, intraoperative ultrasound, choledochoscopy, and intraoperative cholangiography guidance were performed. Stone clearance from the CBD was achieved for all but one of the patients. It was possible to close the common bile duct opening with regular forceps, but this required extra effort compared to conventional laparoscopic surgery. On the other hand, the manual manipulator enabled the optimal penetration angle and was useful for both intracorporeal suturing and ligation for the closure of the common bile duct opening. The manual manipulator also helped to overcome in-line viewing and hand/instruments collisions, which are common problems in LESS surgery. No mortality was associated with this procedure, and two wound infections were drained without anesthesia. No recurrent stones were observed during the follow-up period. CONCLUSIONS: LESS surgery was successfully applied to CBD exploration as an available alternative to conventional laparoscopic surgery. This method is technically feasible and produces superior cosmetic results. The manual manipulator may therefore have several advantages for performing LESS surgery.