James Wei Tatt Toh

The Potential Value of Immunotherapy in Colorectal Cancers: Review of the Evidence for Programmed Death-1 Inhibitor Therapy

Colorectal cancers (CRCs) have been identified as potential targets for immunotherapy with programmed cell death (PD)-1 inhibitors. English-language publications from MedLine and Embase that evaluated PD-1/PD ligand 1 (PD-L1) in the CRC tumor microenvironment and clinical trials that assessed PD-1 inhibitors were included. Sixteen abstracts were screened. Fifteen met the inclusion criteria. After review of the full texts, this resulted in a final reference list of 8 studies eligible for review. Five studies that assessed PD-1/PD-L1 in CRC and 3 trials that assessed PD-1 inhibitors were included. PD-1-positive (PD-1+) tumor-infiltrating lymphocytes and PD-L1+ cancer cells featured more prominently in high-level microsatellite instability (MSI-H) CRCs compared with microsatellite stable (MSS) CRCs, except in 1 study in which PD-L1 expression was higher in MSS CRCs. In the 3 trials that assessed PD-1 inhibitor, all 3 studies recruited patients with metastatic CRC (mCRC). One study also included patients with recurrent CRC. The objective response according to the Response Evaluation Criteria in Solid Tumors criteria was 0% (19 CRC patients with unknown microsatellite instability status) in the nivolumab study. In the pembrolizumab study, the objective response to PD-1 inhibitor was 40% and 0% in patients with MSI-H and MSS mCRC, respectively (10 patients in the MSI-H group, 18 patients in the MSS group). Seventy-eight percent of the patients in the MSI-H mCRC group compared with 11% in the MSS mCRC group (Pxa0< .005) showed no further disease progression at 12 weeks. In the nivolumab with or without ipilimumab study, objective partial response at 12 weeks to PD-1 inhibitor with or without cytotoxic T-lymphocyte-associated protein 4 inhibitor was 25.5% to 33.3% and 5% in the MSI-H and MSS groups, respectively (100 patients in the MSI-H group, 20 patients in the MSS group). Clinical trials that assessed PD-1 inhibitor immunotherapy in patients with CRC have recruited only small cohorts of patients with mCRC. Studies on the tumor microenvironment have been on the basis of archival specimens with different antibody PD-1 and PD-L1 preparations for immunohistochemistry, independent from immunotherapy trials. Immunotherapy with PD-1 therapy has potential benefit for immunogenic MSI-H CRCs whereas there is no evidence to date to suggest immunotherapy benefit in MSS CRCs. The available data are limited, and there is no information on non-mCRCs. Future trials are under way to determine its benefits.

Scanning electron microscope imaging of pilonidal disease

hypnotized that the broken, needle-like sharp ends of the hair may contribute to the hair piercing the skin. This could also explain the occurrence of pilonidal disease between the fingers of barbers. In a recent study, Karahan et al. [5] tried to determine the source of the hair inside the pilonidal sinus using a scanning electron microscope. They were not able to identify the origin of the hair as being from the scalp, back or gluteal region. However, they did find that the hair inside of the sinus was deformed and had lost its cuticle pattern, probably due to inflammation. To date, no study has looked into the frequency of occurrence or the course of the hairs in pilonidal disease. The aim of our study was to assess the orientation of the hairs in the primary pilonidal pit by scanning electron microscopy. Between August 2016 and March 2017, 17 patients were enrolled in this study after giving written informed consent. There were 12 men and 5 women. Median age at the time of surgery was 24 years (range 18–55 years). Fourteen (82%) had undergone ≥ 1 previous incision and drainage of a pilonidal abscess (1x: N = 8, 2x: N = 5, 3x: N = 1). Fourteen patients (82%) underwent primary curative intervention. Three patients underwent secondary curative intervention: two patients after curettage of the pilonidal sinus and one patient because of recurrence after pilonidal excision and modified Karydakis flap repair. The primary pits with visible protruding hair were excised. The primary pit was recognized by its intact epithelial lining. A total of 17 specimens were obtained and immediately transferred into vials containing Karnovsky’s fixative for storage at 4 °C. The specimens were post-fixed in osmium tetroxide, dehydrated in graded ethanol, critically point dried and mounted on aluminum stubs by double-sided adhesive tape. They were gold-coated in a vacuum (Fig. 1) Dear Sir,

Port positioning and docking for single-stage totally robotic dissection for rectal cancer surgery with the Si and Xi Da Vinci Surgical System

Abstract We have previously reported our technique of single-docking totally robotic dissection for rectal cancer surgery using the Da Vinci® Si Surgical System in 2009. However, we have since optimised our port placement for the Si system and have developed a novel configuration of port placement and docking for the Da Vinci® Xi Surgical System. We have performed over 700 cases using this technique with the Si system and have used our Xi technique since 2016 for totally robotic dissection for rectal cancer. We have kept the configuration of port placements for both the Xi and Si system as similar as possible, with the priorities to avoid arm collisions as well as to provide a workable port configuration of two left-handed instruments and one right-handed instrument. To date, there have had no major complications or arm collisions related to this technique of docking, port positioning and instrument placement.

Totally robotic single docking low anterior resection for rectal cancer: pearls and pitfalls

Total robotic resection of mid- and low rectal cancers confers technical advantages within the confines of the pelvis and allows difficult rectal cancer cases to be performed efficiently with less risk of conversion to open. To maximize the advantage of robotic surgery, we utilize the technique of single docking totally robotic dissection for rectal cancer for both the Da Vinci Si and Xi Surgical Systems. All steps are performed robotically, with the surgery divided into two phases. The first phase consists of inferior mesenteric artery and vein ligation, sigmoid and descending colon mobilization and splenic flexure takedown. Phase two is rectal dissection and pelvic total mesorectal excision. In this article, which is complemented by a video, we describe in detail our surgical technique for totally robotic dissection for rectal cancer using a standardized ‘medial to lateral’ approach with emphasis on the pearls and pitfalls of this surgery.

The role of mechanical bowel preparation and oral antibiotics for left-sided laparoscopic and open elective restorative colorectal surgery with and without faecal diversion

BackgroundThere is significant variation in the use of mechanical bowel preparation and oral antibiotics prior to left-sided elective colorectal surgery. There has been no consensus internationally.MethodsThis was a retrospective analysis of the 2015 American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into four groups: those who had mechanical bowel preparation with oral antibiotics, mechanical bowel preparation alone, oral antibiotics alone and no preparation. The main outcome measures included overall, superficial, deep and organ/space surgical site infections. Secondary outcomes included anastomotic leak, ileus and rate of Clostridium difficile.ResultsA total of 5729 patients were included for analysis. The overall surgical site infection rate (any superficial, deep or organ/space infection) was significantly lower in the mechanical bowel preparation and oral antibiotics approach when compared to no preparation (ORu2009=u20090.46, 95% CI 0.36–0.59, Pu2009<u20090.0001). On multivariable logistic regression analysis, mechanical bowel preparation with oral antibiotics maintained a lower risk of overall surgical site infections. MBP and OAB also had a protective effect on anastomotic leak in both the laparoscopic and open cohorts (laparoscopic multivariable adjusted OR = 0.42 (0.19–0.94), P = 0.035; open multivariable adjusted OR = 0.3 (0.12–0.77), P = 0.012). Mechanical bowel preparation alone and oral antibiotics alone was not associated with a significant decrease in surgical site infections. There was no increase in C. difficile occurrences with the use of oral antibiotics.ConclusionMechanical bowel preparation with oral antibiotics significantly minimised surgical site infections and anastomotic leak following both laparoscopic and open left-sided restorative colorectal surgery. Mechanical bowel preparation alone did not reduce surgical site infections. There was a trend to reduction in surgical site infections with oral antibiotics alone.

Peristomal pyoderma gangrenosum: 12‐year experience in a single tertiary referral centre

Peristomal pyoderma gangrenosum (PPG) is an unusual but potentially devastating condition that is difficult to diagnose and manage.

Transvaginal evisceration of small bowel: Images for surgeons

1. Chatzimavroudis G, Kalaitzis S, Voloudakis N et al. Evaluation of four mesh fixation methods in an experimental model of ventral hernia repair. J. Surg. Res. 2017; 212: 253–9. 2. Van Besien J, Vindevoghel K, Sommeling C. Central mesh failure after laparoscopic IPOM procedure. Acta Chir. Belg. 2016; 116: 313–5. 3. Awad ZT, Puri V, LeBlanc K et al. Mechanisms of ventral hernia recurrence after mesh repair and a new proposed classification. J. Am. Coll. Surg. 2005; 201: 132–40. 4. Nardi M, Millo P, Brachet Contul R et al. Laparoscopic ventral hernia repair with composite mesh: analysis of risk factors for recurrence in 185 patients with 5 years follow-up. Int. J. Surg. 2017; 40: 38–44. 5. Mercoli H, Tzedakis S, D’Urso A et al. Postoperative complications as an independent risk factor for recurrence after laparoscopic ventral hernia repair: a prospective study of 417 patients with long-term follow-up. Surg. Endosc. 2017; 31: 1469–77. 6. Reynvoet E, Deschepper E, Rogiers X, Troisi R, Berrevoet F. Laparoscopic ventral hernia repair: is there an optimal mesh fixation technique? A systematic review. Langenbecks Arch. Surg. 2014; 399: 55–63. 7. Sadava EE, Krpata DM, Gao Y, Schomisch S, Rosen MJ, Novitsky YW. Laparoscopic mechanical fixation devices: does firing angle matter? Surg. Endosc. 2013; 27: 2076–81. 8. LeBlanc KA. Tack hernia: a new entity. JSLS 2003; 7: 383–7. 9. Barzana D, Johnson K, Clancy TV, Hope WW. Hernia recurrence through a composite mesh secondary to transfascial suture holes. Hernia 2012; 16: 219–21.

A rare case of peristomal cutaneous B cell lymphoma

Dear Editor, Peristomal malignancies are rare and difficult to diagnose. In the existing literature, there have only been two cases of peristomal cutaneous lymphoma reported, with only a handful of cases of lymphomas arising from the ileostomy mucosa itself. Due to its rarity, diagnosis is difficult as it mimicks other conditions, and there is no evidence base for its management. In this case, we present an unusual case of peristomal B cell lymphoma detected four decades after initial surgery. We present a 61-year-old male who had a total colectomy and end ileostomy for refractory ulcerative colitis when he was 17 years old. He had a completion proctectomy 8 years later. He had no major issues with the stoma for over four decades until he started developing irritation and erythema peristomally, which was initially thought to be contact dermatitis associated with leakage of stomal contents. However, he developed ongoing severe pain around his ileostomy until he was unable to stand upright due to the pain. He was reviewed at our stoma therapy clinic. He had welldemarcated deep ulcers and mucocutaneous separation peristomally with satellite rash-like lesions in a circumferential stellate appearance. The ulcers were thought to be associated with either extra-intestinal manifestations of inflammatory bowel disease such as peristomal pyoderma gangrenosum or severe contact dermatitis. There was no clinical evidence of cellulitis, necrosis or pustules and the patient did not have any septic complications. While biopsies are not essential in making the diagnosis of PPG or contact dermatitis (as results of biopsies are usually non-specific), a biopsy was performed to verify the diagnosis as the appearance of the peristomal changes in this case was unusual. Unexpectedly, the biopsy revealed that the patient had peristomal B cell lymphoma. He subsequently underwent six full cycles of chemotherapy (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisolone (R CHOP) regimen) and two extra cycles of rituximab. The chemotherapy relieved the pain and irritation considerably but he had two readmissions to hospital with pneumonia and severe dehydration, and over the course of the chemotherapy, he lost 20 kg. There have only been two other reports of peristomal cutaneous lymphoma associatedwith ileostomy [1, 2]. In one case, a 54-year-oldmanwas diagnosed with peristomal cutaneous T cell lymphoma. In the other, a 73-year-old man with acquired immune deficiency syndrome (AIDS) developed a high grade non-Hodgkin’s lymphoma with diffuse proliferation into the dermis on the cutaneous side and the muscularis propria on the ileal side. Lymphoma within the ileostomy itself is also rare with only a handful of case reports [3, 4]. There have also been reports of lymphoma arising in ileal conduits [3]. In these case reports, there was not a consensus on standard treatment, with two undergoing chemotherapy, two having resections and another undergoing both chemotherapy and resection.With such limited cases, Chang et al. recommended treatment of stomarelated lymphomas to be extrapolated from treatment of sporadic intestinal lymphomas [4]. In this case, the peristomal ulceration healed completely with chemotherapy. However, the patient went on to develop recurrence of disease in the tonsils, thyroid, and lung. * James W.T. Toh James.Toh@health.nsw.gov.au

Major Abdominal and Perianal Surgery in Crohn’s Disease: Long-term Follow-up of Australian Patients With Crohn’s Disease

BACKGROUND: Most patients with Crohn’s disease still require surgery despite significant advances in medical therapy, surveillance, and management strategies. OBJECTIVE: The purpose of this study was to assess surgical strategies and outcomes in Crohn’s disease, including surgical recurrence and emergency surgery. DESIGN: This was a multicenter, retrospective review of a prospectively collected database. SETTINGS: A specialist-referred cohort of patients with Crohn’s disease between 1970 and 2009 was studied. PATIENTS: Included were 972 patients with Crohn’s disease who were referred to the Sydney Inflammatory Bowel Disease cohort database. MAIN OUTCOME MEASURES: Main outcomes of interest were the rates of major abdominal and perianal surgery between decades (1970–1979, 1980–1989, 1990-1999, and 2000-2009), indications for surgery, types of procedure performed, rate of elective and emergency surgery, risk of surgical recurrence, and predictive factors for surgery. RESULTS: Between 1970 and 2009, the overall risks of surgery within 5, 10, and 15 years of diagnosis were 31.7%, 43.3%, and 48.4%. The median time to first surgery from time of diagnosis was 2 years (range, 0–31 years). A total of 6.7% of patients required emergency surgery within 5 years of diagnosis. In total, 8.8% of patients required emergency surgery within 15 years. The overall risk of surgical recurrence was 35.9%. The risk of major abdominal surgery significantly decreased between 2000 and 2009 when compared with the 1970 to 1979 period (OR = 0.49 (95% CI, 0.34–0.70). However, the rate of perianal surgery significantly increased (OR = 5.76 (95% CI, 2.54–13.06)). The main indications for surgery were enteric stricture or obstruction, perianal disease, and intra-abdominal fistulas/abscess. Of the 972 patients over 4 decades, only 11 patients (1.1%) were diagnosed with colorectal cancer. LIMITATIONS: This was a specialist-referred cohort, not a population-based study. CONCLUSIONS: The rate of major abdominal surgery has decreased, with surgery reserved for more severe and complicated disease. The natural history of patients with more complicated Crohn’s disease and severe phenotypes puts them at higher risk of surgical recurrence and emergency surgery. There has been no reduction in emergency surgery rates and there has been an increase in surgical recurrence despite the reduction in surgical rate morbidity. See Video Abstract at http://links.lww.com/DCR/A483.

Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer

Despite an extensive literature suggesting that high microsatellite instability (MSI‐H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk.