[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

[Observational study on perioperative outcomes of pelvic exenteration].

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.

Prospective evaluation of pentafecta outcomes at 5 years after laparoscopic radical prostatectomy: results of 170 patients at a single center.

A new and more comprehensive methodology for reporting outcomes after radical prostatectomy (RP) has been proposed: the so-called pentafecta. However, no prior studies reported intermediate- and long-term pentafecta outcomes after laparoscopic RP. We collected prospectively the clinical data of 170 consecutive patients with a minimum 60-month follow-up undergoing laparoscopic RP for clinically localized prostate cancer. International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the Sexual Health Inventory for Men score were used to evaluate the functional outcomes. Logistic regression was used to perform univariable and multivariable analyses. Sixty months after surgery, a pentafecta outcome was achieved by 124 patients (72.9%). On univariable regression analysis, patient age at surgery (P<0.001), body mass index (P=0.031), pathological T stage (P<0.001) and prostate volume (P=0.003) were significantly associated with pentafecta rates. On multivariable analysis, only patient age at surgery (odds ratio 0.95; P=0.006) and pathological T stage (odds ratio 0.82; P<0.001) were independent predictors of pentafecta rates. Using validated questionnaires to assess functional outcomes, for the first time, we evaluated pentafecta outcomes at 5 years after laparoscopic RP. This approach may be beneficial and could be used when counseling patients with clinically localized prostate cancer.

Local instillation of Staphylococcus aureus peptidoglycan at operation prevents wound healing impairment after trauma.

BACKGROUND: Considerable experimental evidence and limited clinical evidence indicate that wound healing is impaired after trauma. Because Staphylococcus aureus peptidoglycan (SaPG) accelerates healing in normal rats and prevents wound healing impairment induced by glucocorticoids, cyclophosphamide, and streptozotocin-diabetes, we hypothesized that SaPG would prevent the impaired wound healing after trauma. METHODS: In each of two experiments, 18 Sprague-Dawley male rats were divided into two groups, nine rats each, paired by weight; one group received unilateral comminuted femoral fracture and wounding (two dorsal skin incisions and six subcutaneous polyvinyl alcohol [PVA] sponges), and the other group was only wounded. The incision and PVA sponges on one side were inoculated at operation with saline (200 microL/incision, 50 microL/sponge) and on the other side with SaPG in saline (860 microg of SaPG per centimeter of incision, 0.5 mg of SaPG per sponge). Rats ate chow and drank tap water ad libitum and were killed 7 days postoperatively. RESULTS: In both experiments, the wound breaking strength (WBS) of saline-inoculated incisions was significantly lower in rats with femoral fracture; histologically, reparative granulation tissue was looser and less prominent. WBS of SaPG-inoculated incisions in rats with and without femoral fracture was significantly higher than that of saline-inoculated incisions and, histologically, reparative tissue was more prevalent, more closely packed, and more mature. WBS of SaPG-inoculated incisions in rats with femoral fracture was similar to that of saline-inoculated incisions in rats without femoral fracture. Reparative tissue hydroxyproline and histologic findings of saline-inoculated PVA sponge reparative tissue were similar in all rats, as were the increases induced by SaPG inoculation. CONCLUSION: Wound breaking strength and histologic findings of skin incisions (impaired in rats with unilateral femoral fracture) are more sensitive to the adverse effects of trauma than accumulation of PVA sponge reparative tissue. A single inoculation of SaPG at operation increased wound incision healing in rats both without and with femoral fracture and notably prevented the impaired healing in rats with femoral fracture.

Lethality of standard total parenteral nutrition following major liver resection in rats is prevented by high arginine and high branched chain amino acids but not by glutamine.

Standard total parenteral nutrition (TPN), with or without fat, in amounts approximating the ad libitum intake of normal rats is highly lethal for rats following 70% hepatectomy. Because of significant metabolic changes including alterations of branched chain amino acids (BCAA), arginine (ARG), and glutamine (GLN) associated with serious injury, sepsis, and liver dysfunction, we hypothesized that (1) increasing concentrations of BCAA and ARG in TPN and (2) including glutamine in the TPN may diminish the lethality. Male Sprague-Dawley rats with 70% hepatectomy and jugular vein catheterization were divided into groups. Two sets of experiments were conducted. In Experiment 1, the effects of varying concentrations of BCAA and ARG in the TPN infusate, singly and together, were assessed: Group 1, Standard TPN (19% BCAA, 4.8 g ARG/L); Group II, High BCAA TPN (35% BCAA, 4.8 g ARG/L); Group III, High ARG TPN (19% BCAA, 9.6 g ARG/L); Group IV, High ARG, High BCAA TPN (35% BCAA, 9.6 g ARG/L; Group V, chow and tap water ad libitum. In experiment 2, the effect of 2% GLN in TPN was evaluated: Group A, Standard TPN and Group B, 2% GLN TPN. All infusates were isocaloric (216 Kcal/Kg/d) and isonitrogenous (1.94 g N/Kg/d) delivered at half concentration on postoperative day 1, 3/4 concentration on postoperative day 2, and at full concentration thereafter. Experiment 1: Thirty-three to 36% of rats in Groups I (Standard TPN) (4/11), II (High BCAA TPN) (4/11) and III (High ARG TPN) (4/12) died within 6 days. In sharp contrast, none died in Groups IV (High BCAA, High ARG TPN) and V (rat chow and tap water) (P < 0.05 in each comparison). Among rats in the 4 TPN groups surviving 7 days, there were no significant differences in body weight change (minus 3-4%), spleen or lung weight, extent of liver regeneration (61-66%). Serum total protein and albumin were significantly higher in Group V (chow-fed) (similar to values in normal rats) than in Groups I-IV, P < 0.05 in each case. Serum total bilirubin was significantly higher in Group I than in normals and in Groups II, III, and V. Serum lactate dehydrogenase levels were similar in normals and all 5 groups. Serum aspartate amino transferase level was higher in Group I than in normals but not significantly different from those groups II-V; the latter were similar to normals. Experiment 2: Thirty percent of rats in Groups A (Standard TPN) (3/10) and B (GLN TPN) (3/10) died within 6 days. Among rats surviving for 7 days, body weight change (minus 3-5%), liver regeneration (67-70%), and liver tests were similar in both groups. TPN modified to contain high concentrations of both BCAA and ARG (but not of either alone) prevented the high frequency of lethality induced by standard TPN in rats with 70% hepatectomy. No such salutary effect was shown by modifying the TPN to contain 2% GLN. The striking benefit observed when TPN containing high BCAA and high ARG was infused may be due to the high BCAA leading toward normalization of serum amino acid levels, reducing proteolysis, increasing protein synthesis, and accelerating early liver regeneration, combined with the high ARG likely reducing serum ammonia and leading to increased host defense, and perhaps, thereby, preventing bacterial translocation and bacteremia.

Wound healing: captopril, an angiogenesis inhibitor, and Staphylococcus aureus peptidoglycan.

BACKGROUND: Captopril, an angiotensin-converting enzyme inhibitor, used for treating hypertension and heart failure, inhibits angiogenesis in the corneas of rats in response to basic fibroblast growth factor, slows the growth of experimental tumors in rats, and leads to the regression of Kaposi's sarcoma. Because angiogenesis is key to wound healing, we hypothesized that captopril would impair wound healing. We hypothesized also that because local application at operation of Staphylococcus aureus peptidoglycan (SaPG) increases angiogenesis and accelerates wound healing in rats, SaPG would prevent or ameliorate the postulated captopril-impaired wound healing. MATERIALS AND METHODS: In each experiment, rats were divided randomly into two groups: one drinking tap water, and the other, tap water containing 0.5 mg captopril/ml. All ate chow and drank ad libitum, pre-operatively (4-12 days) and postoperatively (7 days). In experiments 1 and 2, bilateral paravertebral 5.5-cm skin incisions were made aseptically (intraperitoneal sodium pentobarbital), and closed with interrupted No. 35 stainless-steel sutures. On one side, the wound was immediately inoculated with 157 microliter pyrogen-free isotonic saline and on the other side the wound was inoculated with 157 microliter saline containing 4.7 mg SaPG (860 microgram SaPG/cm incision). In the third experiment, polyvinyl alcohol (PVA) sponges (16-17 mg dry wt each) containing either 50 microliter saline or 0.5 mg SaPG in 50 microliter saline were implanted subcutaneously, two on each side, via 1-cm incisions closed with a single suture. In the fourth experiment, 5.5-cm bilateral skin incisions and subcutaneous implantation of PVA sponges were done as described but all sites were instilled with saline only. All rats were euthanized (CO(2) asphyxia) 7 days postoperatively. RESULTS: Wound breaking strength (WBS) of the saline-treated incisions was significantly higher (P < 0.001) in captopril-treated rats than in controls (172 +/- 13 g vs 105 +/- 6 g) in experiment 1 and higher, but not significantly in captopril-treated rats in experiment 2 (153 +/- 8 g vs 114 +/- 6 g) (PNS). SaPG inoculation of the incisions increased WBS significantly in both control and captopril-treated rats: 187 +/- 11 g vs 105 +/- 6 g (P < 0.001) and 283 +/- 16 g vs 172 +/- 13 g (P < 0.001), respectively, in experiment 1, and 217 +/- 13 g vs 114 +/- 6 g (P < 0.0001) (controls) and 266 +/- 17 g vs 153 +/- 8 g (captopril-treated rats) (P < 0.0001) in experiment 2. In experiment 3, subcutaneous PVA saline-inoculated sponge reparative tissue hydroxyproline (OHP) content was similar in control and captopril-treated rats, and SaPG inoculation increased reparative tissue OHP significantly in both groups: 2458 +/- 218 microgram/100 mg dry sponge vs 3869 +/- 230 microgram/100 mg (P < 0.001) (controls) and 2489 +/- 166 microgram/100 mg vs 4176 +/- 418 microgram/100 mg (P < 0.001) (captopril-treated rats). Histologically, angiogenesis and reparative tissue collagen were similar in control and captopril-treated rats, in both saline-inoculated and SaPG-inoculated sponges. In experiment 4 (all incisions and subcutaneous PVA sponges were saline-inoculated), there was no significant difference in WBS between control and captopril-treated rats (107 +/- 6 g vs 96 +/- 5 g, NS). PVA sponge reparative tissue OHP was significantly higher in captopril-treated rats: 3698 +/- 170 microgram/100 mg dry sponge vs 2534 +/- 100 microgram/100 mg (P < 0.0001). CONCLUSION: Unexpectedly, in four experiments, captopril did not inhibit WBS or PVA sponge reparative tissue angiogenesis or collagen accumulation; in fact, WBS was increased significantly in one of three experiments, and PVA sponge reparative tissue OHP was increased significantly in one of two experiments. Also, captopril did not interfere with the wound healing-accelerating effect of SaPG.

Single local instillation of Staphylococcus aureus peptidoglycan prevents diabetes-induced impaired wound healing.

Diabetes-induced impaired wound healing is characterized by inhibition of the inflammatory response to wounding, macrophage infiltration, angiogenesis, fibroplasia, reparative collagen accumulation, and wound breaking strength. Because all of these processes are accelerated in normal rats by a single local application at operation of Staphylococcus aureus peptidoglycan, we hypothesized that S. aureus peptidoglycan would prevent diabetes-induced impaired wound healing, despite persistent, untreated hyperglycemia, polydipsia, glycosuria, and polyuria. Sprague- Dawley male rats were divided into two groups. One group received an intraperitoneal injection of streptozotocin (65 mg/kg) in citrate solution; the other group received an intraperitoneal injection of an equivalent volume of citrate solution. Seventeen days after the injections, the diabetic and control rats received aseptically two 5.5-cm paravertebral incisions and subcutaneous implantation of six polyvinyl alcohol sponges, three on each side. On one side, each sponge contained 0.5 mg S. aureus peptidoglycan in 50 microliter saline solution, and the incision was inoculated along its length with 4.7 mg S. aureus peptidoglycan in 157 microliter saline solution (860 microgram/S. aureus peptidoglycan/cm incision); on the other side, the same respective volumes of saline were used. During the preoperative and postoperative periods, diabetic rats lost a small amount of weight (2%), were hyperglycemic (363 +/- 10 mg/100 ml blood), polydipsic, glycosuric, and polyuric, whereas the controls gained weight (25%) and were normoglycemic (104 +/- 5 mg/100 ml blood); these differences were significantly different (p <.001 in each case). In controls, S. aureus peptidoglycan inoculation increased wound breaking strength (by a factor of 2.0) and hydroxyproline content (by a factor of 1.4; p <.001 in each case); in diabetics, there were significant decreases in wound breaking strength (by a factor of 1.7) and hydroxyproline content (by a factor of 1.3) of saline solution-inoculated incisions and sponges compared with the wound breaking strength and hydroxyproline content of saline solution-inoculated incisions and sponges in controls (p <.02 and p <.001, respectively). These decreases were completely prevented when the incisions and polyvinyl alcohol sponges had been inoculated at operation with S. aureus peptidoglycan; S. aureus peptidoglycan inoculation in the diabetic rats increased wound breaking strength by a factor of 2.2 and sponge reparative tissue hydroxyproline by a factor of 1.6 (p <.001 in each case). Thus, diabetes-induced impaired wound healing was prevented completely by a single local instillation at operation of S. aureus peptidoglycan, despite persistent, untreated hyperglycemia, polydipsia, polyuria, and glycosuria.

Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation.

High mortality occurs in rats with 70% hepatectomy fed intravenous (IV) total parenteral nutrition (TPN; 13.9% glucose, 4.17% amino acids, 1.46% fat, electrolytes, trace minerals, and vitamins providing 216 kcal.kg-1.d-1) but not when the identical nutrients are given at the same rate enterally (gastrostomy). We hypothesized that a difference in bacterial translocation (BT) was a contributing factor to this phenomenon. Forty-five male Sprague-Dawley rats (300-360 g) were divided into five groups and underwent the following: control (no operation), sham (intraperitoneal [IP] pentobarbital anesthesia, central venous and gastrostomy catheters, laparotomy, sham hepatectomy), standard oral feeding (SOF), TPN (IV nutrients), and total enteral nutrition (TEN; gastrostomy). The SOF, TPN, and TEN groups had IP pentobarbital anesthesia, central venous and gastrostomy catheters, and 70% hepatectomy. Postoperatively, control and SOF (both catheters plugged) rats ate a commercial rat chow and drank tap water ad libitum pre- and postoperatively. The sham, TPN, and TEN groups were given the identical infusate composition as above, but the nutrient concentrations were cut in half (110 kcal/kg) and three-quarters (165 kcal/kg) on postoperative days 1 and 2, respectively. At the end of postoperative day 2, all rats were euthanized. BT to mesenteric lymph nodes (MLNs), liver, spleen, and lungs was significantly higher in the TPN rats compared with all other groups, except that BT to the MLNs was similar in the TPN and TEN groups. Bacteremia was found only in the TPN rats. BT in TPN rats with 70% hepatectomy was significantly greater 48 h after operation than in those fed the identical nutrients enterally at the same rate; this correlates with the previously reported significantly greater mortality in rats with 70% hepatectomy receiving TPN.